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

Bayer

Status and phase: Completed; Phase 1

Conditions: Clinical Pharmacology

Treatments: Drug: Riociguat (Adempas, BAY 63-2521)

Study type: Interventional

Funder types: Industry

Identifiers

NCT04366622

2009-017684-42 (EudraCT Number)

15001

Details and patient eligibility

About

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

Enrollment: 32 patients

Sex: All

Ages: 18 to 79 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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32 participants in 4 patient groups

Riociguat, Child Pugh A

Experimental group

Description:

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

Treatment:

Drug: Riociguat (Adempas, BAY 63-2521)

Riociguat, Child Pugh B

Experimental group

Description:

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

Treatment:

Drug: Riociguat (Adempas, BAY 63-2521)

Riociguat, control A

Experimental group

Description:

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

Treatment:

Drug: Riociguat (Adempas, BAY 63-2521)

Riociguat, control B

Experimental group

Description:

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

Treatment:

Drug: Riociguat (Adempas, BAY 63-2521)