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

Phase 1

Completed

• Conditions: Pharmacokinetics; Renal Insufficiency; Hepatic Insufficiency
• Interventions: Drug: BAY1841788

• Registration Number: NCT02894385
• Lead Sponsor: Bayer

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.

Study Timeline

• Study First Submitted: 2016-08-29
• Study First Submitted QC: 2016-09-05
• Study First Posted: 2016-09-09
• Study Start: 2016-09-13
• Primary Completion: 2017-04-10
• Study Completion: 2017-12-15
• Status Verified: 2019-01
• Last Update Submitted: 2019-01-04
• Last Update Posted: 2019-01-07

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Male
• Target Recruitment: 29

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 1 - Healthy subjects	BAY1841788	Healthy subjects received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets).
Part 1 - Subjects with moderate hepatic impairment	BAY1841788	Subjects with moderate hepatic impairment received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets).
Part 1 - Subjects with severe renal impairment	BAY1841788	Subjects with severe renal impairment received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets).

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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,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,S)-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
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