Ignite Creation Date:
2025-12-24 @ 2:35 PM
Ignite Modification Date:
2026-01-10 @ 9:35 AM
Study NCT ID:
NCT02012959
Status:
TERMINATED
Last Update Posted:
2018-09-26
First Post:
2013-12-11
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Study of the Safety and Effectiveness of SAMSCA® (Tolvaptan) in Children and Adolescents With Euvolemic or Hypervolemic Hyponatremia
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['Belgium', 'Czechia', 'Germany', 'Romania', 'Spain', 'Turkey (Türkiye)']}, 'conditionBrowseModule': {'meshes': [{'id': 'D007010', 'term': 'Hyponatremia'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}], 'ancestors': [{'id': 'D014883', 'term': 'Water-Electrolyte Imbalance'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077602', 'term': 'Tolvaptan'}], 'ancestors': [{'id': 'D001552', 'term': 'Benzazepines'}, {'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clinicaltransparency@otsuka-us.com', 'phone': '+1-609-524-6788', 'title': 'Global Clinical Development', 'organization': 'Otsuka Pharmaceutical Development & Commercialization, Inc.'}, 'certainAgreement': {'otherDetails': 'Sponsor reserves the right to review, edit, and authorize publications.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}, 'limitationsAndCaveats': {'description': 'Issues with recruitment and enrollment made trial execution highly impracticable. This ultimately led to termination of the trial. The study was not terminated due to safety reasons.'}}, 'adverseEventsModule': {'timeFrame': 'From screening through early termination or follow-up phase (14 days postrandomization).', 'eventGroups': [{'id': 'EG000', 'title': 'Treatment Phase A', 'description': 'During Treatment Phase A, participants received tolvaptan once daily on Days 1 and 2. If the serum sodium level did not increase at least 4 mEq/L by Day 2, treatment was extended one additional day (to Day 2a). On Day 2a, participants achieving an increase in serum sodium of ≥4 mEq/L were defined as responders, and participants not achieving a ≥4 mEq/L increase in serum sodium were defined as non-responders.', 'otherNumAtRisk': 9, 'deathsNumAtRisk': 9, 'otherNumAffected': 3, 'seriousNumAtRisk': 9, 'deathsNumAffected': 0, 'seriousNumAffected': 2}, {'id': 'EG001', 'title': 'Treatment Phase B: Responder - Late Withdrawal', 'description': 'Participants who were responders (serum sodium increased by ≥4 mEq/L) from Phase A continued to Treatment Phase B (Randomization Phase) on Day 3 and were randomized to the Late Withdrawal group (continuing tolvaptan treatment for Days 3 and 4).', 'otherNumAtRisk': 2, 'deathsNumAtRisk': 2, 'otherNumAffected': 1, 'seriousNumAtRisk': 2, 'deathsNumAffected': 0, 'seriousNumAffected': 1}, {'id': 'EG002', 'title': 'Treatment Phase B: Responder - Early Withdrawal', 'description': "Participants who were responders (serum sodium increased by ≥4 mEq/L) from Phase A continued to Treatment Phase B (Randomization Phase) on Day 3 and were randomized to the Early Withdrawal group (not receiving additional tolvaptan on Days 3 or 4). Participants randomized to Early Withdrawal were monitored for any interventions needed to maintain appropriate serum sodium levels. Where sodium levels declined by ≥4 mEq/L, or where the overall clinical condition warranted further intervention to increase serum sodium levels, participants were treated per the investigator's preferred standard of care. Any intervention, including fluid restriction, during the first 48 hours of the Early Withdrawal phase was defined as rescue therapy, and participant data was censored thereafter.", 'otherNumAtRisk': 3, 'deathsNumAtRisk': 3, 'otherNumAffected': 2, 'seriousNumAtRisk': 3, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG003', 'title': 'Treatment Phase B: Non-responder - Study Drug', 'description': "Participants who were non-responders during Phase A were not randomized in Phase B, but were treated per the investigator's discretion and continued tolvaptan for Days 3 and 4.", 'otherNumAtRisk': 1, 'deathsNumAtRisk': 1, 'otherNumAffected': 1, 'seriousNumAtRisk': 1, 'deathsNumAffected': 0, 'seriousNumAffected': 1}, {'id': 'EG004', 'title': 'Treatment Phase B: Non-responder - Standard of Care', 'description': "Participants