A Study to Examine the Effect of Daridorexant on the Way the Body Absorbs, Distributes, and Gets Rid of Midazolam and Warfarin in Healthy Male Subjects

Idorsia Pharmaceuticals Ltd.18 enrolled

Overview

A study to examine the effect of daridorexant on the way the body absorbs, distributes, and gets rid of midazolam and warfarin in healthy male subjects

Study Type

INTERVENTIONAL

Allocation

Purpose

OTHER

Masking

NONE

Enrollment

Conditions

Healthy

Interventions

MidazolamDRUG

Subjects will receive a single oral dose of 2 mg midazolam (Treatment A, B, and C).

WarfarinDRUG

Subjects will receive a single oral dose of 25 mg warfarin (Treatment A and B).

DaridorexantDRUG

Subjects will receive an o.d. oral dose of 50 mg daridorexant from Day 1 to Day 7 of Treatment B and a single oral dose of 50 mg daridorexant on Day 1 of Treatment C.

Eligibility

Sex: MALEMin age: 18 YearsMax age: 45 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Signed informed consent in a language understandable to the subject prior to any study-mandated procedure. * Healthy male subject aged between 18 and 45 years (inclusive) at Screening. Exclusion Criteria: * Known hypersensitivity to daridorexant, midazolam, warfarin, or treatments of the same class, or any of their excipients. * Any history of hemorrhagic disease, whether or not hereditary. * Any history of complications with bleeding after surgery or tooth extractions and/or frequent nasal, hemorrhoidal, or gingival bleeding. * Activated partial thromboplastin time (aPTT) \> 40 sec and/or international normalized ratio (INR) \> 1.15 at Screening. * Platelet count \< 150 or \>400 x 10\^9/L at Screening. * Clinically relevant findings on the physical examination at Screening. * Clinically relevant abnormalities on 12-lead ECG, measured after 5 min in the supine position at Screening. * Clinically relevant findings in clinical laboratory tests (hematology, coagulation, clinical chemistry) at Screening.

Locations (1)

Nuvisan GmbH

Neu-Ulm, Germany

Outcomes

Primary Outcomes

Maximum concentration (Cmax) of midazolam and its metabolite 1-OH midazolam

Time frame: Blood samples for pharmacokinetic analyses of midazolam will be taken at various time points from Day 1 to 2 of Treatment Period A, from Day 1 to 2 of Treatment Period B, and from Day 1 to 2 of Treatment Period C (total duration: 6 days).

Cmax of S-warfarin

Time frame: Blood samples for pharmacokinetic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days).

Time to reach Cmax (tmax) of midazolam and 1-OH midazolam

Tmax of S-warfarin

Area under the concentration-time curve (AUC) from zero to infinity (AUC0-∞) of midazolam and 1-OH midazolam

AUC0-∞ of S-warfarin

Terminal elimination half-life (t½) of midazolam and 1-OH midazolam

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Secondary Outcomes

AUC0-144 for international normalized ratio (AUC INR)

Time frame: Blood samples for pharmacodynamic analyses of S-warfarin will be taken at various time points from Day 1 to 7 of Treatment Period A and from Day 1 to 7 of Treatment Period B (total duration: 14 days)

The maximum effect on INR (INRmax)

Time to reach maximum effect of INR (t Emax)

AUC0-144 for Factor VII (AUC VII)

The maximum effect on Factor VII (VIImax)

Time to reach maximum effect of Factor VII (t Emax)