Drug-drug Interaction (DDI) Study to Assess ODM-201 as a Victim of CYP3A4 Inhibition or Induction

A Phase I, Non-randomized, Open-label, Fixed-sequence Study to Investigate the Effect of a Probe CYP3A4 Inhibitor and Inducer on the Pharmacokinetics of BAY1841788 (ODM 201) in Healthy Male Volunteers

Evaluate the effect of a probe CYP3A4 inhibitor and inducer on the pharmacokinetics of BAY1841788 (ODM-201)

Study Overview

• Status: Completed
• Conditions: Biological Availability
• Intervention / Treatment: Drug: BAY1841788 (ODM-201); Drug: Itraconazole; Drug: Rifampicin

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • CRS Clinical Research Services Berlin GmbH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Healthy subject - as determined by the investigator or medically qualified designee based on medical evaluations including medical history, physical examination, laboratory tests and cardiac monitoring.
• Gender: Male.
• Age: 45 to 65 years (inclusive) at the screening visit.
• Race: White.
• Body mass index (BMI): ≥18.0 and ≤30 kg/m^2.
• Agree to use condoms as an effective contraception barrier method and refrain from sperm donation during the whole study (starting after informed consent) and for 3 months after the end of treatment with ODM-201. In addition, participants must agree to utilize a second reliable method of contraception simultaneously. The second method which has to be used by a female partner of childbearing potential can be one of the following methods: diaphragm or cervical cap with spermicide or intra-uterine device or hormone-based contraception.
• Results of alcohol tests are negative at screening and on Study Day -1.

Exclusion Criteria:

• Medical and surgical history
• Existing relevant diseases of vital organs (e.g. liver diseases, heart diseases), central nervous system (for example seizures) or other organs (e.g. diabetes mellitus).

Incompletely cured pre-existing diseases for which it can be assumed that the absorption, distribution, metabolism, elimination and effects of the study drugs will not be normal.

• Febrile illness within 1 week before the first study drug administration.
• A medical history of risk factors for Torsades de Pointes (e.g. family history of Long QT Syndrome) or other arrhythmias.
• Known severe allergies, non-allergic drug reactions, or (multiple) drug allergies (excluding untreated, asymptomatic seasonal allergies like non-severe hay fever during the time of study conduct).
• Known history of hypersensitivity (or known allergic reaction) to itraconazole, rifampicin or ODM-201.
• Relevant hepatic disorders like cholestasis, disturbances of bilirubin metabolism, any progressive liver disease.
• Relevant renal disorders like recurrent glomerulonephritis, renal injury, and renal insufficiency. However, a history of a single episode of uncomplicated nephrolithiasis will not prevent participation.
• Subjects with porphyria.
• Subjects with diagnosed malignancy within the past 5 years except for cured skin basal carcinoma.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ODM-201; All subjects will receive a single dose of BAY1841788 (ODM-201) (600 mg) in the first treatment period of the study, then all subjects will receive twice daily 200 mg itraconazole on 1 day and once daily 200 mg itraconazole for the following 6 days and a single dose of BAY1841788 (ODM-201) (600 mg) in the second treatment period, then all subjects will receive once a day 600 mg rifampicin for 10 days and a single dose of BAY1841788 (ODM-201) (600 mg) in the third treatment period

