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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
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| • A (midazolam & warfarin), B (daridorexant, midazolam, & warfarin), & C (daridorexant & midazolam) | Other |
|
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midazolam | Drug | Subjects will receive a single oral dose of 2 mg midazolam (Treatment A, B, and C). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Trials | Idosia Pharmaceuticals Ltd | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nuvisan GmbH | Neu-Ulm | 89231 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38472696 | Derived | Zenklusen I, Dingemanse J, Reh C, Gehin M, Kaufmann P. Effect of Daridorexant on the Pharmacokinetics of Midazolam, and on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Male Subjects. Drugs R D. 2024 Mar;24(1):97-108. doi: 10.1007/s40268-024-00456-8. Epub 2024 Mar 13. |
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This is a prospective, open-label, fixed-sequence Phase 1 study.
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| Warfarin | Drug | Subjects will receive a single oral dose of 25 mg warfarin (Treatment A and B). |
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| Daridorexant | Drug | 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. |
|
| 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). |
| 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) |
| ID | Term |
|---|---|
| D008874 | Midazolam |
| D014859 | Warfarin |
| C000634383 | daridorexant |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
| D015110 | 4-Hydroxycoumarins |
| D003374 | Coumarins |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006573 | Heterocyclic Compounds, 1-Ring |
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