Clinical Pharmacology
Conditions
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
Interventions
0.5 mg riociguat as an immediate-release (IR) tablet
Sponsors
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC | 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) |
| Cmax | 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 |
| t½ | 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 |
| fu | From 2 hours post-dose up to 24 hours post-dose | Fraction unbound for BAY 63-2521 and its metabolite M1 |
| AUCu | From 2 hours post-dose up to 24 hours post-dose | AUC for unbound drug for BAY 63-2521 and its metabolite M1 |
| Cmax,u | From 2 hours post-dose up to 24 hours post-dose | Cmax for unbound drug for BAY 63-2521 and its metabolite M1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax,u,norm | From 2 hours post-dose up to 24 hours post-dose | Cmax,norm for unbound drug for BAY 63-2521 and its metabolite M1 |
| tmax | 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 |
| MRT | 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 |
| CL/F | 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 |
| Cmax/D | 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 |
| Vz/F | 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 |
| AE,ur | Pre-dose and up to 72 hours post-dose | Amount of (total) drug excreted in urine for BAY 63-2521 and its metabolite M1 |
| CLR | Pre-dose and up to 72 hours post-dose | Renal body clearance of drug for BAY 63-2521 and its metabolite M1 |
| Number of participants with adverse events | Approximately 5 weeks | — |
| CLu/F | From 2 hours post-dose up to 24 hours post-dose | CL/F for unbound drug for BAY 63-2521 and its metabolite M1 |
| AUC/D | 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 |
| AUCnorm | 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 |
| AUCu,norm | From 2 hours post-dose up to 24 hours post-dose | AUCnorm for unbound drug for BAY 63-2521 and its metabolite M1 |
| AUC(0-tlast) | 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 |
| Cmax,norm | 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 |
Countries
Germany
Outcome results
None listed