Hepatic Insufficiency, Pharmacokinetics, Renal Insufficiency
Conditions
Brief summary
Evaluate the potential effect of hepatic or renal impairment on the pharmacokinetics, safety and tolerability of BAY 1841788 (ODM-201).
Detailed description
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.
Interventions
DRUGBAY1841788
600 mg single dose, administered as 2 x 300 mg tablets on Day 00.
Sponsors
Orion Corporation, Orion Pharma
Bayer
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
45 Years to 79 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| 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 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 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. |
| 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 diastereomer ((S,R)-darolutamide) in plasma | Pre-dose up to 48 h post dose |
Countries
Germany
Outcome results
None listed