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

Conditions: Prostatic Neoplasms

Summary: evaluate the effect of darolutamide on the pharmacokinetics of a probe cyp3a4 substrate and pgp substrate


Eligibility 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.

Keywords: drug-drug interaction