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

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

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

Study Overview

• Status: Completed
• Conditions: Hepatic Insufficiency; Renal Insufficiency; Pharmacokinetics
• Intervention / Treatment: Drug: BAY1841788

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 Type: Interventional
• Enrollment (Actual): 29
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Lübeck, Germany, 23538
  • Schleswig-Holstein
    • Kiel, Schleswig-Holstein, Germany, 24105

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 79 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	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.

Collaborators and Investigators

• Sponsor: Bayer
• Collaborators: Orion Corporation, Orion Pharma

Publications and helpful links

General Publications

• Zurth C, Nykanen P, Wilkinson G, Taavitsainen P, Vuorela A, Huang F, Reschke S, Koskinen M. Clinical Pharmacokinetics of the Androgen Receptor Inhibitor Darolutamide in Healthy Subjects and Patients with Hepatic or Renal Impairment. Clin Pharmacokinet. 2022 Apr;61(4):565-575. doi: 10.1007/s40262-021-01078-y. Epub 2021 Dec 6.

Helpful Links

• Click here to find results for studies related to Bayer products.
• Click here to find information about studies related to Bayer Healthcare products conducted in Europe.

Study record dates

Study Major Dates

• Study Start (Actual): September 13, 2016
• Primary Completion (Actual): April 10, 2017
• Study Completion (Actual): December 15, 2017

Study Registration Dates

• First Submitted: August 29, 2016
• First Submitted That Met QC Criteria: September 5, 2016
• First Posted (Estimate): September 9, 2016

Study Record Updates

• Last Update Posted (Actual): January 7, 2019
• Last Update Submitted That Met QC Criteria: January 4, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Kidney Diseases; Urologic Diseases; Liver Diseases; Liver Failure; Hepatic Insufficiency; Renal Insufficiency
• Other Study ID Numbers: 17721; 2016-001069-10 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No