Clinical trial NCT04366622: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Clinical Pharmacology
Lead sponsor: Bayer
Sponsor class: INDUSTRY
First posted: 2020-04-29
Enrollment: 32
Sex: ALL
Minimum age (years): 18
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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


Eligibility 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

Primary outcomes:
measure: AUC
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: Cmax
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: t½
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: fu
timeFrame: From 2 hours post-dose up to 24 hours post-dose
measure: AUCu
timeFrame: From 2 hours post-dose up to 24 hours post-dose
measure: Cmax,u
timeFrame: From 2 hours post-dose up to 24 hours post-dose
Secondary outcomes:
measure: AUC/D
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: AUCnorm
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: AUCu,norm
timeFrame: From 2 hours post-dose up to 24 hours post-dose
measure: AUC(0-tlast)
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: Cmax/D
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: Cmax,norm
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: Cmax,u,norm
timeFrame: From 2 hours post-dose up to 24 hours post-dose
measure: tmax
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: MRT
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: CL/F
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: CLu/F
timeFrame: From 2 hours post-dose up to 24 hours post-dose
measure: Vz/F
timeFrame: Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only
measure: AE,ur
timeFrame: Pre-dose and up to 72 hours post-dose
measure: CLR
timeFrame: Pre-dose and up to 72 hours post-dose
measure: Number of participants with adverse events
timeFrame: Approximately 5 weeks
Other outcomes:
Locations:
city: Kiel
country: Germany
state: Schleswig-Holstein
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References: