Clinical trial NCT05480488: 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
Official title: A Single-center, Open-label Study to Investigate the Effect of Single- and Multiple-dose Daridorexant on the Pharmacokinetics of Midazolam and Its Metabolite 1-hydroxymidazolam, and the Effect of Single-dose Daridorexant on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Idorsia Pharmaceuticals Ltd.
Sponsor class: INDUSTRY
First posted: 2022-07-29
Enrollment: 18
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SEQUENTIAL
Intervention model description: This is a prospective, open-label, fixed-sequence Phase 1 study.
Primary purpose: OTHER

Brief summary: 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


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.

Primary outcomes:
measure: Maximum concentration (Cmax) of midazolam and its metabolite 1-OH midazolam
timeFrame: 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).
measure: Cmax of S-warfarin
timeFrame: 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).
measure: Time to reach Cmax (tmax) of midazolam and 1-OH midazolam
timeFrame: 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).
measure: Tmax of S-warfarin
timeFrame: 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).
measure: Area under the concentration-time curve (AUC) from zero to infinity (AUC0-∞) of midazolam and 1-OH midazolam
timeFrame: 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)
measure: AUC0-∞ of S-warfarin
timeFrame: 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).
measure: Terminal elimination half-life (t½) of midazolam and 1-OH midazolam
timeFrame: 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).
measure: T½ of S-warfarin
timeFrame: 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).
Secondary outcomes:
measure: AUC0-144 for international normalized ratio (AUC INR)
timeFrame: 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)
measure: The maximum effect on INR (INRmax)
timeFrame: 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)
measure: Time to reach maximum effect of INR (t Emax)
timeFrame: 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)
measure: AUC0-144 for Factor VII (AUC VII)
timeFrame: 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)
measure: The maximum effect on Factor VII (VIImax)
timeFrame: 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)
measure: Time to reach maximum effect of Factor VII (t Emax)
timeFrame: 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)
Other outcomes:
Locations:
city: Neu-Ulm
country: Germany
facility: Nuvisan GmbH
Study officials:
affiliation: Idosia Pharmaceuticals Ltd
name: Clinical Trials
role: STUDY_DIRECTOR
References: