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Study to evaluate if macitentan is safe and tolerable enough to be used for treatment of subjects with combined pre- and post-capillary pulmonary hypertension (CpcPH) due to left ventricular dysfunction.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Macitentan | Experimental | oral tablet, 10 mg once daily. |
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| Placebo | Placebo Comparator | Matching placebo, once daily. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Macitentan | Drug | oral tablet, 10 mg once daily |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants Experiencing Significant Fluid Retention or Worsening in NYHA Functional Class (FC) up to End-of-treatment | The main endpoint is the number of participants who had at least one of the following: A) significant fluid retention, defined as increase in body weight at any time by ≥ 5% or ≥ 5 kg from baseline due to fluid overload and/or parenteral administration of diuretics. B) Worsening of NYHA functional class from baseline. | From randomization up to End-of-Study (Week 12 + 30 days follow-up) plus 1 calendar day |
| Measure | Description | Time Frame |
|---|---|---|
| NT-proBNP at Week 12 Expressed as Percent of Baseline NT-proBNP at Rest | From randomization up to end of treatment period (Week 12) | |
| PVR at Rest at Week 12 Expressed as Percent of Baseline PVR at Rest | Pulmonary vascular resistance (PVR) was assessed at rest by right heart catheterization (RHC). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Sébastien Roux, PhD | Actelion | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Kentuckiana Pulmonary Associates | Louisville | Kentucky | 40202 | United States | ||
| Boston University School of Medicine |
Of the 88 participants screened 63 were randomized in a 1:1 ratio to macitentan 10 mg (N = 31) or placebo (N = 32).
Participants were screened from 28 sites across Europe and North America in 11 countries (Austria, Belgium, Canada, Czech Republic, Germany, France, Israel, Italy, Spain, Switzerland, USA).
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| ID | Title | Description |
|---|---|---|
| FG000 | Macitentan | Macitentan 10 mg to be taken once daily, oral use, film-coated tablet |
| FG001 | Placebo | Matching placebo to be taken once daily, oral use, film-coated tablet |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
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| Placebo | Drug | matching placebo |
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| From randomization up to end of treatment period (Week 12) |
| Change From Baseline to Week 12 in Mean Pulmonary Arterial Pressure (mPAP) | From randomization up to end of treatment period (Week 12) |
| Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP) | From randomization up to end of treatment period (Week 12) |
| Change From Baseline to Week 12 in Pulmonary Artery Wedge Pressure (PAWP) | From randomization up to end of treatment period (Week 12) |
| Change From Baseline to Week 12 in Cardiac Index (CI) | From randomization up to end of treatment period (Week 12) |
| Change From Baseline to Week 12 in Diastolic Pulmonary Vascular Pressure Gradient (DPG) | From randomization up to end of treatment period (Week 12) |
| Boston |
| Massachusetts |
| 02118 |
| United States |
| University of Michigan Internal Medicine Cardiology, Pulmonary Hypertension Program | Ann Arbor | Michigan | 48109 | United States |
| Washington University School of Medicine - Center for Advanced Med | St Louis | Missouri | United States |
| The Lindner Clinical Trial Center | Cincinnati | Ohio | United States |
| Houston Methodist Hospital - Heart Failure/Pulm Hypertension | Houston | Texas | United States |
| Krankenhaus der Elisabethinen Linz, 2. Interne Abteilung | Linz | Austria |
| Medical University of Vienna and AKH Cardiology | Vienna | A-1090 | Austria |
| Hôpital Erasme, Cliniques Universitaires de Bruxelles, Cardiologie | Brussels | 1070 | Belgium |
| University Hospital Gasthuisberg / Interne Geneeskunde - I.G. Pneumologie | Leuven | 3000 | Belgium |
| Vancouver General Hospital - The Lung | Vancouver | Canada |
| FN Brno-Bohunice, I. internà kardiologická klinika | Brno | Czechia |
| FN Olomouc, 1. Internà klinika - kardiologická | Olomouc | Czechia |
| IKEM (Institut klinické a experimentálnà medicÃny, Institute for Clinical and Experimental Medicine) | Prague | Czechia |
| Lékařská fakulta a Všeobecná fakultnà nemocnice v Praze, II. Internà klinika kardiologie a angiologie | Prague | Czechia |
| Hôpital Charles Nicolle Service de Cardiologie | Rouen | France |
| DRK Klinken Berlin Kopenick Klinik für Innere Medizin Kardiologie | Berlin | Germany |
| Universitätsklinikum Köln Herzzentrum / Klinik III für Innere Medizin (Kardiologie, Pneumologie, Angiologie und Intensivmedizin) | Cologne | Germany |
| Universitätsklinik Schleswig-Holstein Campus Kiel Klinik für Innere Medizin III Kardiologie und Angiologie | Kiel | Germany |
| Klinikum der Universität München Medizinische Klinik und Poliklinik 1 - Großhadern Schwerpunkt Pneumologie | Munich | Germany |
| Carmel Medical Center, Pulmonary Unit | Haifa | 34362 | Israel |
| Institute of Pulmonology Hadassah Medical Centre : Ein Karem | Jerusalem | 91120 | Israel |
| Kaplan Medical Centre / Pulmonary Institute and Department of Medicine | Rehovot | 76100 | Israel |
| The Chaim Sheba Medical Center / The Institute of Pulmonology, Physiology and Exercise | Tel Litwinsky | 52621 | Israel |
| A.O. Universitaria Policlinico S. Orsola-Malpighi - Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale - Unità Operativa di Cardiologia | Bologna | 40138 | Italy |
| Ospedali Riuniti Di Trieste | Trieste | 34149 | Italy |
