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

Bayer

Status and phase: Completed; Phase 1

Conditions: Hepatic Insufficiency; Renal Insufficiency; Pharmacokinetics

Treatments: Drug: BAY1841788

Study type: Interventional

Funder types: Industry

Identifiers

NCT02894385

17721

2016-001069-10 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 29 patients

Sex: Male

Ages: 45 to 79 years old

Volunteers: Accepts 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.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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29 participants in 3 patient groups

Part 1 - Subjects with severe renal impairment

Experimental group

Description:

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

Treatment:

Drug: BAY1841788

Part 1 - Subjects with moderate hepatic impairment

Experimental group

Description:

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

Treatment:

Drug: BAY1841788

Part 1 - Healthy subjects

Experimental group

Description:

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

Treatment:

Drug: BAY1841788