who were non-responders during Phase A were not randomized in Phase B, but were treated per the investigator's discretion. The participants in this arm discontinued tolvaptan and received the investigator's preferred standard of care for Days 3 and 4.", 'otherNumAtRisk': 1, 'deathsNumAtRisk': 1, 'otherNumAffected': 1, 'seriousNumAtRisk': 1, 'deathsNumAffected': 0, 'seriousNumAffected': 0}], 'otherEvents': [{'term': 'Blood sodium decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 1}], 'organSystem': 'Investigations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Bradycardia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Dyspnoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Hypoxia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Nasal congestion', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Nasal inflammation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Pyrexia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Vomiting', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 1}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Fluid overload', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Hyperkalaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Hyponatraemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}], 'seriousEvents': [{'term': 'Catheter site extravasation', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 1}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Medical device site haemorrhage', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Diarrhoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 1}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}, {'term': 'Faecal volume increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 9, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 2, 'numAffected': 0}, {'groupId': 'EG002', 'numAtRisk': 3, 'numAffected': 0}, {'groupId': 'EG003', 'numAtRisk': 1, 'numAffected': 0}, {'groupId': 'EG004', 'numAtRisk': 1, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'NON_SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA 19.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change In Serum Sodium Concentration For Responders', 'denoms': [{'units': 'Participants', 'counts': [{'value': '2', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Responder - Late Withdrawal', 'description': 'Participants who were responders (serum sodium increased by ≥4 mEq/L) from Phase A continued to Treatment Phase B (Randomization Phase) on Day 3 and were randomized to the Late Withdrawal group (continuing tolvaptan treatment for Days 3 and 4).'}, {'id': 'OG001', 'title': 'Responder - Early Withdrawal', 'description': "Participants who were responders (serum sodium increased by ≥4 mEq/L) from Phase A continued to Treatment Phase B (Randomization Phase) on Day 3 and were randomized to the Early Withdrawal group (not receiving additional tolvaptan on Days 3 or 4). Participants randomized to Early Withdrawal were monitored for any interventions needed to maintain appropriate serum sodium levels. Where sodium levels declined by ≥4 mEq/L, or where the overall clinical condition warranted further intervention to increase serum sodium levels, participants were treated per the investigator's preferred standard of care. Any intervention, including fluid restriction, during the first 48 hours of the Early Withdrawal phase was defined as rescue therapy, and participant data was censored thereafter."}], 'classes': [{'categories': [{'measurements': [{'value': '-4.0', 'spread': '4.2', 'groupId': 'OG000'}, {'value': '-1.0', 'spread': '1.0', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Day 2/2a, Day 4', 'description': "Change in serum sodium concentration (mEq/L) for responders from Day 2 (or Day 2a) at the end of Treatment Phase A (where all participants received tolvaptan) to the end of Treatment Phase B for the Early compared to Late Withdrawal groups is reported. Once a participant was randomized to Treatment Phase B, any additional therapies for the purpose of raising serum sodium, including fluid restriction, were considered rescue therapy. Upon receipt of rescue therapy, a participant's endpoint data was collected and then censored from the efficacy analysis thereafter, unless specified.", 'unitOfMeasure': 'mEq/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Treatment Phase B Responders: full analysis dataset comprised of all participants in the Phase B Safety Sample with both baseline and at least 1 postrandomization serum sodium evaluation in Phase B.'