Ignite Creation Date:
2025-12-24 @ 10:35 PM
Ignite Modification Date:
2026-01-26 @ 3:04 AM
Study NCT ID:
NCT02915835
Status:
COMPLETED
Last Update Posted:
2019-09-24
First Post:
2016-09-15
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Riociguat in Scleroderma Associated Digital Ulcers
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D045743', 'term': 'Scleroderma, Diffuse'}, {'id': 'C000721267', 'term': 'digital ulcers'}], 'ancestors': [{'id': 'D012595', 'term': 'Scleroderma, Systemic'}, {'id': 'D003240', 'term': 'Connective Tissue Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}, {'id': 'D012871', 'term': 'Skin Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C542595', 'term': 'riociguat'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'spino@umich.edu', 'phone': '7346155469', 'title': 'Dr. Cathie Spino', 'organization': 'University of Michigan'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'timeFrame': '16 weeks', 'description': 'Coding of adverse events into body system was performed by the study chair for adverse events and by the medical monitors for serious adverse events.', 'eventGroups': [{'id': 'EG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)', 'otherNumAtRisk': 9, 'deathsNumAtRisk': 9, 'otherNumAffected': 9, 'seriousNumAtRisk': 9, 'deathsNumAffected': 0, 'seriousNumAffected': 3}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;', 'otherNumAtRisk': 8, 'deathsNumAtRisk': 8, 'otherNumAffected': 8, 'seriousNumAtRisk': 8, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'Anemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Splenic infarct', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Heart Murmur', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Left bundle bramch block on EKG', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'GERD', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Hot flashes', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Elevated liver enzymes', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Right calf infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Ulcer infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Right arm laceration', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Calcinosis Ulcer over Right Knee', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Left Shoulder Pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Left Shoulder rotator cuff tear', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Left elbow bursitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Lightheadednes', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Shoulder surgery', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Surgical and medical procedures', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Cyanosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': "Worsening Raynaud's", 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Worsening digital ulcer', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'seriousEvents': [{'term': 'Lymphoma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'NSTEMI', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Digital ischemia of the right third toe', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}, {'term': 'Right 4th digit ulcer', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change From Baseline to End of Double-blind Treatment (Week 16) in Digital Ulcer Net Burden', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.22', 'spread': '0.458', 'groupId': 'OG000'}, {'value': '-0.98', 'spread': '0.425', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.70', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': 'Digital ulcer net burden is defined as the total number of "active" and indeterminate digital ulcers at an assessment. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity. A healed ulcer has complete re-epithelialization.', 'unitOfMeasure': 'ulcers', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants With Healing of Their Cardinal DU by Week 16', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '4', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.61', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Week 16', 'description': 'The proportion of participant whose active digital ulcer that was identified and designated by the investigator as the cardinal ulcer at Baseline is healed by week 16. The cardinal ulcer will be selected by the investigator based on the clinical judgment that it was amenable to and evaluable for healing. If there are several active digital ulcers, the cardinal ulcer could be either the largest or the most painful ulcer, or the ulcer that disturbed the patient the most. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants With Healing of All DUs at Baseline by Week 16', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Week 16', 'description': "The proportion of participants whose baseline DUs are considered healed (classified as 'healed' and not 'active' or 'indeterminate') by week 16. All baseline ulcers must be healed for the participant to be classified as having all baseline ulcers healed. Note that this end point does not consider whether a participant develops new DUs during the course of the study. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity. A healed ulcer has complete re-epithelialization.", 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants With no DUs at Week 16', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '2', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Week 16', 'description': "The proportion of participants with no digital ulcers at week 16. This end point does not consider the number of ulcers at baseline or during the course of the study; only the absence of 'active' and 'indeterminate' DUs at week 16. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity. A healed ulcer has complete re-epithelialization.", 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants With New Active and Indeterminate DU(s) Over the Course of the Double-blind Period', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants with new (i.e., not present at baseline) active and indeterminant DUs from baseline to Week 16. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants Who Develop Pressure Ulcers at Distal Interphalangeal (DIP) Location Over the Course of the Double-blind Period.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who develop a DIP pressure ulcer at baseline to Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants Who Develop Pressure Ulcers at Proximal Interphalangeal (PIP) Location Over the Course of the Double-blind Period.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '2', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who develop a PIP pressure ulcer at baseline to Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants Who Develop Pressure Ulcers at Metacarpophalangeal (MCPs) Location Over the Course of the Double-blind Period.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who develop a MCP pressure ulcer at baseline to Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants Who Develop Pressure Ulcers at the Elbows Over the Course of the Double-blind Period.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who develop a pressure ulcer at at the elbows at baseline to Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants With Healing of All Pressure Ulcers at the Distal Interphalangeal (DIP) Over the Course of the Double-blind Period.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants whose DIP pressure ulcers during the double-blind period were healed at Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants With Healing of All Pressure Ulcers at the Proximal Interphalangeal (PIP) Over the Course of the Double-blind Period.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants whose PIP pressure ulcers during the double-blind period were healed at Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants With Healing of All Pressure Ulcers at the Metacarpophalangeal (MCPs) Over the Course of the Double-blind Period.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants whose MCP pressure ulcers during the double-blind period were healed at Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants With Healing of All Pressure Ulcers at the Elbows Over the Course of the Double-blind Period.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants whose pressure ulcers at the elbows during the double-blind period were healed at Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Time to Healing of Cardinal DU', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '16.57', 'groupId': 'OG000', 'lowerLimit': '2.00', 'upperLimit': '17.57'}, {'value': '16.07', 'groupId': 'OG001', 'lowerLimit': '16.00', 'upperLimit': '16.14'}]}]}], 'analyses': [{'pValue': '.56', 'groupIds': ['OG001'], 'statisticalMethod': 'Log Rank', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline to Week 16', 'description': 'This is defined as the number of weeks from randomization to the earliest of healing, end of the double-blind period, or drop-out. Participants are censored if they drop-out or their cardinal DU has not healed by the end of the double-blind period. One active digital ulcer must be identified and designated by the investigator as the cardinal ulcer at Baseline. If several digital ulcers qualified, the cardinal ulcer could be either the largest or the most painful ulcer, or the ulcer that disturbed the patient the most. The cardinal ulcer will be selected by the investigator based on the clinical judgment that it was amenable to and evaluable for healing. