Clinical trial NCT02894385: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Pharmacokinetics
Hepatic Insufficiency
Renal Insufficiency
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Orion Corporation, Orion Pharma
First posted: 2016-09-09
Enrollment: 29
Sex: MALE
Minimum age (years): 45
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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.

Primary outcomes:
measure: Area under the concentration-time curve of darolutamide from time zero to 48 hours (AUC(0-48)) in plasma
timeFrame: Pre-dose up to 48 h post dose
measure: Maximum drug concentration (Cmax) of darolutamide in plasma
timeFrame: Pre-dose up to 48 h post dose
Secondary outcomes:
measure: Area under the concentration-time curve of darolutamide's diastereomer ((S,R)-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma
timeFrame: Pre-dose up to 48 h post dose
measure: Maximum drug concentration (Cmax) of darolutamide's diastereomer ((S,R)-darolutamide) in plasma
timeFrame: Pre-dose up to 48 h post dose
measure: Area under the concentration-time curve of darolutamide's diastereomer ((S,S)-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma
timeFrame: Pre-dose up to 48 h post dose
measure: Maximum drug concentration (Cmax) of darolutamide's diastereomer ((S,S)-darolutamide) in plasma
timeFrame: Pre-dose up to 48 h post dose
measure: Area under the concentration-time curve of darolutamide's major metabolite (keto-darolutamide) from time zero to 48 hours (AUC(0-48)) in plasma
timeFrame: Pre-dose up to 48 h post dose
measure: Maximum drug concentration (Cmax) of darolutamide's major metabolite (keto-darolutamide) in plasma
timeFrame: Pre-dose up to 48 h post dose
measure: Number of subjects with study drug-related treatment-emergent adverse events (TEAEs)
timeFrame: From first application of study medication up to 30 days after end of treatment with study medication.
Other outcomes:
Locations:
city: Kiel
country: Germany
state: Schleswig-Holstein
city: Lübeck
country: Germany
Study officials:
affiliation: Bayer
name: Bayer Study Director
role: STUDY_DIRECTOR
References:
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.