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CompletedNCT03237416Updated Nov 6, 2018

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

A Phase 1 interventional study of Dabigatran etexilate and Midazolam in Prostatic Neoplasms, sponsored by Bayer. Completed at 1 site in Germany. Open to male participants aged 45 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2018-11-06.

Sponsored by Bayer · Phase 1, Interventional, and Other

Phase
Phase 1
Study type
Interventional
Enrollment
15
Allocation
Not applicable
Ages
45 Years to 65 Years
Sex
Male
01

Study summary

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

02

Conditions studied

  • Prostatic Neoplasms

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Keywords

  • Drug-drug interaction
03

In context

Prostatic Neoplasms

6,367 studies on the registry are indexed under Prostatic Neoplasms; 1,397 are open to participants now.

This study's enrollment of 15 is below the median of 58 across 4,821 interventional studies indexed under Prostatic Neoplasms.

Browse Prostatic Neoplasms studies →

Lead sponsor

Bayer is the lead sponsor of 1,643 studies on the registry; 57 are open to participants now.

Of its 209 completed or terminated interventional studies of FDA-regulated products, 129 (62%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
45 Years to 65 Years
Sexes eligible
Male
Accepts healthy volunteers
Yes

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

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.
05

Study design

Phase
Phase 1
Primary purpose
Other
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
15 participants (actual)

Study arms

  • Experimental
    BAY1841788/Healthy subjects

    Period 1: intake of Midazolam and Dabigatran etexilate at day 1 followed by Period 2: intake of Darolutamide at days 1-11 (twice daily), intake of dabigatran etexilate at days 3 and 9, intake of Midazolam at day 9

    Drug: Dabigatran etexilate · Drug: Midazolam · Drug: BAY1841788 (darolutamide)

Interventions

  • DrugDabigatran etexilate

    In Period 1, Day 1 a single dose of 75 mg will be administered after breakfast In Period 2, Day 3 a single dose of 75 mg will be administered prior to breakfast In Period 2, Day 9 a single dose of 75 mg will be administered after breakfast

  • DrugMidazolam

    In Period 1, Day 1 a single dose of 1 mg will be administered after breakfast In Period 2, Day 9 a single dose of 1 mg will be administered after breakfast

  • DrugBAY1841788 (darolutamide)

    In Period 2, Days 1-11 600 mg twice a day (as 2 x 300 mg tablets) will be administered after breakfast

06

What researchers measure

Primary outcomes

  1. 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

  2. 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

  3. 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

  4. 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 outcomes

  1. Number of subjects with study drug-related treatment-emergent Adverse Event (TEAE)

    Time frame: 30 days following last intake of Investigational Product

  2. 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

  3. 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

  4. 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

  5. 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

07

Study locations

1 site
  • CRS Clinical-Research-Services Mannheim GmbH
    Mannheim, Baden-Württemberg 68167, Germany
08

References and documents

09

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Nov 6, 2018, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT03237416
Lead sponsor
Bayer
Collaborators
Orion Corporation, Orion Pharma
Responsible party
Sponsor
First posted
Aug 2, 2017
Start date
Aug 2, 2017
Primary completion
Oct 5, 2017
Completion
Dec 18, 2017
Last update
Nov 6, 2018

Study contacts

Bayer Study Director
study director · Bayer

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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