Ignite Creation Date:
2025-12-24 @ 3:41 PM
Ignite Modification Date:
2026-02-25 @ 4:48 PM
Study NCT ID:
NCT02021292
Status:
COMPLETED
Last Update Posted:
2025-03-30
First Post:
2013-12-20
Is Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Clinical Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'removedCountries': ['Austria', 'Bulgaria', 'Canada', 'Chile', 'Italy', 'Netherlands', 'South Africa', 'United States', 'Vietnam']}, 'interventionBrowseModule': {'meshes': [{'id': 'C533860', 'term': 'macitentan'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'clinical-trials-disclosure@actelion.com', 'title': 'Clinical Trial Disclosure Desk', 'organization': 'Actelion Pharmaceuticals Ltd.'}, 'certainAgreement': {'otherDetails': 'Any study-related publication written independently by investigators must be submitted to Actelion for review at least 30 days prior to submission for publication or presentation. Upon review, Actelion may provide comments, and may also request alterations and/or deletions for the sole purpose of protecting its confidential information and/or patent rights.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}}, 'adverseEventsModule': {'timeFrame': 'From double-blind study treatment initiation up to 30 days after study treatment discontinuation', 'eventGroups': [{'id': 'EG000', 'title': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.', 'otherNumAtRisk': 40, 'deathsNumAtRisk': 40, 'otherNumAffected': 22, 'seriousNumAtRisk': 40, 'deathsNumAffected': 0, 'seriousNumAffected': 3}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily.', 'otherNumAtRisk': 40, 'deathsNumAtRisk': 40, 'otherNumAffected': 19, 'seriousNumAtRisk': 40, 'deathsNumAffected': 2, 'seriousNumAffected': 7}], 'otherEvents': [{'term': 'Alanine aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 4, 'numAffected': 3}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Arthralgia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Aspartate aminotransferase increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 4, 'numAffected': 3}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Bone pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 3, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Cough', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Dizziness', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Dyspnoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Epistaxis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Fatigue', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Haemoglobin decreased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 7, 'numAffected': 6}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Hypomagnesaemia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Metabolism and nutrition disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Hypotension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Nasopharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Oedema peripheral', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 10, 'numAffected': 8}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 4, 'numAffected': 4}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Pain in extremity', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 3, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Pharyngitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 3, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Pulmonary hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Syncope', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 3, 'numAffected': 3}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Upper respiratory tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 4, 'numAffected': 3}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Urinary tract infection', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Ventricular extrasystoles', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}], 'seriousEvents': [{'term': 'Acute right ventricular failure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Back pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Musculoskeletal and connective tissue disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Cardiac failure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Dyspnoea', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Embolism', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Haemorrhagic stroke', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Nervous system disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Oedema peripheral', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Pulmonary hypertension', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Right ventricular failure', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 2, 'numAffected': 2}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Sepsis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Infections and infestations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Supraventricular tachycardia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}, {'term': 'Weight increased', 'stats': [{'groupId': 'EG000', 'numAtRisk': 40, 'numEvents': 1, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 40, 'numEvents': 0, 'numAffected': 0}], 'organSystem': 'Investigations', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'MedDRA'}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) at Rest.