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. Week 16 is defined as the end of the double-blind period; however, the protocol allowed a visit window of +/- 4 weeks.', 'unitOfMeasure': 'weeks', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Time to Healing of All Baseline DU', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '16.00', 'groupId': 'OG000', 'lowerLimit': '2.00', 'upperLimit': '16.86'}, {'value': '16.00', 'groupId': 'OG001', 'lowerLimit': '14.86', 'upperLimit': '16.43'}]}]}], 'analyses': [{'pValue': '.35', 'groupIds': ['OG001'], 'statisticalMethod': 'Log Rank', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline to Week 16', 'description': 'This is defined as the number of weeks from randomization to the earliest of all baseline DU(s) healed, end of the double-blind period, or drop-out. Participants are censored if they drop-out or all of their baseline DU(s) have not healed by the end of the double-blind period. A healed ulcer has complete re-epithelialization. Week 16 is defined as the end of the double-blind period; however, the protocol allowed a visit window of +/- 4 weeks.', 'unitOfMeasure': 'weeks', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Time to Development of New ('Active' or 'Indeterminate') DU", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '16.00', 'groupId': 'OG000', 'lowerLimit': '15.71', 'upperLimit': '16.86'}, {'value': '15.86', 'groupId': 'OG001', 'lowerLimit': '15.57', 'upperLimit': '16.43'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline to Week 16', 'description': 'This is defined as the number of weeks from randomization to the earliest of new DU, end of the double-blind period, or drop-out. Participants are censored if they drop-out or have not developed a new DU by the end of the double-blind period. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity. A healed ulcer has complete re-epithelialization. Week 16 is defined as the end of the double-blind period; however, the protocol allowed a visit window of +/- 4 weeks.', 'unitOfMeasure': 'weeks', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Raynaud's Condition Score", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.15', 'spread': '.691', 'groupId': 'OG000'}, {'value': '-0.82', 'spread': '.691', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.76', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The Raynaud's condition score is a daily patient assessment of Raynaud's phenomenon activity using a 0 -10 ordinal scale. It incorporates the cumulative frequency, duration, severity and impact of Raynaud's phenomenon attacks, reflecting the overall degree that Raynaud's has affected use of the participant's hands. A score of 0 indicates no difficulty and 10 indicates extreme difficulty with Raynaud's condition. A higher score means a worse outcome. The mean score will be calculated across the 7-day screening and week 16 periods for each participant.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Number of Raynaud's Attacks/Day", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.24', 'spread': '.323', 'groupId': 'OG000'}, {'value': '-0.96', 'spread': '.323', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.57', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The mean number of Raynaud's attacks each day will be calculated across the 7-day screening and week 16 periods for each participant. For the days when a participant does not have an attack, a score of 0 will be used.", 'unitOfMeasure': 'attacks per day', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Duration of Raynaud's Attacks", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-44.81', 'spread': '15.846', 'groupId': 'OG000'}, {'value': '150.3', 'spread': '15.846', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.40', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': 'The mean duration of attacks (in minutes) will be calculated across the 7-day screening and week 16 periods for each participant. For the days when a participant does not have an attack, a score of 0 will be used.', 'unitOfMeasure': 'minutes', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Patient's Assessment of Pain During a Raynaud's Attack", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.30', 'spread': '6.600', 'groupId': 'OG000'}, {'value': '-7.01', 'spread': '6.600', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.49', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "Pain because of Raynaud's disease (characterized as pain during a Raynaud's attack) is defined on a visual analogue scale, where 0 indicates no pain and 100 indicates very severe pain. A higher score means a worse outcome. The mean of the scales over a 7-day period are reported. For the days when a participant does not have an attack, a score of 0 will be used. The mean scale score for each symptom will be calculated across the 7-day screening and week 16 periods for each participant.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Patient's Assessment of Numbness During a Raynaud's Attack", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-19.73', 'spread': '8.899', 'groupId': 'OG000'}, {'value': '-15.44', 'spread': '8.899', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.75', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "Numbness because of Raynaud's disease (characterized as numbness during a Raynaud's attack) is defined on a visual analogue scale, where 0 indicates no numbness and 100 indicates very severe numbness. A higher score means a worse outcome. The mean of the scales over a 7-day period are reported. For the days when a participant does not have an attack, a score of 0 will be used. The mean scale score for each symptom will be calculated across the 7-day screening and week 16 periods for each participant.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Patient's Assessment of Tingling During a Raynaud's Attack", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '1.18', 'spread': '7.118', 'groupId': 'OG000'}, {'value': '-7.49', 'spread': '7.118', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.41', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "Tingling because of Raynaud's disease (characterized as tingling during a Raynaud's attack) is defined on a visual analogue scale, where 0 indicates no tingling and 100 indicates very severe tingling. A higher score means a worse outcome. The mean of the scales over a 7-day period are reported. For the days when a participant does not have an attack, a score of 0 will be used. The mean scale score for each symptom will be calculated across the 7-day screening and week 16 periods for each participant.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Physician's Assessment of Severity of Raynaud's Disease", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-3.00', 'spread': '0.736', 'groupId': 'OG000'}, {'value': '-1.86', 'spread': '0.788', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.31', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The severity of Raynaud's phenomenon, as assessed by the physician, ranges from 0 (not at all severe) to 10 (extremely severe). A higher score means a worse outcome.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Physician's Assessment of Severity of Digital Ulcers", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-3.54', 'spread': '0.886', 'groupId': 'OG000'}, {'value': '-3.81', 'spread': '0.948', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.84', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': 'The severity of digital ulcers, as assessed by the physician, ranges from 0 (not at all severe) to 10 (extremely severe). A higher score means a worse outcome.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Patient's Assessment of Severity of Raynaud's Disease", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-3.47', 'spread': '0.764', 'groupId': 'OG000'}, {'value': '-1.41', 'spread': '0.764', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.11', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The severity of Raynaud's phenomenon, as assessed by the patient, ranges from 0 (not at all severe) to 10 (extremely severe). A higher score means a worse outcome.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': "Severity of Raynaud's disease is calculated as the mean response on a 0-10 Likert scale."}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Patient's Assessment of Severity of Digital Ulcers", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-4.63', 'spread': '0.935', 'groupId': 'OG000'}, {'value': '-4.00', 'spread': '0.935', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.66', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': 'The severity of digital ulcers, as assessed by the patient, ranges from 0 (not at all severe) to 10 (extremely severe). A higher score means a worse outcome.', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Severity of digital ulcer(s) is calculated as the mean response on a 0-10 Likert scale.