Resumen

El propósito de este estudio es demostrar la superioridad de macitentan 75 miligramos (mg) en la prolongación del tiempo hasta el primer evento de morbilidad o mortalidad (M/M) adjudicado por el comité de eventos clínicos (CEC) en participantes con hipertensión arterial pulmonar (HAP) sintomática comparado con macitentan 10 mg.

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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

Intervenciones

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.

Ubicaciones

Sanatorio de la Trinidad Mitre

Buenos Aires, Argentina

Sanatorio Guemes

C.a.b.a., Argentina

Hospital Italiano de Buenos Aires

Caba, Argentina

Sanatorio Ramon Cereijo

Caba, Argentina

Centro Médico Dra. De Salvo

Caba, Argentina

Instituto de Cardiologia de Corrientes

Corrientes, Argentina

Instituto Medico de La Fundacion Estudios Clinicos

Rosario, Argentina

Instituto Cardiovascular de Rosario

Rosario, Argentina

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Macitentan 10 mg

Macitentan 37.5 mg

Macitentan 75 mg

Placebo

Ubicaciones

Sanatorio de la Trinidad Mitre

Sanatorio Guemes

Hospital Italiano de Buenos Aires

Sanatorio Ramon Cereijo

Centro Médico Dra. De Salvo

Instituto de Cardiologia de Corrientes

Instituto Medico de La Fundacion Estudios Clinicos

Instituto Cardiovascular de Rosario

Patrocinadores