Ignite Creation Date:
2025-12-24 @ 3:06 PM
Ignite Modification Date:
2026-01-09 @ 8:58 PM
Study NCT ID:
NCT00992459
Status:
COMPLETED
Last Update Posted:
2024-07-09
First Post:
2009-10-08
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Efficacy and Safety of HPN-100 for the Treatment of Adults With Urea Cycle Disorders
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D056806', 'term': 'Urea Cycle Disorders, Inborn'}, {'id': 'D022124', 'term': 'Hyperammonemia'}], 'ancestors': [{'id': 'D020739', 'term': 'Brain Diseases, Metabolic, Inborn'}, {'id': 'D001928', 'term': 'Brain Diseases, Metabolic'}, {'id': 'D001927', 'term': 'Brain Diseases'}, {'id': 'D002493', 'term': 'Central Nervous System Diseases'}, {'id': 'D009422', 'term': 'Nervous System Diseases'}, {'id': 'D000592', 'term': 'Amino Acid Metabolism, Inborn Errors'}, {'id': 'D008661', 'term': 'Metabolism, Inborn Errors'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D010335', 'term': 'Pathologic Processes'}, {'id': 'D013568', 'term': 'Pathological Conditions, Signs and Symptoms'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'C570223', 'term': 'glycerol phenylbutyrate'}, {'id': 'C075773', 'term': '4-phenylbutyric acid'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'bruce.scharschmidt@hyperiontx.com', 'phone': '650-745-7851', 'title': 'Bruce Scharschmidt, MD, SVP, Chief MedicaL & Development Officer', 'organization': 'Hyperion Therapeutics'}, 'certainAgreement': {'restrictionType': 'GT60', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': '29 days', 'eventGroups': [{'id': 'EG000', 'title': 'NaPBA', 'description': 'Patients received NaPBA', 'otherNumAtRisk': 45, 'otherNumAffected': 23, 'seriousNumAtRisk': 45, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': 'HPN-100', 'description': 'Patients received HPN-100', 'otherNumAtRisk': 44, 'otherNumAffected': 27, 'seriousNumAtRisk': 44, 'seriousNumAffected': 1}], 'otherEvents': [{'term': 'Abdominal discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'Oral discomfort', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'abdominal pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'decreased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 3}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'diarrhea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 7}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'dyspepsia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 2}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 3}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'flatulence', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 6}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'food aversion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 1}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'headache', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 6}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'increased appetite', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'nausea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 3}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 4}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 0}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'ammonia increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 2}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'dermatitis contact', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 2}], 'organSystem': 'Skin and subcutaneous tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}], 'seriousEvents': [{'term': 'Gastroenteritis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}, {'term': 'Hyperammonaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 45, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 44, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'CTCAE v3.0'}], 'frequencyThreshold': '4.4'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'The Primary Endpoint Was the 24-hour Area Under the Curve for Blood Ammonia (NH324-hour AUC) on Days 14 and 28.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}, {'value': '44', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NaPBA', 'description': 'Patients treated with NaPBA'}, {'id': 'OG001', 'title': 'HPN-100', 'description': 'Patients treated with HPN-100'}], 'classes': [{'categories': [{'measurements': [{'value': '976.6', 'spread': '865.9', 'groupId': 'OG000'}, {'value': '865.35', 'spread': '660.53', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28', 'description': 'Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28. Arm A day 14 and Arm B day 28 data were combined as a NaPBA treatment Arm. Arm B day 14 and Arm A day 28 data were combined as a HPN-100 treatment Arm.', 'unitOfMeasure': 'μmol∙h/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44'}, {'type': 'SECONDARY', 'title': 'Correlation Between Urinary Phenylacetylglutamine (PAGN) Excretion Over 24 Hours (U-PAGN24-hour Excr) and Venous Ammonia - Area Under the Concentration-time Curve From Time 0 (Predose) to 24 Hours (AUC0-24)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}, {'value': '44', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NaPBA', 'description': 'Patients treated with NaPBA'}, {'id': 'OG001', 'title': 'HPN-100', 'description': 'Patients treated with HPN-100'}], 'classes': [{'categories': [{'measurements': [{'value': '0.437', 'groupId': 'OG000'}, {'value': '0.219', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '28 Days', 'description': 'The correlation between 24-hour urinary phenylacetylglutamine (PAGN) excretion (U-PAGN24-hour Excr) and venous ammonia AUC0-24 was summarized and the correlation was tested using the Spearman rank-order correlation.', 'unitOfMeasure': 'correlation coefficient', 'reportingStatus': 'POSTED', 'populationDescription': 'Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44'}, {'type': 'SECONDARY', 'title': 'Maximum Ammonia Values Observed on NaPBA Versus HPN-100', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}, {'value': '44', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NaPBA', 'description': 'Patients treated with NaPBA'}, {'id': 'OG001', 'title': 'HPN-100', 'description': 'Patients treated with HPN-100'}], 'classes': [{'categories': [{'measurements': [{'value': '70.83', 'spread': '66.705', 'groupId': 'OG000'}, {'value': '60.94', 'spread': '46.213', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28', 'description': 'Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.', 'unitOfMeasure': 'µmol/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44'}, {'type': 'SECONDARY', 'title': 'Rate (Percentage) of Ammonia Values Above Upper Limit of Normal (ULN) on NaPBA Versus HPN-100', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}, {'value': '44', 'groupId': 'OG001'}]}, {'units': 'blood samples', 'counts': [{'value': '345', 'groupId': 'OG000'}, {'value': '343', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NaPBA', 'description': 'Patients treated with NaPBA'}, {'id': 'OG001', 'title': 'HPN-100', 'description': 'Patients treated with HPN-100'}], 'classes': [{'categories': [{'measurements': [{'value': '125', 'groupId': 'OG000'}, {'value': '122', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'on Day 14 and Day 28', 'description': 'NaPBA treated arm: total 345 blood samples were collected. HPN-100 treated arm: 343 blood samples were collected.', 'unitOfMeasure': 'samples', 'reportingStatus': 'POSTED', 'typeUnitsAnalyzed': 'blood samples', 'denomUnitsSelected': 'blood samples', 'populationDescription': 'Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44'}, {'type': 'SECONDARY', 'title': 'Number and Severity of Symptomatic Hyperammonemic Crises', 'denoms': [{'units': 'Participants', 'counts': [{'value': '45', 'groupId': 'OG000'}, {'value': '44', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NaPBA', 'description': 'Patients treated with NaPBA'}, {'id': 'OG001', 'title': 'HPN-100', 'description': 'Patients treated with HPN-100'}], 'classes': [{'categories': [{'measurements': [{'value': '1', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '29 Days', 'description': 'Severity of symptomatic hyperammonemic crises was measured by peak ammonia level (µmol/L) when it is \\>= 100 µmol/L.', 'unitOfMeasure': 'events', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety population: (N=45 for NaPBA; N = 44 for HPN): Patients receiving any amount of NaPBA or HPN-100 comprise the Safety population. Safety population was to be used for safety analysis performed.'}, {'type': 'SECONDARY', 'title': 'Rate of Adverse Events in Each Treatment Group', 'denoms': [{'units': 'Participants', 'counts': [{'value': '45', 'groupId': 'OG000'}, {'value': '44', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NaPBA', 'description': 'Patients treated with NaPBA'}, {'id': 'OG001', 'title': 'HPN-100', 'description': 'Patients treated with HPN-100'}], 'classes': [{'categories': [{'measurements': [{'value': '23', 'groupId': 'OG000'}, {'value': '27', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '29 Days', 'unitOfMeasure': 'participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Safety population: (N=45 for NaPBA; N = 44 for HPN): Patients receiving any amount of NaPBA or HPN-100 comprise the Safety population. Safety population was to be used for safety analysis performed.'}, {'type': 'SECONDARY', 'title': 'Cmax for PAA of NaPBA and HPN-100 in Plasma', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}, {'value': '44', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NaPBA', 'description': 'Patients treated with NaPBA'}, {'id': 'OG001', 'title': 'HPN-100', 'description': 'Patients treated with HPN-100'}], 'classes': [{'categories': [{'measurements': [{'value': '52.2', 'spread': '41.86', 'groupId': 'OG000'}, {'value': '38.5', 'spread': '39.5', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28', 'description': 'Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.', 'unitOfMeasure': 'μg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44'}, {'type': 'SECONDARY', 'title': 'Cmax for PBA of NaPBA and HPN-100 in Plasma', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}, {'value': '44', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NaPBA', 'description': 'Patients treated with NaPBA'}, {'id': 'OG001', 'title': 'HPN-100', 'description': 'Patients treated with HPN-100'}], 'classes': [{'categories': [{'measurements': [{'value': '80.9', 'spread': '52.5', 'groupId': 'OG000'}, {'value': '51.9', 'spread': '34.87', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28', 'description': 'Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.', 'unitOfMeasure': 'μg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44'}, {'type': 'SECONDARY', 'title': 'Cmax PAGN of NaPBA and HPN-100 in Plasma', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}, {'value': '44', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NaPBA', 'description': 'Patients treated with NaPBA'}, {'id': 'OG001', 'title': 'HPN-100', 'description': 'Patients treated with HPN-100'}], 'classes': [{'categories': [{'measurements': [{'value': '78.6', 'spread': '43.86', 'groupId': 'OG000'}, {'value': '86.8', 'spread': '44.7', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28', 'description': 'Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.', 'unitOfMeasure': 'μg/mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44'}, {'type': 'SECONDARY', 'title': 'U-PAGN24-hour Excr of NaPBA and HPN-100', 'denoms': [{'units': 'Participants', 'counts': [{'value': '44', 'groupId': 'OG000'}, {'value': '44', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'NaPBA', 'description': 'Patients treated with NaPBA'}, {'id': 'OG001', 'title': 'HPN-100', 'description': 'Patients treated with HPN-100'}], 'classes': [{'categories': [{'measurements': [{'value': '13627515', 'spread': '7086307.8', 'groupId': 'OG000'}, {'value': '13502745', 'spread': '7088941.1', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '24 hours on Day 14 of each treatments', 'unitOfMeasure': 'μg', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Intent-to-Treat (ITT) (N = 45): Patients receiving any amount of NaPBA or HPN-100 comprise the ITT population. ITT population was to be used for the primary analysis of this secondary endpoint. One subject who withdrew from study after receiving one dose of NaPBA yielding N=44'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Arm A', 'description': 'Subjects in Arm A were assigned to receive NaPBA + HPN 100 placebo for 2 weeks All patients in Arm A received HPN100 placebo (+ concomitant active NaPBA)'}, {'id': 'FG001', 'title': 'Arm B', 'description': 'Subjects in Arm B were assigned to receive HPN-100 + NaPBA placebo for 2 weeks All patients in Arm B received NaPBA placebo (+ concomitant active HPN 100)'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': 'All patients received HPN 100 placebo in Arm A (+ concomitant active NaPBA)', 'groupId': 'FG000', 'numSubjects': '22'}, {'comment': 'All patients received NaPBA placebo in Arm B (+ concomitant active HPN 100)', 'groupId': 'FG001', 'numSubjects': '24'}]}, {'type': 'COMPLETED', 'achievements': [{'comment': 'Totals enrolled and completed in Arm A NaPBA treatment + HPN 100 Placebo are not mutually exclusive.', 'groupId': 'FG000', 'numSubjects': '21'}, {'comment': 'Totals enrolled and completed in Arm B HPN 100 treatment + NaPBA Placebo are not mutually exclusive.', 'groupId': 'FG001', 'numSubjects': '23'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '1'}]}], 'dropWithdraws': [{'type': 'Withdrawal by Subject', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '1'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Forty six subjects were screened and randomized at the participating sites between October 2009 to August 2010.', 'preAssignmentDetails': 'There were no screen failures.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '22', 'groupId': 'BG000'}, {'value': '24', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Treatment Arm A', 'description': 'Patients randomized to receive NaPBA + HPN 100 placebo for 2 weeks (Treatment Period 1) followed by HPN-100 + NaPBA placebo for 2 weeks (Treatment Period 2)'}, {'id': 'BG001', 'title': 'Treatment Arm B', 'description': 'Patients randomized to receive HPN-100 + NaPBA placebo for 2 weeks (Treatment Period 1) followed by NaPBA + HPN-100 placebo for 2 weeks (Treatment Period 2)'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '22', 'groupId': 'BG000'}, {'value': '24', 'groupId': 'BG001'}, {'value': '46', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '15', 'groupId': 'BG000'}, {'value': '17', 'groupId': 'BG001'}, {'value': '32', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '7', 'groupId': 'BG001'}, {'value': '14', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 46}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2009-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2024-06', 'completionDateStruct': {'date': '2010-09', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2024-06-18', 'studyFirstSubmitDate': '2009-10-08', 'resultsFirstSubmitDate': '2013-04-04', 'studyFirstSubmitQcDate': '2009-10-08', 'lastUpdatePostDateStruct': {'date': '2024-07-09', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2013-07-10', 'studyFirstPostDateStruct': {'date': '2009-10-09', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2013-08-12', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2010-09', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'The Primary Endpoint Was the 24-hour Area Under the Curve for Blood Ammonia (NH324-hour AUC) on Days 14 and 28.', 'timeFrame': 'pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28', 'description': 'Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28. Arm A day 14 and Arm B day 28 data were combined as a NaPBA treatment Arm. Arm B day 14 and Arm A day 28 data were combined as a HPN-100 treatment Arm.'}], 'secondaryOutcomes': [{'measure': 'Correlation Between Urinary Phenylacetylglutamine (PAGN) Excretion Over 24 Hours (U-PAGN24-hour Excr) and Venous Ammonia - Area Under the Concentration-time Curve From Time 0 (Predose) to 24 Hours (AUC0-24)', 'timeFrame': '28 Days', 'description': 'The correlation between 24-hour urinary phenylacetylglutamine (PAGN) excretion (U-PAGN24-hour Excr) and venous ammonia AUC0-24 was summarized and the correlation was tested using the Spearman rank-order correlation.'}, {'measure': 'Maximum Ammonia Values Observed on NaPBA Versus HPN-100', 'timeFrame': 'pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28', 'description': 'Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.'}, {'measure': 'Rate (Percentage) of Ammonia Values Above Upper Limit of Normal (ULN) on NaPBA Versus HPN-100', 'timeFrame': 'on Day 14 and Day 28', 'description': 'NaPBA treated arm: total 345 blood samples were collected. HPN-100 treated arm: 343 blood samples were collected.'}, {'measure': 'Number and Severity of Symptomatic Hyperammonemic Crises', 'timeFrame': '29 Days', 'description': 'Severity of symptomatic hyperammonemic crises was measured by peak ammonia level (µmol/L) when it is \\>= 100 µmol/L.'