Ignite Creation Date:
2025-12-24 @ 10:46 PM
Ignite Modification Date:
2026-01-06 @ 9:27 AM
Study NCT ID:
NCT01765569
Status:
COMPLETED
Last Update Posted:
2015-09-23
First Post:
2013-01-09
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
A Pharmacokinetics Study to Investigate the Effect of Vemurafenib on Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Melanoma
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['United States']}, 'conditionBrowseModule': {'meshes': [{'id': 'D008545', 'term': 'Melanoma'}, {'id': 'D009369', 'term': 'Neoplasms'}], 'ancestors': [{'id': 'D018358', 'term': 'Neuroendocrine Tumors'}, {'id': 'D017599', 'term': 'Neuroectodermal Tumors'}, {'id': 'D009373', 'term': 'Neoplasms, Germ Cell and Embryonal'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009380', 'term': 'Neoplasms, Nerve Tissue'}, {'id': 'D018326', 'term': 'Nevi and Melanomas'}, {'id': 'D012878', 'term': 'Skin Neoplasms'}, {'id': 'D009371', 'term': 'Neoplasms by Site'}, {'id': 'D012871', 'term': 'Skin Diseases'}, {'id': 'D017437', 'term': 'Skin and Connective Tissue Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D004077', 'term': 'Digoxin'}, {'id': 'D000077484', 'term': 'Vemurafenib'}], 'ancestors': [{'id': 'D004071', 'term': 'Digitalis Glycosides'}, {'id': 'D002298', 'term': 'Cardenolides'}, {'id': 'D002301', 'term': 'Cardiac Glycosides'}, {'id': 'D002297', 'term': 'Cardanolides'}, {'id': 'D013256', 'term': 'Steroids'}, {'id': 'D000072473', 'term': 'Fused-Ring Compounds'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D006027', 'term': 'Glycosides'}, {'id': 'D002241', 'term': 'Carbohydrates'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D007211', 'term': 'Indoles'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'genentech@druginfo.com', 'phone': '800-821-8590', 'title': 'Medical Communications', 'organization': 'Organization: Hoffmann-LaRoche'}, 'certainAgreement': {'otherDetails': "The study being conducted under this agreement is part of the overall study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the study, but after the first publication or presentation that involves the overall study. Sponsor may request that confidential information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.", 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'From Screening to 28 days after the last dose of study treatment or until initiation of another anticancer therapy, whichever occurred first.', 'eventGroups': [{'id': 'EG000', 'title': 'Period A', 'description': 'Single oral dose of digoxin 0.25 mg tablet on Day 1.', 'otherNumAtRisk': 29, 'otherNumAffected': 0, 'seriousNumAtRisk': 29, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Period B', 'description': 'Vemurafenib 960 mg orally BID from Day 8 to Day 28.', 'otherNumAtRisk': 29, 'otherNumAffected': 20, 'seriousNumAtRisk': 29, 'seriousNumAffected': 2}, {'id': 'EG002', 'title': 'Period C', 'description': 'Single oral dose of digoxin 0.25 mg on Day 29, and vemurafenib 960 mg orally BID from Day 29 to Day 35.', 'otherNumAtRisk': 28, 'otherNumAffected': 11, 'seriousNumAtRisk': 28, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'Skin papilloma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 0}], 'organSystem': 'Neoplasms benign, malignant and unspecified (incl cysts and polyps)', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Asthenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 4}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 7}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 3}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Rash maculo-papular', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 3}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Alopecia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 2}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Hyperkeratosis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 2}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Myalgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 4}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 5}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 2}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}, {'term': 'Decreased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 2}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 17.0'}], 'seriousEvents': [{'term': 'Neutropenia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Rash', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 0}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 29, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 29, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 28, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 16.1'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Digoxin', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period A (Digoxin)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 1.'}, {'id': 'OG001', 'title': 'Period C (Digoxin + Vemurafenib)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 29 and vemurafenib 960 mg tablet orally BID from Day 29 to Day 35.'}], 'classes': [{'categories': [{'measurements': [{'value': '14.9', 'spread': '4.22', 'groupId': 'OG000'}, {'value': '27.7', 'spread': '10.6', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric Mean Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.82', 'ciLowerLimit': '1.63', 'ciUpperLimit': '2.02', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose', 'description': 'AUClast = Area under the plasma-concentration time curve from time zero to the last measurable plasma concentration which is presented in hour\\*nanogram per milliliter (hour\\*ng/mL). Hour 0 (H0) signified pre-dose sampling.', 'unitOfMeasure': 'hour*ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Population included participants for whom PK data were collected.'}, {'type': 'PRIMARY', 'title': 'Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Digoxin', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period A (Digoxin)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 1.'}, {'id': 'OG001', 'title': 'Period C (Digoxin + Vemurafenib)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 29 and vemurafenib 960 mg tablet orally BID from Day 29 to Day 35.'}], 'classes': [{'categories': [{'measurements': [{'value': '18.5', 'spread': '4.64', 'groupId': 'OG000'}, {'value': '35.4', 'spread': '4.16', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose', 'unitOfMeasure': 'hour*ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Population. Number of participants analysed = participants evaluable for the analysis.'}, {'type': 'PRIMARY', 'title': 'Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC24) of Digoxin', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period A (Digoxin)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 1.'}, {'id': 'OG001', 'title': 'Period C (Digoxin + Vemurafenib)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 29 and vemurafenib 960 mg tablet orally BID from Day 29 to Day 35.'}], 'classes': [{'categories': [{'measurements': [{'value': '7.73', 'spread': '1.86', 'groupId': 'OG000'}, {'value': '10.6', 'spread': '2.9', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose', 'unitOfMeasure': 'hour*ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Population.'}, {'type': 'PRIMARY', 'title': 'Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC168) of Digoxin', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period A (Digoxin)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 1.'}, {'id': 'OG001', 'title': 'Period C (Digoxin + Vemurafenib)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 29 and vemurafenib 960 mg tablet orally BID from Day 29 to Day 35.'}], 'classes': [{'categories': [{'measurements': [{'value': '18.2', 'spread': '4.85', 'groupId': 'OG000'}, {'value': '29.7', 'spread': '9.62', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose', 'unitOfMeasure': 'hour*ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Population.'}, {'type': 'PRIMARY', 'title': 'Maximum Plasma Concentration (Cmax) of Digoxin', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period A (Digoxin)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 1.'}, {'id': 'OG001', 'title': 'Period C (Digoxin + Vemurafenib)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 29 and vemurafenib 960 mg tablet orally BID from Day 29 to Day 35.'}], 'classes': [{'categories': [{'measurements': [{'value': '1.36', 'spread': '0.408', 'groupId': 'OG000'}, {'value': '1.99', 'spread': '0.562', 'groupId': 'OG001'}]}]}], 'analyses': [{'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric Mean Ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '90', 'paramValue': '1.47', 'ciLowerLimit': '1.3', 'ciUpperLimit': '1.65', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER', 'testedNonInferiority': False}], 'paramType': 'MEAN', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Population.'}, {'type': 'PRIMARY', 'title': 'Time to Maximum Plasma Concentration (Tmax) of Digoxin', 'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period A (Digoxin)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 1.'}, {'id': 'OG001', 'title': 'Period C (Digoxin + Vemurafenib)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 29 and vemurafenib 960 mg tablet orally BID from Day 29 to Day 35.'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000', 'lowerLimit': '0.5', 'upperLimit': '3'}, {'value': '1', 'groupId': 'OG001', 'lowerLimit': '0.47', 'upperLimit': '2'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Population.'}, {'type': 'PRIMARY', 'title': 'Terminal Half-Life (t1/2) of Digoxin', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period A (Digoxin)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 1.'}, {'id': 'OG001', 'title': 'Period C (Digoxin + Vemurafenib)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 29 and vemurafenib 960 mg tablet orally BID from Day 29 to Day 35.'}], 'classes': [{'categories': [{'measurements': [{'value': '35', 'spread': '8.67', 'groupId': 'OG000'}, {'value': '56.4', 'spread': '11', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose', 'unitOfMeasure': 'hours', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Population. Number of participants analysed = participants evaluable for the analysis.'}, {'type': 'PRIMARY', 'title': 'Apparent Clearance (CL/F) of Digoxin', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Period A (Digoxin)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 1.'