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

NCT03048110 | Completed Phase 1

• 2 other identifiers: 177262016-004469-20
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Biological Availability

Outcome Measures

Primary Outcomes (8)

• 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 Outcomes (1)

• Number of Subjects With Study Drug-Related Treatment Emergent Adverse Events (TEAEs)

  From start of study drug administration up to 30 days after last dose of study medication

Study Arms (1)

ODM-201

EXPERIMENTAL

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); Drug: Itraconazole; Drug: Rifampicin

Interventions

BAY1841788 (ODM-201) DRUG

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.

ODM-201

Itraconazole DRUG

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.

ODM-201

Rifampicin DRUG

600 mg QD administered as 1 x 600 mg tablet per dose in treatment period 3 on Study Days 1 to 10.

ODM-201

Eligibility Criteria

• Age: 45 Years - 65 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Bayer: lead
• Orion Corporation, Orion Pharma: collaborator

Study Sites (1)

CRS Clinical Research Services Berlin GmbH

Berlin, 13353, Germany

Location

MeSH Terms

Interventions

darolutamide; Itraconazole; Rifampin

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Piperazines; Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 8, 2017
• First Posted: February 9, 2017
• Study Start: February 15, 2017
• Primary Completion: May 4, 2017
• Study Completion: July 19, 2017
• Last Updated: July 30, 2018

Record last verified: 2018-07

Locations

DE (1)