Ignite Creation Date:
2025-12-24 @ 11:33 PM
Ignite Modification Date:
2025-12-30 @ 12:59 AM
Study NCT ID:
NCT01389856
Status:
TERMINATED
Last Update Posted:
2025-02-04
First Post:
2011-06-30
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Persistent Pulmonary Hypertension of the Newborn
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['Australia', 'Belgium', 'Czechia', 'France', 'Germany', 'Netherlands', 'Poland', 'Russia', 'Singapore', 'South Korea', 'Switzerland', 'United Kingdom', 'United States']}, 'conditionBrowseModule': {'meshes': [{'id': 'D010547', 'term': 'Persistent Fetal Circulation Syndrome'}], 'ancestors': [{'id': 'D006976', 'term': 'Hypertension, Pulmonary'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D007232', 'term': 'Infant, Newborn, Diseases'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077300', 'term': 'Bosentan'}], 'ancestors': [{'id': 'D000096926', 'term': 'Benzenesulfonamides'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D000577', 'term': 'Amides'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D001555', 'term': 'Benzene Derivatives'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D011743', 'term': 'Pyrimidines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'pegah.nowbakht@actelion.com', 'phone': '+41 61 565 68 41', 'title': 'Pegah Nowbakht/Senior Clinical Trial Scientist', 'organization': 'Actelion Pharmaceuticals Ltd'}, 'certainAgreement': {'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'Up to 21 Days, plus up to 60 days after end of treatment for serious adverse events', 'eventGroups': [{'id': 'EG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.', 'otherNumAtRisk': 13, 'otherNumAffected': 9, 'seriousNumAtRisk': 13, 'seriousNumAffected': 2}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.', 'otherNumAtRisk': 8, 'otherNumAffected': 2, 'seriousNumAtRisk': 8, 'seriousNumAffected': 3}], 'otherEvents': [{'term': 'ANAEMIA', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'GENERALISED OEDEMA', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'COAGULOPATHY', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'VOMITING', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'BILIRUBIN CONJUGATED INCREASED', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'BODY TEMPERATURE INCREASED', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'C-REACTIVE PROTEIN INCREASED', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'DYSPHONIA', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'ENDOTRACHEAL INTUBATION COMPLICATION', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'GASTRIC HAEMORRHAGE', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'HYPOGLYCAEMIA', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'HYPOKALAEMIA', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'HYPOPHOSPHATAEMIA', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'INFECTIOUS DISEASE CARRIER', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'METABOLIC ACIDOSIS', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'METHAEMOGLOBINAEMIA', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'MITRAL VALVE INCOMPETENCE', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'PNEUMOMEDIASTINUM', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'PNEUMOTHORAX', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'PROCEDURAL COMPLICATION', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Injury, poisoning and procedural complications', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'THROMBOCYTOPENIA', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Blood and lymphatic system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}], 'seriousEvents': [{'term': 'HEPATITIS', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Hepatobiliary disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'METABOLIC ACIDOSIS', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'HYPERCAPNIA', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'PNEUMOTHORAX', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'CIRCULATORY COLLAPSE', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 0}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}, {'term': 'SEPSIS', 'stats': [{'groupId': 'EG000', 'numAtRisk': 13, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 8, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA version 16.0'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Percentage of Patients With Treatment Failure', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '7.7', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'NUMBER', 'timeFrame': 'From baseline to up to 21 days', 'description': 'Treatment failure was defined as the need for extra corporeal membrane oxygenation or initiation of alternative pulmonary vasodilator treatment', 'unitOfMeasure': 'percentage of participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients'}, {'type': 'PRIMARY', 'title': 'Time to Complete Weaning From iNO', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '3.7', 'groupId': 'OG000', 'lowerLimit': '1.17', 'upperLimit': '6.95'}, {'value': '2.9', 'groupId': 'OG001', 'lowerLimit': '1.26', 'upperLimit': '4.23'}]}]}], 'analyses': [{'pValue': '0.3407', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Log Rank', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': 'From baseline to up to 21 days', 'description': 'Calculated from the time from first study drug administration to complete weaning from iNO. Weaning from iNO was considered complete if there was no requirement for the re-initiation of iNO within 24 h after stopping', 'unitOfMeasure': 'days', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients'}, {'type': 'PRIMARY', 'title': 'Time to Complete Weaning From Mechanical Ventilation', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '10.8', 'groupId': 'OG000', 'lowerLimit': '3.21', 'upperLimit': '12.21'}, {'value': '8.6', 'groupId': 'OG001', 'lowerLimit': '3.71', 'upperLimit': '9.66'}]}]}], 'analyses': [{'pValue': '0.2399', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Log Rank', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': 'From baseline to up to 21 days', 'description': 'Calculated from the time