Pulmonary Arterial Hypertension
Conditions
Interventions
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:Part
Sponsors
Nakano Masayoshi
Eligibility
Sex/Gender
All
Inclusion 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 PH documented by an Right heart catheterization (RHC) >= 1 year after simple systemic-to pulmonary shuntrepair - PAH diagnosis confirmed by hemodynamic evaluation at rest at any time prior to screening: Mean pulmonary artery pressure (mPAP) > 20 millimeters of mercury (mmHg), and; Pulmonary artery wedge pressure (PAWP) or left ventricular end diastolic pressure (LVEDP) less than or equal to (= 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 and maximum distance of 440 meters 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
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] 1.5*upper limit of normal (ULN) at screening - Hemoglobin < 100 gram per liter (g/L) (< 10 gram per deciliter [g/dL]) at screening
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| -Double-blind Treatment Period: Change From Baseline to Week 24in 6MWD:Baseline up to Week 24: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. -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:Up to 4 years:Number of Participants with CEC-adjudicated death or hospitalization due to PAH will be reported. -Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms Based on PAHSYMPACT Questionnaire- Cardiopulmonary Symptom Domain Score:Baseline up to Week 24: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. -Double-blind Treatment Period: Change From Baseline to Week 24 in PAH Symptoms Based on PAH SYMPACT Questionnaire- Cardiovascular Symptom Domain Score:Baseline up to Week 24: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. -Double-blind Treatment Period: Time to Death Occurring Between Randomization | — |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Brazil, Canada, China, Colombia, Czechia, Denmark, France, Germany, Hungary, Israel, Italy, Japan, Korea, Republic Of, Malaysia, Mexico, Netherlands, Norway, Poland, Portugal, Romania, Russian Federation, Serbia, Singapore, Slovakia, Spain, Sweden
Contacts
Public ContactMedical Information Center
Janssen Pharmaceutical K.K.
Outcome results
None listed