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

• Sponsor: Bayer (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02894385
• Collaborator: Orion Corporation, Orion Pharma (Industry)
• Enrollment: 29
• Locations: 2
• Arms: 3
• Actual Duration (Months): 15
• Patients Per Site: 14.5
• Patients Per Site Per Month: 1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics; Hepatic Insufficiency; Renal Insufficiency	Drug: BAY1841788	Phase 1

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 Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• 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
• Actual Study Start Date: Sep 13, 2016
• Actual Primary Completion Date: Apr 10, 2017
• Actual Study Completion Date: Dec 15, 2017

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

1. 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]

2. Maximum drug concentration (Cmax) of darolutamide in plasma [Pre-dose up to 48 h post dose]

Secondary Outcome Measures

1. 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]

2. Maximum drug concentration (Cmax) of darolutamide's diastereomer ((S,R)-darolutamide) in plasma [Pre-dose up to 48 h post dose]

3. 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]

4. Maximum drug concentration (Cmax) of darolutamide's diastereomer ((S,S)-darolutamide) in plasma [Pre-dose up to 48 h post dose]

5. 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]

6. Maximum drug concentration (Cmax) of darolutamide's major metabolite (keto-darolutamide) in plasma [Pre-dose up to 48 h post dose]

7. 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.]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 45 Years to 79 Years
• Sexes Eligible for Study: Male
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Kiel	Schleswig-Holstein	Germany	24105
2		Lübeck		Germany	23538

Sponsors and Collaborators

• Bayer
• Orion Corporation, Orion Pharma

Investigators

• Study Director: Bayer Study Director, Bayer

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

None provided.

• Responsible Party: Bayer
• ClinicalTrials.gov Identifier: NCT02894385
• Other Study ID Numbers: 17721; 2016-001069-10
• First Posted: Sep 9, 2016
• Last Update Posted: Jan 7, 2019
• Last Verified: Jan 1, 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Hepatic Insufficiency; Liver Failure; Renal Insufficiency

Study Results

No Results Posted as of Jan 7, 2019