}, {'id': 'OG001', 'title': 'Period C (Digoxin + Vemurafenib)', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 29 and vemurafenib 960 mg tablet orally BID from Day 29 to Day 35.'}], 'classes': [{'categories': [{'measurements': [{'value': '14.5', 'spread': '4.95', 'groupId': 'OG000'}, {'value': '7.15', 'spread': '0.808', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose', 'description': 'Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.', 'unitOfMeasure': 'liters/hour', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'PK Population. Number of participants analysed = participants evaluable for the analysis.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Vemurafenib + Digoxin', 'description': 'Single oral dose of digoxin 0.25 mg tablet on Day 1 in Period A, followed by vemurafenib 960 mg orally BID from Day 8 to Day 28 in Period B, and then single oral dose of digoxin 0.25 mg on Day 29, and vemurafenib 960 mg orally BID from Day 29 to Day 35 in Period C.\n\nDigoxin: Participants received single oral dose of digoxin 0.25 mg tablet on Day 1 and Day 29.\n\nVemurafenib: Participants received vemurafenib 960 mg tablet orally BID from Day 8 to Day 35.'}], 'periods': [{'title': 'Period A', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '29'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '29'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}, {'title': 'Period B', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '29'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '28'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}, {'title': 'Period C', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '28'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '27'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '29', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Vemurafenib + Digoxin', 'description': 'Single oral dose of digoxin 0.25 mg tablet on Day 1 in Period A, followed by vemurafenib 960 mg orally BID from Day 8 to Day 28 in Period B, and then single oral dose of digoxin 0.25 mg on Day 29, and vemurafenib 960 mg orally BID from Day 29 to Day 35 in Period C.\n\nDigoxin: Participants received single oral dose of digoxin 0.25 mg tablet on Day 1 and Day 29.\n\nVemurafenib: Participants received vemurafenib 960 mg tablet orally BID from Day 8 to Day 35.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '47.8', 'spread': '13.7', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '16', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '13', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 29}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-07'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-08', 'completionDateStruct': {'date': '2014-06', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-08-24', 'studyFirstSubmitDate': '2013-01-09', 'resultsFirstSubmitDate': '2015-07-14', 'studyFirstSubmitQcDate': '2013-01-09', 'lastUpdatePostDateStruct': {'date': '2015-09-23', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2015-07-14', 'studyFirstPostDateStruct': {'date': '2013-01-10', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2015-08-10', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) of Digoxin', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose', 'description': 'AUClast = Area under the plasma-concentration time curve from time zero to the last measurable plasma concentration which is presented in hour\\*nanogram per milliliter (hour\\*ng/mL). Hour 0 (H0) signified pre-dose sampling.'}, {'measure': 'Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Digoxin', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose'}, {'measure': 'Area Under the Plasma Concentration-Time Curve From Time Zero to 24 Hours (AUC24) of Digoxin', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose'}, {'measure': 'Area Under the Plasma Concentration-Time Curve From Time Zero to 168 Hours (AUC168) of Digoxin', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose'}, {'measure': 'Maximum Plasma Concentration (Cmax) of Digoxin', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose'}, {'measure': 'Time to Maximum Plasma Concentration (Tmax) of Digoxin', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose'}, {'measure': 'Terminal Half-Life (t1/2) of Digoxin', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose'}, {'measure': 'Apparent Clearance (CL/F) of Digoxin', 'timeFrame': 'Hour [H] 0, 0.5, 1, 2, 3, 4, 6, 8, 10-12 (Day [D] 1), 24, 30-32 (D2), 48 (D3), 72 (D4), 96 (D5), 168 (D8) post-digoxin dose; H0, 0.5, 1, 2, 3, 4, 6, 8, and 10-12H (D29), 24, 30-32 (D30), 48 (D31), 72 (D32), 96 (D33), 168 (D36) post digoxin dose', 'description': 'Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population PK modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood.'}]}, 'conditionsModule': {'conditions': ['Malignant Melanoma, Neoplasms']}, 'descriptionModule': {'briefSummary': 'This open-label, multi-center, three-period, one sequence study will investigate the effect of vemurafenib on the pharmacokinetics of digoxin in patients with unresectable BRAFV600-mutation positive metastatic melanoma or other malignant tumor type that harbors a V600-activating mutation of BRAF without acceptable standard treatment options. Patients will receive multiple doses of vemurafenib in Periods B and C and a single dose of digoxin in Periods A and C. Eligible patients will have the option to continue treatment with vemurafenib as part of an extension study (NCT01739764). The anticipated time on study treatment is approximately 36 days.