}, {'measure': 'Rate of Adverse Events in Each Treatment Group', 'timeFrame': '29 Days'}, {'measure': 'Cmax for PAA of NaPBA and HPN-100 in Plasma', 'timeFrame': 'pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28', 'description': 'Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.'}, {'measure': 'Cmax for PBA of NaPBA and HPN-100 in Plasma', 'timeFrame': 'pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28', 'description': 'Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.'}, {'measure': 'Cmax PAGN of NaPBA and HPN-100 in Plasma', 'timeFrame': 'pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28', 'description': 'Blood samples were collected at pre-dose, 2, 4, 8, 12, 16, 20 and 24 hours after first dose on days 14 and 28.'}, {'measure': 'U-PAGN24-hour Excr of NaPBA and HPN-100', 'timeFrame': '24 hours on Day 14 of each treatments'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Urea Cycle Disorder (UCD)', 'UCD', 'hyperammonemia', 'Buphenyl (NaPBA)', 'glycerol phenylbutyrate (GPB)', 'Sodium Phenylbutyrate (NaPBA)'], 'conditions': ['Urea Cycle Disorders']}, 'referencesModule': {'references': [{'pmid': '22961727', 'type': 'BACKGROUND', 'citation': 'Diaz GA, Krivitzky LS, Mokhtarani M, Rhead W, Bartley J, Feigenbaum A, Longo N, Berquist W, Berry SA, Gallagher R, Lichter-Konecki U, Bartholomew D, Harding CO, Cederbaum S, McCandless SE, Smith W, Vockley G, Bart SA, Korson MS, Kronn D, Zori R, Merritt JL 2nd, C S Nagamani S, Mauney J, Lemons C, Dickinson K, Moors TL, Coakley DF, Scharschmidt BF, Lee B. Ammonia control and neurocognitive outcome among urea cycle disorder patients treated with glycerol phenylbutyrate. Hepatology. 2013 Jun;57(6):2171-9. doi: 10.1002/hep.26058. Epub 2013 Jan 3.'}, {'pmid': '24144944', 'type': 'DERIVED', 'citation': 'Mokhtarani M, Diaz GA, Rhead W, Berry SA, Lichter-Konecki U, Feigenbaum A, Schulze A, Longo N, Bartley J, Berquist W, Gallagher R, Smith W, McCandless SE, Harding C, Rockey DC, Vierling JM, Mantry P, Ghabril M, Brown RS Jr, Dickinson K, Moors T, Norris C, Coakley D, Milikien DA, Nagamani SC, Lemons C, Lee B, Scharschmidt BF. Elevated phenylacetic acid levels do not correlate with adverse events in patients with urea cycle disorders or hepatic encephalopathy and can be predicted based on the plasma PAA to PAGN ratio. Mol Genet Metab. 2013 Dec;110(4):446-53. doi: 10.1016/j.ymgme.2013.09.017. Epub 2013 Oct 8.'}]}, 'descriptionModule': {'briefSummary': 'This was a randomized, active-controlled, double-blind, cross-over study designed to enroll subjects with UCDs who are being treated with NaPBA.', 'detailedDescription': 'This was a randomized, active-controlled, double-blind, cross-over study designed to enroll subjects with UCDs who are being treated with NaPBA. Subjects were randomly assigned to receive either HPN-100 + NaPBA placebo or NaPBA + HPN 100 placebo for 2 weeks, and then crossed over to receive the other treatment for 2 weeks. Venous ammonia was the primary outcome measure. Subjects were admitted to the clinical research unit for 24 hours of pharmacokinetic (PK) blood and urine sampling (including an overnight stay) at the end of each treatment period, by which time the study drug had reached steady state.\n\nSubjects followed a stable diet throughout the study as prescribed by the investigator and dietician. Throughout the study, diet diaries were completed by the subject and dietary protein intake were assessed by a dietician based on completed dietary diaries and consultation with the subject.\n\nSubjects who completed this study and met the study entry criteria, were offered the opportunity to enroll in the HPN-100 open-label safety protocol (HPN-100-007).\n\nStudy acquired from Horizon in 2024.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Diagnosis of UCD (Urea Cycle Disorder) involving deficiencies of Carbamyl phosphate synthetase (CPS), Ornithine transcarbamylase (OTC), or Arginosuccinate (ASS), confirmed via enzymatic, biochemical, or genetic testing\n* Adult UCD subjects 18 years of age or older who are being treated with Buphenyl/Sodium phenylbuterate (NaPBA) for their UCD; subjects must be on a stable dose of NaPBA for at least 1 week prior to the Day 1 visit. Subjects who are not receiving NaPBA at the initial screening visit, but who have the potential to benefit from treatment, may start receiving NaPBA during the screening period and be enrolled as long as they are on a stable dose of NaPBA for at least 1 week prior to Day 1.