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}, {'value': '40', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily'}], 'classes': [{'categories': [{'measurements': [{'value': '73.0', 'groupId': 'OG000', 'lowerLimit': '63.6', 'upperLimit': '83.8'}, {'value': '87.2', 'groupId': 'OG001', 'lowerLimit': '78.5', 'upperLimit': '96.7'}]}]}], 'analyses': [{'pValue': '0.0410', 'groupIds': ['OG000', 'OG001'], 'paramType': 'ratio of geometric means', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.84', 'ciLowerLimit': '0.70', 'ciUpperLimit': '0.99', 'groupDescription': 'The null hypothesis (change of PVR at rest in Week 16 in percent of baseline PVR in subjects treated with placebo or macitentan is the same) is tested on the primary endpoint by means of an analysis of covariance (ANCOVA) model on the log(e) transformed % of baseline PVR at rest at Week 16.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'ANCOVA model on log-transformed % of baseline PVR at Week 16 adjusted by treatment as a factor and log transformed PVR at baseline as a covariate.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'From baseline to Week 16', 'description': 'The primary efficacy endpoint is defined as the PVR at rest at Week 16 expressed as percent of baseline PVR at rest.', 'unitOfMeasure': 'percent of baseline PVR', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set included all subjects assigned to a study treatment.'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 24 in Exercise Capacity, as Measured by the 6-minute Walk Distance (6MWD).', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}, {'value': '40', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily.'}], 'classes': [{'title': '6MWD (m) at baseline', 'categories': [{'measurements': [{'value': '353.0', 'spread': '87.90', 'groupId': 'OG000'}, {'value': '351.2', 'spread': '73.79', 'groupId': 'OG001'}]}]}, {'title': '6MWD (m) at Week 24', 'categories': [{'measurements': [{'value': '388.0', 'spread': '83.31', 'groupId': 'OG000'}, {'value': '352.2', 'spread': '121.29', 'groupId': 'OG001'}]}]}, {'title': 'Change in 6MWD (m) from baseline to Week 24', 'categories': [{'measurements': [{'value': '35.0', 'spread': '52.52', 'groupId': 'OG000'}, {'value': '1.0', 'spread': '83.24', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.0326', 'groupIds': ['OG000', 'OG001'], 'paramType': 'least squares (LS) mean difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '34.04', 'ciLowerLimit': '2.9', 'ciUpperLimit': '65.2', 'pValueComment': 'To control multiplicity across all endpoints, secondary endpoints were analyzed in sequence using hierarchical approach based on order and significance as pre-specified in protocol eliminating further adjustment for multiple comparisons.', 'groupDescription': 'The null hypothesis is that the mean change from baseline in 6MWD at Week 24 is the same in the placebo and the macitentan group. Statistical model is ANCOVA including 6MWD at baseline as a covariate, with treatment as factor in the model.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'From baseline to Week 24', 'description': 'The purpose of the six minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.', 'unitOfMeasure': 'meter', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set'}, {'type': 'SECONDARY', 'title': 'Change From Baseline to Week 24 in Borg Dyspnea Index Collected at the End of the 6-minute Walk Test (6MWT).', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}, {'value': '40', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily.'}], 'classes': [{'title': 'Borg dyspnea index score at baseline', 'categories': [{'measurements': [{'value': '4.2', 'spread': '2.52', 'groupId': 'OG000'}, {'value': '4.2', 'spread': '2.14', 'groupId': 'OG001'}]}]}, {'title': 'Borg dyspnea index score at Week 24', 'categories': [{'measurements': [{'value': '4.1', 'spread': '2.52', 'groupId': 'OG000'}, {'value': '4.4', 'spread': '2.45', 'groupId': 'OG001'}]}]}, {'title': 'Change from baseline to Week 24', 'categories': [{'measurements': [{'value': '-0.1', 'spread': '1.86', 'groupId': 'OG000'}, {'value': '0.3', 'spread': '2.04', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.3492', 'groupIds': ['OG000', 'OG001'], 'paramType': 'least squares (LS) mean difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '-0.39', 'ciLowerLimit': '-1.21', 'ciUpperLimit': '0.43', 'pValueComment': 'To control multiplicity across all endpoints, secondary endpoints were analyzed in sequence using hierarchical approach based on order and significance as pre-specified in protocol eliminating further adjustment for multiple comparisons.', 'groupDescription': 'The null hypothesis is that the mean change from baseline is the same in the placebo and the macitentan group. Statistical model is Analysis of Covariance including Borg dyspnea index at baseline as a covariate, with Treatment as factor in the model.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'From baseline to Week 24', 'description': "This outcome measures the difference in the Borg dyspnea index collected at the end of the 6-minute walk test (6MWT) at Week 24 compared to baseline. The Borg dyspnea index rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the Borg dyspnea index indicates an improvement.", 'unitOfMeasure': 'Score on a scale', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set'}, {'type': 'SECONDARY', 'title': 'Proportion of Subjects With Worsening in WHO Functional Class (FC) From Baseline to Week 24', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}, {'value': '40', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily.'}], 'classes': [{'title': 'WHO functional class I at baseline', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}]}, {'title': 'WHO functional class II at baseline', 'categories': [{'measurements': [{'value': '12', 'groupId': 'OG000'}, {'value': '6', 'groupId': 'OG001'}]}]}, {'title': 'WHO functional class III at baseline', 'categories': [{'measurements': [{'value': '28', 'groupId': 'OG000'}, {'value': '33', 'groupId': 'OG001'}]}]}, {'title': 'WHO functional class IV at baseline', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'WHO functional class I at Week 24', 'categories': [{'measurements': [{'value': '3', 'groupId': 'OG000'}, {'value': '1', 'groupId': 'OG001'}]}]}, {'title': 'WHO functional class II at Week 24', 'categories': [{'measurements': [{'value': '15', 'groupId': 'OG000'}, {'value': '10', 'groupId': 'OG001'}]}]}, {'title': 'WHO functional class III at Week 24', 'categories': [{'measurements': [{'value': '22', 'groupId': 'OG000'}, {'value': '26', 'groupId': 'OG001'}]}]}, {'title': 'WHO functional class IV at Week 24', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'Worsened', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}, {'value': '3', 'groupId': 'OG001'}]}]}, {'title': 'Not worsened - total', 'categories': [{'measurements': [{'value': '40', 'groupId': 'OG000'}, {'value': '37', 'groupId': 'OG001'}]}]}, {'title': 'Not Worsened - unchanged', 'categories': [{'measurements': [{'value': '31', 'groupId': 'OG000'}, {'value': '29', 'groupId': 'OG001'}]}]}, {'title': 'Not worsened - improved', 'categories': [{'measurements': [{'value': '9', 'groupId': 'OG000'}, {'value': '8', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.0962', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Odds Ratio (OR)', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.212', 'ciLowerLimit': '0.001', 'ciUpperLimit': '1.464', 'pValueComment': 'To control multiplicity across all endpoints, secondary endpoints were analyzed in sequence using hierarchical approach based on order and significance as pre-specified in protocol eliminating further adjustment for multiple comparisons.', 'groupDescription': 'The null hypothesis is the odds of worsening are the same in the placebo and the macitentan group. Logistic regression is used for Treatment Group vs. Placebo comparison to generate odds ratio, confidence levels, and p-values with treatment and WHO functional class at baseline as factors in the model.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'timeFrame': 'From baseline to Week 24', 'description': "WHO functional classes are defined as follows: 1) class I: no symptoms with exercise or at rest. No limitation of activity. 2) class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing a flight of stairs, grocery shopping, or making the bed). 3) class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. 4) class IV: symptoms at rest (such as dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms (e.g. may faint especially while bending over with their heads lowered). Patients in class IV manifest signs of right heart failure. Shifting to a higher class (e.g. from class III to class IV) represents a 'worsening' while shifting to a lower class (e.g. from class III to class II) means an 'improvement'.", 'unitOfMeasure': 'Participants', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set'}, {'type': 'POST_HOC', 'title': 'Post-hoc Analysis of Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) at Rest Including Subjects With Corrected Hemodynamic Values', 'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'OG000'}, {'value': '40', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily.'