Pulmonary arterial hypertension

Inclusion Criteria

- Male and female patients aged 18 to 75 years.
- Patients with symptomatic PAH with a pulmonary vascular resistance (PVR) > 400 dyn*sec*cm-5, mean pulmonary artery pressure ≥ 25 mmHg, and pulmonary capillary wedge pressure (PCWP) ≤ 15 mmHg as assessed by the most recent right heart catheterization (RHC) from medical history prior to screening to confirm the diagnosis. Alternatively, PCWP can be replaced by left ventricular end-diastolic pressure (≤ 15 mmHg). PAH of the following types:
-- Idiopathic
-- Hereditary
-- Drug and toxin induced PAH
-- Associated with PAH due to:
--- Connective tissue disease (CTD)
--- Congenital heart disease, but only if the patient underwent surgical repair more than one year before enrolment
--- Portal hypertension with liver cirrhosis (Note: patients with clinical relevant hepatic dysfunction are excluded; see exclusions related to disorders in organ function)
- Patients who are on stable doses of a PDE-5i and ERA combination therapy or on stable PDE-5i monotherapy 6 weeks prior to and at randomization but not at treatment goal (tadalafil 20 to 40 mg once daily or sildenafil at least 60 mg daily dose).
- WHO FC III at screening and at randomization.
- 6MWD test between 165 m and 440 m at screening and at randomization.
- Stable dose of diuretics, if used, for at least 30 days prior to and at randomization.
- Patients who are able to understand and follow instructions and who are able to participate in the study for the entire study.
- Women of childbearing potential must agree to use adequate contraception when sexually active. Adequate contraception is defined as any combination of at least 2 effective methods of birth control, of which at least 1 is a physical barrier (e.g. condom with hormonal contraception like implants or combined oral contraceptives, condom with intrauterine devices). This applies beginning with signing of the informed consent form until 30 (+5) days after the last administration of study drug.
- Patients must have given their written informed consent to participate in the study after having received adequate previous information and prior to any study-specific procedures.

Exclusion Criteria

- Participation in another interventional clinical study within 30 days prior to screening.
- All types of PH (including PH-IIP) except subtypes of Dana Point Group I specified in the inclusion criteria.
- Previous treatment with riociguat.
- Pregnant women (i.e., positive serum ß-human-chorionic-gonadotropin test or other signs of pregnancy), or breast feeding women, or women with childbearing potential not using a combination of 2 effective contraception methods (as laid out in inclusion criterion) throughout the study.
- Patients with a medical disorder, condition, or history of such that would impair the patient’s ability to participate or complete this study, in the opinion of the investigator.
- Relevant obstructive and restrictive or other lung diseases.  
- Patients with underlying medical disorders with an anticipated life expectancy below 2 years (e.g., active cancer disease with localized and/or metastasized tumor mass).
- Cardiovascular exclusion criteria like left ventricular disease, coronary heart disease or stroke within previous 3 months. 
- Patients with hypersensitivity to the investigational drug or any of the excipients.
- Patients unable to perform a valid 6MWD test (e.g., orthopedic disease, peripheral artery occlusive disease, which affects the patient’s ability to walk). Note: Patients, who require walking aids, may be included if in the opinion of the investigator the walking distance is not impaired. Patients with a variance of more than 15% between the screening and the randomization (i.e., baseline) 6MWD test.