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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
935
Participants will receive macitentan 10 mg film-coated tablets orally.
Participants will receive macitentan 37.5 mg film-coated tablets orally.
Participants will receive macitentan 75 mg film-coated tablets orally.
Double-blind Treatment Period: Time to First Clinical Events Committee (CEC)-adjudicated Morbidity or Mortality (M/M) Events
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.
Time frame: Up to 4 years
Double-blind Treatment Period: Change From Baseline to Week 24 in 6MWD
The 6MWT is a non-encouraged test performed to quantify exercise tolerance and capacity. This standardized 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.
Time frame: Baseline up to Week 24
Double-blind Treatment Period: Number of Participants with CEC-adjudicated Death due to PAH and/or Hospitalizations for PAH (First and Recurrent) Events on-treatment
Number of Participants with CEC-adjudicated death or hospitalization due to PAH will be reported.
Time frame: Up to 4 years
Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms Based on PAH-SYMPACT Questionnaire- Cardiopulmonary Symptom Domain Score
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Participants will receive matching placebo film-coated tablets orally.
Mayo Clinic
Phoenix, Arizona, United States
Arizona Pulmonary Specialists, Ltd
Scottsdale, Arizona, United States
Scripps Memorial Hospital
La Jolla, California, United States
USC Keck
Los Angeles, California, United States
Jeffrey S. Sager, MD Medical Corporation
Santa Barbara, California, United States
Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center
Torrance, California, United States
National Jewish Health
Denver, Colorado, United States
Cleveland Clinic
Weston, Florida, United States
Piedmont Healthcare
Atlanta, Georgia, United States
Northside Hospital
Atlanta, Georgia, United States
...and 264 more locations
The Cardiopulmonary Symptoms domain consists of 6 items reported on a 5-point Likert scale (from 0 to 4). The value 0 means "no symptom" and value 4 corresponds to "very severe symptoms". The symptoms part of the PAH symptoms and impact questionnaire (PAH-SYMPACT) is completed daily for a 7-day period. The recall period of symptom items is the last 24 hours. An average Cardiopulmonary Symptoms domain score is determined based on the daily scores of the 6 items.
Time frame: Baseline up to Week 24
Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms Based on PAH-SYMPACT Questionnaire- Cardiovascular Symptom Domain Score
The Cardiovascular Symptoms domain consists of 5 items reported on a 5-point Likert scale (from 0 to 4). The value 0 corresponds to "no symptoms" and value 4 corresponds to "very severe symptoms". The symptoms part of the PAH-SYMPACT is completed daily for a 7 day period. The recall period of symptom items is the last 24 hours. An average cardiovascular symptoms domain score is determined based on the daily scores of the 5 items.
Time frame: Baseline up to Week 24
Double-blind Treatment Period: Time to Death Occurring Between Randomization and End of Double-blind Treatment (EDBT)
Time to death occurring between randomization and EDBT will be reported.
Time frame: Up to 4 years
Treatment Extension Period: Time to Death Occurring Between Randomization and End of Study (EOS)
Time to death occurring between randomization and EOS will be reported.
Time frame: Up to 6 years