}, {'type': 'SECONDARY', 'title': 'Change In Serum Sodium Concentration During Treatment Phase A', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase A: All Participants', 'description': 'During Treatment Phase A, participants received tolvaptan once daily on Days 1 and 2. If the serum sodium level did not increase at least 4 mEq/L by Day 2, treatment was extended one additional day (Day 2a). On Day 2a, participants achieving an increase in serum sodium of ≥4 mEq/L were defined as responders, and participants not achieving a ≥4 mEq/L increase in serum sodium were defined as non-responders.'}], 'classes': [{'title': 'Day 1: 24 hours Post Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '1', 'spread': '3', 'groupId': 'OG000'}]}]}, {'title': 'Day 2: 24 hours Post Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '3.4', 'spread': '4.8', 'groupId': 'OG000'}]}]}, {'title': 'Day 2a: 24 hours Post Dose', 'denoms': [{'units': 'Participants', 'counts': [{'value': '3', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '2.3', 'spread': '2.1', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Baseline, Day 2/2a', 'description': 'Change in serum sodium concentration (mEq/L) from baseline to the end of Day 2 (or 2a) during Treatment Phase A for all participants (responders and non-responders) is reported.', 'unitOfMeasure': 'mEq/L', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Treatment Phase A: all participants in the Phase A Safety Sample and who had baseline and at least 1 postbaseline serum sodium evaluation in Phase A.'}, {'type': 'SECONDARY', 'title': 'Fluid Balance (Intake Minus Output) During Treatment Phase A', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Phase A: All Participants', 'description': 'During Treatment Phase A, participants received tolvaptan once daily on Days 1 and 2. If the serum sodium level did not increase at least 4 mEq/L by Day 2, treatment was extended one additional day (Day 2a). On Day 2a, participants achieving an increase in serum sodium of ≥4 mEq/L were defined as responders, and participants not achieving a ≥4 mEq/L increase in serum sodium were defined as non-responders.'}], 'classes': [{'title': 'Day 1: 0-6 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-1', 'spread': '505', 'groupId': 'OG000'}]}]}, {'title': 'Day 1: 6-12 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-261', 'spread': '533', 'groupId': 'OG000'}]}]}, {'title': 'Day 1: 12-18 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-36', 'spread': '253', 'groupId': 'OG000'}]}]}, {'title': 'Day 1: 18-24 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '31', 'spread': '344', 'groupId': 'OG000'}]}]}, {'title': 'Day 1: 0-24 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-268', 'spread': '849', 'groupId': 'OG000'}]}]}, {'title': 'Day 2: 0-6 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-101', 'spread': '376', 'groupId': 'OG000'}]}]}, {'title': 'Day 2: 6-12 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '6', 'spread': '513', 'groupId': 'OG000'}]}]}, {'title': 'Day 2: 12-18 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-45', 'spread': '400', 'groupId': 'OG000'}]}]}, {'title': 'Day 2: 18-24 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-21', 'spread': '191', 'groupId': 'OG000'}]}]}, {'title': 'Day 2: 0-24 hours', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'categories': [{'measurements': [{'value': '-160', 'spread': '733', 'groupId': 'OG000'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'Every 6 hours on Days 1 and 2', 'description': 'Every 6 hours and for the 24-hour daily interval on Days 1 and 2 during Treatment Phase A, fluid balance (milliliters \\[mL\\]) was determined by fluid intake (oral and intravenous) minus urine output. Improved fluid balance would be indicated through the induction of increased urine volume. Fluid balance was monitored per institutional guidelines.', 'unitOfMeasure': 'mL', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Treatment Phase A: all participants in the Phase A Safety Sample and who had baseline and at least 1 postbaseline serum sodium evaluation in Phase A.