check_circleStudy 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
  • - 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.

  • - 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
15
Trial Dates
August 2017 - December 2017
Phase
Phase 1
Could I Receive a placebo
No
Products
Nubeqa (Darolutamide, BAY1841788)
Accepts Healthy Volunteer
Yes

Where to participate

StatusInstitutionLocation
Completed
CRS Clinical-Research-Services Mannheim GmbHMannheim, 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
    date_rangeTime 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
    date_rangeTime 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
    date_rangeTime 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
    date_rangeTime 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)
    date_rangeTime 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
    date_rangeTime 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
    date_rangeTime 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
    date_rangeTime 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
    date_rangeTime 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
1

Additional Information

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