Active, not recruiting
Phase 3
Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension
Condition(s) studied
Pulmonary Arterial Hypertension
Investigational drug(s) / intervention(s)
Macitentan 10 mgMacitentan 37.5 mgMacitentan 75 mgPlacebo
Macitentan 10 mg: Participants will receive macitentan 10 mg film-coated tablets orally.
Macitentan 37.5 mg: Participants will receive macitentan 37.5 mg film-coated tablets orally.
Macitentan 75 mg: Participants will receive macitentan 75 mg film-coated tablets orally.
Placebo: Participants will receive matching placebo film-coated tablets orally.
Study summary
The purpose of this study is to demonstrate superiority of macitentan 75 milligrams (mg) in prolonging the time to the first clinical events committee (CEC)-adjudicated morbidity or mortality (M/M) event in participants with symptomatic pulmonary arterial hypertension (PAH) compared to macitentan 10 mg.
Eligibility
Inclusion Criteria:
* Target population: greater than or equal to (\>=) 18 (or the legal age of consent in the jurisdiction in which the study is taking place) years of age
* Target population: Symptomatic Pulmonary Arterial Hypertension (PAH) in World Health Organization Functional Class (WHO FC) II, III, or IV
* Target population: PAH subtype falling in one of the below classifications: Idiopathic; Heritable; Drug- or toxin-induced; Related to: Connective tissue disease, HIV infection, Portal hypertension, and Congenital heart disease with small/coincidental cardiac defect with systemic-to-pulmonary shunt (for example atrial septal defect, ventricular septal defect, patent ductus arteriosus, atrioventricular septal defect) which does not account for the elevated pulmonary vascular resistance (PVR) or persistent PAH documented by an Right heart catheterization (RHC) \>= 1 year after simple systemic-to pulmonary shunt repair
* PAH diagnosis confirmed by hemodynamic evaluation at rest at any time prior to screening: Mean pulmonary artery pressure (mPAP) greater than (\>) 20 millimeters of mercury (mm Hg), and; Pulmonary artery wedge pressure (PAWP) or left ventricular end diastolic pressure (LVEDP) less than or equal to (\<=) 15 mm Hg, and PVR \>= 3 Wood Units (that is, \>= 240 dyn\*sec/cm\^5)
* Able to perform the 6-minute walking test (6MWT) with a minimum distance of 50 meters (m) and maximum distance of 440m at screening. Participants able to walk more than 440m at screening are eligible if they are in WHO FC III or IV and n-terminal prohormone of brain natriuretic peptide or n-terminal pro B-type natriuretic peptide (NT-proBNP) level is \>=300 nanograms per liter (ng/L) at screening, based on central laboratory results
Exclusion Criteria:
* Known presence of three or more of the following risk factors for heart failure with preserved ejection fraction at screening, based on records that confirm documented medical history: Body mass index (BMI) \> 30 kilograms per meter square (kg/m\^2), Diabetes mellitus of any type, Essential hypertension (even if well controlled); Coronary artery disease, that is, any of the following: history of stable angina, or known more than 50 percent (%) stenosis in a coronary artery, or history of myocardial infarction, or history of or planned coronary artery bypass grafting and/or coronary artery stenting
* Presence of moderate or severe obstructive lung disease (forced expiratory volume in 1 second \[FEV1\] / forced vital capacity \[FVC\] \< 70%; and FEV1 \< 60% of predicted after bronchodilator administration) ) in participants with a known or suspected history of significant lung disease as documented by a spirometry test performed within 1 year prior to screening
* Known moderate to severe hepatic impairment, defined as Child-Pugh Class B or C, based on records that confirm documented medical history
* Serum aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \> 1.5\*upper limit of normal (ULN) at screening
* Hemoglobin \< 100 gram per liter (g/L) (\< 10 gram per deciliter \[g/dL\]) at screening
Primary outcome measure(s)
- Double-blind Treatment Period: Time to First Clinical Events Committee (CEC)-adjudicated Morbidity or Mortality (M/M) Events — Up to 4 years
Time to first CEC-adjudicated M/M event on-treatment (ie.,up to 7 days after last dose of DB study intervention) is defined as time from randomization to first of following events: All-cause death, including death caused by on-treatment adverse event that occur within 4 weeks of study DB treatment discontinuation;non-planned Pulmonary Arterial Hypertension(PAH)-related hospitalization(including for worsening of PAH, atrial septostomy, lung transplantation with or without heart transplantation, or initiation of parenteral prostacyclins);PAH-related disease progression, defined as worsening of World Health Organization(WHO) Functional Class(FC) from baseline or deterioration by at least 15% in exercise capacity, as measured by 6-minute walk distance(6MWD), from baseline and confirmed by second 6MWD test performed on different day within 2 week of initial test or appearance or worsening of signs or symptoms of right-sided heart failure that require initiation of intravenous diuretics.