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Treatment Phase A', 'description': 'During Treatment Phase A, participants received tolvaptan once daily on Days 1 and 2. If the serum sodium level did not increase at least 4 milliequivalent (mEq)/liter (L) by Day 2, treatment was extended one additional day (Day 2a). On Day 2a, participants achieving an increase in serum sodium of ≥4 mEq/L were defined as responders, and participants not achieving a ≥4 mEq/L increase in serum sodium were defined as non-responders.'}, {'id': 'FG001', 'title': 'Treatment Phase B: Responder - Late Withdrawal', 'description': 'Participants who were responders (serum sodium increased by ≥4 mEq/L) from Phase A continued to Treatment Phase B (Randomization Phase) on Day 3 and were randomized to the Late Withdrawal group (continuing tolvaptan treatment for Days 3 and 4).'}, {'id': 'FG002', 'title': 'Treatment Phase B: Responder - Early Withdrawal', 'description': "Participants who were responders (serum sodium increased by ≥4 mEq/L) from Phase A continued to Treatment Phase B (Randomization Phase) on Day 3 and were randomized to the Early Withdrawal group (not receiving additional tolvaptan on Days 3 or 4). Participants randomized to Early Withdrawal were monitored for any interventions needed to maintain appropriate serum sodium levels. Where sodium levels declined by ≥4 mEq/L, or where the overall clinical condition warranted further intervention to increase serum sodium levels, participants were treated per the investigator's preferred standard of care. Any intervention, including fluid restriction, during the first 48 hours of the Early Withdrawal phase was defined as rescue therapy, and participant data was censored thereafter."}, {'id': 'FG003', 'title': 'Treatment Phase B: Non-responder - Study Drug', 'description': "Participants who were non-responders during Phase A were not randomized in Phase B, but were treated per the investigator's discretion and continued tolvaptan for Days 3 and 4."}, {'id': 'FG004', 'title': 'Treatment Phase B: Non-responder - Standard of Care', 'description': "Participants who were non-responders during Phase A were not randomized in Phase B, but were treated per the investigator's discretion. The participants in this arm discontinued tolvaptan and received the investigator's preferred standard of care for Days 3 and 4."}], 'periods': [{'title': 'Treatment Phase A', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'comment': 'Zero participants noted because participants did not start Phase B yet', 'groupId': 'FG001', 'numSubjects': '0'}, {'comment': 'Zero participants noted because participants did not start Phase B yet', 'groupId': 'FG002', 'numSubjects': '0'}, {'comment': 'Zero participants noted because participants did not start Phase B yet', 'groupId': 'FG003', 'numSubjects': '0'}, {'comment': 'Zero participants noted because participants did not start Phase B yet', 'groupId': 'FG004', 'numSubjects': '0'}]}, {'type': 'Received At Least 1 Dose of Study Drug', 'comment': 'Phase A Safety Sample', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}], 'dropWithdraws': [{'type': 'Adverse Event', 'reasons': [{'groupId': 'FG000', 'numSubjects': '2'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}]}, {'title': 'Treatment Phase B', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': 'Zero participants noted because participants had completed Phase A', 'groupId': 'FG000', 'numSubjects': '0'}, {'comment': 'Participants in this group continued treatment with the study drug', 'groupId': 'FG001', 'numSubjects': '2'}, {'comment': 'Participants in this group did not receive additional study drug after Phase A', 'groupId': 'FG002', 'numSubjects': '3'}, {'comment': "Participants in this group could continue study drug treatment, per the investigator's discretion", 'groupId': 'FG003', 'numSubjects': '1'}, {'comment': "Participants in this group could receive the investigator's preferred standard of care", 'groupId': 'FG004', 