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Male or female patients \\>= 18 years old\n* Patients with either unresectable Stage IIIc or Stage IV metastatic melanoma positive for the BRAFV600 mutation or other malignant tumor type that harbors a V600-activating mutation of BRAF, as determined by results of cobas® 4800 BRAF V600 mutation test or a DNA sequencing method, and who have no acceptable standard treatment options\n* Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2\n* Life expectancy \\>= 12 weeks\n* Full recovery from the effects of any major surgery or significant traumatic injury within 14 days prior to the first dose of study treatment\n* Adequate hematologic and end organ function\n* Female patients of childbearing potential and male patients with partners of childbearing potential must agree to always use two effective methods of contraception\n* Negative serum pregnancy test within 7 days prior to commencement of dosing in women of childbearing potential\n\nExclusion Criteria:\n\n* Prior treatment with vemurafenib or other BRAF inhibitor within 42 days of first dose of study drug\n* Prior anti-cancer therapy within 28 days before the first dose of study drug\n* History of clinically significant cardiac or pulmonary dysfunction\n* History of symptomatic congestive heart failure of any New York Heart Association class or serious cardiac arrhythmia requiring treatment\n* History of myocardial infarction within 6 months prior to first dose of study drug\n* Current dyspnea at rest, owing to complications of advanced malignancy or any requirement for supplemental oxygen to perform activities of daily living\n* History of congenital long QT syndrome or QTc \\> 450 ms\n* Current digoxin therapy or anticipated requirement to take digoxin therapy during the study\n* Active central nervous system lesions\n* Uncontrolled or poorly controlled diabetes\n* Current severe, uncontrolled systemic disease'}, 'identificationModule': {'nctId': 'NCT01765569', 'briefTitle': 'A Pharmacokinetics Study to Investigate the Effect of Vemurafenib on Digoxin in Patients With BRAFV600 Mutation-Positive Metastatic Melanoma', 'organization': {'class': 'INDUSTRY', 'fullName': 'Hoffmann-La Roche'}, 'officialTitle': 'A Phase I, Open-Label, Multicenter, 3-Period, Fixed-Sequence Study To Investigate The Effect Of Vemurafenib On The Pharmacokinetics Of A Single Dose Of Digoxin In Patients With BRAFV600 Mutation-Positive Metastatic Malignancy', 'orgStudyIdInfo': {'id': 'GO28394'}, 'secondaryIdInfos': [{'id': '2012-003459-13', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Vemurafenib + Digoxin', 'description': 'Single oral dose of digoxin 0.25 mg tablet on Day 1 in Period A, followed by vemurafenib 960 mg tablet orally BID from Day 8 to Day 28 in Period B, and then single oral dose of digoxin 0.25 mg on Day 29, and vemurafenib 960 mg orally BID from Day 29 to Day 35 in Period C.', 'interventionNames': ['Drug: Digoxin', 'Drug: Vemurafenib']}], 'interventions': [{'name': 'Digoxin', 'type': 'DRUG', 'description': 'Participants received single oral dose of digoxin 0.25 mg tablet on Day 1 and Day 29.', 'armGroupLabels': ['Vemurafenib + Digoxin']}, {'name': 'Vemurafenib', 'type': 'DRUG', 'description': 'Participants received vemurafenib 960 mg tablet orally BID from Day 8 to Day 35.', 'armGroupLabels': ['Vemurafenib + Digoxin']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'BU-220013', 'city': 'Minsk', 'country': 'Belarus', 'geoPoint': {'lat': 53.90019, 'lon': 27.56653}}, {'zip': '223040', 'city': 'Minsk District', 'country': 'Belarus'}, {'zip': 'BU-210603', 'city': 'Vitebsk', 'country': 'Belarus', 'geoPoint': {'lat': 55.1904, 'lon': 30.2049}}, {'zip': '31096', 'city': 'Haifa', 'country': 'Israel', 'geoPoint': {'lat': 32.81303, 'lon': 34.99928}}, {'zip': '6423906', 'city': 'Tel Aviv', 'country': 'Israel', 'geoPoint': {'lat': 32.08088, 'lon': 34.78057}}, {'zip': '52661', 'city': 'Tel Litwinsky', 'country': 'Israel', 'geoPoint': {'lat': 32.05096, 'lon': 34.84588}}, {'zip': '420029', 'city': "Kazan'", 'country': 'Russia', 'geoPoint': {'lat': 55.78874, 'lon': 49.12214}}, {'zip': '115478', 'city': 'Moscow', 'country': 'Russia', 'geoPoint': {'lat': 55.75204, 'lon': 37.61781}}, {'zip': '197758', 'city': 'Saint Petersburg', 'country': 'Russia', 'geoPoint': {'lat': 59.93863, 'lon': 30.31413}}, {'zip': '2193', 'city': 'Johannesburg', 'country': 'South Africa', 'geoPoint': {'lat': -26.20227, 'lon': 28.04363}}, {'zip': '702-911', 'city': 'Daegu', 'country': 'South Korea', 'geoPoint': {'lat': 35.87028, 'lon': 128.59111}}, {'zip': '110-774', 'city': 'Seoul', 'country': 'South Korea', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}, {'zip': '135-710', 'city': 'Seoul', 'country': 'South Korea', 'geoPoint': {'lat': 37.566, 'lon': 126.9784}}], 'overallOfficials': [{'name': 'Clinical Trials', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Hoffmann-La Roche'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Hoffmann-La Roche', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}