Evaluation of the Pharmacodynamic Effect of the Combination of Sildenafil and Riociguat on Blood Pressure and Other Safety Parameters.

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 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.