Trial sites (274)
| Facility | City | Region | Status |
| Mayo Clinic |
Phoenix |
Arizona |
|
| Arizona Pulmonary Specialists, Ltd |
Scottsdale |
Arizona |
|
| Scripps Memorial Hospital |
La Jolla |
California |
|
| USC Keck |
Los Angeles |
California |
|
| Jeffrey S. Sager, MD Medical Corporation |
Santa Barbara |
California |
|
| Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center |
Torrance |
California |
|
| National Jewish Health |
Denver |
Colorado |
|
| Cleveland Clinic |
Weston |
Florida |
|
| Piedmont Healthcare |
Atlanta |
Georgia |
|
| Northside Hospital |
Atlanta |
Georgia |
|
| Advocate Christ Medical Center |
Oak Lawn |
Illinois |
|
| Indiana University |
Indianapolis |
Indiana |
|
| St. Vincent Medical Group, Inc. |
Indianapolis |
Indiana |
|
| University Of Iowa - Hospitals & Clinics |
Iowa City |
Iowa |
|
| Norton Pulmonary Specialists |
Louisville |
Kentucky |
|
| Louisiana State University |
New Orleans |
Louisiana |
|
| University of Michigan |
Ann Arbor |
Michigan |
|
| Troy Beaumont |
Troy |
Michigan |
|
| Washington University School Of Medicine |
St Louis |
Missouri |
|
| Saint Louis University Academic Pavillion |
St Louis |
Missouri |
|
| University of Nebraska Medical Center |
Omaha |
Nebraska |
|
| Reno Heart Institute |
Reno |
Nevada |
|
| Winthrop University Hospital |
Mineola |
New York |
|
| Mount Sinai |
New York |
New York |
|
| Columbia University |
New York |
New York |
|
| Stony Brook University Medical Center |
Stony Brook |
New York |
|
| Duke |
Durham |
North Carolina |
|
| Lindner Clinical Trial Center/Christ Hospital |
Cincinnati |
Ohio |
|
| Integris Baptist Office |
Oklahoma City |
Oklahoma |
|
| The Oregon Clinic Pulmonary West |
Beaverton |
Oregon |
|
| The Oregon Clinic |
Portland |
Oregon |
|
| Oregon Health And Science University |
Portland |
Oregon |
|
| University of Pennsylvania |
Philadelphia |
Pennsylvania |
|
| Allegheny General Hospital of Research |
Pittsburgh |
Pennsylvania |
|
| Lankenau Medical Center |
Wynnewood |
Pennsylvania |
|
| AnMed Health |
Anderson |
South Carolina |
|
| UT Southwestern Medical Center |
Dallas |
Texas |
|
| Baylor College of Medicine (BCM) - Baylor Heart Clinic |
Houston |
Texas |
|
| Baylor Scott White - Plano |
Plano |
Texas |
|
| San Antonio Methodist TX Transplant Physicians Group |
San Antonio |
Texas |
|
+ 234 more sites — see the full list on the official registry below.