Drug: BAY1841788 (ODM-201); In Period 1, 600 mg single dose administered as 2x300 mg tablets on Study Day 1, In Period 2, 600 mg single dose administered as 2x300 mg tablets on Study Day 5, In Period 3, 600 mg single dose administered as 2x300 mg tablets at Study Day 8.; Drug: Itraconazole; 200 mg twice daily (BID) administered as 2 x 100 mg capsules per dose in treatment period 2 on Study Day 1, 200 mg once daily (QD) administered as 2 x 100 mg capsules per dose in treatment period 2 on Study Days 2 to 7.; Drug: Rifampicin; 600 mg QD administered as 1 x 600 mg tablet per dose in treatment period 3 on Study Days 1 to 10.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration Versus Time Curve From Time Zero to 72 Hours (AUC[0-72h]) of Darolutamide in Plasma After Single Dose Administration of Darolutamide	Area under the concentration versus time curve from time zero to 72 hours of Darolutamide after single dose administration in plasma were measured.	Pre dose to 72 hours post dose of darolutamide
Maximum Observed Concentration (Cmax) of Darolutamide in Plasma After Single Dose Administration of Darolutamide	Maximum observed concentration after single dose administration in plasma were measured.	Pre dose up to 72 hours post dose of darolutamide
Area Under the Concentration Versus Time Curve From Time Zero to 72 Hours (AUC[0-72h]) of (S,R)-Darolutamide in Plasma After Single Dose Administration of Darolutamide	Area under the concentration versus time curve from time zero to 72 hours of (S,R)-Darolutamide in plasma after single dose administration of Darolutamide were measured.	Pre dose up to 72 hours post dose of darolutamide
Maximum Observed Concentration (Cmax) of (S,R)-Darolutamide in Plasma After Single Dose Administration of Darolutamide	Maximum observed concentration of (S,R)-darolutamide in plasma after single dose administration of darolutamide were measured.	Pre dose up to 72 hours post dose of darolutamide
Area Under the Concentration Versus Time Curve From Time Zero to 72 Hours (AUC[0-72h]) of (S,S)-Darolutamide in Plasma After Single Dose Administration of Darolutamide	Area under the concentration versus time curve from time zero to 72 hours of (S,S)-darolutamide in plasma after single dose administration of darolutamide were measured.	Pre dose up to 72 hours post dose of darolutamide
Maximum Observed Concentration (Cmax) of (S,S)-Darolutamide in Plasma After Single Dose Administration of Darolutamide	Maximum observed concentration of (S,S)-darolutamide in plasma after single dose administration of darolutamide were measured.	Pre dose up to 72 hours post dose of darolutamide
Area Under the Concentration Versus Time Curve From Time Zero to 72 Hours (AUC[0-72h]) of Keto-Darolutamide in Plasma After Single Dose Administration of Darolutamide	Area under the concentration versus time curve from time zero to 72 hours (AUC[0-72h]) of keto-Darolutamide in plasma after single dose administration of darolutamide were measured.	Pre dose up to 72 hours post dose of darolutamide
Maximum Observed Concentration (Cmax) of Keto-Darolutamide in Plasma After Single Dose Administration of Darolutamide	Maximum observed concentration of keto-darolutamide in plasma after single dose administration of darolutamide were measured.	Pre dose up to 72 hours post dose of darolutamide

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Subjects With Study Drug-Related Treatment Emergent Adverse Events (TEAEs)	An adverse event (AE) was any untoward medical occurrence in subject who received study drug without regard to possibility of causal relationship. AEs that started or worsened after first administration of study medication up to 30 days after end of treatment with study medication were considered to be treatment-emergent (TE). AEs that occurred on study drug administration were termed as study drug related adverse events.	From start of study drug administration up to 30 days after last dose of study medication

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2017
• Primary Completion (Actual): May 4, 2017
• Study Completion (Actual): July 19, 2017

Study Registration Dates

• First Submitted: February 8, 2017
• First Submitted That Met QC Criteria: February 8, 2017
• First Posted (Estimate): February 9, 2017

Study Record Updates

• Last Update Posted (Actual): July 30, 2018
• Last Update Submitted That Met QC Criteria: July 27, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Hormone Antagonists; Cytochrome P-450 Enzyme Inducers; Antifungal Agents; Steroid Synthesis Inhibitors; Cytochrome P-450 CYP3A Inducers; Antitubercular Agents; 14-alpha Demethylase Inhibitors; Antibiotics, Antitubercular; Cytochrome P-450 CYP2B6 Inducers; Cytochrome P-450 CYP2C8 Inducers; Cytochrome P-450 CYP2C19 Inducers; Cytochrome P-450 CYP2C9 Inducers; Rifampin; Itraconazole
• Other Study ID Numbers: 17726; 2016-004469-20 (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