Clinical trial NCT00454558: An Open Multiple Dose Titration Study In Patients With Pulmonary Hypertension
Official title: A Multicenter, Non-randomized, Non-blinded, Noncontrolled Study to Investigate the Impact of Multiple Doses of BAY 63-2521 on Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics in Patients With Pulmonary Hypertension in a 12-week 3 Times a Day Individual Dose Titration Scheme
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension, Pulmonary
Keywords: Pulmonary Arterial Hypertension (PAH)
Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2007-03-30
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a study to demonstrate the feasibility of an individual dose titration scheme based on the systolic blood pressure with a dose range from 1.0 mg TID to 2.5 mg TID. Patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH) will be included. After diagnosis by an expert center, patients receive medication three times a day starting with 1.0 mg TID. The first tablets are given in the hospital, then the patients are allowed to go home and take the medication at home. After 2 weeks, patients return to the hospital for an ambulatory visit and the dose may be increased based on the actual condition of the patient (blood pressure and adverse events). Several measurements will be performed to test the efficacy of the drug and whether there are any unwanted reactions to the drug (blood tests, ECG, 6 minute walk test, imaging by Echo, quality of life scores). The dose of the drug will then be increased further until unwanted effects may occur or the blood pressure drops to low. The highest dose tested will be 2.5 mg TID. After 12 weeks the patient is going to stay in the hospital again and a right heart catheter is performed to examine the changes in hemodynamics after 12 weeks of treatment with the drug. If the patients give their consent they can enter a long-term extension trial continuing on BAY63-2521 with the dose reached after 12 weeks. Every 3 months an ambulatory visit at the specialist center will be performed including measurements of safety (blood tests, ECG, clinical assessment) and efficacy (6 minute walk test, Borg dyspnea scale, NT-pro BNP). Blood tests and ECG have been removed begin of 2013 as safety parameter by amendment 7; furthermore Borg dyspnea score and NT-proBNP have been removed as efficacy parameter.

Initially the inclusion of ten patients suffering from chronic thromboembolic pulmonary hypertension (CTEPH) or pulmonary arterial hypertension (PAH) was planned. Later on the patient number was amended and 75 patients entered the trial.

Furthermore the trial duration was extended and a long term treatment with BAY63-2521 was offered to the patients. Finally 68 patients moved over to the long term extension period of the trial.

Detailed description: Specification of primary outcome measures for long-term safety and tolerability: Adverse events, blood pressure and heart rate, 12 lead ECG, clinical chemistry and hematology, Troponin I

Eligibility criteria: Inclusion Criteria:

* Patients with CTEPH or PAH in NYHA class II or III

Exclusion Criteria:

* Patients with PDE 5 inhibitor or prostacycline pretreatment, relevant pulmonary diseases, relevant cardiac diseases, severe coagulation disorders, moderate to severe hepatic or renal insufficiency, pregnancy, hypotension

Primary outcomes:
measure: To investigate the safety, tolerability and feasibility of individual titration of BAY63-2521 according to peripheral systolic blood pressure
timeFrame: 3 months
measure: To investigate the long term safety and tolerability of BAY63-2521
timeFrame: max. 84 months
Secondary outcomes:
measure: 6MWT
timeFrame: max. 84 months
measure: Right heart catheter invasive hemodynamics
timeFrame: 3 months
measure: WHO functional class assessment
timeFrame: max. 84 months
measure: NT-pro BNP
timeFrame: 75 months
measure: Imaging by echo
timeFrame: 3 months
Other outcomes:
Locations:
city: Heidelberg
country: Germany
state: Baden-Württemberg
city: Löwenstein
country: Germany
state: Baden-Württemberg
city: München
country: Germany
state: Bayern
city: Regensburg
country: Germany
state: Bayern
city: Bad Nauheim
country: Germany
state: Hessen
city: Gießen
country: Germany
state: Hessen
city: Greifswald
country: Germany
state: Mecklenburg-Vorpommern
city: Hannover
country: Germany
state: Niedersachsen
city: Köln
country: Germany
state: Nordrhein-Westfalen
city: Homburg
country: Germany
state: Saarland
city: Halle
country: Germany
state: Sachsen-Anhalt
city: Dresden
country: Germany
state: Sachsen
city: Leipzig
country: Germany
state: Sachsen
city: Berlin
country: Germany
city: Hamburg
country: Germany
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
citation: Belik J. Riociguat, an oral soluble guanylate cyclase stimulator for the treatment of pulmonary hypertension. Curr Opin Investig Drugs. 2009 Sep;10(9):971-9.
citation: Ghofrani HA, Hoeper MM, Halank M, Meyer FJ, Staehler G, Behr J, Ewert R, Weimann G, Grimminger F. Riociguat for chronic thromboembolic pulmonary hypertension and pulmonary arterial hypertension: a phase II study. Eur Respir J. 2010 Oct;36(4):792-9. doi: 10.1183/09031936.00182909. Epub 2010 Jun 7.
citation: Halank M, Hoeper MM, Ghofrani HA, Meyer FJ, Stahler G, Behr J, Ewert R, Fletcher M, Colorado P, Nikkho S, Grimminger F. Riociguat for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Results from a phase II long-term extension study. Respir Med. 2017 Jul;128:50-56. doi: 10.1016/j.rmed.2017.05.008. Epub 2017 May 16.