from first study drug administration to complete weaning from mechanical ventilation', 'unitOfMeasure': 'days', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients'}, {'type': 'SECONDARY', 'title': 'Percentage of Patients Requiring Re-initiation of iNO Therapy', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}], 'paramType': 'NUMBER', 'timeFrame': 'From baseline to up to 21 days', 'description': 'Re-initiation of iNO therapy following weaning from iNO therapy', 'unitOfMeasure': 'percentage of participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients'}, {'type': 'SECONDARY', 'title': 'Percentage of Patients With Pulmonary Hypertension (PH) at End of Treatment', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '41.7', 'groupId': 'OG000'}, {'value': '37.5', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '1.000', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Fisher Exact', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'NUMBER', 'timeFrame': 'From baseline to up to 14 days', 'description': "The presence of PH was assessed by echocardiography. PH was reported as 'present' if at least one of the following criteria was met:\n\n* Shunt through ductus arteriosus was either 'predominant right to left' or 'bidirectional'\n* Shunt through foramen ovale was either 'predominant right to left' or 'bidirectional'\n* Marked right ventricular dilation was ticked 'present'\n* Paradoxical shift of intraventricular septum was ticked 'present'\n* Right ventricular systolic pressure (mmHg) was \\> 2/3 of the reported systemic blood pressure", 'unitOfMeasure': 'percentage of participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients'}, {'type': 'SECONDARY', 'title': 'Change in Oxygenation Index (OI) From Baseline to 3 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '18.3', 'groupId': 'OG000', 'lowerLimit': '8.2', 'upperLimit': '35.4'}, {'value': '13.2', 'groupId': 'OG001', 'lowerLimit': '7.9', 'upperLimit': '39.4'}]}]}, {'title': '3 hours', 'categories': [{'measurements': [{'value': '17.3', 'groupId': 'OG000', 'lowerLimit': '6.9', 'upperLimit': '33.3'}, {'value': '13.0', 'groupId': 'OG001', 'lowerLimit': '8.5', 'upperLimit': '42.9'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '-1.6', 'groupId': 'OG000', 'lowerLimit': '-5.1', 'upperLimit': '3.3'}, {'value': '1.1', 'groupId': 'OG001', 'lowerLimit': '-6.1', 'upperLimit': '6.1'}]}]}], 'analyses': [{'pValue': '0.2235', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '3 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.', 'unitOfMeasure': 'oxygenation index', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients'}, {'type': 'SECONDARY', 'title': 'Change in Oxygenation Index (OI) From Baseline to 5 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '18.3', 'groupId': 'OG000', 'lowerLimit': '8.2', 'upperLimit': '35.4'}, {'value': '13.2', 'groupId': 'OG001', 'lowerLimit': '7.9', 'upperLimit': '39.4'}]}]}, {'title': '5 hours', 'categories': [{'measurements': [{'value': '16.7', 'groupId': 'OG000', 'lowerLimit': '7.9', 'upperLimit': '36.7'}, {'value': '13.3', 'groupId': 'OG001', 'lowerLimit': '6.7', 'upperLimit': '28.6'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '-0.9', 'groupId': 'OG000', 'lowerLimit': '-4.7', 'upperLimit': '4.5'}, {'value': '-5.6', 'groupId': 'OG001', 'lowerLimit': '-7.5', 'upperLimit': '15.7'}]}]}], 'analyses': [{'pValue': '0.1468', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '5 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.', 'unitOfMeasure': 'oxygenation index', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients'}, {'type': 'SECONDARY', 'title': 'Change in Oxygenation Index (OI) From Baseline to 12 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '18.3', 'groupId': 'OG000', 'lowerLimit': '8.2', 'upperLimit': '35.4'}, {'value': '13.2', 'groupId': 'OG001', 'lowerLimit': '7.9', 'upperLimit': '39.4'}]}]}, {'title': '12 hours', 'categories': [{'measurements': [{'value': '14.3', 'groupId': 'OG000', 'lowerLimit': '8.3', 'upperLimit': '26.7'}, {'value': '11.1', 'groupId': 'OG001', 'lowerLimit': '4.9', 'upperLimit': '19.6'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '-0.8', 'groupId': 'OG000', 'lowerLimit': '-12.9', 'upperLimit': '2.8'}, {'value': '-3.9', 'groupId': 'OG001', 'lowerLimit': '-14.6', 'upperLimit': '12.5'}]}]}], 'analyses': [{'pValue': '0.0789', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '12 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.', 'unitOfMeasure': 'oxygenation index', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients'}, {'type': 'SECONDARY', 'title': 'Change in Oxygenation Index (OI) From Baseline to 24 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '18.3', 'groupId': 'OG000', 'lowerLimit': '8.2', 'upperLimit': '35.4'}, {'value': '13.2', 'groupId': 'OG001', 'lowerLimit': '7.9', 'upperLimit': '39.4'}]}]}, {'title': '24 hours', 'categories': [{'measurements': [{'value': '13.1', 'groupId': 'OG000', 'lowerLimit': '6.5', 'upperLimit': '32.9'}, {'value': '11.8', 'groupId': 'OG001', 'lowerLimit': '5.2', 'upperLimit': '26.4'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '-4.9', 'groupId': 'OG000', 'lowerLimit': '-17.0', 'upperLimit': '1.1'}, {'value': '-6.9', 'groupId': 'OG001', 'lowerLimit': '-9.9', 'upperLimit': '19.4'}]}]}], 'analyses': [{'pValue': '0.3723', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '24 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.', 'unitOfMeasure': 'oxygenation index', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients'}, {'type': 'SECONDARY', 'title': 'Change in Oxygenation Index (OI) From Baseline to 48 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '19.4', 'groupId': 'OG000', 'lowerLimit': '8.2', 'upperLimit': '35.4'}, {'value': '13.2', 'groupId': 'OG001', 'lowerLimit': '7.9', 'upperLimit': '39.4'}]}]}, {'title': '48 hours', 'categories': [{'measurements': [{'value': '11.5', 'groupId': 'OG000', 'lowerLimit': '4.7', 'upperLimit': '21.0'}, {'value': '3.8', 'groupId': 'OG001', 'lowerLimit': '2.5', 'upperLimit': '10.8'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '-4.9', 'groupId': 'OG000', 'lowerLimit': '-15.5', 'upperLimit': '-2.1'}, {'value': '-9.9', 