Conditions: Pulmonary Hypertension
Keywords: Pulmonary Hypertension Riociguat Blood Pressure
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 18
Healthy volunteers: no

Brief summary:
Pulmonary Arterial Hypertension (PAH) is a severe progressive disease with a high mortality. Although several drugs are available for the treatment of PAH none offer a cure, therefore there is still a high medical need for new treatments.

Soluble guanylate cyclase (sGC) is one of the chemicals involved in the pathways controlling vascular tone, which is impaired in patients with PAH. This causes constriction and thickening of the blood vessels wall in the lungs and increase of blood pressure in the lungs. This can lead to the very debilitating symptoms of PAH such as tiredness, shortness of breath on exertion, collapse and often the inability of the patient to perform their daily life activities.

Inhalation of Nitric Oxide, which activates sGC is used to treat PAH, but its effect wears off as soon as inhalation stops. Direct stimulation of sGC using this new compound Riociguat may be a new approach for the treatment of PAH.

The phosphodiesterase 5 (PDE5)-inhibitor Sildenafil is one of licensed treatments for PAH. The Patent Plus is a double-blind, placebo-controlled safety study, designed to investigate the effect of Riociguat on blood pressure in patients with PAH when given in combination with Sildenafil.

Detailed description:
Main objective: Evaluation of the pharmacodynamic effect of the combination of Sildenafil and Riociguat on blood pressure and other safety parameters in patients with symptomatic PAH Secondary objectives:To investigate the safety of the riociguat/sildenafil combination and changes in 6-minute walk test, World Health Organization (WHO) functional class, N terminal pro-brain natriuretic peptide, and variables obtained during right-heart catheterization after 12 weeks of treatment; pharmacokinetics of riociguat and sildenafil.

The study consists of one part. In study Part 1 only subjects (18) on stable sildenafil treatment of 20 mg tid have been enrolled. Study Part 2 will not start.

Arms:
arm 1: Participants received Riociguat orally as a film-coated tablet up to 2.5mg three times daily (tid) (titration between 1.0 mg and 2.5 mg tid based on an individual dose titration (IDT) scheme) for 12 weeks. Participants continued to take daily stable sildenafil background treatment according to their prescriptions. arm 2: Participants received Placebo orally as a film-coated tablet three times daily (tid) for 12 weeks. Participants continued to take daily stable sildenafil background treatment according to their prescriptions.

Interventions: intervention 1: Riociguat (Adempas, BAY63-2521) intervention 2: Placebo intervention 3: Sildenafil
Intervention descriptions: intervention 1: BAY63-2521: 1 mg tid - 2,5 mg tid oral for 12 weeks. intervention 2: Placebo for 12 weeks intervention 3: Participants continued to take daily stable sildenafil background treatment according to their prescriptions.

Protocol document: