Clinical PharmacologyPhase 1NCT04366622
Study on the Safety of BAY 63-2521, How it is Tolerated and the Way the Body Absorbs, Distributes and Gets Rid of the Study Drug Given as a Single Oral Dose of 1 mg Tablet in Participants With Impaired Liver Function and Healthy Participants Matched for Age-, Gender-, and Weight
A Phase 1 study testing Riociguat (Adempas, BAY 63-2521) in people with Clinical Pharmacology, run by Bayer at 1 site in Germany.
Trial summary
BAY 63-2521 is intended to be used for a disease that affects the blood flow through the lungs. Renal impairment is a common condition in patients with this disease. The goal of the study is to learn more about the safety of BAY 63-2521, how it is tolerated and the way the body absorbs, distributes and gets rid of the… Read more about this study
- Who is it for?
- Ages 18 to 79 yearsHealthy volunteers can take part
- Conditions the study is for
- Clinical Pharmacology
- What is being tested?
- Riociguat (Adempas, BAY 63-2521)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteGermany
- Study dates
- 14 Apr 2010to 15 Sep 2011
- Phase
- Phase 1
- 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 79 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and female White subjects 18 to ≤79 years of age, BMI between 18 and 34 kg/m^2
- Women without childbearing potential or with childbearing potential but only if the pregnancy test is negative and are under highly effective contraception
- Documented liver cirrhosis confirmed by histopathology, eg previous liver biopsy, laparoscopy, or ultrasound Hepatic impairment (Child Pugh A or B)
- Stable liver disease
- Age- (+/-10 years), weight- (+/-10 kg body weight), and gender-matched to a subject with liver cirrhosis as far as possible
Who cannot join
- Febrile illness within 1 week before the start of the study
- Hypersensitivity to riociguat and / or to inactive constituents
- Smoking
- Hemoglobin <8 g/dL
- Severe cerebrovascular or cardiac disorders, eg myocardial infarction less than 6 months prior to dosing, congestive heart failure of NYHA grade III or IV, severe arrhythmia requiring antiarrhythmic treatment
- Evidence of hepatic encephalopathy related to chronic liver disease > Grade II
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- Renal failure with a creatinine clearance <40 mL/min
- Resting heart rate in the awake subject below 45 BPM or above 100 BPM
- Systolic blood pressure (SBP) below 100 mmHg or above 160 mmHg, Diastolic blood pressure (DBP) above 95 mmHg
- Platelet count <30 x 10^9/L
- History of bleeding within the past 3 months
- AP >4 times the upper limit of normal (ULN)
- AST or ALT in conjunction with GGT >= 4 times the ULN (an isolated elevation of GGT >4 times ULN did not exclude the subject)
- Serum albumin <20 g/L
- Diabetes mellitus with a fasting blood glucose >220 mg/dL or HbA1c >10%
- Prothrombin time (Quick test) <30%
- Subjects who had undergone porto-caval shunt surgery
- Use of medications known to interfere with hepatic metabolism (eg cimetidine, barbiturates, phenothiazines, etc) or known to alter other major organs or systems within 30 days prior to dosing
- Severe infection, malignancy, psychosis, or any clinically significant illness within 4 weeks prior to dosing
- Concomitant use of any medication except medications necessary for the treatment of the kidney disease or related complications
- Concomitant use of phosphodiesterase-5 inhibitors, endothelin receptor antagonists (ERAs, eg bosentan), intravenous or inhalative prostacyclins, or nitrates
- Concomitant use of potent CYP3A4 and P-gp inhibitors
- Conspicuous findings in medical history or pre-study examination
- History of relevant diseases of vital organs, central nervous system, or other organs
- Resting heart rate in the awake subject below 45 BPM or above 90 BPM
- SBP below 100 mmHg or above 145 mmHg, DBP above 95 mmHg
- Regular daily consumption of more than 1 liter of usual beer or the equivalent quantity of approximately 40 g of alcohol in another form
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Investigation of Pharmacokinetics, Safety, and Tolerability of BAY 63-2521 in Male and Female Subjects With Hepatic Impairment (Classified as Child Pugh A or B) and in Age-, Weight- and Gender-matched Healthy Subjects Following a Single Oral Dose of 1 mg BAY 63-2521 in a Single-center, Non-randomized, Non-controlled, Non-blinded, Observational Study With Group Stratification
BAY 63-2521 is intended to be used for a disease that affects the blood flow through the lungs. Renal impairment is a common condition in patients with this disease. The goal of the study is to learn more about the safety of BAY 63-2521, how it is tolerated and the way the body absorbs, distributes and gets rid of the study dug given as a single oral dose of 1 mg tablet in participants with renal impairment and healthy participants matched for age-, gender-, and weight
- Conditions
- Clinical Pharmacology
- Being tested
- Riociguat (Adempas, BAY 63-2521)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Riociguat (Adempas, BAY 63-2521)Drug