'numSubjects': '1'}]}, {'type': 'Received At Least 1 Dose of Study Drug', 'comment': 'Phase B Safety Sample', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '3'}, {'groupId': 'FG003', 'numSubjects': '1'}, {'groupId': 'FG004', 'numSubjects': '1'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '2'}, {'groupId': 'FG002', 'numSubjects': '3'}, {'groupId': 'FG003', 'numSubjects': '1'}, {'groupId': 'FG004', 'numSubjects': '1'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}, {'groupId': 'FG003', 'numSubjects': '0'}, {'groupId': 'FG004', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Treatment Phase A', 'description': 'During Treatment Phase A, participants received tolvaptan once daily on Days 1 and 2. If the serum sodium level did not increase at least 4 mEq/L by Day 2, treatment was extended one additional day (Day 2a). On Day 2a, participants achieving an increase in serum sodium of ≥4 mEq/L were defined as responders, and participants not achieving a ≥4 mEq/L increase in serum sodium were defined as non-responders. Participants who were responders (serum sodium increased by ≥4 mEq/L) continued to Treatment Phase B (Randomization Phase) on Day 3.'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '6.1', 'spread': '5.1', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '6', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '3', 'groupId': 'BG000'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '5', 'groupId': 'BG000'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'White', 'categories': [{'measurements': [{'value': '6', 'groupId': 'BG000'}]}]}, {'title': 'Black or African American', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}]}]}, {'title': 'American Indian or Alaskan Native', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Asian', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}, {'title': 'Other', 'categories': [{'measurements': [{'value': '2', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}], 'populationDescription': 'Intent-to-treat (ITT) population - Provided following 3 core datasets used for all efficacy analyses: Treatment Phase A; Treatment Phase B responders; Treatment Phase B non-responders.'}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2015-11-17', 'size': 4245597, 'label': 'Study Protocol', 'hasIcf': False, 'hasSap': False, 'filename': 'Prot_000.pdf', 'typeAbbrev': 'Prot', 'uploadDate': '2018-07-31T14:23', 'hasProtocol': True}, {'date': '2015-11-17', 'size': 1562779, 'label': 'Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'SAP_001.pdf', 'typeAbbrev': 'SAP', 'uploadDate': '2018-07-31T14:25', 'hasProtocol': False}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 9}}, 'statusModule': {'whyStopped': 'Issues with participant recruitment \\& enrollment which made the trial impossible or highly impracticable. Trial termination was not due to safety reasons.', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2015-09-22', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2018-07', 'completionDateStruct': {'date': '2017-07-24', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2018-08-29', 'studyFirstSubmitDate': '2013-12-11', 'resultsFirstSubmitDate': '2018-07-31', 'studyFirstSubmitQcDate': '2013-12-16', 'lastUpdatePostDateStruct': {'date': '2018-09-26', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2018-07-31', 'studyFirstPostDateStruct': {'date': '2013-12-17', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-08-28', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2017-07-24', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change In Serum Sodium Concentration For Responders', 'timeFrame': 'Day 2/2a, Day 4', 'description': "Change in serum sodium concentration (mEq/L) for responders from Day 2 (or Day 2a) at the end of Treatment Phase A (where all participants received tolvaptan) to the end of Treatment Phase B for the Early compared to Late Withdrawal groups is reported. Once a participant was randomized to Treatment Phase B, any additional therapies for the purpose of raising serum sodium, including fluid restriction, were considered rescue therapy. Upon receipt of rescue therapy, a participant's endpoint data was collected and then censored from the efficacy analysis thereafter, unless specified."