Drug-drug-interaction Study to Assess the Effect of Darolutamide on the Pharmacokinetics of Probe Substrates of CYP3A4 and P-gp in Healthy Male Volunteers

• Status: Completed
• Trial end date: 2017-12-18
• Target enrollment: 0
• Participant gender: Male

Summary

Evaluate the effect of darolutamide on the pharmacokinetics of a probe CYP3A4 substrate and Pgp substrate

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Bayer
• Collaborator: Orion Corporation, Orion Pharma
• Treatments: Dabigatran; Midazolam

Criteria

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 ≤30.0 kg/m2.

• 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 darolutamide.

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. Therefore, contraception methods to be used by male subjects and female partners are in line with clinical trial facilitation group recommendations related to contraception in clinical trials.

• Ability to understand and follow study-related instructions.

• Results of alcohol tests are negative at screening and on Study Day -1.

• Confirmation of the subject's health insurance coverage prior to the first screening examination/visit.

Exclusion Criteria:

• 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.

• Known history of hypersensitivity (or known allergic reaction) to medications including any ingredient of midazolam, benzodiazepines, dabigatran etexilate, or darolutamide.

• 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.

• CYP3A4 inhibitors within 1 week or 5 drug half-lives, whichever is longer, before start of study treatment or during the study.

• CYP3A4 inducers as well as St John's Wort within 28 days or 5 drug half-lives, whichever is longer, before start of study treatment or during the study.

• Known BCRP and OATP substrates within 28 days or 5 drug half-lives, whichever is longer, before start of study treatment or during the study.

• P-gp inducers (e.g. rifampin) within 28 days or 5 drug half-lives, whichever is longer, before start of study treatment or during the study.

• P-gp inhibitors within 1 week or 5 drug half-lives, whichever is longer, before start of study treatment or during the study.