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

April 25, 2020 updated by: Bayer

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

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
32

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

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
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 79 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion criteria for all subjects:

  • 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

Inclusion criteria for subjects with liver cirrhosis:

  • Documented liver cirrhosis confirmed by histopathology, eg previous liver biopsy, laparoscopy, or ultrasound Hepatic impairment (Child Pugh A or B)
  • Stable liver disease

Inclusion criteria for healthy subjects:

- Age- (+/-10 years), weight- (+/-10 kg body weight), and gender-matched to a subject with liver cirrhosis as far as possible

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 liver cirrhosis:

  • 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
  • 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

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
  • 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

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: BASIC_SCIENCE
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: Riociguat, Child Pugh A
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
Drug: Riociguat (Adempas, BAY 63-2521)
0.5 mg riociguat as an immediate-release (IR) tablet
EXPERIMENTAL: Riociguat, Child Pugh B
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
Drug: Riociguat (Adempas, BAY 63-2521)
0.5 mg riociguat as an immediate-release (IR) tablet
EXPERIMENTAL: Riociguat, control A
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
Drug: Riociguat (Adempas, BAY 63-2521)
0.5 mg riociguat as an immediate-release (IR) tablet
EXPERIMENTAL: Riociguat, control B
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
Drug: Riociguat (Adempas, BAY 63-2521)
0.5 mg riociguat as an immediate-release (IR) tablet

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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)
Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
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
Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
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
Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
fu
Time Frame: From 2 hours post-dose up to 24 hours post-dose
Fraction unbound for BAY 63-2521 and its metabolite M1
From 2 hours post-dose up to 24 hours post-dose
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
From 2 hours post-dose up to 24 hours post-dose
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
From 2 hours post-dose up to 24 hours post-dose

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Number of participants with adverse events
Time Frame: Approximately 5 weeks
Approximately 5 weeks
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
AUC divided by dose (mg) for BAY 63-2521 and its metabolite M1
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
AUC divided by dose (mg) per kg body weight for BAY 63-2521 and its metabolite M1
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
AUCnorm for unbound drug for BAY 63-2521 and its metabolite M1
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
AUC from time 0 to the last data point for BAY 63-2521 and its metabolite M1
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 divided by dose (mg) for BAY 63-2521 and its metabolite M1
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 divided by dose (mg) per kg body weight for BAY 63-2521 and its metabolite M1
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
Cmax,norm for unbound drug for BAY 63-2521 and its metabolite M1
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
Time to reach maximum drug concentration in plasma after single dose for BAY 63-2521 and its metabolite M1
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
Mean residence time for BAY 63-2521 and its metabolite M1
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
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
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
CL/F for unbound drug for BAY 63-2521 and its metabolite M1
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
Apparent volume of distribution during terminal phase after oral administration for BAY 63-2521 and its metabolite M1
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
Amount of (total) drug excreted in urine for BAY 63-2521 and its metabolite M1
Pre-dose and up to 72 hours post-dose
CLR
Time Frame: Pre-dose and up to 72 hours post-dose
Renal body clearance of drug for BAY 63-2521 and its metabolite M1
Pre-dose and up to 72 hours post-dose

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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.

Helpful Links

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 14, 2010

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 28, 2011

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 15, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 23, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2020

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 29, 2020

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 29, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 25, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 15001
  • 2009-017684-42 (EUDRACT_NUMBER)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD 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.

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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