}], 'secondaryOutcomes': [{'measure': 'Change In Serum Sodium Concentration During Treatment Phase A', 'timeFrame': 'Baseline, Day 2/2a', 'description': 'Change in serum sodium concentration (mEq/L) from baseline to the end of Day 2 (or 2a) during Treatment Phase A for all participants (responders and non-responders) is reported.'}, {'measure': 'Fluid Balance (Intake Minus Output) During Treatment Phase A', 'timeFrame': 'Every 6 hours on Days 1 and 2', 'description': 'Every 6 hours and for the 24-hour daily interval on Days 1 and 2 during Treatment Phase A, fluid balance (milliliters \\[mL\\]) was determined by fluid intake (oral and intravenous) minus urine output. Improved fluid balance would be indicated through the induction of increased urine volume. Fluid balance was monitored per institutional guidelines.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Hyponatremia', 'Euvolemic', 'Hypervolemic', 'Serum sodium', 'Dilutional hyponatremia', 'Electrolyte abnormality', 'Electrolyte imbalance', 'Metabolic disease'], 'conditions': ['Hyponatremia']}, 'descriptionModule': {'briefSummary': 'The purpose of this trial was to demonstrate that tolvaptan effectively and safely increases and maintains serum sodium concentrations in children and adolescent participants with euvolemic or hypervolemic hyponatremia.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '17 Years', 'minimumAge': '4 Weeks', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion:\n\n* Male and female participants ≥4 weeks (or ≥44 weeks adjusted gestational age) to \\<18 years old\n* Participants hospitalized with euvolemic or hypervolemic hyponatremia resistant to initial standard background therapy\n* Persistent euvolemic or hypervolemic hyponatremia defined as being documented as \\<130 milliequivalent (mEq)/L and present for at least 48 hours, evidenced by at least 2 serum sodium assessments (12 hours apart)\n* Ability to maintain adequate fluid intake (orally or intravenously)\n* Ability to take oral medications\n* Ability to comply with all requirements of the trial\n* Completion of the trial-specific informed consent/assent as age appropriate\n* Ability to commit to remain fully abstinent or practice double-barrier birth control as required by the trial\n\nExclusion:\n\n* Evidence of hypovolemia or intravascular volume depletion\n* Serum sodium \\<120 mEq/L\n* Use of potent cytochrome P450 3A4 (CYP3A4) inhibitors in participants \\<12 kilogram (kg) or moderate CYP3A4 inhibitors in participants \\<6 kg\n* Lacks free access to water (inability to respond to thirst) or without intensive care unit level fluid monitoring and management\n* History or current diagnosis of nephrotic syndrome\n* Transient hyponatremia likely to resolve\n* Hyperkalemia\n* Estimated glomerular filtration rate \\<30 milliliters/minute/1.73 meters squared\n* Acute kidney injury\n* Severe or acute neurological symptoms requiring other intervention\n* Prior treatment for hyponatremia with hypertonic saline within 8 hours of qualifying serum sodium assessments; urea, lithium, demeclocycline, conivaptan, or tolvaptan within 4 days of qualifying serum sodium assessments; any other treatments for the purpose of increasing serum sodium concurrent with dosing of trial medication\n* Anuria or urinary outflow obstruction, unless participant is/can be catheterized\n* History of hypersensitivity and/or idiosyncratic reaction to benzazepine or benzazepine derivatives\n* Psychogenic polydipsia\n* Uncontrolled diabetes mellitus (defined as fasting glucose \\>300 milligrams/deciliter)\n* Screening liver function values \\>3 times the upper limit of normal\n* Participants who have cirrhosis and meet any of the following conditions: a major GI bleed within the past 6 months, evidence of active bleeding, platelet count \\<50,000/microliter, or use of concomitant medications known to increase bleeding risk\n* Hyponatremia due to the result of any medication that can safely be withdrawn or that is most appropriately corrected by alternative therapies\n* History of drug or medication abuse within 3 months prior to screening or current alcohol abuse\n* Participants who require suspension formulation and have a