PAH patients (group I) belonging to one of the following subgroups:

• Schistosomiasis
• HIV infection
• Portal hypertension
• Diffuse systemic sclerosis
• Uncorrected congenital heart disease including uncorrected systemic-to-pulmonary shunts

Any PAH-specific drug therapy in the past 3 months

Patients responding to vasoreactivity testing with calcium channel blockers (CCB)

Post-capillary PH and left heart disease

Known or suspected pulmonary veno-occlusive disease (PVOD)

Any PH due to lung disease

Any disorder of the respiratory system expressed by Diffusing Capacity of Lung for Carbon Monoxide (DLCO) <40% and a noticeable imaging result (e.g., CT) and (Total Lung Capacity) TLC <60% and (Forced Expiratory Volume) FEV1 <70% by plethysmography (a pulmonary function test)

Patients with need of ambulatory or long-term oxygen therapy

Electrocardiogram (ECG) with Fridericia's corrected QT interval (QTcF) > 480 msec at screening

Body mass index (BMI) > 35 (kg/m2)

Age > 70 years

History of restrictive, constrictive or congestive cardiomyopathy, atrial septostomy, any symptomatic coronary disease events within 6 months, severe uncontrolled arterial hypertension, acutely decompensated heart failure and myocardial infarction within 30 days, significant (≥ 2+ regurgitation) mitral regurgitation or aortic regurgitation valvular disease, chronic systemic hypotension, unstable angina pectoris, permanent/persistent atrial fibrillation and/or need for pacemaker

Patients with acute anemia with hemoglobin (Hb) values <11g/dL

Cerebrovascular accident within 3 months

Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3× upper limit of the normal range (ULN) accompanied by aspartate aminotransferase (AST) > ULN and/or Child-Pugh Class C

Documented renal insufficiency with Glomerular Filtration Rate (GFR) <30 ml/min

Patients with untreated sleep apnea

Patient with other cardiovascular, liver, renal, hematologic, gastrointestinal (including active gastrointestinal ulcer), immunologic, endocrine (e.g., uncontrolled diabetes), metabolic, or central nervous system disease and acute bleeding and injuries (e.g., intracranial hemorrhage) that, in the opinion of the investigator, may adversely affect the safety of the patient and /or efficacy of the therapy or significantly limit the lifespan (< 12 months)

Patients with major surgery in the last 12 months

Known history of alcohol abuse

Treatment of a a cytochrome P450 (CYP)2C8 enzyme inducer (e.g., rifampicin) ≤ 28 days and/or treatment of a CYP2C8 enzyme inhibitor (e.g., gemfibrozil) ≤ 28 days

Treatment with another investigational drug (planned, or taken ≤ 12 weeks)

Hypersensitivity to any of the trial treatments or any excipient of their formulations

Pregnancy, breastfeeding, or intention to become pregnant during the trial

Any other significant disease or disorder which, in the opinion of the investigator, may put the patients at risk when participating in the trial

Any factor or condition likely to affect protocol compliance of the patient, as judged by the investigator.