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Patient's Global Assessment for Overall Disease.", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0.31', 'spread': '0.915', 'groupId': 'OG000'}, {'value': '-1.19', 'spread': '0.915', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.27', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "This assessment represents the patient's assessment of the patient's global scleroderma on a 0 (excellent) -10 (extremely poor) Likert scale. A higher score means a worse outcome.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Physician's Global Assessment for Overall Disease.", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.17', 'spread': '0.548', 'groupId': 'OG000'}, {'value': '-0.66', 'spread': '0.586', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.54', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "This assessment represents the physician's assessment of the patient's current disease activity on a 0 (excellent) -10 (extremely poor) Likert scale. A higher score means a worse outcome.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in PROMIS-29 Physical Function', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-2.46', 'spread': '1.27', 'groupId': 'OG000'}, {'value': '-2.24', 'spread': '1.227', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.90', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline/Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the physical function domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome).', 'unitOfMeasure': 't-score', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in PROMIS-29 Anxiety', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-3.11', 'spread': '2.578', 'groupId': 'OG000'}, {'value': '-1.50', 'spread': '2.578', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.68', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the anxiety domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).y.', 'unitOfMeasure': 't-score', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in PROMIS-29 Depression', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-3.35', 'spread': '1.731', 'groupId': 'OG000'}, {'value': '-0.25', 'spread': '1.731', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.25', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the depression domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).', 'unitOfMeasure': 't-score', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in PROMIS-29 Fatigue', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0.64', 'spread': '1.903', 'groupId': 'OG000'}, {'value': '0.46', 'spread': '1.903', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.95', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the fatigue domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).', 'unitOfMeasure': 't-score', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in PROMIS-29 Sleep Disturbance', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.47', 'spread': '1.091', 'groupId': 'OG000'}, {'value': '0.94', 'spread': '1.091', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.38', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline/Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the sleep disturbance domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e.,worse outcome).', 'unitOfMeasure': 't-score', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in PROMIS-29 Pain Interference', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-3.69', 'spread': '1.798', 'groupId': 'OG000'}, {'value': '-3.06', 'spread': '1.798', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.82', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the pain interference domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).', 'unitOfMeasure': 't-score', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in PROMIS-29 Ability to Participate in Social Roles and Activities', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.68', 'spread': '1.104', 'groupId': 'OG000'}, {'value': '-0.46', 'spread': '1.104', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '.47', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the ability to participate in social roles and activities domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome).', 'unitOfMeasure': 't-score', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in PROMIS-29 Pain Intensity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-2.74', 'spread': '0.702', 'groupId': 'OG000'}, {'value': '-1.63', 'spread': '0.702', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.35', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the pain intensity domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).', 'unitOfMeasure': 't-score', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Overall HAQ-DI Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.01', 'spread': '0.149', 'groupId': 'OG000'}, {'value': '-0.06', 'spread': '0.160', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.84', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI overall score ranges from 0 (no disability) to 3 (severe disability). Higher score means worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in HAQ-DI Dressing and Grooming', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.16', 'spread': '0.18', 'groupId': 'OG000'}, {'value': '0.05', 'spread': '0.236', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.55', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in HAQ-DI Hygiene', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.39', 'spread': '0.279', 'groupId': 'OG000'}, {'value': '-0.27', 'spread': '0.298', 'groupId': 'OG001'}]}]}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in HAQ-DI Arising', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0.36', 'spread': '0.235', 'groupId': 'OG000'}, {'value': '0.02', 'spread': '0.251', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.34', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in HAQ-DI Reach', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0.37', 'spread': '0.253', 'groupId': 'OG000'}, {'value': '0.01', 'spread': '0.271', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.36', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in HAQ-DI Eating', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.53', 'spread': '0.154', 'groupId': 'OG000'}, {'value': '0.03', 'spread': '0.166', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.04', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in HAQ-DI Grip', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0.16', 'spread': '0.215', 'groupId': 'OG000'}, {'value': '-0.18', 'spread': '0.230', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.32', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in HAQ-DI Walking', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0.35', 'spread': '0.199', 'groupId': 'OG000'}, {'value': '-0.12', 'spread': '0.214', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.14', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in HAQ-DI Common Daily Activities (IADL).', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.29', 'spread': '0.260', 'groupId': 'OG000'}, {'value': '0.04', 'spread': '0.278', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.41', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in HAQ-DI Composite Score for Hand Function', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.47', 'spread': '0.492', 'groupId': 'OG000'}, {'value': '-0.32', 'spread': '0.527', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.85', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability).The sum of the individual scores for dressing, hygiene, and grip from the HAQ-DI defines the composite score for hand function. The HAQ-DI composite score for hand function ranges from 0 (no disability) to 9 (severe disability). A higher score means worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Total Hand Disability in Systemic Sclerosis-DU (HDISS-DU) Score', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-0.47', 'spread': '0.492', 'groupId': 'OG000'}, {'value': '-0.32', 'spread': '0.527', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.85', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': 'The Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) questionnaire is a 24-item PRO measure. Each item is scored from 1-6 (1=yes, without difficulty; 2=yes, with a little difficulty; 3=yes, with some difficulty; 4=yes with much difficulty; 5=nearly impossible to do \\& used unaffected hand only; 6=impossible). The total HDISS-DU score is the mean of valid items, ranging from 1 to 6. Higher scores represent increased disability in hand functioning.', 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Scleroderma-HAQ-DI Visual Analogue Scales (VAS) Assessing Burden of Digital Ulcers', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-43.09', 'spread': '18.457', 'groupId': 'OG000'}, {'value': '-53.47', 'spread': '20.159', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.75', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much finger ulcers interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': "Change From Baseline to Week 16 in Scleroderma-HAQ-DI Visual Analogue Scales (VAS) Assessing Raynaud's Disease", 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-23.78', 'spread': '15.6', 'groupId': 'OG000'}, {'value': '-25.40', 