Hereditary Fructose Intolerance\n* Has hyponatremia that is more appropriately corrected by alternative therapies\n* Is pregnant or currently breastfeeding\n* Has any medical condition that could interfere with evaluation of trial objectives or participant safety\n* Has participated in another investigational drug trial in the last 30 days\n* Weighs \\<3 kg\n* Unable to swallow tablets, if suspension unavailable\n* Is deemed unsuitable for trial participation in the opinion of the investigator'}, 'identificationModule': {'nctId': 'NCT02012959', 'briefTitle': 'Study of the Safety and Effectiveness of SAMSCA® (Tolvaptan) in Children and Adolescents With Euvolemic or Hypervolemic Hyponatremia', 'organization': {'class': 'INDUSTRY', 'fullName': 'Otsuka Pharmaceutical Development & Commercialization, Inc.'}, 'officialTitle': 'A Phase 3b, Multicenter, Open-label, Randomized Withdrawal Trial of the Effects of Titrated Oral SAMSCA ® (Tolvaptan) on Serum Sodium, Pharmacokinetics, and Safety in Children and Adolescent Subjects Hospitalized With Euvolemic or Hypervolemic Hyponatremia', 'orgStudyIdInfo': {'id': '156-08-276'}, 'secondaryIdInfos': [{'id': '2013-002005-59', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Tolvaptan Early Withdrawal', 'description': "All participants initially received tolvaptan once daily for the first 2 days. A third day of treatment was permitted if a participant had not reached the desired sodium target improvement per the investigator's judgment.\n\nAt the end of Day 2 (or Day 3), responders (participants who achieved an increase in serum sodium by ≥4 millimoles/liter \\[mmol/L\\]) were randomized to either the Early or Late Withdrawal Group. Non-responders could continue treatment with tolvaptan for an additional 2 days.\n\nDiscontinued tolvaptan treatment immediately after randomization.\n\nAll participants were observed up to 14 days post randomization.", 'interventionNames': ['Drug: Tolvaptan']}, {'type': 'EXPERIMENTAL', 'label': 'Tolvaptan Late Withdrawal', 'description': "All participants initially received tolvaptan once daily for the first 2 days. A third day of treatment was permitted if a participant had not reached the desired sodium target improvement per the investigator's judgment.\n\nAt the end of Day 2 (or Day 3), responders (participants who achieved an increase in serum sodium by ≥4 mmol/L) were randomized to either the Early or Late Withdrawal Group in Treatment Phase B. Non-responders could continue treatment with tolvaptan for an additional 2 days.\n\nContinued treatment for 2 additional days.\n\nAll participants were observed up to 14 days post randomization.", 'interventionNames': ['Drug: Tolvaptan']}], 'interventions': [{'name': 'Tolvaptan', 'type': 'DRUG', 'otherNames': ['SAMSCA®'], 'armGroupLabels': ['Tolvaptan Early Withdrawal', 'Tolvaptan Late Withdrawal']}]}, 'contactsLocationsModule': {'locations': [{'zip': '80045', 'city': 'Aurora', 'state': 'Colorado', 'country': 'United States', 'geoPoint': {'lat': 39.72943, 'lon': -104.83192}}, {'zip': '20010', 'city': 'Washington D.C.', 'state': 'District of Columbia', 'country': 'United States', 'geoPoint': {'lat': 38.89511, 'lon': -77.03637}}, {'zip': '10032', 'city': 'New York', 'state': 'New York', 'country': 'United States', 'geoPoint': {'lat': 40.71427, 'lon': -74.00597}}, {'zip': '23298-0270', 'city': 'Richmond', 'state': 'Virginia', 'country': 'United States', 'geoPoint': {'lat': 37.55376, 'lon': -77.46026}}, {'zip': '98105', 'city': 'Seattle', 'state': 'Washington', 'country': 'United States', 'geoPoint': {'lat': 47.60621, 'lon': -122.33207}}, {'zip': '00165', 'city': 'Rome', 'country': 'Italy', 'geoPoint': {'lat': 41.89193, 'lon': 12.51133}}, {'zip': 'WC1N 3JH', 'city': 'London', 'country': 'United Kingdom', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'overallOfficials': [{'name': 'Global Clinical Development', 'role': 'STUDY_DIRECTOR', 'affiliation': 'Otsuka Pharmaceutical Development & Commercialization, Inc.'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Otsuka Pharmaceutical Development & Commercialization, Inc.', 'class': 'INDUSTRY'}, 'collaborators': [{'name': 'Syneos Health', 'class': 'OTHER'}], 'responsibleParty': {'type': 'SPONSOR'}}}}