Effect of Hepatic and Renal Impairment on the Pharmacokinetics, Safety and Tolerability of BAY1841788 (ODM-201)

Study Overview
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Brief Summary
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Evaluate the potential effect of hepatic or renal impairment on the pharmacokinetics, safety and tolerability of BAY 1841788 (ODM-201).

Detailed Description
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The study was closed after Part 1 because additional investigation in volunteers with moderate renal impairment in Part 2 was not deemed to be ethically or scientifically justified.

Official Title
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A Phase I, Non-randomized, Open-label, Single-dose Study to Investigate the Pharmacokinetics, Safety and Tolerability of BAY 1841788 (ODM-201) in Male Subjects With Hepatic Impairment, Renal Impairment and Normal Hepatic and Renal Function

Conditions
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Pharmacokinetics, Hepatic Insufficiency, Renal Insufficiency

Intervention / Treatment
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* Drug: BAY1841788


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All subjects -- Male and white subjects between 45 and 79 years of age with a body mass index between 18 to 34 kg/m*2 (both inclusive). Patients with moderate hepatic impairment (Part 1) -- Patients with documented liver cirrhosis confirmed by histopathology, e.g., previous liver biopsy, laparoscopy, ultrasound, or fibroscan and with moderate hepatic impairment (defined as Child Pugh class B). Patients with severe renal impairment (Part 1) -- Patients with severe renal impairment with an estimated glomerular filtration rate 15-29 mL/min/1.73 m*2, who are not on dialysis and are not expected to start dialysis in the next 3 months (Stage 4). Healthy subjects -- Healthy as determined by the investigator or medically qualified designee based on a medical evaluation including medical history, physical examination, laboratory tests and cardiac monitoring and with estimated glomerular filtration rate >90 mL/min (according to Modified Diet of Renal Disease equation). Patients with moderate renal impairment (Part 2) -- Patients with moderate renal impairment with an estimated glomerular filtration rate 30-59 mL/min/1.73 m*2 (Stage 3). Patients with mild renal impairment (Part 2) -- Patients with mild renal impairment with an estimated glomerular filtration rate (eGFR) 60-79 mL/min/1.73 m*2 (Stage 2). Patients with mild hepatic impairment (Part 2) Patients with documented liver cirrhosis confirmed by histopathology, e.g., previous liver biopsy, laparoscopy, ultrasound, or fibroscan. Patients with mild hepatic impairment (defined as Child Pugh class A). Exclusion Criteria: Severe cerebrovascular or cardiac disorders, e.g., myocardial infarction less than 6 months prior to dosing, congestive heart failure of New York Heart Association (NYHA) grade III or IV. Subjects with percutaneous transluminal coronary angioplasty or coronary artery bypass graft less than 6 months prior to study drug administration. Strong cytochrome P450 (CYP) 3A4 inhibitors or strong CYP3A4 inducers within 28 days or 5 drug half-lives (if drug half-life in patients is known), before start of study treatment. Known BCRP (breast cancer resistant protein) and OATP (organic anion-transporting polypeptide) substrates not specifically mentioned in the protocol within 28 days or 5 drug half-lives (if drug half-life in patients is known), before start of study treatment. Smoking more than 20 cigarettes daily.

Ages Eligible for Study
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Minimum Age: 45 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1 - Subjects with severe renal impairment<br>Subjects with severe renal impairment received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets). | Drug: BAY1841788<br>* 600 mg single dose, administered as 2 x 300 mg tablets on Day 00.<br>|
| Experimental: Part 1 - Subjects with moderate hepatic impairment<br>Subjects with moderate hepatic impairment received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets). | Drug: BAY1841788<br>* 600 mg single dose, administered as 2 x 300 mg tablets on Day 00.<br>|
| Experimental: Part 1 - Healthy subjects<br>Healthy subjects received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets). | Drug: BAY1841788<br>* 600 mg single dose, administered as 2 x 300 mg tablets on Day 00.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of darolutamide from time zero to 48 hours (AUC(0-48)) in plasma |  | Pre-dose up to 48 h post dose | 
| Maximum drug concentration (Cmax) of darolutamide in plasma |  | Pre-dose up to 48 h post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve of darolutamide's diastereomer ((S,R)-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma |  | Pre-dose up to 48 h post dose | 
| Maximum drug concentration (Cmax) of darolutamide's diastereomer ((S,R)-darolutamide) in plasma |  | Pre-dose up to 48 h post dose | 
| Area under the concentration-time curve of darolutamide's diastereomer ((S,S)-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma |  | Pre-dose up to 48 h post dose | 
| Maximum drug concentration (Cmax) of darolutamide's diastereomer ((S,S)-darolutamide) in plasma |  | Pre-dose up to 48 h post dose | 
| Area under the concentration-time curve of darolutamide's major metabolite (keto-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma |  | Pre-dose up to 48 h post dose | 
| Maximum drug concentration (Cmax) of darolutamide's major metabolite (keto-darolutamide) in plasma |  | Pre-dose up to 48 h post dose | 
| Number of subjects with study drug-related treatment-emergent adverse events (TEAEs) |  | From first application of study medication up to 30 days after end of treatment with study medication. |