'groupId': 'OG001', 'lowerLimit': '-18.0', 'upperLimit': '3.4'}]}]}], 'analyses': [{'pValue': '0.0569', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '48 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.', 'unitOfMeasure': 'oxygenation index', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients with available data'}, {'type': 'SECONDARY', 'title': 'Change in Oxygenation Index (OI) From Baseline to 72 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '19.4', 'groupId': 'OG000', 'lowerLimit': '8.2', 'upperLimit': '35.4'}, {'value': '13.2', 'groupId': 'OG001', 'lowerLimit': '7.9', 'upperLimit': '39.4'}]}]}, {'title': '72 hours', 'categories': [{'measurements': [{'value': '6.7', 'groupId': 'OG000', 'lowerLimit': '4.2', 'upperLimit': '17.0'}, {'value': '3.9', 'groupId': 'OG001', 'lowerLimit': '3.7', 'upperLimit': '10.8'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '-8.9', 'groupId': 'OG000', 'lowerLimit': '-23.1', 'upperLimit': '-1.8'}, {'value': '-9.4', 'groupId': 'OG001', 'lowerLimit': '-17.7', 'upperLimit': '2.2'}]}]}], 'analyses': [{'pValue': '0.1015', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '72 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.', 'unitOfMeasure': 'oxygenation index', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients with available data'}, {'type': 'SECONDARY', 'title': 'Change in Arterial Blood Gas (ABG) pH From Baseline to 72 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '7.37', 'groupId': 'OG000', 'lowerLimit': '7.30', 'upperLimit': '7.43'}, {'value': '7.31', 'groupId': 'OG001', 'lowerLimit': '7.21', 'upperLimit': '7.49'}]}]}, {'title': '72 hours', 'categories': [{'measurements': [{'value': '7.37', 'groupId': 'OG000', 'lowerLimit': '7.36', 'upperLimit': '7.43'}, {'value': '7.36', 'groupId': 'OG001', 'lowerLimit': '7.30', 'upperLimit': '7.39'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '0.04', 'groupId': 'OG000', 'lowerLimit': '-0.06', 'upperLimit': '0.07'}, {'value': '0.02', 'groupId': 'OG001', 'lowerLimit': '-0.09', 'upperLimit': '0.19'}]}]}], 'analyses': [{'pValue': '0.0824', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '72 hours', 'description': 'pH was determined in arterial blood samples at baseline and 72 h after the first study drug administration', 'unitOfMeasure': 'pH', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients with available data'}, {'type': 'SECONDARY', 'title': 'Change in Arterial Blood Oxygen Saturation (SaO2) From Baseline to 72 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '95.0', 'groupId': 'OG000', 'lowerLimit': '92.0', 'upperLimit': '99.0'}, {'value': '95.5', 'groupId': 'OG001', 'lowerLimit': '89.0', 'upperLimit': '99.0'}]}]}, {'title': '72 hours', 'categories': [{'measurements': [{'value': '98.0', 'groupId': 'OG000', 'lowerLimit': '95.0', 'upperLimit': '100.0'}, {'value': '97.0', 'groupId': 'OG001', 'lowerLimit': '93.0', 'upperLimit': '100.0'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '1.0', 'groupId': 'OG000', 'lowerLimit': '0.0', 'upperLimit': '8.0'}, {'value': '0.0', 'groupId': 'OG001', 'lowerLimit': '-4.0', 'upperLimit': '21.0'}]}]}], 'analyses': [{'pValue': '0.3863', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '72 hours', 'description': 'SaO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration', 'unitOfMeasure': 'percentage saturation', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients with available data'}, {'type': 'SECONDARY', 'title': 'Change in Partial Pressure of Oxygen (PaO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '61.0', 'groupId': 'OG000', 'lowerLimit': '53.0', 'upperLimit': '132.0'}, {'value': '69.5', 'groupId': 'OG001', 'lowerLimit': '46.0', 'upperLimit': '111.0'}]}]}, {'title': '72 hours', 'categories': [{'measurements': [{'value': '81.0', 'groupId': 'OG000', 'lowerLimit': '61.0', 'upperLimit': '104.0'}, {'value': '81.5', 'groupId': 'OG001', 'lowerLimit': '56.0', 'upperLimit': '187.0'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '18.0', 'groupId': 'OG000', 'lowerLimit': '-13.0', 'upperLimit': '32.0'}, {'value': '6.0', 'groupId': 'OG001', 'lowerLimit': '-12.0', 'upperLimit': '115.0'}]}]}], 'analyses': [{'pValue': '0.3936', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '72 hours', 'description': 'PaO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration', 'unitOfMeasure': 'mm Hg', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients with available data'}, {'type': 'SECONDARY', 'title': 'Change in Partial Pressure of Carbon Dioxide (PaCO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '40.5', 'groupId': 'OG000', 'lowerLimit': '31.0', 'upperLimit': '47.0'}, {'value': '46.0', 'groupId': 'OG001', 'lowerLimit': '35.0', 'upperLimit': '57.0'}]}]}, {'title': '72 hours', 'categories': [{'measurements': [{'value': '45.5', 'groupId': 'OG000', 'lowerLimit': '36.0', 'upperLimit': '49.0'}, {'value': '46.0', 'groupId': 'OG001', 'lowerLimit': '41.0', 'upperLimit': '64.0'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '6.0', 'groupId': 'OG000', 'lowerLimit': '-1.0', 'upperLimit': '12.0'}, {'value': '8.0', 'groupId': 'OG001', 'lowerLimit': '-8.0', 'upperLimit': '21.0'}]}]}], 'analyses': [{'pValue': '0.2436', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '72 hours', 'description': 'PaCO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration', 'unitOfMeasure': 'mm Hg', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients with available data'}, {'type': 'SECONDARY', 'title': 'Change in Pre-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '7', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '95.00', 'groupId': 'OG000', 'lowerLimit': '91.00', 'upperLimit': '99.00'}, {'value': '97.00', 'groupId': 'OG001', 'lowerLimit': '91.00', 'upperLimit': '99.00'}]}]}, {'title': '72 hours', 'categories': [{'measurements': [{'value': '96.00', 'groupId': 'OG000', 'lowerLimit': '93.00', 'upperLimit': '100.00'}, {'value': '96.00', 'groupId': 'OG001', 'lowerLimit': '85.00', 'upperLimit': '100.00'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '0.50', 'groupId': 'OG000', 'lowerLimit': '-2.00', 'upperLimit': '2.00'}, {'value': '-1.00', 'groupId': 'OG001', 'lowerLimit': '-10.00', 'upperLimit': '2.00'}]}]}], 'analyses': [{'pValue': '0.1756', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '72 hours', 'description': 'Simultaneous pre- (right hand) and post-ductal (lower extremities) SpO2 were measured using pulse oximetry device at baseline and 72 h after the first study drug administration', 'unitOfMeasure': 'percentage saturation', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients with available data'}, {'type': 'SECONDARY', 'title': 'Change in Post-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '96.5', 'groupId': 'OG000', 'lowerLimit': '92.0', 'upperLimit': '99.0'}, {'value': '96.0', 'groupId': 'OG001', 'lowerLimit': '89.0', 'upperLimit': '98.0'}]}]}, {'title': '72 hours', 'categories': [{'measurements': [{'value': '95.5', 'groupId': 'OG000', 'lowerLimit': '94.0', 'upperLimit': '99.0'}, {'value': '97.5', 'groupId': 'OG001', 'lowerLimit': '95.0', 'upperLimit': '100.0'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '0.0', 'groupId': 'OG000', 'lowerLimit': '-2.0', 'upperLimit': '3.0'}, {'value': '2.0', 'groupId': 'OG001', 'lowerLimit': '1.0', 'upperLimit': '12.0'}]}]}], 'analyses': [{'pValue': '0.1155', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '72 hours', 'description': 'Simultaneous pre- (right hand) and post-ductal (lower extremities) SpO2 were measured using pulse oximetry device at baseline and 72 h after the first study drug administration', 'unitOfMeasure': 'percentage saturation', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients with available data'}, {'type': 'SECONDARY', 'title': 'Change in Fraction of Inspired Oxygen (FiO2) From Baseline to 72 Hours Following Study Drug Administration', 'denoms': [{'units': 'Participants', 'counts': [{'value': '12', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '90.0', 'groupId': 'OG000', 'lowerLimit': '62.0', 'upperLimit': '97.0'}, {'value': '78.0', 'groupId': 'OG001', 'lowerLimit': '60.0', 'upperLimit': '100.0'}]}]}, {'title': '72 hours', 'categories': [{'measurements': [{'value': '51.5', 'groupId': 'OG000', 'lowerLimit': '28.0', 'upperLimit': '60.0'}, {'value': '40.0', 'groupId': 'OG001', 'lowerLimit': '25.0', 'upperLimit': '60.0'}]}]}, {'title': 'Change from baseline', 'categories': [{'measurements': [{'value': '-33.5', 'groupId': 'OG000', 'lowerLimit': '-50.0', 'upperLimit': '-15.0'}, {'value': '-35.5', 'groupId': 'OG001', 'lowerLimit': '-60.0', 'upperLimit': '0.0'}]}]}], 'analyses': [{'pValue': '0.1400', 'groupIds': ['OG000', 'OG001'], 'ciNumSides': 'TWO_SIDED', 'statisticalMethod': 'Non-parametric ANCOVA', 'nonInferiorityType': 'SUPERIORITY_OR_OTHER_LEGACY'}], 'paramType': 'MEDIAN', 'timeFrame': '72 hours', 'description': "FiO2 was determined according to each study centers' standard procedure at baseline and 72 h after the first study drug administration", 'unitOfMeasure': 'percentage of oxygen', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Randomized and treated patients with available data'}, {'type': 'SECONDARY', 'title': 'Maximum Whole Blood Concentration (Cmax) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Bosentan', 'categories': [{'measurements': [{'value': '30.1', 'groupId': 'OG000', 'lowerLimit': '2.4', 'upperLimit': '372.2'}]}]}, {'title': 'Ro 47-8634', 'categories': [{'measurements': [{'value': '0.1', 'groupId': 'OG000', 'lowerLimit': '0.0', 'upperLimit': '1.1'}]}]}, {'title': 'Ro 48-5033', 'categories': [{'measurements': [{'value': '0.6', 'groupId': 'OG000', 'lowerLimit': '0.0', 'upperLimit': '18.3'}]}]}, {'title': 'Ro 64-1056', 'categories': [{'measurements': [{'value': '0.9', 'groupId': 'OG000', 'lowerLimit': '0.0', 'upperLimit': '16.2'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'up to 12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Cmax was obtained directly from the measured concentrations. Cmax was corrected to a dose of 2 mg/kg bosentan (Cmaxc). The target dose was 2 mg/kg. However, as the smallest dose unit was 8 mg (quarter of a tablet), it was not possible to achieve the exact target dose in all patients. Therefore, Cmax was divided by the actual dose (in mg/kg) and multiplied by 2 mg/kg.', 'unitOfMeasure': 'ng/mL', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Pharmacokinetic (PK) analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Cmax for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 5', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Bosentan', 'categories': [{'measurements': [{'value': '880.0', 'groupId': 'OG000', 'lowerLimit': '339.2', 'upperLimit': '2282.7'}]}]}, {'title': 'Ro 47-8634', 'categories': [{'measurements': [{'value': '24.9', 'groupId': 'OG000', 'lowerLimit': '9.0', 'upperLimit': '69.1'}]}]}, {'title': 'Ro 48-5033', 'categories': [{'measurements': [{'value': '292.3', 'groupId': 'OG000', 'lowerLimit': '115.8', 'upperLimit': '738.1'}]}]}, {'title': 'Ro 64-1056', 'categories': [{'measurements': [{'value': '136.0', 'groupId': 'OG000', 'lowerLimit': '77.4', 'upperLimit': '238.8'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Cmax obtained directly from the measured concentrations . Cmax was corrected to a dose of 2 mg/kg bosentan (Cmaxc). The target dose was 2 mg/kg. However, as the smallest dose unit was 8 mg (quarter of a tablet), it was not possible to achieve the exact target dose in all patients. Therefore, Cmax was divided by the actual dose (in mg/kg) and multiplied by 2 mg/kg.', 'unitOfMeasure': 'ng/mL', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Time to Maximum Whole Blood Concentration (Tmax) for Bosentan on Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '12.0', 'groupId': 'OG000', 'lowerLimit': '7.5', 'upperLimit': '12.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'up to 12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Tmax for Ro 47-8634 on Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '12.0', 'groupId': 'OG000', 'lowerLimit': '7.5', 'upperLimit': '12.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'up to 12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Tmax for Ro 48-5033 on Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '12.0', 'groupId': 'OG000', 'lowerLimit': '12.0', 'upperLimit': '12.