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

Primary Purpose

Pharmacokinetics, Hepatic Insufficiency, Renal Insufficiency

Status

Completed

Phase

Phase 1

Locations

Germany

Study Type

Interventional

Intervention

BAY1841788

About this trial

This is an interventional other trial for Pharmacokinetics

Eligibility Criteria

45 Years - 79 Years (Adult, Older Adult)MaleAccepts Healthy Volunteers

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.

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Arm Label

Part 1 - Subjects with severe renal impairment

Part 1 - Subjects with moderate hepatic impairment

Part 1 - Healthy subjects

Arm Description

Subjects with severe renal impairment received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets).

Subjects with moderate hepatic impairment received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets).

Healthy subjects received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets).

Outcomes

Primary Outcome Measures

Area under the concentration-time curve of darolutamide from time zero to 48 hours (AUC(0-48)) in plasma

Maximum drug concentration (Cmax) of darolutamide in plasma

Secondary Outcome Measures

Area under the concentration-time curve of darolutamide's diastereomer ((S,R)-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma

Maximum drug concentration (Cmax) of darolutamide's diastereomer ((S,R)-darolutamide) in plasma

Area under the concentration-time curve of darolutamide's diastereomer ((S,S)-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma

Maximum drug concentration (Cmax) of darolutamide's diastereomer ((S,S)-darolutamide) in plasma

Area under the concentration-time curve of darolutamide's major metabolite (keto-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma

Maximum drug concentration (Cmax) of darolutamide's major metabolite (keto-darolutamide) in plasma

Number of subjects with study drug-related treatment-emergent adverse events (TEAEs)

Full Information

NCT ID

NCT02894385

First Posted

August 29, 2016

Last Updated

January 4, 2019

Sponsor

Bayer

Collaborators

Orion Corporation, Orion Pharma

1. Study Identification

Unique Protocol Identification Number

NCT02894385

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

January 2019

Overall Recruitment Status

Completed

Study Start Date

September 13, 2016 (Actual)

Primary Completion Date

April 10, 2017 (Actual)

Study Completion Date

December 15, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Bayer

Collaborators

Orion Corporation, Orion Pharma

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Pharmacokinetics, Hepatic Insufficiency, Renal Insufficiency

7. Study Design

Primary Purpose

Other

Study Phase

Phase 1

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

29 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Part 1 - Subjects with severe renal impairment

Arm Type

Experimental

Arm Description

Subjects with severe renal impairment received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets).

Arm Title

Part 1 - Subjects with moderate hepatic impairment

Arm Type

Experimental

Arm Description

Subjects with moderate hepatic impairment received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets).

Arm Title

Part 1 - Healthy subjects

Arm Type

Experimental

Arm Description

Healthy subjects received a single oral dose of darolutamide 600 mg (2 x 300 mg tablets).

Intervention Type

Drug

Intervention Name(s)

BAY1841788

Intervention Description

600 mg single dose, administered as 2 x 300 mg tablets on Day 00.

Primary Outcome Measure Information:

Title

Area under the concentration-time curve of darolutamide from time zero to 48 hours (AUC(0-48)) in plasma

Time Frame

Pre-dose up to 48 h post dose

Title

Maximum drug concentration (Cmax) of darolutamide in plasma

Time Frame

Pre-dose up to 48 h post dose

Secondary Outcome Measure Information:

Title

Area under the concentration-time curve of darolutamide's diastereomer ((S,R)-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma

Time Frame

Pre-dose up to 48 h post dose

Title

Maximum drug concentration (Cmax) of darolutamide's diastereomer ((S,R)-darolutamide) in plasma

Time Frame

Pre-dose up to 48 h post dose

Title

Area under the concentration-time curve of darolutamide's diastereomer ((S,S)-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma

Time Frame

Pre-dose up to 48 h post dose

Title

Maximum drug concentration (Cmax) of darolutamide's diastereomer ((S,S)-darolutamide) in plasma

Time Frame

Pre-dose up to 48 h post dose

Title

Area under the concentration-time curve of darolutamide's major metabolite (keto-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma

Time Frame

Pre-dose up to 48 h post dose

Title

Maximum drug concentration (Cmax) of darolutamide's major metabolite (keto-darolutamide) in plasma

Time Frame

Pre-dose up to 48 h post dose

Title

Number of subjects with study drug-related treatment-emergent adverse events (TEAEs)

Time Frame

From first application of study medication up to 30 days after end of treatment with study medication.

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

45 Years

Maximum Age & Unit of Time

79 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bayer Study Director

Organizational Affiliation

Bayer

Official's Role

Study Director

Facility Information:

City

Kiel

State/Province

Schleswig-Holstein

ZIP/Postal Code

24105

Country

Germany

City

Lübeck

ZIP/Postal Code

23538

Country

Germany

12. IPD Sharing Statement

Citations:

PubMed Identifier

34866168

Citation

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.

Results Reference

derived

Links:

URL

http://www.clinicaltrialsregister.eu/

Description

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

URL

https://clinicaltrials.bayer.com/

Description

Click here to find results for studies related to Bayer products.

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

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