Hypertension, PulmonaryPhase 3RESPITENCT02007629
Riociguat Clinical Effects Studied in Patients With Insufficient Treatment Response to Phosphodiesterase-5 Inhibitor
A Phase 3 study testing Riociguat (Adempas, BAY63-2521) in people with Hypertension, Pulmonary, run by Bayer at 27 sites in 9 countries.
Trial summary
BAY63-2521 Riociguat leads to the relaxation of smooth muscle cells in pulmonary arteria and may also inhibit abnormal remodeling of lung blood vessels. In patients with pulmonary arterial hypertension Riociguat showed to reduce the pulmonary blood pressure and improved the right heart function without unacceptable… Read more about this study
- Who is it for?
- Ages 18 to 75 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
- 61 participants
- Where
- 27 sitesin 9 countries
- Study dates
- 18 Feb 2014to 29 Dec 2016
- Phase
- Phase 3
- 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients (18 -75 years of age) with idiopathic, familial, drug/toxin induced and associated PAH due to congenital heart disease (Group I / Dana Point Classification of PH) demonstrating insufficient response to treatment with PDE-5i for at least 3 months
- Patients with and without endothelin receptor antagonist (ERA) therapy
- World Health Organization Functional Class (WHO FC) III at screening
- 6-minute walking distance (6MWD) of 165-440 m
- Cardiac index <3.0 L/min/m*2.
Who cannot join
- All types of PH except subtypes of Dana Point Group I specified in the inclusion criteria
- Evidence of clinically significant restrictive or obstructive parenchymal lung diseases
- Diffusing capacity of the lung for carbon monoxide (DLCO) <30% predicted
- History or active state of serious hemoptysis / pulmonary hemorrhage including those managed by bronchial artery embolization
- Patients unable to perform a valid 6MWD test
- Pregnant women (i.e. positive pregnancy test or other signs of pregnancy), or breast feeding women, or women with childbearing potential not using a combination of 2 effective methods of birth control, for example a combination of condoms with a safe and highly effective contraception method (prescription oral contraceptives, contraceptive injections, contraceptive patch, intrauterine device) or a double barrier method is used throughout the study.
Trial locations and contacts
27 sites in 9 countries.
27 sites in 9 countries
United States7 sites
Study site
Boston, Massachusetts, 02111
Study site
Iowa City, Iowa, 52242-1089
Study site
La Jolla, California, 92093
Study site
Pittsburgh, Pennsylvania, 15212
Study site
Providence, Rhode Island, 02903
Study site
Sacramento, California, 95817
Study site
St Louis, Missouri, 63110
Germany6 sites
Study site
Cologne, North Rhine-Westphalia, 50924
Study site
Dresden, Saxony, 01307
Study site
Hanover, Lower Saxony, 30625
Study site
Heidelberg, Baden-Wurttemberg, 69126
Study site
Leipzig, Saxony, 04103
Study site
Regensburg, Bavaria, 93053
United Kingdom4 sites
Study site
Clydebank, West Dunbartonshire, G81 4DY
Study site
London, NW3 2QG
Study site
London, SW3 6NP
Study site
Newcastle upon Tyne, Tyne and Wear, NE7 7DN
France3 sites
Study site
Grenoble, 38043
Study site
Le Kremlin-Bicêtre, 94275
Study site
Marseille, 13005
About this study
Official title: An Open-label, International, Multicenter, Single-arm, Uncontrolled, Phase IIIb Study of Riociguat in Patients With Pulmonary Arterial Hypertension (PAH) Who Demonstrate an Insufficient Response to Treatment With Phosphodiesterase-5 Inhibitors (PDE-5i)
BAY63-2521 Riociguat leads to the relaxation of smooth muscle cells in pulmonary arteria and may also inhibit abnormal remodeling of lung blood vessels. In patients with pulmonary arterial hypertension Riociguat showed to reduce the pulmonary blood pressure and improved the right heart function without unacceptable side effects. Here dose of Riociguat will be adjusted over 8 weeks then a Maintenance Phase of 16 weeks follows. Patients with Pulmonary Arterial Hypertension treated with stable doses of Phosphodiesterase Type-5 Inhibitors (Eg Sildenafil, Tadalafil) not appropriately responding to therapy will be included. Based on previous evidence and on the different modes of action an improvement of exercise capacity, heart function and quality of life may be expected if PDE5i treatment is transitioned to riociguat.
Where Riociguat is pending market approval or reimbursement once the treatment phase is completed drug can be made available for another 18 months (Extended Drug Supply Phase - EDSP) under study conditions. Patients may also transition at the end of the maintenance period or any time during the EDSP to any program that is intended to provide riociguat until drug approval/reimbursement, e.g. a long-term extension study, compassionate use or named patient program. Study termination is also possible at any time.
