Back to resultsStudy 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 Renal Impairment and Healthy Participants Matched for Age-, Gender-, and Weight
Primary Purpose
Clinical Pharmacology
Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Riociguat (Adempas, BAY 63-2521)
Sponsored by
About this trial
This is an interventional basic science trial for Clinical Pharmacology
Eligibility Criteria
Inclusion criteria for all subjects:
- Male and female white subjects with 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
Inclusion criteria for subjects with renal failure:
- Stable renal disease, ie. a serum creatinine value determined at least 3 - 6 months before the pre-study visit was not allowed to vary by more than 20% from the serum creatinine value determined at the pre-study visit
Inclusion criteria for healthy subjects:
- Mean age and body weight not allowed to vary by more than +/- 10 years and +/- 10 kg from the subjects with renal impairment, respectively
Exclusion criteria for all subjects:
- Febrile illness within 1 week before the start of the study
- Hypersensitivity to riociguat and / or to inactive constituents
- Smoking
Exclusion criteria for subjects with renal failure:
- Resting heart rate in the awake subject below 45 BPM or above 90 BPM
- Acute renal failure or nephritis
- Any organ transplant
- Diastolic blood pressure (DBP) >100 mmHg and / or systolic blood pressure (SBP) >180 mmHg
- Hemoglobin <8 g/dL, Proteinuria >8 g/24 hours, Serum albumin <30 g/L, Platelet count <100 x 109/L
- History of bleeding within the past 3 months
- Diabetes mellitus with a fasting blood glucose >220 mg/dL or HbA1c >10%
- 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 inhibitors
Exclusion criteria for healthy subjects:
- Conspicuous findings in medical history or pre-study examination
- History of relevant diseases of vital organs, central nervous system, or other organs
- SBP below 100 mmHg or above 145 mmHg and / or 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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
Riociguat, healthy participants
Riociguat, mild renal impairment
Riociguat, moderate renal impairment
Riociguat, severe renal impairment
Arm Description
Participants with creatinine clearance (CLCR) >80 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state
Participants with CLCR 50-80 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state
Participants with CLCR 30-<50 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state
Participants with CLCR <30 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state
Outcomes
Primary Outcome Measures
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)
Cmax
Maximum total (bound and unbound) drug concentration in plasma after single dose administration for BAY 63-2521 and its metabolite M1
t½
Half-life associated with the terminal slope for BAY 63-2521 and its metabolite M1
fu
Fraction unbound for BAY 63-2521 and its metabolite M1
AUCu
AUC for unbound drug for BAY 63-2521 and its metabolite M1
Cmax,u
Cmax for unbound drug for BAY 63-2521 and its metabolite M1
Secondary Outcome Measures
AUC/D
AUC divided by dose for BAY 63-2521 and its metabolite M1
AUCnorm
AUC divided by dose per kg body weight for BAY 63-2521 and its metabolite M1
AUCu,norm
AUCnorm for unbound drug for BAY 63-2521 and its metabolite M1
AUC(0-tlast)
AUC from time 0 to the last data point for BAY 63-2521 and its metabolite M1
Cmax/D
Cmax divided by dose for BAY 63-2521 and its metabolite M1
Cmax,norm
Cmax divided by dose per kg body weight for BAY 63-2521 and its metabolite M1
Cmax,u,norm
Cmax,norm for unbound drug for BAY 63-2521 and its metabolite M1
tmax
Time to reach Cmax (in case of two identical Cmax values, the first tmax was used) for BAY 63-2521 and its metabolite M1
MRT
Mean residence time for BAY 63-2521 and its metabolite M1
CL/F
Total body clearance of drug calculated after extravascular administration (eg apparent oral clearance) for BAY 63-2521 and its metabolite M1
CLu/F
CL/F for unbound drug for BAY 63-2521 and its metabolite M1
Vz/F
Apparent volume of distribution during terminal phase after extravascular administration for BAY 63-2521 and its metabolite M1
AE,ur
Amount of (total) drug excreted in urine for BAY 63-2521 and its metabolite M1
CLR
Renal body clearance of drug for BAY 63-2521 and its metabolite M1
Number of participants with adverse events
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04364464
Brief Title
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 Renal Impairment and Healthy Participants Matched for Age-, Gender-, and Weight
Official Title
Investigation of Pharmacokinetics, Safety, and Tolerability of BAY 63-2521 in Male and Female Subjects With Renal Impairment and in Age- and Weight- 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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2020
Overall Recruitment Status
Completed
Study Start Date
February 19, 2010 (Actual)
Primary Completion Date
March 17, 2011 (Actual)
Study Completion Date
September 20, 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Bayer
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clinical Pharmacology
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Riociguat, healthy participants
Arm Type
Experimental
Arm Description
Participants with creatinine clearance (CLCR) >80 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state
Arm Title
Riociguat, mild renal impairment
Arm Type
Experimental
Arm Description
Participants with CLCR 50-80 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state
Arm Title
Riociguat, moderate renal impairment
Arm Type
Experimental
Arm Description
Participants with CLCR 30-<50 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state
Arm Title
Riociguat, severe renal impairment
Arm Type
Experimental