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'up to 12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Tmax for Ro 64-1056 on Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '12', 'groupId': 'OG000', 'lowerLimit': '0.5', 'upperLimit': '12.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': 'up to 12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Tmax for Bosentan on Day 5', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '7.5', 'groupId': 'OG000', 'lowerLimit': '0.8', 'upperLimit': '12.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Tmax for Ro 47-8634 on Day 5', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '6.5', 'groupId': 'OG000', 'lowerLimit': '0.8', 'upperLimit': '12.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Tmax for Ro 48-5033 on Day 5', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '7.5', 'groupId': 'OG000', 'lowerLimit': '0.8', 'upperLimit': '12.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Tmax for Ro 64-1056 on Day 5', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '12.0', 'groupId': 'OG000', 'lowerLimit': '7.5', 'upperLimit': '12.0'}]}]}], 'paramType': 'MEDIAN', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.', 'unitOfMeasure': 'hours', 'dispersionType': 'Full Range', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Area Under the Concentration-time Curve Over a Period of 12 h (AUC0-12 Day 1)) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Bosentan', 'categories': [{'measurements': [{'value': '163.9', 'groupId': 'OG000', 'lowerLimit': '9.6', 'upperLimit': '2795.4'}]}]}, {'title': 'Ro 47-8634', 'categories': [{'measurements': [{'value': '0.1', 'groupId': 'OG000', 'lowerLimit': '0.0', 'upperLimit': '3.7'}]}]}, {'title': 'Ro 48-5033', 'categories': [{'measurements': [{'value': '1.4', 'groupId': 'OG000', 'lowerLimit': '0.0', 'upperLimit': '69.9'}]}]}, {'title': 'Ro 64-1056', 'categories': [{'measurements': [{'value': '2.2', 'groupId': 'OG000', 'lowerLimit': '0.1', 'upperLimit': '64.1'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-12 Day 1 was calculated according to the trapezoidal rule using the measured concentration-time values above the limit of quantification.', 'unitOfMeasure': 'h*ng/mL', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Area Under the Concentration-time Curve Over a Dosing Interval at Steady State on Day 5 (AUCtau) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Bosentan', 'categories': [{'measurements': [{'value': '6165.4', 'groupId': 'OG000', 'lowerLimit': '2429.6', 'upperLimit': '15645.3'}]}]}, {'title': 'Ro 47-8634', 'categories': [{'measurements': [{'value': '217.3', 'groupId': 'OG000', 'lowerLimit': '75.3', 'upperLimit': '626.8'}]}]}, {'title': 'Ro 48-5033', 'categories': [{'measurements': [{'value': '2839.5', 'groupId': 'OG000', 'lowerLimit': '1155.2', 'upperLimit': '6979.2'}]}]}, {'title': 'Ro 64-1056', 'categories': [{'measurements': [{'value': '1321.7', 'groupId': 'OG000', 'lowerLimit': '729.5', 'upperLimit': '2395.0'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '5 days', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUCtau Day 5 was calculated according to the trapezoidal rule using the measured concentration-time values above the limit of quantification.', 'unitOfMeasure': 'h*ng/mL', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Area Under the Concentration-time Curve Over a Period of 24 h (Dose-corrected to 2 mg/kg) on Day 1 (AUC0-24C Day 1) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056', 'denoms': [{'units': 'Participants', 'counts': [{'value': '11', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Bosentan', 'categories': [{'measurements': [{'value': '287.5', 'groupId': 'OG000', 'lowerLimit': '15.0', 'upperLimit': '5504.7'}]}]}, {'title': 'Ro 47-8634', 'categories': [{'measurements': [{'value': '0.1', 'groupId': 'OG000', 'lowerLimit': '0.0', 'upperLimit': '6.1'}]}]}, {'title': 'Ro 48-5033', 'categories': [{'measurements': [{'value': '2.0', 'groupId': 'OG000', 'lowerLimit': '0.0', 'upperLimit': '125.8'}]}]}, {'title': 'Ro 64-1056', 'categories': [{'measurements': [{'value': '3.4', 'groupId': 'OG000', 'lowerLimit': '0.1', 'upperLimit': '120.8'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '24 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-24C Day 1 was calculated as a multiple of AUC0-12, (2 × AUC0-12 for 2 times daily dosing) corrected to 2 mg/kg.', 'unitOfMeasure': 'h*ng/mL', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Area Under the Concentration-time Curve Over a Period of 24 h (Dose-corrected to 2 mg/kg) on Day 5 (AUC0-24C Day 5) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'title': 'Bosentan', 'categories': [{'measurements': [{'value': '11530.2', 'groupId': 'OG000', 'lowerLimit': '4507.0', 'upperLimit': '29497.5'}]}]}, {'title': 'Ro 47-8634', 'categories': [{'measurements': [{'value': '406.3', 'groupId': 'OG000', 'lowerLimit': '139.8', 'upperLimit': '1180.9'}]}]}, {'title': 'Ro 48-5033', 'categories': [{'measurements': [{'value': '5310.3', 'groupId': 'OG000', 'lowerLimit': '2184.4', 'upperLimit': '12908.9'}]}]}, {'title': 'Ro 64-1056', 'categories': [{'measurements': [{'value': '2471.9', 'groupId': 'OG000', 'lowerLimit': '1386.1', 'upperLimit': '4408.0'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '24 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-24C Day 5 was calculated as a multiple of AUCtau, (2 × AUCtau for 2 times daily dosing) corrected to 2 mg/kg.', 'unitOfMeasure': 'h*ng/mL', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}, {'type': 'SECONDARY', 'title': 'Accumulation Index (AI) for Bosentan', 'denoms': [{'units': 'Participants', 'counts': [{'value': '7', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'classes': [{'categories': [{'measurements': [{'value': '61.6', 'groupId': 'OG000', 'lowerLimit': '0.5', 'upperLimit': '7813.9'}]}]}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': '5 days', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Days 1 and 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AI was calculated as the ratio AUCtau /AUC0-12 for the subjects having PK samples collected on Day 1 and Day 5 and with AUC0-12 \\> 0 ng.h/mL.', 'unitOfMeasure': 'accumulation index', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'PK analysis set. This analysis set comprised all patients included in the all-treated set who were able to provide at least 5 of the 7 blood samples requested for at least one evaluable profile of PK assessment and who did not violate the protocol in a way that might affect the evaluation of the PK endpoints.