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An Open Multiple Dose Titration Study In Patients With Pulmonary Hypertension

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Bayer
ClinicalTrials.gov Identifier:
NCT00454558
First received: March 28, 2007
Last updated: September 15, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Hypertension, Pulmonary
Drug: Riociguat (Adempas, BAY63-2521)
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Bayer:

Primary Outcome Measures:
  • To investigate the safety, tolerability and feasibility of individual titration of BAY63-2521 according to peripheral systolic blood pressure [ Time Frame: 3 months ] [ Designated as safety issue: Yes ]
  • To investigate the long term safety and tolerability of BAY63-2521 [ Time Frame: max. 84 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 6MWT [ Time Frame: max. 84 months ] [ Designated as safety issue: No ]
  • Right heart catheter invasive hemodynamics [ Time Frame: 3 months ] [ Designated as safety issue: No ]
  • WHO functional class assessment [ Time Frame: max. 84 months ] [ Designated as safety issue: No ]
  • NT-pro BNP [ Time Frame: 75 months ] [ Designated as safety issue: No ]
  • Imaging by echo [ Time Frame: 3 months ] [ Designated as safety issue: No ]

Enrollment: 75
Study Start Date: January 2007
Study Completion Date: July 2014
Primary Completion Date: July 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1 Drug: Riociguat (Adempas, BAY63-2521)
Biweekly uptitration of BAY63-2521 (Oral sGC Stimulator) starting from 1.0 mg TID up to 2.5 mg TID in steps of +0.5 mg according to safety and tolerability.

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00454558

Locations
Germany
Heidelberg, Baden-Württemberg, Germany, 69120
Löwenstein, Baden-Württemberg, Germany, 74245
München, Bayern, Germany, 81377
Regensburg, Bayern, Germany, 93042
Bad Nauheim, Hessen, Germany, 61231
Gießen, Hessen, Germany, 35392
Greifswald, Mecklenburg-Vorpommern, Germany, 17475
Hannover, Niedersachsen, Germany, 30625
Köln, Nordrhein-Westfalen, Germany, 50924
Homburg, Saarland, Germany, 66421
Halle, Sachsen-Anhalt, Germany, 06120
Dresden, Sachsen, Germany, 01307
Leipzig, Sachsen, Germany, 04103
Berlin, Germany, 12559
Hamburg, Germany, 20246
Sponsors and Collaborators
Bayer
Investigators
Study Director: Bayer Study Director Bayer
  More Information

Additional Information:
Publications:
Responsible Party: Bayer
ClinicalTrials.gov Identifier: NCT00454558     History of Changes
Other Study ID Numbers: 12166, 2006-003520-10
Study First Received: March 28, 2007
Last Updated: September 15, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Bayer:
Pulmonary Arterial Hypertension (PAH)
Chronic Thromboembolic Pulmonary Hypertension (CTEPH)

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on November 20, 2014