Arm Description
Participants with CLCR <30 mL/min received a single dose of 1 mg (2 x 0.5 mg IR tablet) of riociguat in the fasted state
Intervention Type
Drug
Intervention Name(s)
Riociguat (Adempas, BAY 63-2521)
Intervention Description
0.5 mg riociguat as an immediate-release (IR) tablet
Primary Outcome Measure Information:
Title
AUC
Description
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)
Time Frame
Pre-dose up to 72 hours post-dose
Title
Cmax
Description
Maximum total (bound and unbound) drug concentration in plasma after single dose administration for BAY 63-2521 and its metabolite M1
Time Frame
Pre-dose up to 72 hours post-dose
Title
t½
Description
Half-life associated with the terminal slope for BAY 63-2521 and its metabolite M1
Time Frame
Pre-dose up to 72 hours post-dose
Title
fu
Description
Fraction unbound for BAY 63-2521 and its metabolite M1
Time Frame
From 2 hours post-dose up to 24 hours post-dose
Title
AUCu
Description
AUC for unbound drug for BAY 63-2521 and its metabolite M1
Time Frame
From 2 hours post-dose up to 24 hours post-dose
Title
Cmax,u
Description
Cmax for unbound drug for BAY 63-2521 and its metabolite M1
Time Frame
From 2 hours post-dose up to 24 hours post-dose
Secondary Outcome Measure Information:
Title
AUC/D
Description
AUC divided by dose for BAY 63-2521 and its metabolite M1
Time Frame
Pre-dose up to 72 hours post-dose
Title
AUCnorm
Description
AUC divided by dose per kg body weight for BAY 63-2521 and its metabolite M1
Time Frame
Pre-dose up to 72 hours post-dose
Title
AUCu,norm
Description
AUCnorm for unbound drug for BAY 63-2521 and its metabolite M1
Time Frame
From 2 hours post-dose up to 24 hours post-dose
Title
AUC(0-tlast)
Description
AUC from time 0 to the last data point for BAY 63-2521 and its metabolite M1
Time Frame
Pre-dose up to 72 hours post-dose
Title
Cmax/D
Description
Cmax divided by dose for BAY 63-2521 and its metabolite M1
Time Frame
Pre-dose up to 72 hours post-dose
Title
Cmax,norm
Description
Cmax divided by dose per kg body weight for BAY 63-2521 and its metabolite M1
Time Frame
Pre-dose up to 72 hours post-dose
Title
Cmax,u,norm
Description
Cmax,norm for unbound drug for BAY 63-2521 and its metabolite M1
Time Frame
From 2 hours post-dose up to 24 hours post-dose
Title
tmax
Description
Time to reach Cmax (in case of two identical Cmax values, the first tmax was used) for BAY 63-2521 and its metabolite M1
Time Frame
Pre-dose up to 72 hours post-dose
Title
MRT
Description
Mean residence time for BAY 63-2521 and its metabolite M1
Time Frame
Pre-dose up to 72 hours post-dose
Title
CL/F
Description
Total body clearance of drug calculated after extravascular administration (eg apparent oral clearance) for BAY 63-2521 and its metabolite M1
Time Frame
Pre-dose up to 72 hours post-dose
Title
CLu/F
Description
CL/F for unbound drug for BAY 63-2521 and its metabolite M1
Time Frame
From 2 hours post-dose up to 24 hours post-dose
Title
Vz/F
Description
Apparent volume of distribution during terminal phase after extravascular administration for BAY 63-2521 and its metabolite M1
Time Frame
Pre-dose up to 72 hours post-dose
Title
AE,ur
Description
Amount of (total) drug excreted in urine for BAY 63-2521 and its metabolite M1
Time Frame
From 24 hours prior to drug administration up to 72 hours post-dose
Title
CLR
Description
Renal body clearance of drug for BAY 63-2521 and its metabolite M1
Time Frame
From 24 hours prior to drug administration up to 72 hours post-dose
Title
Number of participants with adverse events
Time Frame
Approximately 5 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion criteria for all subjects:
Male and female white subjects with 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
Inclusion criteria for subjects with renal failure:
- Stable renal disease, ie. a serum creatinine value determined at least 3 - 6 months before the pre-study visit was not allowed to vary by more than 20% from the serum creatinine value determined at the pre-study visit
Inclusion criteria for healthy subjects:
- Mean age and body weight not allowed to vary by more than +/- 10 years and +/- 10 kg from the subjects with renal impairment, respectively
Exclusion criteria for all subjects:
Febrile illness within 1 week before the start of the study
Hypersensitivity to riociguat and / or to inactive constituents
Smoking
Exclusion criteria for subjects with renal failure:
Resting heart rate in the awake subject below 45 BPM or above 90 BPM
Acute renal failure or nephritis
Any organ transplant
Diastolic blood pressure (DBP) >100 mmHg and / or systolic blood pressure (SBP) >180 mmHg
Hemoglobin <8 g/dL, Proteinuria >8 g/24 hours, Serum albumin <30 g/L, Platelet count <100 x 109/L
History of bleeding within the past 3 months
Diabetes mellitus with a fasting blood glucose >220 mg/dL or HbA1c >10%
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 inhibitors
Exclusion criteria for healthy subjects:
Conspicuous findings in medical history or pre-study examination
History of relevant diseases of vital organs, central nervous system, or other organs
SBP below 100 mmHg or above 145 mmHg and / or 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bayer Study Director
Organizational Affiliation
Bayer
Official's Role
Study Director
Facility Information:
City
Kiel
State/Province
Schleswig-Holstein
ZIP/Postal Code
24105
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
Undecided
IPD Sharing Plan Description
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.
Links:
URL
http://clinicaltrials.bayer.com/
Description
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Learn more about this trial
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 Renal Impairment and Healthy Participants Matched for Age-, Gender-, and Weight
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