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'comment': 'Randomized and treated. An additional 2 patients were randomized but not treated.', 'groupId': 'FG000', 'numSubjects': '13'}, {'comment': 'Randomized and treated.', 'groupId': 'FG001', 'numSubjects': '8'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '13'}, {'groupId': 'FG001', 'numSubjects': '8'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'First patient, first visit was 8 December 2011 and last patient, last visit was 5 December 2013. The investigational sites were tertiary care centers with neonatal intensive care unit facilities at which inhaled nitric oxide (iNO) was used as standard of care for persistent pulmonary hypertension of the newborn (PPHN).', 'preAssignmentDetails': 'Term or near-term (gestational age \\> 34 weeks) hypoxic newborns with respiratory distress refractory to supplemental oxygen were considered, provided they had no significant structural cardiac anomalies documented in the pre-natal period and had no immediate need for extra corporeal membrane oxygenation (ECMO).'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '13', 'groupId': 'BG000'}, {'value': '8', 'groupId': 'BG001'}, {'value': '21', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Bosentan', 'description': 'Bosentan\n\nBosentan: 2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'Matching placebo\n\nMatching placebo: twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '1.4', 'groupId': 'BG000', 'lowerLimit': '0.6', 'upperLimit': '5.6'}, {'value': '1.7', 'groupId': 'BG001', 'lowerLimit': '0.6', 'upperLimit': '5.9'}, {'value': '1.4', 'groupId': 'BG002', 'lowerLimit': '0.6', 'upperLimit': '5.9'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'days', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '15', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race/Ethnicity, Customized', 'classes': [{'title': 'Caucasian/white', 'categories': [{'measurements': [{'value': '11', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '17', 'groupId': 'BG002'}]}]}, {'title': 'Asian', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}, {'title': 'Hispanic', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}]}, {'title': 'Other', 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Czech Republic', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}]}, {'title': 'France', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}, {'title': 'Korea, Republic of', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}, {'title': 'Poland', 'categories': [{'measurements': [{'value': '5', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '8', 'groupId': 'BG002'}]}]}, {'title': 'United Kingdom', 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '6', 'groupId': 'BG002'}]}]}, {'title': 'United States', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '2', 'groupId': 'BG001'}, {'value': '3', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Gestational age', 'classes': [{'categories': [{'measurements': [{'value': '40.0', 'groupId': 'BG000', 'lowerLimit': '36.0', 'upperLimit': '41.0'}, {'value': '38.5', 'groupId': 'BG001', 'lowerLimit': '36.0', 'upperLimit': '42.0'}, {'value': '39.0', 'groupId': 'BG002', 'lowerLimit': '36.0', 'upperLimit': '42.0'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'weeks', 'dispersionType': 'FULL_RANGE'}], 'populationDescription': 'Randomized and treated patients'}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 23}}, 'statusModule': {'whyStopped': 'To be compliant with the timelines as agreed with Paediatric Committee (PC) within the Paediatric Investigational Plan', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2011-12'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-01', 'completionDateStruct': {'date': '2014-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-01-31', 'studyFirstSubmitDate': '2011-06-30', 'resultsFirstSubmitDate': '2015-03-09', 'studyFirstSubmitQcDate': '2011-07-07', 'lastUpdatePostDateStruct': {'date': '2025-02-04', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2015-03-09', 'studyFirstPostDateStruct': {'date': '2011-07-08', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2015-03-23', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2013-12', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Percentage of Patients With Treatment Failure', 'timeFrame': 'From baseline to up to 21 days', 'description': 'Treatment failure was defined as the need for extra corporeal membrane oxygenation or initiation of alternative pulmonary vasodilator treatment'}, {'measure': 'Time to Complete Weaning From iNO', 'timeFrame': 'From baseline to up to 21 days', 'description': 'Calculated from the time from first study drug administration to complete weaning from iNO. Weaning from iNO was considered complete if there was no requirement for the re-initiation of iNO within 24 h after stopping'}, {'measure': 'Time to Complete Weaning From Mechanical Ventilation', 'timeFrame': 'From baseline to up to 21 days', 'description': 'Calculated from the time from first study drug administration to complete weaning from mechanical ventilation'}], 'secondaryOutcomes': [{'measure': 'Percentage of Patients Requiring Re-initiation of iNO Therapy', 'timeFrame': 'From baseline to up to 21 days', 'description': 'Re-initiation of iNO therapy following weaning from iNO therapy'}, {'measure': 'Percentage of Patients With Pulmonary Hypertension (PH) at End of Treatment', 'timeFrame': 'From baseline to up to 14 days', 'description': "The presence of PH was assessed by echocardiography. PH was reported as 'present' if at least one of the following criteria was met:\n\n* Shunt through ductus arteriosus was either 'predominant right to left' or 'bidirectional'\n* Shunt through foramen ovale was either 'predominant right to left' or 'bidirectional'\n* Marked right ventricular dilation was ticked 'present'\n* Paradoxical shift of intraventricular septum was ticked 'present'\n* Right ventricular systolic pressure (mmHg) was \\> 2/3 of the reported systemic blood pressure"}, {'measure': 'Change in Oxygenation Index (OI) From Baseline to 3 Hours Following Study Drug Administration', 'timeFrame': '3 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.'}, {'measure': 'Change in Oxygenation Index (OI) From Baseline to 5 Hours Following Study Drug Administration', 'timeFrame': '5 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.'}, {'measure': 'Change in Oxygenation Index (OI) From Baseline to 12 Hours Following Study Drug Administration', 'timeFrame': '12 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.'}, {'measure': 'Change in Oxygenation Index (OI) From Baseline to 24 Hours Following Study Drug Administration', 'timeFrame': '24 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.'}, {'measure': 'Change in Oxygenation Index (OI) From Baseline to 48 Hours Following Study Drug Administration', 'timeFrame': '48 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.'}, {'measure': 'Change in Oxygenation Index (OI) From Baseline to 72 Hours Following Study Drug Administration', 'timeFrame': '72 hours', 'description': 'The change in OI from baseline following study drug administration was determined. OI was calculated as the mean airway pressure multiplied by the fraction of inspired oxygen (expressed in %), and the product was divided by the partial pressure of oxygen in arterial blood.'}, {'measure': 'Change in Arterial Blood Gas (ABG) pH From Baseline to 72 Hours Following Study Drug Administration', 'timeFrame': '72 hours', 'description': 'pH was determined in arterial blood samples at baseline and 72 h after the first study drug administration'}, {'measure': 'Change in Arterial Blood Oxygen Saturation (SaO2) From Baseline to 72 Hours Following Study Drug Administration', 'timeFrame': '72 hours', 'description': 'SaO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration'}, {'measure': 'Change in Partial Pressure of Oxygen (PaO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration', 'timeFrame': '72 hours', 'description': 'PaO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration'}, {'measure': 'Change in Partial Pressure of Carbon Dioxide (PaCO2) in Arterial Blood From Baseline to 72 Hours Following Study Drug Administration', 'timeFrame': '72 hours', 'description': 'PaCO2 was determined in arterial blood samples at baseline and 72 h after the first study drug administration'}, {'measure': 'Change in Pre-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration', 'timeFrame': '72 hours', 'description': 'Simultaneous pre- (right hand) and post-ductal (lower extremities) SpO2 were measured using pulse oximetry device at baseline and 72 h after the first study drug administration'}, {'measure': 'Change in Post-ductal Peripheral Oxygen Saturation (SpO2) From Baseline to 72 Hours Following Study Drug Administration', 'timeFrame': '72 hours', 'description': 'Simultaneous pre- (right hand) and post-ductal (lower extremities) SpO2 were measured using pulse oximetry device at baseline and 72 h after the first study drug administration'}, {'measure': 'Change in Fraction of Inspired Oxygen (FiO2) From Baseline to 72 Hours Following Study Drug Administration', 'timeFrame': '72 hours', 'description': "FiO2 was determined according to each study centers' standard procedure at baseline and 72 h after the first study drug administration"}, {'measure': 'Maximum Whole Blood Concentration (Cmax) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1', 'timeFrame': 'up to 12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Cmax was obtained directly from the measured concentrations. Cmax was corrected to a dose of 2 mg/kg bosentan (Cmaxc). The target dose was 2 mg/kg. However, as the smallest dose unit was 8 mg (quarter of a tablet), it was not possible to achieve the exact target dose in all patients. Therefore, Cmax was divided by the actual dose (in mg/kg) and multiplied by 2 mg/kg.'}, {'measure': 'Cmax for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 5', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Cmax obtained directly from the measured concentrations . Cmax was corrected to a dose of 2 mg/kg bosentan (Cmaxc). The target dose was 2 mg/kg. However, as the smallest dose unit was 8 mg (quarter of a tablet), it was not possible to achieve the exact target dose in all patients. Therefore, Cmax was divided by the actual dose (in mg/kg) and multiplied by 2 mg/kg.'}, {'measure': 'Time to Maximum Whole Blood Concentration (Tmax) for Bosentan on Day 1', 'timeFrame': 'up to 12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.'}, {'measure': 'Tmax for Ro 47-8634 on Day 1', 'timeFrame': 'up to 12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.'}, {'measure': 'Tmax for Ro 48-5033 on Day 1', 'timeFrame': 'up to 12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.'}, {'measure': 'Tmax for Ro 64-1056 on Day 1', 'timeFrame': 'up to 12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Tmax was obtained directly from the measured concentrations.'}, {'measure': 'Tmax for Bosentan on Day 5', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.'}, {'measure': 'Tmax for Ro 47-8634 on Day 5', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.'}, {'measure': 'Tmax for Ro 48-5033 on Day 5', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.'}, {'measure': 'Tmax for Ro 64-1056 on Day 5', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Tmax was obtained directly from the measured concentrations.'}, {'measure': 'Area Under the Concentration-time Curve Over a Period of 12 h (AUC0-12 Day 1)) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056 on Day 1', 'timeFrame': '12 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-12 Day 1 was calculated according to the trapezoidal rule using the measured concentration-time values above the limit of quantification.'