Study Completed

Prostatic Neoplasms

Bayer Identifier:

18860

ClinicalTrials.gov Identifier:

NCT03237416

EudraCT Number:

2017-001116-11

EU CT Number:

Not Available

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

Trial purpose

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

Key Participants Requirements

Sex

Male

Age

45 - 65 Years

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.

Trial summary

Enrollment Goal

Trial Dates

August 2017 - December 2017

Phase

Phase 1

Could I Receive a placebo

Products

Nubeqa (Darolutamide, BAY1841788)

Accepts Healthy Volunteer

Yes

Where to participate

Status	Institution	Location
Completed	CRS Clinical-Research-Services Mannheim GmbH	Mannheim, 68167, Germany

Primary Outcome

AUC in plasma of non-conjugated dabigatran (AUC(0-tlast), if AUC cannot be calculated)
Exposure of non-conjugated dabigatran in plasma following a single administration of dabigatran etexilate AUC: area under the concentration vs. time curve from zero to infinity after single (first) dose AUC(0-tlast): AUC from time 0 to the last data point > LLOQ
Time Frame:
Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing
C(max) in plasma of non-conjugated dabigatran
Maximum plasma concentration of non-conjugated dabigatran in plasma following a single administration of dabigatran etexilate Cmax: maximum observed drug concentration in measured matrix after single dose administration
Time Frame:
Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing
AUC in plasma of midazolam (AUC(0-tlast), if AUC cannot be calculated)
Exposure of midazolam in plasma following a single administration of midazolam
Time Frame:
PPeriod 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing
C(max) in plasma of midazolam
Maximum plasma concentration of midazolam in plasma following a single administration of midazolam
Time Frame:
Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing

Secondary Outcome

Number of subjects with study drug-related treatment-emergent Adverse Event (TEAE)
Time Frame:
30 days following last intake of Investigational Product
AUC in plasma of total dabigatran (AUC(0-tlast), if AUC cannot be calculated)
Exposure of total dabigatran in plasma following a single administration of dabigatran etexilate
Time Frame:
Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing
C(max) in plasma of total dabigatran
Maximum plasma concentration of total dabigatran in plasma following a single administration of dabigatran etexilate
Time Frame:
Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing
AUC in plasma of 1-OH midazolam (AUC(0-tlast), if AUC cannot be calculated)
Exposure of 1-OH midazolam in plasma following a single administration of midazolam
Time Frame:
Period 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing
C(max) in plasma of 1-OH midazolam
Maximum plasma concentration of 1-OH midazolam in plasma following a single administration of midazolam
Time Frame:
PPeriod 1, Day 1: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing Period 2, Day 3 and 9: Predose, and 0.25, 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10, 12, 15, 24, 36, 48, 72 hours post dosing

Trial design

A Phase I, non-randomized, open-label, fixed-sequence study to investigate the effect of darolutamide (ODM-201) on the pharmacokinetics of a probe substrate of CYP3A4 and P-gp in healthy male volunteers

Trial Type

Interventional

Intervention Type

Drug

Trial Purpose

Other

Allocation

N/A

Blinding

N/A

Assignment

Single Group Assignment

Trial Arms

Additional Information

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