| Hospital Vall d´Hebron Servicio de Cardiologia | Barcelona | 08035 | Spain |
| Hospital Clinic Servicio de Cardiologia | Barcelona | 08036 | Spain |
| Hospital Reina Sofia Servicio de Cardiologia | Córdoba | 14004 | Spain |
| Hospital Universitario 12 Octubre Servicio de CardiologÃa | Madrid | 28041 | Spain |
| Universitätsklinik für Kardiologie Schweizer Herz- und Gefässzentrum Bern | Bern | Switzerland |
| Centre Hospitalier Universitaire Vaudois Service de Cardiologie | Lausanne | Switzerland |
| COMPLETED |
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| NOT COMPLETED |
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| ID | Title | Description |
|---|---|---|
| BG000 | Macitentan | Macitentan 10 mg to be taken once daily, oral use, film-coated tablet |
| BG001 | Placebo | Matching placebo to be taken once daily, oral use, film-coated tablet |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Median | Inter-Quartile Range | Years |
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| Age, Customized | Count of Participants | Participants |
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| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Time from Left Ventricular Dysfunction (LVD) diagnosis | Median | Inter-Quartile Range | years |
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| Time from Combined pre- and post-capillary Pulmonary Hypertension (CpcPH) diagnosis | The value of 1 patient is missing in the macitentan group. | Median | Inter-Quartile Range | years |
| ||||||||||||||
| New York Heart Association (NYHA) Functional Class at baseline | Class I: No symptoms and no limitation in ordinary physical activity, e.g., shortness of breath when walking, climbing stairs etc. Class II: Mild symptoms (mild shortness of breath and/or angina) and slight limitation during ordinary activity. Class III: Marked limitation in activity due to symptoms, even during less-than ordinary activity, e.g., walking short distances (20-100 m). Comfortable only at rest. Class IV: Severe limitations. Experiences symptoms even while at rest. Mostly bedbound patients. | Count of Participants | Participants |
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| 6-minute walk distance (6MWD) at baseline | Median | Inter-Quartile Range | meter |
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| Participants with Atrial Fibrillation at baseline | Count of Participants | Participants |
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| Participants with Diabetes Mellitus Type II | Count of Participants | Participants |
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| Participants with Right Heart Failure (RHF) | Count of Participants | Participants |
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| Participants with Systemic Hypertension | Count of Participants | Participants |
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| Participants with Chronic Kidney Disease (CKD) | Count of Participants | Participants |
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| Left Ventricular Ejection Fraction (LEVF) at baseline as measured by Investigator | Count of Participants | Participants |
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| Pulmonary Vascular Resistance (PVR) at baseline | Median | Inter-Quartile Range | dyn*sec/cm^5 |
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| Body Mass Index (BMI) at baseline | Median | Inter-Quartile Range | kg/m^2 |
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| Participants with obesity (BMI > 30 kg/m^2) | Count of Participants | Participants |
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| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants Experiencing Significant Fluid Retention or Worsening in NYHA Functional Class (FC) up to End-of-treatment | The main endpoint is the number of participants who had at least one of the following: A) significant fluid retention, defined as increase in body weight at any time by ≥ 5% or ≥ 5 kg from baseline due to fluid overload and/or parenteral administration of diuretics. B) Worsening of NYHA functional class from baseline. | Posted | Count of Participants | Participants | From randomization up to End-of-Study (Week 12 + 30 days follow-up) plus 1 calendar day |
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| Secondary | NT-proBNP at Week 12 Expressed as Percent of Baseline NT-proBNP at Rest | The values of 6 patients are missing in both the macitentan and the placebo group. | Posted | Geometric Mean | 95% Confidence Interval | percentage of baseline NT-proBNP | From randomization up to end of treatment period (Week 12) |
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| Secondary | PVR at Rest at Week 12 Expressed as Percent of Baseline PVR at Rest | Pulmonary vascular resistance (PVR) was assessed at rest by right heart catheterization (RHC). | The values of 11 patients in the macitentan group and of 8 patients in the placebo group are missing. | Posted | Geometric Mean | 95% Confidence Interval | percentage of baseline PVR | From randomization up to end of treatment period (Week 12) |
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| Secondary | Change From Baseline to Week 12 in Mean Pulmonary Arterial Pressure (mPAP) | The values of 10 patients in the macitentan group and of 7 patients in the placebo group are missing. | Posted | Mean | 95% Confidence Interval | mmHg | From randomization up to end of treatment period (Week 12) |
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| Secondary | Change From Baseline to Week 12 in Mean Right Atrial Pressure (mRAP) | The values of 10 patients in the macitentan group and of 7 patients in the placebo group are missing. | Posted | Mean | 95% Confidence Interval | mmHg | From randomization up to end of treatment period (Week 12) |