}], 'classes': [{'categories': [{'measurements': [{'value': '71.5', 'groupId': 'OG000', 'lowerLimit': '63.5', 'upperLimit': '80.4'}, {'value': '87.6', 'groupId': 'OG001', 'lowerLimit': '79.0', 'upperLimit': '97.2'}]}]}], 'analyses': [{'pValue': '0.0098', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Model-adjusted geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.81', 'ciLowerLimit': '0.70', 'ciUpperLimit': '0.95', 'pValueComment': 'This is the post-hoc analysis and p-value is an exploratory p-value.', 'groupDescription': 'The same statistical model as for the predefined analysis (ANCOVA) was applied, including 13 subjects with corrected hemodynamic values.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'ANCOVA model on log-transformed % of baseline PVR at Week 16 adjusted by treatment as a factor and log transformed PVR at baseline as a covariate.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'From baseline to Week 16', 'description': 'The main analysis of the primary efficacy endpoint of PVR was repeated after the voluntary right heart catheterization source data verification (SDV) and independent medical review of hemodynamic data corrected for 13 subjects reported after the clinical database closure.', 'unitOfMeasure': 'Percent of baseline PVR', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set for this post-hoc analysis included all subjects assigned to a study treatment with SDV values.'}, {'type': 'POST_HOC', 'title': 'Post-hoc Analysis of Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) at Rest Excluding Subjects With Corrected Hemodynamic Values', 'denoms': [{'units': 'Participants', 'counts': [{'value': '33', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily.'}], 'classes': [{'categories': [{'measurements': [{'value': '68.4', 'groupId': 'OG000', 'lowerLimit': '60.3', 'upperLimit': '77.5'}, {'value': '86.1', 'groupId': 'OG001', 'lowerLimit': '77.3', 'upperLimit': '95.7'}]}]}], 'analyses': [{'pValue': '0.0061', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Model-adjusted geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.79', 'ciLowerLimit': '0.68', 'ciUpperLimit': '0.93', 'pValueComment': 'This is the post-hoc analysis and p-value is an exploratory p-value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'ANCOVA model on log-transformed % of baseline PVR at Week 16 adjusted by treatment as a factor and log transformed PVR at baseline as a covariate.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'From baseline to Week 16', 'description': 'The main analysis of the primary efficacy endpoint of PVR was repeated which excluded data for 13 subjects with corrected hemodynamic values. The hemodynamic values were reported after the SDV assessment clinical database closure.', 'unitOfMeasure': 'Percent of baseline PVR', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set excluding subjects with corrected hemodynamic values.'}, {'type': 'POST_HOC', 'title': 'Post-hoc Analysis of Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) at Rest Excluding Subjects With Implausible Hemodynamic Findings', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily.'}], 'classes': [{'categories': [{'measurements': [{'value': '73.9', 'groupId': 'OG000', 'lowerLimit': '66.2', 'upperLimit': '82.4'}, {'value': '86.6', 'groupId': 'OG001', 'lowerLimit': '77.9', 'upperLimit': '96.4'}]}]}], 'analyses': [{'pValue': '0.0414', 'groupIds': ['OG000', 'OG001'], 'paramType': 'Geometric mean ratio', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '0.85', 'ciLowerLimit': '0.73', 'ciUpperLimit': '0.99', 'pValueComment': 'This is the post-hoc analysis and p-value is an exploratory p-value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'ANCOVA model on log-transformed % of baseline PVR at Week 16 adjusted by treatment as a factor and log transformed PVR at baseline as a covariate.'}], 'paramType': 'GEOMETRIC_MEAN', 'timeFrame': 'From baseline to Week 16', 'description': 'The main analysis of the primary efficacy endpoint of PVR was repeated which excluded 14 subjects with implausible hemodynamic findings.', 'unitOfMeasure': 'Percent of baseline PVR', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set excluding subjects with implausible hemodynamic findings.'}, {'type': 'POST_HOC', 'title': 'Post-hoc Analysis of Change From Baseline to Week 24 in Exercise Capacity, as Measured by the 6-minute Walk Distance (6MWD) Excluding Subjects With Implausible Hemodynamic Findings', 'denoms': [{'units': 'Participants', 'counts': [{'value': '32', 'groupId': 'OG000'}, {'value': '34', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily.'