A Study to Evaluate Efficacy and Safety of Macitentan 75 mg in Inoperable or Persistent/Recurrent Chronic Thromboembolic Pulmonary Hypertension

Open to people ages 18-80

• Chronic thromboembolic pulmonary hypertension (CTEPH) (World Health Organization [WHO]

  Group 4) fulfilling one of the following criteria: a) inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), b) persistent/recurrent CTEPH after balloon pulmonary angioplasty (BPA), and deemed inoperable due to the localization of the obstruction being surgically inaccessible (that is, distal disease), c) persistent/recurrent CTEPH after rescue pulmonary endarterectomy (PEA)

• 6-minute walk distance (6MWD) greater than or equal to (>=) 100 meter (m) and less than or equal to (<=) 450 meters (m), documented by an eligibility and a baseline 6-minute walk test (6MWT). The baseline 6MWD must not differ by more than 15 percent (%) from the eligibility test
• World Health Organization functional class (WHO FC) >= II
• Participants are to receive riociguat as per local standard of care, unless it is contraindicated or unavailable

• Acute pulmonary embolism within 3 months prior to or during Screening
• Planned balloon pulmonary angioplasty (BPA) during the fixed duration part of the double-blind period
• Significant obstructive and restrictive lung disease
• Acute or chronic conditions (other than dyspnea) that limit the ability to comply with study requirements, in particular with 6MWT (for example, intermittent claudication).
• Symptomatic coronary artery disease requiring an intervention within 3 months prior to or during Screening or anticipated during the fixed duration part of the study
• Decompensated cardiac failure if not under close supervision
• Known and documented life-threatening cardiac arrhythmias
• Acute myocardial infarction within 6 months prior to, or during Screening
• Cerebrovascular events (including transient ischemic attack) within 3 months prior to, or during Screening
• Known or suspicion of pulmonary veno-occlusive disease (PVOD)
• Administration of ERAs, intravenous prostacyclins / prostacyclin analogs, or investigational treatment within 90 days prior to Randomization
• Change in dose or initiation of Phosphodiesterase type-5 (PDE-5) inhibitors, oral, inhaled or subcutaneous (SC) prostacyclins / prostacyclin analogues, prostacyclin receptor agonists or riociguat, a) within 90 days prior to Randomization, or b) anticipated during the fixed duration part of the double-blind [DB] period
• Hypotension, that is, systolic blood pressure (SBP) less than (<) 90 millimeters of mercury (mmHg) or diastolic blood pressure (DBP) <50 mmHg at Screening.
• Severe renal dysfunction with an estimated Glomerular Filtration Rate <30 milliliters per minute per 1.73 meter square (mL/min/1.73 m²) using the Chronic Kidney Disease Epidemiology Collaboration formula at 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) greater than or equal to (>=) 1.5*upper limit of normal (ULN) at Screening
• Hemoglobin <100 g/L (<10 gram per deciliter [g/dL]) at Screening