Healthy
Conditions
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
Interventions
DRUGMidazolam
Subjects will receive a single oral dose of 2 mg midazolam (Treatment A, B, and C).
DRUGWarfarin
Subjects will receive a single oral dose of 25 mg warfarin (Treatment A and B).
DRUGDaridorexant
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.
Sponsors
Idorsia Pharmaceuticals Ltd.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
OTHER
Masking
NONE
Intervention model description
This is a prospective, open-label, fixed-sequence Phase 1 study.
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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). |
| 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). |
| 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). |
Secondary
| Measure | Time frame |
|---|---|
| The maximum effect on INR (INRmax) | 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) |
| Time to reach maximum effect of INR (t Emax) | 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) |
| AUC0-144 for Factor VII (AUC VII) | 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 Factor VII (VIImax) | 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) |
| Time to reach maximum effect of Factor VII (t Emax) | 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) |
| AUC0-144 for international normalized ratio (AUC INR) | 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) |
Countries
Germany
Outcome results
None listed