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| Secondary | Change From Baseline to Week 12 in Pulmonary Artery Wedge Pressure (PAWP) | The values of 11 patients in the macitentan group and of 8 patients in the placebo group are missing. | Posted | Mean | 95% Confidence Interval | mmHg | From randomization up to end of treatment period (Week 12) |
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| Secondary | Change From Baseline to Week 12 in Cardiac Index (CI) | The values of 11 patients in the macitentan group and of 8 patients in the placebo group are missing. | Posted | Mean | 95% Confidence Interval | L/min/m^2 | From randomization up to end of treatment period (Week 12) |
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| Secondary | Change From Baseline to Week 12 in Diastolic Pulmonary Vascular Pressure Gradient (DPG) | The values of 11 patients in the macitentan group and of 8 patients in the placebo group are missing. | Posted | Mean | 95% Confidence Interval | mmHg | From randomization up to end of treatment period (Week 12) |
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From study treatment initiation up to 30 days after study treatment discontinuation (Week 12 + 30 days)
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Macitentan | Macitentan 10 mg to be taken once daily, oral use, film-coated tablet | 2 | 31 | 11 | 31 | 16 | 31 |
| EG001 | Placebo | Matching placebo to be taken once daily, oral use, film-coated tablet | 0 | 32 | 6 | 32 | 15 | 32 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Atrial fibrillation | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Cardiac failure acute | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Cardiac failure congestive | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Cardiorenal syndrome | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Left ventricular failure | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Right ventricular failure | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Ventricular tachycardia | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Mouth haemorrhage | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Sudden death | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Pneumonia | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Respiratory tract infection bacterial | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Fall | Injury, poisoning and procedural complications | MedDRA 18.0 | Systematic Assessment |
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| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
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| Acute kidney injury | Renal and urinary disorders | MedDRA 18.0 | Systematic Assessment |
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| Chronic respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Pulmonary congestion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Pulmonary mass | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Pulmonary oedema | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Jugular vein thrombosis | Vascular disorders | MedDRA 18.0 | Systematic Assessment |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA 18.0 | Systematic Assessment |
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| Atrial fibrillation | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Mitral valve incompetence | Cardiac disorders | MedDRA 18.0 | Systematic Assessment |
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| Diarrhoea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Nausea | Gastrointestinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Fatigue | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Oedema peripheral | General disorders | MedDRA 18.0 | Systematic Assessment |
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| Respiratory tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Urinary tract infection | Infections and infestations | MedDRA 18.0 | Systematic Assessment |
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| Blood bilirubin increased | Investigations | MedDRA 18.0 | Systematic Assessment |
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| Haemoglobin decreased | Investigations | MedDRA 18.0 | Systematic Assessment |
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| Walking distance test abnormal | Investigations | MedDRA 18.0 | Systematic Assessment |
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| Fluid retention | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
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| Hypokalaemia | Metabolism and nutrition disorders | MedDRA 18.0 | Systematic Assessment |
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| Hepatic neoplasm | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 18.0 | Systematic Assessment |
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| Dizziness | Nervous system disorders | MedDRA 18.0 | Systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA 18.0 | Systematic Assessment |
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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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Clinical Trial Disclosure Desk | Actelion Pharmaceuticals Ltd | +41 61 565 6565 | clinical-trials-disclosure@its.jnj.com |
| ID | Term |
|---|---|
| D006976 | Hypertension, Pulmonary |
| ID | Term |
|---|---|
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D006973 | Hypertension |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| C533860 | macitentan |
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| Participants with worsening in NYHA FC |
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| Participants with both conditions |
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