An Open Multiple Dose Titration Study In Patients With Pulmonary Hypertension

October 14, 2015 updated by: Bayer

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Study Type

Interventional

Enrollment (Actual)

75

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Germany
      • Berlin, Germany, 12559
      • Hamburg, Germany, 20246
    • Baden-Württemberg
      • Heidelberg, Baden-Württemberg, Germany, 69120
      • Löwenstein, Baden-Württemberg, Germany, 74245
    • Bayern
      • München, Bayern, Germany, 81377
      • Regensburg, Bayern, Germany, 93042
    • Hessen
      • Bad Nauheim, Hessen, Germany, 61231
      • Gießen, Hessen, Germany, 35392
    • Mecklenburg-Vorpommern
      • Greifswald, Mecklenburg-Vorpommern, Germany, 17475
    • Niedersachsen
      • Hannover, Niedersachsen, Germany, 30625
    • Nordrhein-Westfalen
      • Köln, Nordrhein-Westfalen, Germany, 50924
    • Saarland
      • Homburg, Saarland, Germany, 66421
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
      • Leipzig, Sachsen, Germany, 04103
    • Sachsen-Anhalt
      • Halle, Sachsen-Anhalt, Germany, 06120

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
To investigate the safety, tolerability and feasibility of individual titration of BAY63-2521 according to peripheral systolic blood pressure
Time Frame: 3 months
3 months
To investigate the long term safety and tolerability of BAY63-2521
Time Frame: max. 84 months
max. 84 months

Secondary Outcome Measures

Outcome Measure
Time Frame
6MWT
Time Frame: max. 84 months
max. 84 months
Right heart catheter invasive hemodynamics
Time Frame: 3 months
3 months
WHO functional class assessment
Time Frame: max. 84 months
max. 84 months
NT-pro BNP
Time Frame: 75 months
75 months
Imaging by echo
Time Frame: 3 months
3 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Bayer

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2007

Primary Completion (Actual)

July 1, 2014

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

March 28, 2007

First Submitted That Met QC Criteria

March 29, 2007

First Posted (Estimate)

March 30, 2007

Study Record Updates

Last Update Posted (Estimate)

October 16, 2015

Last Update Submitted That Met QC Criteria

October 14, 2015

Last Verified

September 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 12166
  • 2006-003520-10 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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