'spread': '16.982', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.95', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much Raynaud's interfered with daily activities ranges from 0 (does not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Scleroderma-HAQ-DI Visual Analogue Scales (VAS) Assessing Gastrointestinal Involvement', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '16.72', 'spread': '13.787', 'groupId': 'OG000'}, {'value': '-7.39', 'spread': '14.975', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.31', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much intestinal problems interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Scleroderma-HAQ-DI Visual Analogue Scales (VAS) Assessing Breathing', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '8.35', 'spread': '8.90', 'groupId': 'OG000'}, {'value': '-12.69', 'spread': '8.978', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.14', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much breathing problems interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Scleroderma-HAQ-DI Visual Analogue Scales (VAS) Assessing Overall Disease,', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-50.35', 'spread': '9.039', 'groupId': 'OG000'}, {'value': '-35.74', 'spread': '9.751', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.32', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline to Week 16', 'description': "Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for disease severity ranges from 0 (no disease) to 150 (very severe). A higher score means a worse outcome.", 'unitOfMeasure': 'score on a scale', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants Who Experience Digital Ischemia Requiring Intravenous Prostacyclin or Digital Gangrene or Amputation During the Trial.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.47', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who experience digital ischemia requiring intravenous prostacyclin or digital gangrene or amputation during the double-blind period of the trial. These outcomes are collected within Adverse Events', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Proportion of Participants Who Develop Osteomyelitis During The Trial', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.00', 'groupIds': ['OG001'], 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who developed osteomyelitis during the double-blind period of the trial. Osteomyelitis is collected as an Adverse Event.', 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Vascular Biomarker VEGF in the Plasma', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-29.8', 'spread': '9.5', 'groupId': 'OG000'}, {'value': '-34.7', 'spread': '10.1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.73', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 16', 'unitOfMeasure': 'pg/ml', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Vascular Biomarker tPA in the Plasma', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-1.2', 'spread': '0.5', 'groupId': 'OG000'}, {'value': '-0.5', 'spread': '0.5', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.32', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 16', 'unitOfMeasure': 'ng/ml', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Vascular Biomarker sE-Selectin in the Plasma', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '-4.7', 'spread': '1.9', 'groupId': 'OG000'}, {'value': '-2.5', 'spread': '2.0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.45', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 16', 'unitOfMeasure': 'ng/ml', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Vascular Biomarker BFGF in the Plasma', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '0.20', 'spread': '0.28', 'groupId': 'OG000'}, {'value': '-0.03', 'spread': '0.29', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.58', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 16', 'unitOfMeasure': 'pg/ml', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Vascular Biomarker VCAM-1 in the Plasma', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '10.3', 'spread': '10.4', 'groupId': 'OG000'}, {'value': '-3.4', 'spread': '11.0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.39', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 16', 'unitOfMeasure': 'ng/ml', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 16 in Vascular Biomarker ICAM in the Plasma', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'classes': [{'categories': [{'measurements': [{'value': '70.5', 'spread': '47.3', 'groupId': 'OG000'}, {'value': '-39.', 'spread': '50.2', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.14', 'groupIds': ['OG001'], 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'Baseline and Week 16', 'unitOfMeasure': 'ng/ml', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED', 'populationDescription': 'Modified Intent to Treat Population is defined as all participants randomized, receiving at least one dose of treatment, and having at least one post-baseline efficacy assessment.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '8'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '7'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Physician Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}, {'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '17', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)\n\nRiociguat: riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.\n\nPlacebo: Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '43', 'spread': '14', 'groupId': 'BG000'}, {'value': '61', 'spread': '17', 'groupId': 'BG001'}, {'value': '51', 'spread': '18', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Age, Customized', 'classes': [{'title': 'Age Categories', 'categories': [{'title': '18 to 35 years', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}, {'title': '>35 to 55 years', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}, {'title': '>55 to 75 years', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}]}, {'title': '>75 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '5', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '17', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Black or African American', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}, {'title': 'White', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}]}, {'title': 'More than one race', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Number of digital ulcers at screening', 'classes': [{'categories': [{'measurements': [{'value': '2.67', 'spread': '1.803', 'groupId': 'BG000'}, {'value': '2.50', 'spread': '1.690', 'groupId': 'BG001'}, {'value': '2.59', 'spread': '1.698', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'defined as active and painful indeterminate digital ulcers', 'unitOfMeasure': 'number of digital ulcers', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Type of scleroderma at screening', 'classes': [{'categories': [{'title': 'limited cutaneous', 'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '9', 'groupId': 'BG002'}]}, {'title': 'diffuse cutaneous', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': "Time since first non-Raynaud's Symptom", 'classes': [{'categories': [{'measurements': [{'value': '7.09', 'spread': '5.933', 'groupId': 'BG000'}, {'value': '17.49', 'spread': '11.09', 'groupId': 'BG001'}, {'value': '11.98', 'spread': '10.060', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': "time since first non-Raynaud's symptom until screening visit", 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': "Time since first Raynaud's Phenomenon symptom", 'classes': [{'categories': [{'measurements': [{'value': '7.49', 'spread': '6.649', 'groupId': 'BG000'}, {'value': '14.5', 'spread': '7.872', 'groupId': 'BG001'}, {'value': '11.01', 'spread': '7.920', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': "Time since first Raynaud's Phenomenon symptom until the screening visit", 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Time since Scleroderma Diagnosis', 'classes': [{'categories': [{'measurements': [{'value': '6.23', 'spread': '5.765', 'groupId': 'BG000'}, {'value': '15.0', 'spread': '8.05', 'groupId': 'BG001'}, {'value': '10.37', 'spread': '8.156', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'Time since the diagnosis of scleroderma until the screening visit', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Time since first Digital Ulcer', 'classes': [{'categories': [{'measurements': [{'value': '5.41', 'spread': '4.563', 'groupId': 'BG000'}, {'value': '8.07', 'spread': '6.842', 'groupId': 'BG001'}, {'value': '6.66', 'spread': '5.725', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'SHAQ: Finger ulcers interfere with daily activities in past week', 'classes': [{'categories': [{'measurements': [{'value': '116', 'groupId': 'BG000', 'lowerLimit': '98', 'upperLimit': '125'}, {'value': '55', 'groupId': 'BG001', 'lowerLimit': '36', 'upperLimit': '102'}, {'value': '98', 'groupId': 'BG002', 'lowerLimit': '62', 'upperLimit': '124'}]}]}], 'paramType': 'MEDIAN', 'description': 'The Scleroderma Health Assessment Questionnaire (SHAQ) visual analogue scale assessing the burden of digital ulcers (In the past week, how much have your finger ulcers interfered with your daily activities?). The score indicates degree of limitation of activity from a scale of 0 (no limitation) to 150 (most limitation).', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': "Raynaud's condition score", 'classes': [{'categories': [{'measurements': [{'value': '3.4', 'spread': '2.2', 'groupId': 'BG000'}, {'value': '5.4', 'spread': '1.6', 'groupId': 'BG001'}, {'value': '4.5', 'spread': '2.1', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': "The Raynaud's condition score is a daily patient assessment of Raynaud's phenomenon activity using a 0 -10 ordinal scale. It incorporates the cumulative frequency, duration, severity and impact of Raynaud's phenomenon attacks, reflecting the overall degree that Raynaud's has affected use of the participant's hands. A score of 0 indicates no difficulty and 10 indicates extreme difficulty with Raynaud's condition.