}, {'measure': 'Area Under the Concentration-time Curve Over a Dosing Interval at Steady State on Day 5 (AUCtau) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056', 'timeFrame': '5 days', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUCtau Day 5 was calculated according to the trapezoidal rule using the measured concentration-time values above the limit of quantification.'}, {'measure': 'Area Under the Concentration-time Curve Over a Period of 24 h (Dose-corrected to 2 mg/kg) on Day 1 (AUC0-24C Day 1) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056', 'timeFrame': '24 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Day 1. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-24C Day 1 was calculated as a multiple of AUC0-12, (2 × AUC0-12 for 2 times daily dosing) corrected to 2 mg/kg.'}, {'measure': 'Area Under the Concentration-time Curve Over a Period of 24 h (Dose-corrected to 2 mg/kg) on Day 5 (AUC0-24C Day 5) for Bosentan and Its Metabolites, Ro 47-8634, Ro 48-5033, and Ro 64-1056', 'timeFrame': '24 hours', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to study drug administration and at 0.5, 1, 2, 3, 7.5, and 12 hours post-dose on Day 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AUC0-24C Day 5 was calculated as a multiple of AUCtau, (2 × AUCtau for 2 times daily dosing) corrected to 2 mg/kg.'}, {'measure': 'Accumulation Index (AI) for Bosentan', 'timeFrame': '5 days', 'description': 'Concentrations were measured directly in dried blood spot samples scheduled to be taken immediately prior to first study drug administration and at 0.5, 1, 2, 3, 7.5 and 12 hours post-dose on Days 1 and 5. Pharmacokinetic parameters were determined on the basis of scheduled blood sampling time points using non-compartmental analysis. Actual blood sampling times were used only if there was a deviation of more than 5% from the scheduled times. AI was calculated as the ratio AUCtau /AUC0-12 for the subjects having PK samples collected on Day 1 and Day 5 and with AUC0-12 \\> 0 ng.h/mL.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Persistent pulmonary hypertension, newborn', 'PPHN'], 'conditions': ['Persistent Pulmonary Hypertension of the Newborn']}, 'referencesModule': {'references': [{'pmid': '27502103', 'type': 'DERIVED', 'citation': 'Steinhorn RH, Fineman J, Kusic-Pajic A, Cornelisse P, Gehin M, Nowbakht P, Pierce CM, Beghetti M; FUTURE-4 study investigators. Bosentan as Adjunctive Therapy for Persistent Pulmonary Hypertension of the Newborn: Results of the Randomized Multicenter Placebo-Controlled Exploratory Trial. J Pediatr. 2016 Oct;177:90-96.e3. doi: 10.1016/j.jpeds.2016.06.078. Epub 2016 Aug 5.'}]}, 'descriptionModule': {'briefSummary': 'The AC-052-391-study is a phase 3 study to investigate whether adding bosentan to inhaled nitric oxide in newborns with persistent pulmonary hypertension of newborns (PPHN) is a supporting and safe therapy and to evaluate the pharmacokinetics of bosentan and its metabolites.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD'], 'maximumAge': '7 Days', 'minimumAge': '12 Hours', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n1. Signed informed consent by the parent(s) or the legal representative(s).\n2. Term and near term newborns (gestational age \\> 34 weeks).\n3. Post natal age ≥ 12 hours and \\< 7 days.\n4. Weight at birth ≥ 2,000 g.\n5. Idiopathic PPHN or PPHN due to parenchymal lung disease\n6. Documented diagnosis of pulmonary hypertension (PH) confirmed by echocardiography.\n7. Need for continued inhaled nitric oxide (iNO) at a dose \\> 10ppm after at least 4 hours of continuous iNO treatment.\n8. Two oxygenation index (OI) values ≥ 12 taken at least 30 minutes apart, in the 12 hours prior to randomization and while the patient is receiving iNO treatment.\n9. Mechanical ventilation with fraction of inspired oxygen (FiO2) ≥ 50% at randomization.\n\nExclusion Criteria:\n\n1. PH associated with conditions other than PPHN.\n2. Immediate need for cardiac resuscitation or extracorporeal membrane oxygenation (ECMO).\n3. Lethal congenital anomalies.\n4. Congenital Diaphragmatic Hernia.\n5. Significant structural cardiac anomalies.\n6. Medically significant pneumothorax.\n7. Active seizures.\n8. Expected duration of mechanical ventilation of less than 48 hours.\n9. Mean systemic blood pressure \\< 35 mmHg despite therapy with volume infusions and cardiotonic support.\n10. Hepatic failure or all conditions with alanine aminotransferase (ALT) values \\> 2 x upper limit of normal (ULN).\n11. Renal function impairment such as serum creatinine \\> 3 x ULN or anuria.\n12. Known intracranial hemorrhage grade III or IV.\n13. Either hemoglobin or hematocrit level \\< 75% of the lower limit of normal (LLN).\n14. Thrombocytopenia (platelet count \\< 50,000 cells /µL).\n15. Leukopenia (WBC \\< 2,500 cells/ µL).\n16. Any condition precluding the use of a nasogastric/orogastric tube.\n17. Administration of prohibited medication prior to randomization.'}, 'identificationModule': {'nctId': 'NCT01389856', 'acronym': 'FUTURE 4', 'briefTitle': 'Persistent Pulmonary Hypertension of the Newborn', 'organization': {'class': 'INDUSTRY', 'fullName': 'Actelion'}, 'officialTitle': 'Multicenter, Double-blind, Placebo-controlled, Randomized, Prospective Study of Bosentan as Adjunctive Therapy to Inhaled Nitric Oxide in the Management of Persistent Pulmonary Hypertension of the Newborn (PPHN)', 'orgStudyIdInfo': {'id': 'AC-052-391'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': '1', 'description': 'Bosentan', 'interventionNames': ['Drug: Bosentan']}, {'type': 'PLACEBO_COMPARATOR', 'label': '2', 'description': 'Matching placebo', 'interventionNames': ['Drug: Matching placebo']}], 'interventions': [{'name': 'Bosentan', 'type': 'DRUG', 'otherNames': ['Tracleer'], 'description': '2 mg/kg of weight at birth twice daily (b.i.d); quadrisectable 32 mg tablet of bosentan dispersed in sterile water and administered by nasogastric or orogastric tube.', 'armGroupLabels': ['1']}, {'name': 'Matching placebo', 'type': 'DRUG', 'description': 'twice daily (b.i.d); quadrisectable 32 mg tablet of matching placebo dispersed in sterile water and administered by nasogastric or orogastric tube.', 'armGroupLabels': ['2']}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Actelion', 'class': 'INDUSTRY'}, 'responsibleParty': {'type': 'SPONSOR'}}}}