- Conditions
- Hypertension, Pulmonary
- Being tested
- Riociguat (Adempas, BAY63-2521)
- Medical subject headings
- Hypertension, Pulmonary
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Riociguat (Adempas, BAY63-2521)Drug
Riociguat / BAY63-2521 film-coated tablets will be used in this study at a dosage of either 0.5, 1.0, 1.5, 2.0, and 2.5 mg. 3 times daily
| Study group | Role | What they receive |
|---|---|---|
| Riociguat | Experimental | Subjects received riociguat film coated immediate-release (IR) tablet 3 times a day (tid) with or without food at a starting dose of 1.0 milligram (mg) and increased by 0.5 mg increments at 2-weekly intervals to a maximum of 2.5 mg tid, until Week 8 (titration phase). An optimal dose was determined based on systolic blood pressure (SBP) and well-being. Thereafter, riociguat continued at the optimal individual dose until Week 24 (Main phase). Dose reductions or stop of study medication for safety reasons were allowed at any time. Increases or re-increases in 0.5 mg steps (maximum dose 2.5 mg) were possible at the investigator's discretion weighing the benefit with potential risks implied. Subjects were offered participation in EDSP and received riociguat 2.5 mg film coated IR tablet 3 tid with or without food for 18 months or until reimbursement. Receives: Drug: Riociguat (Adempas, BAY63-2521) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in 6 Minute Walking Distance (6MWD)
6MWD test was used to measure the subjects functional exercise capacity. Subjects were instructed to walk alone, not run, from one end to the other end of the walking course, at their own pace, while attempting to cover as much ground as possible in 6 minutes. No "warm-up" period was performed before the test. Investigators have not walked with the subjects. This was an encouraged test (the person conducting the test encouraged subjects to walk farther or faster by using only standardized phrases).
Measured: Baseline, Week 12 and Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2013 (estimated)
- Study start18 Feb 2014
- Primary completion29 Dec 2016
- Study completion29 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 61 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
- NCT02007629
- Sponsor's protocol ID
- 16719
- Other IDs
- 2013-001759-10
- Acronym
- RESPITE
- Status last verified
- Dec 2018
- First submitted
- 6 Dec 2013
- Last updated
- 21 Feb 2019
- Results posted
- No
- Data monitoring committee
- No
Publications
Hoeper MM, Klinger JR, Benza RL, Simonneau G, Langleben D, Naeije R, Corris PA. Rationale and study design of RESPITE: An open-label, phase 3b study of riociguat in patients with pulmonary arterial hypertension who demonstrate an insufficient response to treatment with phosphodiesterase-5 inhibitors. Respir Med. 2017 Jan;122 Suppl 1:S18-S22. doi: 10.1016/j.rmed.2016.11.001. Epub 2016 Nov 5.
PubMed 27887774Hoeper MM, Simonneau G, Corris PA, Ghofrani HA, Klinger JR, Langleben D, Naeije R, Jansa P, Rosenkranz S, Scelsi L, Grunig E, Vizza CD, Chang M, Colorado P, Meier C, Busse D, Benza RL. RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors. Eur Respir J. 2017 Sep 9;50(3):1602425. doi: 10.1183/13993003.02425-2016. Print 2017 Sep.
PubMed 28889107
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, International, Multicenter, Single-arm, Uncontrolled, Phase IIIb Study of Riociguat in Patients With Pulmonary Arterial Hypertension (PAH) Who Demonstrate an Insufficient Response to Treatment With Phosphodiesterase-5 Inhibitors (PDE-5i)
- ClinicalTrials.gov ID
- NCT02007629
- Acronym / sponsor ID
- RESPITE / 16719
- Conditions
- Hypertension, Pulmonary
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 61 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 18 Feb 2014
- Primary completion
- 29 Dec 2016 (actual)
- Study completion
- 29 Dec 2016 (actual)
- First posted
- 11 Dec 2013 (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.
BAY63-2521 Riociguat leads to the relaxation of smooth muscle cells in pulmonary arteria and may also inhibit abnormal remodeling of lung blood vessels. In patients with pulmonary arterial hypertension Riociguat showed to reduce the pulmonary blood pressure and improved the right heart function without unacceptable side effects. Here dose of Riociguat will be adjusted over 8 weeks then a Maintenance Phase of 16 weeks follows. Patients with Pulmonary Arterial Hypertension treated with stable doses of Phosphodiesterase Type-5 Inhibitors (Eg Sildenafil, Tadalafil) not appropriately responding to therapy will be included. Based on previous evidence and on the different modes of action an improvement of exercise capacity, heart function and quality of life may be expected if PDE5i treatment is transitioned to riociguat.
