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

NCT04366622 | Completed Phase 1

• 2 other identifiers: 150012009-017684-42
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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

Conditions

Clinical Pharmacology

Outcome Measures

Primary Outcomes (6)

• AUC

  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

  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

  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

  Fraction unbound for BAY 63-2521 and its metabolite M1

  From 2 hours post-dose up to 24 hours post-dose

• AUCu

  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

  Cmax for unbound drug for BAY 63-2521 and its metabolite M1

  From 2 hours post-dose up to 24 hours post-dose

Secondary Outcomes (15)

• AUC/D

  Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only

• AUCnorm

  Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only

• AUCu,norm

  From 2 hours post-dose up to 24 hours post-dose

• 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

• Cmax/D

  Pre-dose and up to 72 hours post-dose, additionally up to 96 hours post-dose for Child Pugh B group only

Study Arms (4)

Riociguat, Child Pugh A

EXPERIMENTAL

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)

Riociguat, Child Pugh B

EXPERIMENTAL

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)

Riociguat, control A

EXPERIMENTAL

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)

Riociguat, control B

EXPERIMENTAL

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)

Interventions

Riociguat (Adempas, BAY 63-2521) DRUG

0.5 mg riociguat as an immediate-release (IR) tablet

Riociguat, Child Pugh A; Riociguat, Child Pugh B; Riociguat, control A; Riociguat, control B

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Documented liver cirrhosis confirmed by histopathology, eg previous liver biopsy, laparoscopy, or ultrasound Hepatic impairment (Child Pugh A or B)
• Stable liver disease
• \- Age- (+/-10 years), weight- (+/-10 kg body weight), and gender-matched to a subject with liver cirrhosis as far as possible

You may not qualify if:

• Febrile illness within 1 week before the start of the study
• Hypersensitivity to riociguat and / or to inactive constituents
• Smoking
• 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%

Sponsors & Collaborators

• Bayer: lead

Study Sites (1)

Unknown Facility

Kiel, Schleswig-Holstein, 24105, Germany

Location

Related Links

• Click here to find results for studies related to Bayer products

MeSH Terms

Interventions

riociguat

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2020
• First Posted: April 29, 2020
• Study Start: April 14, 2010
• Primary Completion: April 28, 2011
• Study Completion: September 15, 2011
• Last Updated: April 29, 2020

Record last verified: 2020-04

Locations

DE (1)