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 Renal Impairment 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

NCT04364464

2009-017685-23 (EudraCT Number)

15000

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: 40 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 with 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 renal failure:

• Stable renal disease, ie. a serum creatinine value determined at least 3 - 6 months before the pre-study visit was not allowed to vary by more than 20% from the serum creatinine value determined at the pre-study visit

Inclusion criteria for healthy subjects:

• Mean age and body weight not allowed to vary by more than +/- 10 years and +/- 10 kg from the subjects with renal impairment, respectively

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 renal failure:

• Resting heart rate in the awake subject below 45 BPM or above 90 BPM
• Acute renal failure or nephritis
• Any organ transplant
• Diastolic blood pressure (DBP) >100 mmHg and / or systolic blood pressure (SBP) >180 mmHg
• Hemoglobin <8 g/dL, Proteinuria >8 g/24 hours, Serum albumin <30 g/L, Platelet count <100 x 109/L
• History of bleeding within the past 3 months
• Diabetes mellitus with a fasting blood glucose >220 mg/dL or HbA1c >10%
• 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 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
• SBP below 100 mmHg or above 145 mmHg and / or 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)

---

40 participants in 4 patient groups

Riociguat, healthy participants

Experimental group

Description:

Participants with creatinine clearance (CLCR) \>80 mL/min 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, mild renal impairment

Experimental group

Description:

Participants with CLCR 50-80 mL/min 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, moderate renal impairment

Experimental group

Description:

Participants with CLCR 30-\<50 mL/min 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, severe renal impairment

Experimental group

Description:

Participants with CLCR \<30 mL/min 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)

Sponsor of this trial

Lead Sponsor

Bayer