Evaluation of the Pharmacodynamic Effect of the Combination of Sildenafil and Riociguat on Blood Pressure and Other Safety Parameters. (PATENT PLUS)
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.
Drug: Riociguat (BAY63-2521)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||An Interaction Study to Evaluate Changes in Blood Pressure Following 1, 1.5, 2, and 2.5 mg Riociguat Tid (Dose Titration) Compared to Placebo Treatment on the Background of Stable Sildenafil Pretreatment in Subjects With Symptomatic Pulmonary Arterial Hypertension|
- Maximum change in supine systolic blood pressure from baseline within 4 h of dosing with riociguat for the individual dose steps or placebo. [ Time Frame: every two weeks over 8 weeks ] [ Designated as safety issue: Yes ]
- Maximum change in standing SBP from baseline within 4 h of dosing with study medication. [ Time Frame: Every 2 weeks over 8 weeks ] [ Designated as safety issue: Yes ]
- Maximum change in standing diastolic blood pressure (DBP) from baseline within 4 h of dosing with study medication. [ Time Frame: Every 2 weeks over 8 weeks ] [ Designated as safety issue: Yes ]
- Maximum change in supine DBP from baseline within 4 h of dosing with study medication. [ Time Frame: Every 2 weeks over 8 weeks ] [ Designated as safety issue: Yes ]
- Maximum change in supine and standing HR from baseline within 4 h of dosing with study medication [ Time Frame: Every 2 weeks over 8 weeks ] [ Designated as safety issue: Yes ]
- Area under effect curve (AUEC) for change from baseline in standing and supine systolic and diastolic BP, and HR within 6 h of dosing with riociguat or placebo. [ Time Frame: Every 2 weeks over 8 weeks ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2010|
|Study Completion Date:||May 2013|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
|Experimental: Arm 1||
Drug: Riociguat (BAY63-2521)
BAY63-2521: 1 mg tid - 2,5 mg tid oral for 12 weeks.
|Placebo Comparator: Arm 2||
Placebo for 12 weeks
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, 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.
|United States, Colorado|
|Aurora, Colorado, United States, 80045|
|United States, Ohio|
|Columbus, Ohio, United States, 43221|
|United States, Rhode Island|
|Providence, Rhode Island, United States, 02903|
|Innsbruck, Austria, 6020|
|Villach, Austria, 9500|
|Praha 2, Czech Republic, 12808|
|Heidelberg, Baden-Württemberg, Germany, 69126|
|Regensburg, Bayern, Germany, 93042|
|Würzburg, Bayern, Germany, 97074|
|Gießen, Hessen, Germany, 35392|
|Hannover, Niedersachsen, Germany, 30625|
|Köln, Nordrhein-Westfalen, Germany, 50924|
|Mönchengladbach, Nordrhein-Westfalen, Germany, 41063|
|Dresden, Sachsen, Germany, 01307|
|Berlin, Germany, 13353|
|Hamburg, Germany, 20246|
|Bologna, Italy, 40138|
|Pavia, Italy, 27100|
|Auckland, New Zealand, 1051|
|Christchurch, New Zealand, 8011|
|Otwock, Poland, 05-400|
|Warszawa, Poland, 01-138|
|Barcelona, Spain, 08036|
|Cambridge, Cambridgeshire, United Kingdom, CB23 3RE|
|Clydebank, West Dunbartonshire, United Kingdom, G81 4DY|
|Study Director:||Bayer Study Director||Bayer|