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': "Number of Raynaud's attacks per day", 'classes': [{'categories': [{'measurements': [{'value': '4.3', 'spread': '1.7', 'groupId': 'BG000'}, {'value': '2.2', 'spread': '1.7', 'groupId': 'BG001'}, {'value': '3.3', 'spread': '2.0', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': "The number of Raynaud's attacks is the mean number of Raynaud's attacks per day over a 7-day period.", 'unitOfMeasure': 'attacks per day', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': "Pain during a Raynaud's attack", 'classes': [{'categories': [{'measurements': [{'value': '54.9', 'spread': '13.1', 'groupId': 'BG000'}, {'value': '37.2', 'spread': '24.6', 'groupId': 'BG001'}, {'value': '46.6', 'spread': '20.7', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': "Pain because of Raynaud's disease (characterized as pain during a Raynaud's attack) is defined on a visual analogue scale, where 0 indicates no pain and 100 indicates very severe pain. The mean of the scales over a 7-day period are reported.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': "Numbness during a Raynaud's attack", 'classes': [{'categories': [{'measurements': [{'value': '40.5', 'spread': '15.9', 'groupId': 'BG000'}, {'value': '32.0', 'spread': '30.2', 'groupId': 'BG001'}, {'value': '36.5', 'spread': '23.2', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': "Numbness because of Raynaud's disease (characterized as numbness during a Raynaud's attack) is defined on a visual analogue scale, where 0 indicates no numbness and 100 indicates very severe numbness. The mean of the scales over a 7-day period are reported.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': "Tingling during a Raynaud's attack", 'classes': [{'categories': [{'measurements': [{'value': '34.8', 'spread': '16.6', 'groupId': 'BG000'}, {'value': '26.9', 'spread': '16.1', 'groupId': 'BG001'}, {'value': '31.1', 'spread': '16.3', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': "Tingling because of Raynaud's disease (characterized as tingling during a Raynaud's attack) is defined on a visual analogue scale, where 0 indicates no tingling and 100 indicates very severe tingling. The mean of the scales over a 7-day period are reported.", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': "Duration of Raynaud's attacks", 'classes': [{'categories': [{'measurements': [{'value': '101.4', 'spread': '117.3', 'groupId': 'BG000'}, {'value': '47.9', 'spread': '51.6', 'groupId': 'BG001'}, {'value': '76.4', 'spread': '93.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': "The mean duration of a Raynaud's attack (in minutes) is calculated across a 7-day period. For the days when a participant does not have an attack, a value of 0 is used in the calculation.", 'unitOfMeasure': 'minutes', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': "Severity of patient assessment of Raynaud's phenomenon", 'classes': [{'categories': [{'measurements': [{'value': '7.1', 'spread': '1.4', 'groupId': 'BG000'}, {'value': '4.2', 'spread': '2.7', 'groupId': 'BG001'}, {'value': '5.8', 'spread': '2.5', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': "The severity of Raynaud's phenomenon, as assessed by the patient, ranges from 0 (not at all severe) to 10 (extremely severe).", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Severity of patient assessment of digital ulcers', 'classes': [{'categories': [{'measurements': [{'value': '8.0', 'spread': '1.5', 'groupId': 'BG000'}, {'value': '6.7', 'spread': '1.9', 'groupId': 'BG001'}, {'value': '7.4', 'spread': '1.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'The severity of digital ulcers, as assessed by the patient, ranges from 0 (not at all severe) to 10 (extremely severe).', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': "Severity of physician assessment of Raynaud's phenomenon", 'classes': [{'categories': [{'measurements': [{'value': '6.1', 'spread': '1.0', 'groupId': 'BG000'}, {'value': '5.4', 'spread': '3.0', 'groupId': 'BG001'}, {'value': '5.8', 'spread': '2.1', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': "The severity of Raynaud's phenomenon, as assessed by the physician, ranges from 0 (not at all severe) to 10 (extremely severe).", 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Severity of physician assessment of digital ulcers', 'classes': [{'categories': [{'measurements': [{'value': '6.4', 'spread': '1.9', 'groupId': 'BG000'}, {'value': '6.3', 'spread': '2.6', 'groupId': 'BG001'}, {'value': '6.4', 'spread': '2.1', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'description': 'The severity of digital ulcers, as assessed by the physician, ranges from 0 (not at all severe) to 10 (extremely severe).', 'unitOfMeasure': 'units on a scale', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Systemic scleroderma-related antibodies', 'classes': [{'categories': [{'title': 'Anti-centromere B', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}]}, {'title': 'Anti-topoisomerase I', 'measurements': [{'value': '2', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}, {'title': 'Anti-RNA polymerase III', 'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}, {'title': 'Not done', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '5', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Baseline use of vasodilators', 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'All randomized participants who received at least one dose of study medication.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2017-07-10', 'size': 1033128, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2019-07-24T22:00', 'hasProtocol': True}, {'date': '2018-08-22', 'size': 801493, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2019-07-24T22:01', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 17}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2016-09'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-09', 'completionDateStruct': {'date': '2018-07-24', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-09-03', 'studyFirstSubmitDate': '2016-09-15', 'resultsFirstSubmitDate': '2019-07-25', 'studyFirstSubmitQcDate': '2016-09-22', 'lastUpdatePostDateStruct': {'date': '2019-09-24', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2019-09-03', 'studyFirstPostDateStruct': {'date': '2016-09-27', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2019-09-24', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2018-07-24', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change From Baseline to End of Double-blind Treatment (Week 16) in Digital Ulcer Net Burden', 'timeFrame': 'Baseline to Week 16', 'description': 'Digital ulcer net burden is defined as the total number of "active" and indeterminate digital ulcers at an assessment. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity. A healed ulcer has complete re-epithelialization.'}], 'secondaryOutcomes': [{'measure': 'Proportion of Participants With Healing of Their Cardinal DU by Week 16', 'timeFrame': 'Week 16', 'description': 'The proportion of participant whose active digital ulcer that was identified and designated by the investigator as the cardinal ulcer at Baseline is healed by week 16. The cardinal ulcer will be selected by the investigator based on the clinical judgment that it was amenable to and evaluable for healing. If there are several active digital ulcers, the cardinal ulcer could be either the largest or the most painful ulcer, or the ulcer that disturbed the patient the most. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis.'}, {'measure': 'Proportion of Participants With Healing of All DUs at Baseline by Week 16', 'timeFrame': 'Week 16', 'description': "The proportion of participants whose baseline DUs are considered healed (classified as 'healed' and not 'active' or 'indeterminate') by week 16. All baseline ulcers must be healed for the participant to be classified as having all baseline ulcers healed. Note that this end point does not consider whether a participant develops new DUs during the course of the study. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity. A healed ulcer has complete re-epithelialization."}, {'measure': 'Proportion of Participants With no DUs at Week 16', 'timeFrame': 'Week 16', 'description': "The proportion of participants with no digital ulcers at week 16. This end point does not consider the number of ulcers at baseline or during the course of the study; only the absence of 'active' and 'indeterminate' DUs at week 16. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity. A healed ulcer has complete re-epithelialization."}, {'measure': 'Proportion of Participants With New Active and Indeterminate DU(s) Over the Course of the Double-blind Period', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants with new (i.e., not present at baseline) active and indeterminant DUs from baseline to Week 16. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.'}, {'measure': 'Proportion of Participants Who Develop Pressure Ulcers at Distal Interphalangeal (DIP) Location Over the Course of the Double-blind Period.', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who develop a DIP pressure ulcer at baseline to Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.'}, {'measure': 'Proportion of Participants Who Develop Pressure Ulcers at Proximal Interphalangeal (PIP) Location Over the Course of the Double-blind Period.', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who develop a PIP pressure ulcer at baseline to Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.'}, {'measure': 'Proportion of Participants Who Develop Pressure Ulcers at Metacarpophalangeal (MCPs) Location Over the Course of the Double-blind Period.', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who develop a MCP pressure ulcer at baseline to Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.'}, {'measure': 'Proportion of Participants Who Develop Pressure Ulcers at the Elbows Over the Course of the Double-blind Period.', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who develop a pressure ulcer at at the elbows at baseline to Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.'}, {'measure': 'Proportion of Participants With Healing of All Pressure Ulcers at the Distal Interphalangeal (DIP) Over the Course of the Double-blind Period.', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants whose DIP pressure ulcers during the double-blind period were healed at Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.'}, {'measure': 'Proportion of Participants With Healing of All Pressure Ulcers at the Proximal Interphalangeal (PIP) Over the Course of the Double-blind Period.', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants whose PIP pressure ulcers during the double-blind period were healed at Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.'}, {'measure': 'Proportion of Participants With Healing of All Pressure Ulcers at the Metacarpophalangeal (MCPs) Over the Course of the Double-blind Period.', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants whose MCP pressure ulcers during the double-blind period were healed at Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.'}, {'measure': 'Proportion of Participants With Healing of All Pressure Ulcers at the Elbows Over the Course of the Double-blind Period.', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants whose pressure ulcers at the elbows during the double-blind period were healed at Week 16. Pressure ulcer is defined as an active or indeterminate ulcer. An active ulcer is defined as a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity.'}, {'measure': 'Time to Healing of Cardinal DU', 'timeFrame': 'Baseline to Week 16', 'description': 'This is defined as the number of weeks from randomization to the earliest of healing, end of the double-blind period, or drop-out. Participants are censored if they drop-out or their cardinal DU has not healed by the end of the double-blind period. One active digital ulcer must be identified and designated by the investigator as the cardinal ulcer at Baseline. If several digital ulcers qualified, the cardinal ulcer could be either the largest or the most painful ulcer, or the ulcer that disturbed the patient the most. The cardinal ulcer will be selected by the investigator based on the clinical judgment that it was amenable to and evaluable for healing. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. Week 16 is defined as the end of the double-blind period; however, the protocol allowed a visit window of +/- 4 weeks.'}, {'measure': 'Time to Healing of All Baseline DU', 'timeFrame': 'Baseline to Week 16', 'description': 'This is defined as the number of weeks from randomization to the earliest of all baseline DU(s) healed, end of the double-blind period, or drop-out. Participants are censored if they drop-out or all of their baseline DU(s) have not healed by the end of the double-blind period. A healed ulcer has complete re-epithelialization. Week 16 is defined as the end of the double-blind period; however, the protocol allowed a visit window of +/- 4 weeks.'}, {'measure': "Time to Development of New ('Active' or 'Indeterminate') DU", 'timeFrame': 'Baseline to Week 16', 'description': 'This is defined as the number of weeks from randomization to the earliest of new DU, end of the double-blind period, or drop-out. Participants are censored if they drop-out or have not developed a new DU by the end of the double-blind period. Active ulcers are defined as having a denuded area with defined border and loss of epithelialization, loss of epidermis and dermis. An indeterminate ulcer is defined as denudation that could not be visualized and no other clinical features of activity. A healed ulcer has complete re-epithelialization. Week 16 is defined as the end of the double-blind period; however, the protocol allowed a visit window of +/- 4 weeks.'}, {'measure': "Change From Baseline to Week 16 in Raynaud's Condition Score", 'timeFrame': 'Baseline to Week 16', 'description': "The Raynaud's condition score is a daily patient assessment of Raynaud's phenomenon activity using a 0 -10 ordinal scale. It incorporates the cumulative frequency, duration, severity and impact of Raynaud's phenomenon attacks, reflecting the overall degree that Raynaud's has affected use of the participant's hands. A score of 0 indicates no difficulty and 10 indicates extreme difficulty with Raynaud's condition. A higher score means a worse outcome. The mean score will be calculated across the 7-day screening and week 16 periods for each participant."}, {'measure': "Change From Baseline to Week 16 in Number of Raynaud's Attacks/Day", 'timeFrame': 'Baseline to Week 16', 'description': "The mean number of Raynaud's attacks each day will be calculated across the 7-day screening and week 16 periods for each participant. For the days when a participant does not have an attack, a score of 0 will be used."}, {'measure': "Change From Baseline to Week 16 in Duration of Raynaud's Attacks", 'timeFrame': 'Baseline to Week 16', 'description': 'The mean duration of attacks (in minutes) will be calculated across the 7-day screening and week 16 periods for each participant. For the days when a participant does not have an attack, a score of 0 will be used.'}, {'measure': "Change From Baseline to Week 16 in Patient's Assessment of Pain During a Raynaud's Attack", 'timeFrame': 'Baseline to Week 16', 'description': "Pain because of Raynaud's disease (characterized as pain during a Raynaud's attack) is defined on a visual analogue scale, where 0 indicates no pain and 100 indicates very severe pain. A higher score means a worse outcome. The mean of the scales over a 7-day period are reported. For the days when a participant does not have an attack, a score of 0 will be used. The mean scale score for each symptom will be calculated across the 7-day screening and week 16 periods for each participant."}, {'measure': "Change From Baseline to Week 16 in Patient's Assessment of Numbness During a Raynaud's Attack", 'timeFrame': 'Baseline to Week 16', 'description': "Numbness because of Raynaud's disease (characterized as numbness during a Raynaud's attack) is defined on a visual analogue scale, where 0 indicates no numbness and 100 indicates very severe numbness. A higher score means a worse outcome. The mean of the scales over a 7-day period are reported. For the days when a participant does not have an attack, a score of 0 will be used. The mean scale score for each symptom will be calculated across the 7-day screening and week 16 periods for each participant."}, {'measure': "Change From Baseline to Week 16 in Patient's Assessment of Tingling During a Raynaud's Attack", 'timeFrame': 'Baseline to Week 16', 'description': "Tingling because of Raynaud's disease (characterized as tingling during a Raynaud's attack) is defined on a visual analogue scale, where 0 indicates no tingling and 100 indicates very severe tingling. A higher score means a worse outcome. The mean of the scales over a 7-day period are reported. For the days when a participant does not have an attack, a score of 0 will be used. The mean scale score for each symptom will be calculated across the 7-day screening and week 16 periods for each participant."}, {'measure': "Change From Baseline to Week 16 in Physician's Assessment of Severity of Raynaud's Disease", 'timeFrame': 'Baseline to Week 16', 'description': "The severity of Raynaud's phenomenon, as assessed by the physician, ranges from 0 (not at all severe) to 10 (extremely severe). A higher score means a worse outcome."}, {'measure': "Change From Baseline to Week 16 in Physician's Assessment of Severity of Digital Ulcers", 'timeFrame': 'Baseline to Week 16', 'description': 'The severity of digital ulcers, as assessed by the physician, ranges from 0 (not at all severe) to 10 (extremely severe). A higher score means a worse outcome.'}, {'measure': "Change From Baseline to Week 16 in Patient's Assessment of Severity of Raynaud's Disease", 'timeFrame': 'Baseline to Week 16', 'description': "The severity of Raynaud's phenomenon, as assessed by the patient, ranges from 0 (not at all severe) to 10 (extremely severe). A higher score means a worse outcome."}, {'measure': "Change From Baseline to Week 16 in Patient's Assessment of Severity of Digital Ulcers", 'timeFrame': 'Baseline to Week 16', 'description': 'The severity of digital ulcers, as assessed by the patient, ranges from 0 (not at all severe) to 10 (extremely severe). A higher score means a worse outcome.'}, {'measure': "Change From Baseline to Week 16 in Patient's Global Assessment for Overall Disease.", 'timeFrame': 'Baseline to Week 16', 'description': "This assessment represents the patient's assessment of the patient's global scleroderma on a 0 (excellent) -10 (extremely poor) Likert scale. A higher score means a worse outcome."}, {'measure': "Change From Baseline to Week 16 in Physician's Global Assessment for Overall Disease.", 'timeFrame': 'Baseline to Week 16', 'description': "This assessment represents the physician's assessment of the patient's current disease activity on a 0 (excellent) -10 (extremely poor) Likert scale. A higher score means a worse outcome."}, {'measure': 'Change From Baseline to Week 16 in PROMIS-29 Physical Function', 'timeFrame': 'Baseline/Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the physical function domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome).'}, {'measure': 'Change From Baseline to Week 16 in PROMIS-29 Anxiety', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the anxiety domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).y.'}, {'measure': 'Change From Baseline to Week 16 in PROMIS-29 Depression', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the depression domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).'}, {'measure': 'Change From Baseline to Week 16 in PROMIS-29 Fatigue', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the fatigue domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).'}, {'measure': 'Change From Baseline to Week 16 in PROMIS-29 Sleep Disturbance', 'timeFrame': 'Baseline/Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the sleep disturbance domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e.,worse outcome).'}, {'measure': 'Change From Baseline to Week 16 in PROMIS-29 Pain Interference', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the pain interference domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).'}, {'measure': 'Change From Baseline to Week 16 in PROMIS-29 Ability to Participate in Social Roles and Activities', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the ability to participate in social roles and activities domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., better outcome).'}, {'measure': 'Change From Baseline to Week 16 in PROMIS-29 Pain Intensity', 'timeFrame': 'Baseline to Week 16', 'description': 'The Patient-Reported Outcomes Measurement Information System (PROMIS) 29-item short-form health-reported quality of life measures (PROMIS-29) were administered. The transformed score (T-score) for the pain intensity domain was used, where 50 (10) is the mean (standard deviation) of a relevant reference population. Higher scores equals more of the concept being measured (i.e., worse outcome).'}, {'measure': 'Change From Baseline to Week 16 in Overall HAQ-DI Score', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI overall score ranges from 0 (no disability) to 3 (severe disability). Higher score means worse outcome."}, {'measure': 'Change From Baseline to Week 16 in HAQ-DI Dressing and Grooming', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome."}, {'measure': 'Change From Baseline to Week 16 in HAQ-DI Hygiene', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome."}, {'measure': 'Change From Baseline to Week 16 in HAQ-DI Arising', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome."}, {'measure': 'Change From Baseline to Week 16 in HAQ-DI Reach', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome."}, {'measure': 'Change From Baseline to Week 16 in HAQ-DI Eating', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome."}, {'measure': 'Change From Baseline to Week 16 in HAQ-DI Grip', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome."}, {'measure': 'Change From Baseline to Week 16 in HAQ-DI Walking', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome."}, {'measure': 'Change From Baseline to Week 16 in HAQ-DI Common Daily Activities (IADL).', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability). A higher score means worse outcome."}, {'measure': 'Change From Baseline to Week 16 in HAQ-DI Composite Score for Hand Function', 'timeFrame': 'Baseline to Week 16', 'description': "The HAQ-DI is the Health Assessment Question Disability Index that assesses the extent of a patient's functional ability. The HAQ-DI subscore ranges from 0 (no disability) to 3 (severe disability).The sum of the individual scores for dressing, hygiene, and grip from the HAQ-DI defines the composite score for hand function. The HAQ-DI composite score for hand function ranges from 0 (no disability) to 9 (severe disability). A higher score means worse outcome."}, {'measure': 'Change From Baseline to Week 16 in Total Hand Disability in Systemic Sclerosis-DU (HDISS-DU) Score', 'timeFrame': 'Baseline to Week 16', 'description': 'The Hand Disability in Systemic Sclerosis - Digital Ulcers (HDISS-DU) questionnaire is a 24-item PRO measure. Each item is scored from 1-6 (1=yes, without difficulty; 2=yes, with a little difficulty; 3=yes, with some difficulty; 4=yes with much difficulty; 5=nearly impossible to do \\& used unaffected hand only; 6=impossible). The total HDISS-DU score is the mean of valid items, ranging from 1 to 6. Higher scores represent increased disability in hand functioning.'}, {'measure': 'Change From Baseline to Week 16 in Scleroderma-HAQ-DI Visual Analogue Scales (VAS) Assessing Burden of Digital Ulcers', 'timeFrame': 'Baseline to Week 16', 'description': "Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much finger ulcers interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome."}, {'measure': "Change From Baseline to Week 16 in Scleroderma-HAQ-DI Visual Analogue Scales (VAS) Assessing Raynaud's Disease", 'timeFrame': 'Baseline to Week 16', 'description': "Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much Raynaud's interfered with daily activities ranges from 0 (does not limit activities) to 150 (very severe limitation). A higher score means a worse outcome."}, {'measure': 'Change From Baseline to Week 16 in Scleroderma-HAQ-DI Visual Analogue Scales (VAS) Assessing Gastrointestinal Involvement', 'timeFrame': 'Baseline to Week 16', 'description': "Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much intestinal problems interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome."}, {'measure': 'Change From Baseline to Week 16 in Scleroderma-HAQ-DI Visual Analogue Scales (VAS) Assessing Breathing', 'timeFrame': 'Baseline to Week 16', 'description': "Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for how much breathing problems interfered with daily activities ranges from 0 (do not limit activities) to 150 (very severe limitation). A higher score means a worse outcome."}, {'measure': 'Change From Baseline to Week 16 in Scleroderma-HAQ-DI Visual Analogue Scales (VAS) Assessing Overall Disease,', 'timeFrame': 'Baseline to Week 16', 'description': "Scleroderma-Health Assessment Question Disability Index visual analogue scales (VAS) assess the burden of digital ulcers, Raynaud's, gastrointestinal involvement, breathing, and overall disease. The VAS scale for disease severity ranges from 0 (no disease) to 150 (very severe). A higher score means a worse outcome."}, {'measure': 'Proportion of Participants Who Experience Digital Ischemia Requiring Intravenous Prostacyclin or Digital Gangrene or Amputation During the Trial.', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who experience digital ischemia requiring intravenous prostacyclin or digital gangrene or amputation during the double-blind period of the trial. These outcomes are collected within Adverse Events'}, {'measure': 'Proportion of Participants Who Develop Osteomyelitis During The Trial', 'timeFrame': 'Baseline to Week 16', 'description': 'The proportion of participants who developed osteomyelitis during the double-blind period of the trial. Osteomyelitis is collected as an Adverse Event.'}, {'measure': 'Change From Baseline to Week 16 in Vascular Biomarker VEGF in the Plasma', 'timeFrame': 'Baseline and Week 16'}, {'measure': 'Change From Baseline to Week 16 in Vascular Biomarker tPA in the Plasma', 'timeFrame': 'Baseline and Week 16'}, {'measure': 'Change From Baseline to Week 16 in Vascular Biomarker sE-Selectin in the Plasma', 'timeFrame': 'Baseline and Week 16'}, {'measure': 'Change From Baseline to Week 16 in Vascular Biomarker BFGF in the Plasma', 'timeFrame': 'Baseline and Week 16'}, {'measure': 'Change From Baseline to Week 16 in Vascular Biomarker VCAM-1 in the Plasma', 'timeFrame': 'Baseline and Week 16'}, {'measure': 'Change From Baseline to Week 16 in Vascular Biomarker ICAM in the Plasma', 'timeFrame': 'Baseline and Week 16'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Scleroderma', 'Digital Ulcer'], 'conditions': ['Scleroderma', 'Digital Ulcers']}, 'referencesModule': {'references': [{'pmid': '31481106', 'type': 'DERIVED', 'citation': 'Nagaraja V, Spino C, Bush E, Tsou PS, Domsic RT, Lafyatis R, Frech T, Gordon JK, Steen VD, Khanna D. A multicenter randomized, double-blind, placebo-controlled pilot study to assess the efficacy and safety of riociguat in systemic sclerosis-associated digital ulcers. Arthritis Res Ther. 2019 Sep 3;21(1):202. doi: 10.1186/s13075-019-1979-7.'}]}, 'descriptionModule': {'briefSummary': 'The primary objective of this study is to provide preliminary data on the efficacy (digital ulcer net burden) and safety of riociguat administered 3 times daily (TID) in comparison to placebo in patients with scleroderma-associated digital ulcers', 'detailedDescription': "This clinical trial is a US, multicenter, double-blind, randomized placebo-controlled, parallel- group study with a total of 20 participants planned to be randomized (approximately 10 participants to the riociguat group and 10 to the placebo group). In addition, a standardized wound care protocol will be followed by the investigators and digital photography will be taken of the cardinal ulcer.\n\nThe study will allow standard of care medications for the management of DU as background therapy. These may include calcium channel blockers, low dose aspirin, angiotensin enzyme inhibitors, etc. and will be determined by the participant's local physician.\n\nThe study design consists of three phases:\n\n* Screening phase: up to 2 weeks\n* Double-blind Treatment phase: 16 weeks of double-blind treatment, consisting of:\n* Dose titration period of up to 8 weeks, and\n* Stable dosing period of up to 8 weeks\n* Open-label Extension phase for participants with active DU at the end of the double- blind treatment phase or development of an active DU within a month of completing double-blind phase, consisting of:\n* Dose titration phase of up to 8 weeks\n* Stable dosing period for 8 weeks"}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n1. Signed written informed consent\n2. Men or women aged 18 years and older\n3. Diagnosis of Systemic sclerosis, as defined by 2013 American College of Rheumatology/ European Union League Against Rheumatism classification of SSc\n4. Patients had to have at least one visible, active ischemic DU at baseline located at or distal to the proximal interphalangeal joint, and that developed or worsened within 8 weeks prior to screening. NOTE: Presence of eschar will not be considered an active ulcer\n5. Females of reproductive potential (FRP) must have a negative, pre-treatment urine pregnancy test.\n6. FRP must obtain monthly urine pregnancy tests during treatment and one month after treatment discontinuation. Post-menopausal women (defined as no menses for at least 1 year or post-surgical from bilateral oophorectomy) are not required to undergo a pregnancy test.\n7. FRP and all non-vasectomized male participants must agree to use reliable contraception when sexually active. (For FRP's, 'Adequate contraception' is defined as any combination of at least 2 effective methods of birth control, of which at least one is a physical barrier (e.g., condoms with hormonal contraception or implants or combined oral contraceptives, certain intrauterine devices). This applies from the time of signing the informed consent form until one month after the last study drug administration.)\n8. Oral corticosteroids (≤ 10 mg/day of prednisone or equivalent), nonsteroidal anti- inflammatory drugs (NSAIDs), angiotensin receptor blockers, angiotensin converting enzyme (ACE) inhibitors and calcium channel blockers are permitted if the participant is on a stable dose for ≥ 2 weeks prior to and including the baseline visit\n9. Ability to comply with the clinical visits schedule and the study-related procedures.\n\nExclusion Criteria:\n\n1. Active DU related to calcinosis (as assessed by clinical examination or radiographic evaluation at screening)\n2. Medical and surgical history\n\n * Major surgery (including joint surgery) within 8 weeks prior to screening\n * Participants with a history of malignancy in the last 5 years other than non-melanoma skin cell cancers cured by local resection or carcinoma in situ\n3. Hepatic-related criteria\n\n \\- Hepatic insufficiency classified as Child-Pugh C at screening (see Appendix 11.1 for classification table) at screening visit\n4. Renal-related criteria\n\n * Estimated glomerular filtration rate (eGFR) \\< 15 mL/min/1.73m2 (MDRD formula) or on dialysis at the screening visit\n * Cardiovascular-related criteria\n * Sitting systolic blood pressure \\< 95 mmHg at the screening visit\n * Sitting heart rate \\< 50 beats per minute (BPM) at the screening visit\n * Left ventricular ejection fraction \\< 40% prior to screening on echocardiogram done as part of clinical care\n5. Pulmonary-related criteria\n\n * Active state of hemoptysis or pulmonary hemorrhage, including those events managed by bronchial artery embolization\n * Any history of bronchial artery embolization or massive hemoptysis within 3 months prior to screening. Massive hemoptysis being defined as acute bleeding \\>240 mL in a 24-hour period or recurrent bleeding \\>100 mL/d over several days\n * PAH requiring pharmacologic therapy.\n * Significant pulmonary disease with FVC ≤ 50% of predicted, or DLCO (uncorrected for hemoglobin ) ≤ 40% of predicted\n6. Laboratory examinations\n\n \\- Participants with hemoglobin \\< 9.0 g/dL, white blood cell (WBC) count \\< 3000/mm3 (\\< 3 × 109/L), platelet count \\< 100,000/mm3 (\\< 3 × 109/L) at the screening visit\n7. Prior and concomitant therapy\n\n * Concomitant use of nitrates or NO donors (such as amyl nitrate) in any form, including topical; phosphodiesterase (PDE) 5 (PDE5) inhibitors (such as sildenafil, tadalafil, vardenafil); and nonspecific PDE5 inhibitors (theophylline,dipyridamole). If the patient is on PDE5 inhibitors, a wash out of 3 days is required for sildenafil and 7 days for tadalafil or vardenafil prior to the baseline visit\n * Concomitant Endothelin receptor antagonist\n * Patients who are actively smoking at time of consent. (Quit date of two weeks prior to screening acceptable)\n8. Pregnant or breastfeeding women\n9. Other\n\n * Any other condition or therapy that would make the participant unsuitable for this study and will not allow participation for the full planned study period\n * Participation in another clinical study with an investigational drug or medical device within 30 days prior to randomization (phase I-III clinical studies)"}, 'identificationModule': {'nctId': 'NCT02915835', 'acronym': 'RESCUE', 'briefTitle': 'Riociguat in Scleroderma Associated Digital Ulcers', 'organization': {'class': 'OTHER', 'fullName': 'University of Michigan'}, 'officialTitle': 'A Multi-center Randomized, Double Blind, Placebo-controlled, Pilot Study to Assess the Efficacy and Safety of Riociguat in Scleroderma - Associated Digital Ulcers', 'orgStudyIdInfo': {'id': 'BAY63-2521'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'riociguat', 'description': 'Riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)', 'interventionNames': ['Drug: Riociguat']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Matching placebo tablets: 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg matching placebo tablet.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Riociguat', 'type': 'DRUG', 'otherNames': ['Adempas'], 'description': 'riociguat 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID; dose titration starting with 1.0 mg (planned up-titration every 2 weeks, with possibility of dose reduction for tolerability; 0.5 mg is the lowest dose and 2.5 mg is the highest dose to be administered)', 'armGroupLabels': ['riociguat']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo 0.5 mg, 1 mg, 1.5 mg, 2 mg and 2.5 mg administered TID;', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '20007', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': 'Georgetown University', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '48109', 'city': 'Ann Arbor', 'state': 'Michigan', 'country': 'United States', 'facility': 'University of Michigan', 'geoPoint': {'lat': 42.27756, 'lon': -83.74088}}, {'zip': '10035', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Hospital of Special Surgery (HSS)', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '15261', 'city': 'Pittsburgh', 'state': 'Pennsylvania', 'country': 'United States', 'facility': 'University of Pittsburgh', 'geoPoint': {'lat': 40.44062, 'lon': -79.99589}}, {'zip': '84132', 'city': 'Salt Lake City', 'state': 'Utah', 'country': 'United States', 'facility': 'University of Utah', 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}], 'overallOfficials': [{'name': 'Dinesh Khanna, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Michigan'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Dinesh Khanna, MD, MS', 'class': 'OTHER'}, 'collaborators': [{'name': 'Bayer', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR_INVESTIGATOR', 'investigatorTitle': 'Professor of Rheumatology/ Internal Medicine', 'investigatorFullName': 'Dinesh Khanna, MD, MS', 'investigatorAffiliation': 'University of Michigan'}}}}