\n* No clinical evidence of hyperammonemia associated with an ammonia level of ≥ 100 μmol/L during the 2 weeks preceding screening\n* Signed informed consent by subject\n* Able to perform and comply with study activities, including blood draws and 24-hour urine samples\n* Negative pregnancy test for all females of childbearing potential\n* All females of childbearing age and all sexually active males must agree to use an acceptable method of contraception throughout the study. Appropriate contraceptive methods include hormonal contraceptives (oral, injected, implanted, or transdermal), tubal ligation, intrauterine device, hysterectomy, vasectomy, or double barrier methods. Abstinence is an acceptable form of birth control, though appropriate contraception must be used if the subject becomes sexually active.\n\nExclusion Criteria:\n\n* Screening or baseline ammonia level of ≥ 100 μmol/L or signs and symptoms indicative of hyperammonemia during the 2-week period preceding screening or enrollment; subjects may be re-screened after their ammonia is controlled and are stable for at least 14 days, at the discretion of the investigator\n* Use of any investigational drug within 30 days of Day 1\n* Active infection (viral or bacterial) or any other intercurrent condition (apart from UCD) that may increase ammonia levels\n* Any clinical or laboratory abnormality of Grade 3 or greater severity according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0, except Grade 3 elevations in liver enzymes, defined as levels 5-20 times upper limit of normal (ULN) in alanine aminotransferase (ALT/SGPT), aspartate aminotransferase (AST/SGOT), or gamma glutamyl transpeptidase (GGT) in a clinically stable subject\n* Any clinical or laboratory abnormality or medical condition that, at the discretion of the investigator, may put the subject at increased risk by participating in this study\n* Use of any medication known to significantly affect renal clearance (e.g., probenecid) or to increase protein catabolism (e.g., corticosteroids), or other medication known to increase ammonia levels (e.g., valproate), within the 24 hours prior to Day 1 and throughout the study\n* Use of sodium benzoate within one week of Day 1\n* History of corrected QT interval (QTc) prolongation or QTc interval \\> 450 msec at screening or baseline\n* Known hypersensitivity to phenylacetate (PAA) or phenylbutyrate (PBA)\n* Liver transplant, including hepatocellular transplant\n* Breastfeeding or lactating females'}, 'identificationModule': {'nctId': 'NCT00992459', 'briefTitle': 'Efficacy and Safety of HPN-100 for the Treatment of Adults With Urea Cycle Disorders', 'organization': {'class': 'INDUSTRY', 'fullName': 'Amgen'}, 'officialTitle': 'A Phase 3, Randomized, Double-Blind, Cross-Over, Active-Controlled Study of the Efficacy and Safety of HPN-100, Glyceryl Tri-(4-phenylbutyrate), for the Treatment of Adults With Urea Cycle Disorders (Help UCD)', 'orgStudyIdInfo': {'id': 'HPN-100-006'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Buphenyl (NaPBA) /HPN 100 Placebo', 'description': 'Subjects in Arm A were randomly assigned to receive NaPBA + HPN 100 placebo for 2 weeks and then crossed over to receive HPN 100 + NaPBA Placebo for 2 weeks.', 'interventionNames': ['Drug: Buphenyl (NaPBA)']}, {'type': 'EXPERIMENTAL', 'label': 'HPN-100/NaPBA Placebo', 'description': 'Subjects in Arm B were randomly assigned to receive HPN-100 + NaPBA placebo for 2 weeks and then crossed over to receive NaPBA + HPN 100 placebo for 2 weeks.', 'interventionNames': ['Drug: HPN-100']}], 'interventions': [{'name': 'HPN-100', 'type': 'DRUG', 'otherNames': ['GT4P, glyceryl tri-(4-phenylbutyrate)'], 'description': 'HPN-100 is a triglyceride that has a similar mechanism of action as NaPBA. It is a liquid with minimal taste and odor. Three teaspoons of HPN-100 (\\~17.4mL) delivers equivalent amount of PBA in 40 tablets of NaPBA.', 'armGroupLabels': ['HPN-100/NaPBA Placebo']}, {'name': 'Buphenyl (NaPBA)', 'type': 'DRUG', 'otherNames': ['sodium phenylbutyrate'], 'description': 'Buphenyl (NaPBA) will be the comparator drug to HPN-100 in this study.', 'armGroupLabels': ['Buphenyl (NaPBA) /HPN 100 Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '90806', 'city': 'Long Beach', 