Where Riociguat is pending market approval or reimbursement once the treatment phase is completed drug can be made available for another 18 months (Extended Drug Supply Phase - EDSP) under study conditions. Patients may also transition at the end of the maintenance period or any time during the EDSP to any program that is intended to provide riociguat until drug approval/reimbursement, e.g. a long-term extension study, compassionate use or named patient program. Study termination is also possible at any time.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Riociguat | Experimental | Drug: Riociguat (Adempas, BAY63-2521)Subjects received riociguat film coated immediate-release (IR) tablet 3 times a day (tid) with or without food at a starting dose of 1.0 milligram (mg) and increased by 0.5 mg increments at 2-weekly intervals to a maximum of 2.5 mg tid, until Week 8 (titration phase). An optimal dose was determined based on systolic blood pressure (SBP) and well-being. Thereafter, riociguat continued at the optimal individual dose until Week 24 (Main phase). Dose reductions or stop of study medication for safety reasons were allowed at any time. Increases or re-increases in 0.5 mg steps (maximum dose 2.5 mg) were possible at the investigator's discretion weighing the benefit with potential risks implied. Subjects were offered participation in EDSP and received riociguat 2.5 mg film coated IR tablet 3 tid with or without food for 18 months or until reimbursement. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female patients (18 -75 years of age) with idiopathic, familial, drug/toxin induced and associated PAH due to congenital heart disease (Group I / Dana Point Classification of PH) demonstrating insufficient response to treatment with PDE-5i for at least 3 months
- Patients with and without endothelin receptor antagonist (ERA) therapy
- World Health Organization Functional Class (WHO FC) III at screening
- 6-minute walking distance (6MWD) of 165-440 m
- Cardiac index <3.0 L/min/m*2.
Key exclusion criteria (6 listed)
- All types of PH except subtypes of Dana Point Group I specified in the inclusion criteria
- Evidence of clinically significant restrictive or obstructive parenchymal lung diseases
- Diffusing capacity of the lung for carbon monoxide (DLCO) <30% predicted
- History or active state of serious hemoptysis / pulmonary hemorrhage including those managed by bronchial artery embolization
- Patients unable to perform a valid 6MWD test
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)Riociguat / BAY63-2521 film-coated tablets will be used in this study at a dosage of either 0.5, 1.0, 1.5, 2.0, and 2.5 mg. 3 times daily | Drug | Riociguat |
Primary outcome
Change from baseline in 6 Minute Walking Distance (6MWD)
Time frame: Baseline, Week 12 and Week 24
6MWD test was used to measure the subjects functional exercise capacity. Subjects were instructed to walk alone, not run, from one end to the other end of the walking course, at their own pace, while attempting to cover as much ground as possible in 6 minutes. No "warm-up" period was performed before the test. Investigators have not walked with the subjects. This was an encouraged test (the person conducting the test encouraged subjects to walk farther or faster by using only standardized phrases).
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 21 Feb 2019.
- Results publication: PubMed 27887774Hoeper MM, Klinger JR, Benza RL, Simonneau G, Langleben D, Naeije R, Corris PA. Rationale and study design of RESPITE: An open-label, phase 3b study of riociguat in patients with pulmonary arterial hypertension who demonstrate an insufficient response to treatment with phosphodiesterase-5 inhibitors. Respir Med. 2017 Jan;122 Suppl 1:S18-S22. doi: 10.1016/j.rmed.2016.11.001. Epub 2016 Nov 5.
- Results publication: PubMed 28889107Hoeper MM, Simonneau G, Corris PA, Ghofrani HA, Klinger JR, Langleben D, Naeije R, Jansa P, Rosenkranz S, Scelsi L, Grunig E, Vizza CD, Chang M, Colorado P, Meier C, Busse D, Benza RL. RESPITE: switching to riociguat in pulmonary arterial hypertension patients with inadequate response to phosphodiesterase-5 inhibitors. Eur Respir J. 2017 Sep 9;50(3):1602425. doi: 10.1183/13993003.02425-2016. Print 2017 Sep.
- Click here to find information about studies related to Bayer Healthcare products conducted in Europe.Link provided by the sponsor.
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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
27 sites in 9 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Riociguat (Adempas, BAY63-2521) in people with Hypertension, Pulmonary, run by Bayer at 27 sites in 9 countries.
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 5 inclusion and 6 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 21 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 27 sites in United States, Germany, United Kingdom, France, Belgium and 4 more countries. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Change from baseline in 6 Minute Walking Distance (6MWD) (time frame: Baseline, Week 12 and Week 24). 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 NCT02007629, which also lists 2 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 21 Feb 2019.