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A Trial to Learn How Safe Vericiguat (BAY1021189) is and the Way the Body Absorbs, Distributes and Gets Rid of Vericiguat in Participants With Liver Disease and in Age-, Weight- and Gender-matched Healthy Participants

Phase 1
Completed
Conditions
Heart Failure
Interventions
Registration Number
NCT04722562
Lead Sponsor
Bayer
Brief Summary

Vericiguat (BAY1021189) is under development to treat heart failure, a condition in in which the heart has trouble pumping blood through the body. Liver impairment which co-occurs in patients with heart failure is a common condition in which the liver is not removing the drugs from the blood as well as it should.

The goal of the study was to learn more about the safety of vericiguat (BAY1021189), how it was tolerated and the way the body absorbed, distributed and excreted the study dug given as a single oral dose of 2.5 mg tablet in participants with liver impairment and healthy participants matched for age-, gender-, and weight.

The participants stayed at the trial site for about 5 days. During this time, the doctors took blood and urine samples and checked the participants' health. About 7 after the participants took vericiguat (BAY1021189), the researchers checked the participants' health again and asked about any medical problems they had.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
27
Inclusion Criteria

For all subjects:

  • Aged between 18 and 79 years (inclusive) with body mass index 18 to 34 kg/m^2 (both inclusive)
  • Women without childbearing potential; women of childbearing potential only if the pregnancy test was negative and a combination of condoms with a safe and highly effective

For subjects with hepatic impairment:

  • Subjects with documented liver cirrhosis confirmed by histopathology, e.g., previous liver biopsy, laparoscopy, ultrasound, or fibroscan
  • Subjects with hepatic impairment (Child Pugh A or B)
  • Subjects with stable liver disease in the last 2 months

For healthy subjects:

  • Mean age and body weight in the control group and in the two groups with hepatic impairment (Child Pugh A and B) should not vary by more than ± 10 years and ± 10 kg
  • Gender matched
Exclusion Criteria

For all subjects:

  • Subjects with a medical disorder, condition, or history of such that would impair the subject's ability to participate or complete this study in the opinion of the investigator or the sponsor
  • Medical history of Kock pouch (ileostomy after proctocolectomy)
  • Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal
  • Known gastrointestinal (GI) disorders (eg stomach ulcers, duodenal ulcers, GI bleeding) or inflammatory bowel disease (eg Crohn's disease, ulcerative colitis)
  • Febrile illness within 1 week prior to admission to study center
  • Relevant diseases within the last 4 weeks prior to admission to study center
  • Known severe allergies, non-allergic drug reactions, or multiple drug allergies
  • Known hypersensitivity to the study drugs (active substances or excipients of the preparations)
  • Subjects with diagnosed malignancy within the past 5 years

For subjects with hepatic impairment:

  • Severe cerebrovascular or cardiac disorders, e.g., myocardial infarction less than 6 months prior to dosing, congestive heart failure of New York Heart Association grade III or IV, severe arrhythmia requiring anti-arrhythmic treatment
  • Evidence of hepatic encephalopathy related to chronic liver disease > grade 2 (exclusion by Number Connection Test (NCT))
  • Subjects with percutaneous transluminal coronary angioplasty or coronary artery bypass graft less than 6 months prior to study drug administration
  • History of bleeding within the past 3 months
  • Thrombotic disorder
  • Subjects with diabetes mellitus with a glycohemoglobin A1c (HbA1c) >10%
  • Severe ascites of more than 6 L (estimated by ultrasound)
  • Subjects with primary and secondary biliary cirrhosis
  • Subjects with sclerosing cholangitis
  • Failure of any other major organ system other than the liver
  • Severe infection, malignancy, or psychosis, or any clinically significant illness within 4 weeks prior to study drug administration

For healthy subjects:

  • Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination, and effects of the study drugs will not be normal
  • Subjects with conspicuous findings in medical history or pre-study examination
  • A history of relevant diseases of vital organs, the central nervous system, or other organs

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Child Pugh AVericiguat (BAY1021189)Participants with mild hepatic impairment
Child Pugh BVericiguat (BAY1021189)Participants with moderate hepatic impairment
Healthy participantsVericiguat (BAY1021189)Participants with normal hepatic function
Primary Outcome Measures
NameTimeMethod
AUC of vericiguatUp to 96 hours

Area under the concentration vs. time curve from zero to infinity after single dose administration

AUCu of vericiguatUp to 96 hours

AUC unbound

Cmax of vericiguatUp to 96 hours

Maximum observed drug concentration in measured matrix after single dose administration

Cmax,u of vericiguatUp to 96 hours

Cmax unbound

Secondary Outcome Measures
NameTimeMethod
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