Drug-drug-interaction Study to Assess the Effect of Darol... | NCT03237416

ID	Type	Description	Link
2017-001116-11	EudraCT Number

Status Module

Name	Class
Orion Corporation, Orion Pharma	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
BAY1841788/Healthy subjects	Experimental	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

Name	Type	Description	Arm Group Labels	Other Names
Dabigatran etexilate	Drug	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

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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	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	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	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	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

Measure	Description	Time Frame
Number of subjects with study drug-related treatment-emergent Adverse Event (TEAE)		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

Eligibility Module

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.

ID	Term
D005834	Genital Neoplasms, Male
D014565	Urogenital Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D005832	Genital Diseases, Male
D000091662	Genital Diseases
D000091642	Urogenital Diseases
D011469	Prostatic Diseases
D052801	Male Urogenital Diseases

ID	Term
D011725	Pyridines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D001562	Benzimidazoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D001569	Benzodiazepines
D001552	Benzazepines

ID	Term
D000069604	Dabigatran
D008874	Midazolam
C000607739	darolutamide