Hypertension, PulmonaryPhase 2NCT00454558
An Open Multiple Dose Titration Study In Patients With Pulmonary Hypertension
A Phase 2 study testing Riociguat (Adempas, BAY63-2521) in people with Hypertension, Pulmonary, run by Bayer at 15 sites in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hypertension, Pulmonary
- What is being tested?
- Riociguat (Adempas, BAY63-2521)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 15 sitesGermany
- Study dates
- Jan 2007to Sep 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with CTEPH or PAH in NYHA class II or III
Who cannot join
- 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
Trial locations and contacts
15 sites in 1 country.
15 sites in 1 country
Germany15 sites
Study site
Bad Nauheim, Hesse, 61231
Study site
Berlin, State of Berlin, 12559
Study site
Cologne, North Rhine-Westphalia, 50924
Study site
Dresden, Saxony, 01307
Study site
Giessen, Hesse, 35392
Study site
Greifswald, Mecklenburg-Vorpommern, 17475
Study site
Halle, Saxony-Anhalt, 06120
Study site
Hamburg, Free and Hanseatic City of Hamburg, 20246
Study site
Hanover, Lower Saxony, 30625
Study site
Heidelberg, Baden-Wurttemberg, 69120
Study site
Homburg, Saarland, 66421
Study site
Leipzig, Saxony, 04103
Study site
Löwenstein, Baden-Wurttemberg, 74245
Study site
München, Bavaria, 81377
Study site
Regensburg, Bavaria, 93042
About this study
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
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.
Read the 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
- Conditions
- Hypertension, Pulmonary
- Being tested
- Riociguat (Adempas, BAY63-2521)
- Keywords
- Pulmonary Arterial Hypertension (PAH), Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
- Medical subject headings
- Hypertension, Pulmonary, Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Riociguat (Adempas, BAY63-2521)Drug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Not described Receives: Drug: Riociguat (Adempas, BAY63-2521) |
What is being measured
The primary outcome is the main question the study is designed to answer.
To investigate the safety, tolerability and feasibility of individual titration of BAY63-2521 according to peripheral systolic blood pressure
Measured: 3 months
To investigate the long term safety and tolerability of BAY63-2521
Measured: max. 84 months
Secondary outcomes (5)
6MWT
Measured: max. 84 months
Right heart catheter invasive hemodynamics
Measured: 3 months
WHO functional class assessment
Measured: max. 84 months
NT-pro BNP
Measured: 75 months
Imaging by echo
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2007 (estimated)
- Study startJan 2007
- Primary completionJul 2014
- Study completionSep 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Hypertension, PulmonaryStudies of the same condition, open and under way.
- More trials run by BayerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bayer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bayer Study Director, Study director, Bayer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00454558
- Sponsor's protocol ID
- 12166
- Other IDs
- 2006-003520-10
- Status last verified
- Sep 2015
- First submitted
- 28 Mar 2007
- Last updated
- 16 Oct 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 19705340Ghofrani 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.
PubMed 20530034Halank 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.
PubMed 28610669
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00454558
- Acronym / sponsor ID
- 12166
- Conditions
- Hypertension, Pulmonary
- Keywords
- Pulmonary Arterial Hypertension (PAH), Chronic Thromboembolic Pulmonary Hypertension (CTEPH)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- Jan 2007
- Primary completion
- Jul 2014 (actual)
- Study completion
- Sep 2014 (actual)
- First posted
- 30 Mar 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Riociguat (Adempas, BAY63-2521) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patients with CTEPH or PAH in NYHA class II or III
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Drug | Arm 1 |
Primary outcome
To investigate the safety, tolerability and feasibility of individual titration of BAY63-2521 according to peripheral systolic blood pressure
Time frame: 3 months
To investigate the long term safety and tolerability of BAY63-2521
Time frame: max. 84 months
5 secondary outcomes
6MWT
Time frame: max. 84 months
Right heart catheter invasive hemodynamics
Time frame: 3 months
WHO functional class assessment
Time frame: max. 84 months
NT-pro BNP
Time frame: 75 months
Imaging by echo
Time frame: 3 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2015.
- Results publication: PubMed 19705340Belik J. Riociguat, an oral soluble guanylate cyclase stimulator for the treatment of pulmonary hypertension. Curr Opin Investig Drugs. 2009 Sep;10(9):971-9.
- Results publication: PubMed 20530034Ghofrani 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.
- Derived from this study: PubMed 28610669Halank 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bayer Study Director study director
Bayer
15 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Riociguat (Adempas, BAY63-2521) in people with Hypertension, Pulmonary, run by Bayer at 15 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To investigate the safety, tolerability and feasibility of individual titration of BAY63-2521 according to peripheral systolic blood pressure (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00454558, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2015; AzTrials last refreshed its copy on 30 Oct 2026.