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
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
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.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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