0.5 mg riociguat as an immediate-release (IR) tablet
| Study group | Role | What they receive |
|---|---|---|
| Riociguat, Child Pugh A | Experimental | Participants with liver cirrhosis and mild hepatic impairment received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state Receives: Drug: Riociguat (Adempas, BAY 63-2521) |
| Riociguat, Child Pugh B | Experimental | Participants with liver cirrhosis and moderate hepatic impairment received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state Receives: Drug: Riociguat (Adempas, BAY 63-2521) |
| Riociguat, control A | Experimental | Healthy age-, weight-, and gender- matched participants to Child Pugh A group received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state Receives: Drug: Riociguat (Adempas, BAY 63-2521) |
| Riociguat, control B | Experimental | Healthy age-, weight-, and gender- matched participants to Child Pugh B group received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state Receives: Drug: Riociguat (Adempas, BAY 63-2521) |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC
Area under the plasma concentration vs time curve from zero to infinity for total (bound and unbound) drug after single dose for BAY 63-2521 and its metabolite M1 (BAY 60-4552)
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
Cmax
Maximum total (bound and unbound) drug concentration in plasma after single dose administration for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
t½
Half-life associated with the terminal slope for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
fu
Fraction unbound for BAY 63-2521 and its metabolite M1
Measured: From 2 hours post-dose up to 24 hours post-dose
AUCu
AUC for unbound drug for BAY 63-2521 and its metabolite M1
Measured: From 2 hours post-dose up to 24 hours post-dose
Cmax,u
Cmax for unbound drug for BAY 63-2521 and its metabolite M1
Measured: From 2 hours post-dose up to 24 hours post-dose
Secondary outcomes (15)
AUC/D
AUC divided by dose (mg) for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
AUCnorm
AUC divided by dose (mg) per kg body weight for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
AUCu,norm
AUCnorm for unbound drug for BAY 63-2521 and its metabolite M1
Measured: From 2 hours post-dose up to 24 hours post-dose
AUC(0-tlast)
AUC from time 0 to the last data point for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
Cmax/D
Cmax divided by dose (mg) for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
Cmax,norm
Cmax divided by dose (mg) per kg body weight for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
Cmax,u,norm
Cmax,norm for unbound drug for BAY 63-2521 and its metabolite M1
Measured: From 2 hours post-dose up to 24 hours post-dose
tmax
Time to reach maximum drug concentration in plasma after single dose for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
MRT
Mean residence time for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
CL/F
Total body clearance of total (bound and unbound) drug from plasma calculated after oral administration (apparent oral clearance) for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
CLu/F
CL/F for unbound drug for BAY 63-2521 and its metabolite M1
Measured: From 2 hours post-dose up to 24 hours post-dose
Vz/F
Apparent volume of distribution during terminal phase after oral administration for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
AE,ur
Amount of (total) drug excreted in urine for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose
CLR
Renal body clearance of drug for BAY 63-2521 and its metabolite M1
Measured: Pre-dose and up to 72 hours post-dose
Number of participants with adverse events
Measured: Approximately 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Apr 2020
- Study start14 Apr 2010
- Primary completion28 Apr 2011
- Study completion15 Sep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clinical PharmacologyStudies 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 1
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 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
- NCT04366622
- Sponsor's protocol ID
- 15001
- Other IDs
- 2009-017684-42, 2009
- Status last verified
- Apr 2020
- First submitted
- 23 Apr 2020
- Last updated
- 29 Apr 2020
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided: Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of Pharmacokinetics, Safety, and Tolerability of BAY 63-2521 in Male and Female Subjects With Hepatic Impairment (Classified as Child Pugh A or B) and in Age-, Weight- and Gender-matched Healthy Subjects Following a Single Oral Dose of 1 mg BAY 63-2521 in a Single-center, Non-randomized, Non-controlled, Non-blinded, Observational Study With Group Stratification
- ClinicalTrials.gov ID
- NCT04366622
- Acronym / sponsor ID
- 15001
- Conditions
- Clinical Pharmacology
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- BayerIndustry (pharma, biotech, devices)
- Study start
- 14 Apr 2010
- Primary completion
- 28 Apr 2011 (actual)
- Study completion
- 15 Sep 2011 (actual)
- First posted
- 29 Apr 2020 (actual)
- 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.
BAY 63-2521 is intended to be used for a disease that affects the blood flow through the lungs. Renal impairment is a common condition in patients with this disease. The goal of the study is to learn more about the safety of BAY 63-2521, how it is tolerated and the way the body absorbs, distributes and gets rid of the study dug given as a single oral dose of 1 mg tablet in participants with renal impairment and healthy participants matched for age-, gender-, and weight
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Riociguat, Child Pugh A | Experimental | Drug: Riociguat (Adempas, BAY 63-2521)Participants with liver cirrhosis and mild hepatic impairment received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
| Riociguat, Child Pugh B | Experimental | Drug: Riociguat (Adempas, BAY 63-2521)Participants with liver cirrhosis and moderate hepatic impairment received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
| Riociguat, control A | Experimental | Drug: Riociguat (Adempas, BAY 63-2521)Healthy age-, weight-, and gender- matched participants to Child Pugh A group received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
| Riociguat, control B | Experimental | Drug: Riociguat (Adempas, BAY 63-2521)Healthy age-, weight-, and gender- matched participants to Child Pugh B group received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male and female White subjects 18 to ≤79 years of age, BMI between 18 and 34 kg/m^2
- Women without childbearing potential or with childbearing potential but only if the pregnancy test is negative and are under highly effective contraception
- Documented liver cirrhosis confirmed by histopathology, eg previous liver biopsy, laparoscopy, or ultrasound Hepatic impairment (Child Pugh A or B)
- Stable liver disease
- Age- (+/-10 years), weight- (+/-10 kg body weight), and gender-matched to a subject with liver cirrhosis as far as possible
Key exclusion criteria (27 listed)
- Febrile illness within 1 week before the start of the study
- Hypersensitivity to riociguat and / or to inactive constituents
- Smoking
- Hemoglobin <8 g/dL
- Severe cerebrovascular or cardiac disorders, eg myocardial infarction less than 6 months prior to dosing, congestive heart failure of NYHA grade III or IV, severe arrhythmia requiring antiarrhythmic treatment
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, BAY 63-2521)0.5 mg riociguat as an immediate-release (IR) tablet | Drug | Riociguat, Child Pugh A, Riociguat, Child Pugh B, Riociguat, control A, Riociguat, control B |
Primary outcome
AUC
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
Area under the plasma concentration vs time curve from zero to infinity for total (bound and unbound) drug after single dose for BAY 63-2521 and its metabolite M1 (BAY 60-4552)
Cmax
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
Maximum total (bound and unbound) drug concentration in plasma after single dose administration for BAY 63-2521 and its metabolite M1
t½
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
Half-life associated with the terminal slope for BAY 63-2521 and its metabolite M1
fu
Time frame: From 2 hours post-dose up to 24 hours post-dose
Fraction unbound for BAY 63-2521 and its metabolite M1
AUCu
Time frame: From 2 hours post-dose up to 24 hours post-dose
AUC for unbound drug for BAY 63-2521 and its metabolite M1
Cmax,u
Time frame: From 2 hours post-dose up to 24 hours post-dose
Cmax for unbound drug for BAY 63-2521 and its metabolite M1
15 secondary outcomes
AUC/D
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
AUCnorm
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
AUCu,norm
Time frame: From 2 hours post-dose up to 24 hours post-dose
AUC(0-tlast)
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
Cmax/D
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
Cmax,norm
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
Cmax,u,norm
Time frame: From 2 hours post-dose up to 24 hours post-dose
tmax
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
MRT
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
CL/F
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
CLu/F
Time frame: From 2 hours post-dose up to 24 hours post-dose
Vz/F
Time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
AE,ur
Time frame: Pre-dose and up to 72 hours post-dose
CLR
Time frame: Pre-dose and up to 72 hours post-dose
Number of participants with adverse events
Time frame: Approximately 5 weeks
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 29 Apr 2020.
- Individual participant dataSharing planned: Undecided. Availability of this study's data will be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access. As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014. Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.
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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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Riociguat (Adempas, BAY 63-2521) in people with Clinical Pharmacology, run by Bayer at 1 site 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 5 inclusion and 27 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 29 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
AUC (time frame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 29 Apr 2020.