}], 'classes': [{'categories': [{'measurements': [{'value': '37.41', 'groupId': 'OG000', 'lowerLimit': '11.12', 'upperLimit': '63.71'}, {'value': '0.23', 'groupId': 'OG001', 'lowerLimit': '-25.28', 'upperLimit': '25.74'}]}]}], 'analyses': [{'pValue': '0.0468', 'groupIds': ['OG000', 'OG001'], 'paramType': 'least squares (LS) mean difference', 'ciNumSides': 'TWO_SIDED', 'ciPctValue': '95', 'paramValue': '37.19', 'ciLowerLimit': '0.54', 'ciUpperLimit': '73.83', 'pValueComment': 'This is the post-hoc analysis and p-value is an exploratory p-value.', 'statisticalMethod': 'ANCOVA', 'nonInferiorityType': 'SUPERIORITY', 'statisticalComment': 'Statistical model is ANCOVA including 6MWD at baseline as a covariate, with treatment as factor in the model.'}], 'paramType': 'LEAST_SQUARES_MEAN', 'timeFrame': 'From baseline to Week 24', 'description': 'The same analysis for the secondary endpoint, 6MWD, is repeated on the full analysis set excluding 14 subjects with implausible hemodynamic findings.', 'unitOfMeasure': 'meter', 'dispersionType': '95% Confidence Interval', 'reportingStatus': 'POSTED', 'populationDescription': 'Full analysis set excluding subjects with implausible hemodynamic findings.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '40'}, {'groupId': 'FG001', 'numSubjects': '40'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '40'}, {'groupId': 'FG001', 'numSubjects': '37'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '3'}]}], 'dropWithdraws': [{'type': 'Physician Decision', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Lost to Follow-up', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}, {'type': 'Death', 'reasons': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '1'}]}]}], 'recruitmentDetails': 'A total of 48 sites in 20 countries screened subjects for recruitment. The study was conducted (i.e., randomized subjects) in a total of 36 sites across 16 countries: Belgium, China, Czech Republic, France, Germany, Hungary, Lithuania, Mexico, Poland, Russia, Thailand, Turkey, South Korea, Switzerland, Ukraine, and the United Kingdom).', 'preAssignmentDetails': 'Target screening period from Visit 1 up to Randomization was maximum of 30 days, but longer period (up to 60 days) was permitted with pre-approval from Actelion. Total of 186 subjects were screened. Of these, 80 subjects were randomized in 1:1 ratio to macitentan 10 milligram (mg) (n = 40) and placebo (n = 40). All randomized subjects were treated.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '40', 'groupId': 'BG000'}, {'value': '40', 'groupId': 'BG001'}, {'value': '80', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '26', 'groupId': 'BG000'}, {'value': '26', 'groupId': 'BG001'}, {'value': '52', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '14', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '28', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '60.0', 'groupId': 'BG000', 'lowerLimit': '20', 'upperLimit': '80'}, {'value': '58.0', 'groupId': 'BG001', 'lowerLimit': '23', 'upperLimit': '78'}, {'value': '59.0', 'groupId': 'BG002', 'lowerLimit': '20', 'upperLimit': '80'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'years', 'dispersionType': 'FULL_RANGE'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '26', 'groupId': 'BG000'}, {'value': '25', 'groupId': 'BG001'}, {'value': '51', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '14', 'groupId': 'BG000'}, {'value': '15', 'groupId': 'BG001'}, {'value': '29', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Asia', 'categories': [{'measurements': [{'value': '15', 'groupId': 'BG000'}, {'value': '14', 'groupId': 'BG001'}, {'value': '29', 'groupId': 'BG002'}]}]}, {'title': 'Eastern Europe', 'categories': [{'measurements': [{'value': '17', 'groupId': 'BG000'}, {'value': '19', 'groupId': 'BG001'}, {'value': '36', 'groupId': 'BG002'}]}]}, {'title': 'Latin America', 'categories': [{'measurements': [{'value': '1', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}]}]}, {'title': 'Western Europe', 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '13', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Asia includes: China, South Korea, Thailand; Eastern Europe: Czech Republic, Hungary, Lithuania, Poland, Russia, Ukraine; Latin America: Mexico; Western Europe: Belgium, France, Germany, Switzerland, Turkey and the United Kingdom.'