Outcome Study Assessing a 75 Milligrams (mg) Dose of Macitentan in Patients With Pulmonary Arterial Hypertension

Study Purpose

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.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT04273945
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Actelion
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Actelion Clinical Trials
Principal Investigator Affiliation	Actelion
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czechia, Denmark, France, Germany, Greece, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Russian Federation, Saudi Arabia, Serbia, Singapore, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States, Vietnam
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Pulmonary Arterial Hypertension

Arms & Interventions

Arms

Active Comparator: Macitentan 10 milligrams (mg) + Placebo

Run-in period:Participants who are either endothelin receptor antagonist (ERA)-naïve or who are receiving daily dose of macitentan or ambrisentan less (<) 10 milligrams (mg), or daily dose of bosentan <250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated participants will bypass run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.Double-blind Treatment (DBT) Period:Participants will receive macitentan 10 mg orally up to End of DBT.To maintain blind, participants will receive macitentan 37.5 mg-matching placebo for 4 weeks and macitentan 75 mg-matching placebo thereafter up to DBT.Treatment Extension Period:After EDBT, participants will receive macitentan 37.5 mg once a day (qd) orally for 4 weeks, prior to receiving open-label macitentan 75 mg qd orally for 2 years. To maintain blind, participants will receive macitentan 75 mg-matching placebo during 4-week uptitration.

Experimental: Macitentan 75 mg + Placebo

Run-in period:Participants who are either ERA-naive or who are receiving a daily dose of macitentan or ambrisentan <10 mg, or a daily dose of bosentan <250 mg, will enter 4-week open-label run-in period with macitentan 10 mg prior to randomization. ERA-pre-treated patients will bypass the run-in period and will be randomized to either macitentan 75 mg or macitentan 10 mg directly.DBT Period: participants will receive macitentan 37.5 mg orally for 4 weeks and macitentan 75 mg thereafter up to End of DBT. To maintain the blind, participants will receive macitentan 10 mg-matching placebo up to End of DBT.Treatment Extension Period: After EDBT, participants will continue to receive macitentan 75 mg orally for 2 years. To maintain the blind, participants will receive macitentan 37.5 mg-matching placebo during the 4-week up-titration period.

Interventions

Drug: - Macitentan 10 mg

Participants will receive macitentan 10 mg film-coated tablets orally.

Drug: - Macitentan 37.5 mg

Participants will receive macitentan 37.5 mg film-coated tablets orally.

Drug: - Macitentan 75 mg

Participants will receive macitentan 75 mg film-coated tablets orally.

Drug: - Placebo

Participants will receive matching placebo film-coated tablets orally.

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Arizona Pulmonary Specialists, Ltd, Phoenix, Arizona

Status

Recruiting

Address

Arizona Pulmonary Specialists, Ltd

Phoenix, Arizona, 85012

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