'state': 'California', 'country': 'United States', 'facility': 'Long Beach Memorial', 'geoPoint': {'lat': 33.76696, 'lon': -118.18923}}, {'zip': '90095', 'city': 'Los Angeles', 'state': 'California', 'country': 'United States', 'facility': 'UCLA', 'geoPoint': {'lat': 34.05223, 'lon': -118.24368}}, {'zip': '94304', 'city': 'Stanford', 'state': 'California', 'country': 'United States', 'facility': 'Stanford University', 'geoPoint': {'lat': 37.42411, 'lon': -122.16608}}, {'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'facility': "Denver Children's Hospital", 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '06510', 'city': 'New Haven', 'state': 'Connecticut', 'country': 'United States', 'facility': 'Yale School of Medicine', 'geoPoint': {'lat': 41.30815, 'lon': -72.92816}}, {'zip': '20010', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'facility': "Children's National Medical Center", 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '32611', 'city': 'Gainesville', 'state': 'Florida', 'country': 'United States', 'facility': 'University of Florida', 'geoPoint': {'lat': 29.65163, 'lon': -82.32483}}, {'zip': '52242', 'city': 'Iowa City', 'state': 'Iowa', 'country': 'United States', 'facility': 'University of Iowa', 'geoPoint': {'lat': 41.66113, 'lon': -91.53017}}, {'zip': '04102', 'city': 'Portland', 'state': 'Maine', 'country': 'United States', 'facility': 'Maine Medical Center', 'geoPoint': {'lat': 43.65737, 'lon': -70.2589}}, {'zip': '21201', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'SNBL-Clinical Pharmacology Center', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}, {'zip': '02111', 'city': 'Boston', 'state': 'Massachusetts', 'country': 'United States', 'facility': 'Tufts-New England Medical Center', 'geoPoint': {'lat': 42.35843, 'lon': -71.05977}}, {'zip': '55454', 'city': 'Minneapolis', 'state': 'Minnesota', 'country': 'United States', 'facility': 'University of Minnesota Medical Center', 'geoPoint': {'lat': 44.97997, 'lon': -93.26384}}, {'zip': '10029', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'facility': 'Mount Sinai School of Medicine', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '10595', 'city': 'Valhalla', 'state': 'New York', 'country': 'United States', 'facility': 'Westchester Medical Center', 'geoPoint': {'lat': 41.07482, 'lon': -73.77513}}, {'zip': '44106', 'city': 'Cleveland', 'state': 'Ohio', 'country': 'United States', 'facility': 'University Hospitals Case Medical Center', 'geoPoint': {'lat': 41.4995, 'lon': -81.69541}}, {'zip': '43205', 'city': 'Columbus', 'state': 'Ohio', 'country': 'United States', 'facility': "Nationwide Children's Hospital", 'geoPoint': {'lat': 39.96118, 'lon': -82.99879}}, {'zip': '97239', 'city': 'Portland', 'state': 'Oregon', 'country': 'United States', 'facility': 'Oregon Health & Science University', 'geoPoint': {'lat': 45.52345, 'lon': -122.67621}}, {'zip': '15224', 'city': 'Pittsburgh', 'state': 'Pennsylvania', 'country': 'United States', 'facility': "Children's Hospital of Pittsburgh of UPMC", 'geoPoint': {'lat': 40.44062, 'lon': -79.99589}}, {'zip': '77030', 'city': 'Houston', 'state': 'Texas', 'country': 'United States', 'facility': 'Baylor College of Medicine', 'geoPoint': {'lat': 29.76328, 'lon': -95.36327}}, {'zip': '84132', 'city': 'Salt Lake City', 'state': 'Utah', 'country': 'United States', 'facility': 'University of Utah', 'geoPoint': {'lat': 40.76078, 'lon': -111.89105}}, {'zip': '53226', 'city': 'Milwaukee', 'state': 'Wisconsin', 'country': 'United States', 'facility': 'Medical College of Wisconsin', 'geoPoint': {'lat': 43.0389, 'lon': -87.90647}}, {'zip': 'M5G 1X8', 'city': 'Toronto', 'state': 'Ontario', 'country': 'Canada', 'facility': 'The Hospital for Sick Children', 'geoPoint': {'lat': 43.70643, 'lon': -79.39864}}], 'overallOfficials': [{'name': 'MD', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Amgen'}]}, 'ipdSharingStatementModule': {'url': 'https://www.amgen.com/datasharing', 'infoTypes': ['STUDY_PROTOCOL', 'SAP', 'ICF', 'CSR'], 'timeFrame': 'Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.', 'ipdSharing': 'YES', 'description': 'De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.', 'accessCriteria': 'Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Amgen', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}