}, {'title': 'Body Mass Index (BMI)', 'classes': [{'categories': [{'measurements': [{'value': '25.7', 'groupId': 'BG000', 'lowerLimit': '19.8', 'upperLimit': '47.5'}, {'value': '26.0', 'groupId': 'BG001', 'lowerLimit': '18.3', 'upperLimit': '36.2'}, {'value': '25.7', 'groupId': 'BG002', 'lowerLimit': '18.3', 'upperLimit': '47.5'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'kg/m^2', 'dispersionType': 'FULL_RANGE'}, {'title': 'Time since diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH)', 'classes': [{'categories': [{'measurements': [{'value': '1.7', 'spread': '2.36', 'groupId': 'BG000'}, {'value': '1.2', 'spread': '1.95', 'groupId': 'BG001'}, {'value': '1.5', 'spread': '2.16', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': '6-minute walk distance (6MWD)', 'classes': [{'categories': [{'measurements': [{'value': '353.0', 'spread': '87.90', 'groupId': 'BG000'}, {'value': '351.2', 'spread': '73.79', 'groupId': 'BG001'}, {'value': '352.1', 'spread': '80.64', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'meter', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Pulmonary vascular resistance (PVR)', 'classes': [{'categories': [{'measurements': [{'value': '929.2', 'spread': '379.65', 'groupId': 'BG000'}, {'value': '984.3', 'spread': '487.06', 'groupId': 'BG001'}, {'value': '956.8', 'spread': '434.78', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'dynes*sec/cm^5', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'WHO functional class', 'classes': [{'categories': [{'title': 'class I', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'class II', 'measurements': [{'value': '12', 'groupId': 'BG000'}, {'value': '6', 'groupId': 'BG001'}, {'value': '18', 'groupId': 'BG002'}]}, {'title': 'class III', 'measurements': [{'value': '28', 'groupId': 'BG000'}, {'value': '33', 'groupId': 'BG001'}, {'value': '61', 'groupId': 'BG002'}]}, {'title': 'class IV', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '1', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'description': 'Class I: no symptoms with exercise or at rest. Class II: No symptoms at rest but uncomfortable and short of breath with normal activity such as climbing a flight of stairs, grocery shopping, or making the bed. Class III: May not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting (e.g. doing normal chores around the house, have to take breaks while doing activities of daily living). Class IV: Symptoms at rest and severe symptoms with any activity. Most patients also have edema in the feet and ankles as result of right heart failure.', 'unitOfMeasure': 'Participants'}, {'title': 'Use of pulmonary arterial hypertension (PAH) medication', 'classes': [{'title': 'NO', 'categories': [{'measurements': [{'value': '16', 'groupId': 'BG000'}, {'value': '15', 'groupId': 'BG001'}, {'value': '31', 'groupId': 'BG002'}]}]}, {'title': 'YES', 'categories': [{'measurements': [{'value': '24', 'groupId': 'BG000'}, {'value': '25', 'groupId': 'BG001'}, {'value': '49', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 80}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2014-08-20', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-03', 'completionDateStruct': {'date': '2016-09-28', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2025-03-28', 'studyFirstSubmitDate': '2013-12-20', 'resultsFirstSubmitDate': '2017-09-26', 'studyFirstSubmitQcDate': '2013-12-20', 'lastUpdatePostDateStruct': {'date': '2025-03-30', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2017-12-20', 'studyFirstPostDateStruct': {'date': '2013-12-27', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2018-01-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2016-09-28', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change From Baseline to Week 16 in Pulmonary Vascular Resistance (PVR) at Rest.', 'timeFrame': 'From baseline to Week 16', 'description': 'The primary efficacy endpoint is defined as the PVR at rest at Week 16 expressed as percent of baseline PVR at rest.'}], 'secondaryOutcomes': [{'measure': 'Change From Baseline to Week 24 in Exercise Capacity, as Measured by the 6-minute Walk Distance (6MWD).', 'timeFrame': 'From baseline to Week 24', 'description': 'The purpose of the six minute walk is to test exercise tolerance and capacity. The test measures the distance an individual is able to walk over a total of six minutes on a hard, flat surface. The goal is for the individual to walk as far as possible in six minutes.'}, {'measure': 'Change From Baseline to Week 24 in Borg Dyspnea Index Collected at the End of the 6-minute Walk Test (6MWT).', 'timeFrame': 'From baseline to Week 24', 'description': "This outcome measures the difference in the Borg dyspnea index collected at the end of the 6-minute walk test (6MWT) at Week 24 compared to baseline. The Borg dyspnea index rates the severity of dyspnea (difficult or labored breathing) on a scale from 0 ('Nothing at all') to 10 ('Very, very severe - maximal'). A decrease in the Borg dyspnea index indicates an improvement."}, {'measure': 'Proportion of Subjects With Worsening in WHO Functional Class (FC) From Baseline to Week 24', 'timeFrame': 'From baseline to Week 24', 'description': "WHO functional classes are defined as follows: 1) class I: no symptoms with exercise or at rest. No limitation of activity. 2) class II: No symptoms at rest but slight limitation with ordinary activities causing symptoms (e.g. short of breath with climbing a flight of stairs, grocery shopping, or making the bed). 3) class III: may not have symptoms at rest but activities greatly limited by shortness of breath, fatigue, or near fainting. 4) class IV: symptoms at rest (such as dyspnea and/or fatigue) and inability to carry out any physical activity without symptoms (e.g. may faint especially while bending over with their heads lowered). Patients in class IV manifest signs of right heart failure. Shifting to a higher class (e.g. from class III to class IV) represents a 'worsening' while shifting to a lower class (e.g. from class III to class II) means an 'improvement'."}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'keywords': ['Chronic thromboembolic pulmonary hypertension (CTEPH)'], 'conditions': ['Chronic Thromboembolic Pulmonary Hypertension']}, 'referencesModule': {'references': [{'pmid': '28919201', 'type': 'RESULT', 'citation': "Ghofrani HA, Simonneau G, D'Armini AM, Fedullo P, Howard LS, Jais X, Jenkins DP, Jing ZC, Madani MM, Martin N, Mayer E, Papadakis K, Richard D, Kim NH; MERIT study investigators. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med. 2017 Oct;5(10):785-794. doi: 10.1016/S2213-2600(17)30305-3. Epub 2017 Sep 11."}, {'pmid': '39520648', 'type': 'DERIVED', 'citation': "Kim NH, D'Armini AM, Howard LS, Jenkins DP, Jing ZC, Mayer E, Chamitava L, Lack G, Rofael H, Solonets M, Ghofrani HA. Long-Term Safety and Efficacy of Macitentan in Inoperable Chronic Thromboembolic Pulmonary Hypertension: Results from MERIT and its Open-Label Extension. Pulm Ther. 2025 Mar;11(1):101-116. doi: 10.1007/s41030-024-00276-w. Epub 2024 Nov 9."}, {'pmid': '38548406', 'type': 'DERIVED', 'citation': "Ghofrani HA, Simonneau G, D'Armini AM, Fedullo P, Howard LS, Jais X, Jenkins DP, Jing ZC, Madani MM, Martin N, Mayer E, Papadakis K, Richard D, Kim NH; MERIT study investigators. Macitentan for the treatment of inoperable chronic thromboembolic pulmonary hypertension (MERIT-1): results from the multicentre, phase 2, randomised, double-blind, placebo-controlled study. Lancet Respir Med. 2024 Apr;12(4):e21-e30. doi: 10.1016/S2213-2600(24)00027-4."}]}, 'descriptionModule': {'briefSummary': 'Study to evaluate if macitentan is efficient, safe and tolerable enough to be used for treatment of inoperable chronic thromboembolic pulmonary hypertension (CTEPH).'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '84 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Written informed consent\n* Subject with CTEPH (WHO Group 4) judged as inoperable due to the localization of the obstruction being surgically inaccessible (i.e., distal disease).\n* Female of childbearing potential must have a negative pre-treatment serum pregnancy test, be advised on appropriate methods of contraception, and agree to use 2 reliable methods of contraception.\n\nExclusion Criteria:\n\n* Previous pulmonary endarterectomy.\n* Recurrent thromboembolism despite sufficient oral anticoagulants.\n* Symptomatic acute pulmonary embolism in the 6-month period prior to randomization.\n* Known moderate-to-severe restrictive lung disease (i.e., TLC \\< 60% of predicted value) or obstructive lung disease (i.e., FEV1 \\< 70% of predicted, with FEV1/FVC \\< 65%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema).\n* Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements in the 3-month period prior to Screening visit or during the Screening period.'}, 'identificationModule': {'nctId': 'NCT02021292', 'acronym': 'MERIT-1', 'briefTitle': 'Clinical Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension', 'organization': {'class': 'INDUSTRY', 'fullName': 'Actelion'}, 'officialTitle': 'Prospective, Randomized, Placebo-controlled, Double-blind, Multicenter, Parallel-group, 24-week Study to Assess the Efficacy, Safety and Tolerability of Macitentan in Subjects With Inoperable Chronic Thromboembolic Pulmonary Hypertension', 'orgStudyIdInfo': {'id': 'AC-055E201'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Macitentan', 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.', 'interventionNames': ['Drug: Macitentan']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Matching placebo oral tablet, to be taken once daily.', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Macitentan', 'type': 'DRUG', 'otherNames': ['ACT-064992'], 'description': 'Macitentan 10 mg, oral tablet, to be taken once daily.', 'armGroupLabels': ['Macitentan']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Matching placebo oral tablet, to be taken once daily.', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': '3000', 'city': 'Leuven', 'country': 'Belgium', 'facility': 'University Hospital Gasthuisberg / Interne Geneeskunde - I.G. 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