Optic

ID

Name

ID-078-126

Description

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

Trial arms

Trial start

2022-08-23

Estimated PCD

2022-09-23

Trial end

2022-10-06

Status

Completed

Phase

Early phase I

Treatment

Midazolam

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

Arms:

• A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam)

Warfarin

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

Arms:

• A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam)

Daridorexant

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.

Arms:

• A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam)

Size

18

Primary endpoint

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

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

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

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).

Tmax of S-warfarin

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).

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

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)

AUC0-∞ of S-warfarin

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).

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

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).

T½ of S-warfarin

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).

Eligibility criteria

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.

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NA', 'interventionModel': 'SEQUENTIAL', 'interventionModelDescription': 'This is a prospective, open-label, fixed-sequence Phase 1 study.', 'primaryPurpose': 'OTHER', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 18, 'type': 'ACTUAL'}}

Updated at

2022-11-08

Organization

Idorsia Pharmaceuticals

Product

Indication

Product

Product