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 Details
Study Description
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
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Other: • A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam) Treatment A - midazolam and warfarin: In the morning of Day 1, subjects will receive a single oral dose of 2 mg midazolam concomitantly with a single oral dose of 25 mg warfarin under fasted conditions. Treatment B - daridorexant, midazolam, and warfarin: Subjects will receive an o.d. oral dose of 50 mg daridorexant in the morning from Day 1 to Day 7 under fasted conditions. In addition, in the morning of Day 1, the oral administration of 50 mg daridorexant will be followed 1 h later by a single oral dose of 2 mg midazolam concomitantly with a single oral dose of 25 mg warfarin under fasted conditions. Treatment C - daridorexant and midazolam: In the morning of Day 1, subjects will receive a single oral dose of 50 mg daridorexant followed 1 h later by a single oral dose of 2 mg midazolam under fasted conditions. |
Drug: Midazolam
Subjects will receive a single oral dose of 2 mg midazolam (Treatment A, B, and C).
Drug: Warfarin
Subjects will receive a single oral dose of 25 mg warfarin (Treatment A and B).
Drug: 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.
|
Outcome Measures
Primary Outcome Measures
- 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).]
Secondary Outcome Measures
- 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)]
- 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)]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Signed informed consent in a language understandable to the subject prior to any study-mandated procedure.
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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.
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Any history of hemorrhagic disease, whether or not hereditary.
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Any history of complications with bleeding after surgery or tooth extractions and/or frequent nasal, hemorrhoidal, or gingival bleeding.
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Activated partial thromboplastin time (aPTT) > 40 sec and/or international normalized ratio (INR) > 1.15 at Screening.
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Platelet count < 150 or >400 x 10^9/L at Screening.
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Clinically relevant findings on the physical examination at Screening.
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Clinically relevant abnormalities on 12-lead ECG, measured after 5 min in the supine position at Screening.
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Clinically relevant findings in clinical laboratory tests (hematology, coagulation, clinical chemistry) at Screening.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Nuvisan GmbH | Neu-Ulm | Germany | 89231 |
Sponsors and Collaborators
- Idorsia Pharmaceuticals Ltd.
Investigators
- Study Director: Clinical Trials, Idosia Pharmaceuticals Ltd
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- ID-078-126