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| ID | Type | Description | Link |
|---|---|---|---|
| 2016-003490-18 | EudraCT Number |
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The main objectives of this phase 1 trial are to evaluate the effect of food on the pharmacokinetics (i.e. how long and how much a compound is present in the blood) of ACT-541468 and to evaluate whether ACT-541468 can affect the pharmacokinetics of midazolam, a CYP3A4 substrate.
Food effect will be assessed by comparing the pharmacokinetic (PK) parameters of a single dose of ACT-541468 under fasted (Treatment B) and fed (Treatment C) conditions.
Potential CYP3A4 inhibiting / inducing effects of ACT-541468 will be assessed by comparing the PK parameters of midazolam alone (Treatment A) and midazolam given with a single dose of ACT-541468 (Treatment B) or with multiple doses of ACT-541468 (Treatment D).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Food effect and Drug-Drug interaction | Experimental | Treatments will be given to all subjects in the same fixed sequence: Treatment A (Day 1, single dose of midazolam, fasted), Treatment B (Day 2, single dose of ACT-541468 followed by single dose of midazolam, fasted), Treatment C (Day 4, single dose ACT-541468, fed), Treatment D (multiple doses of ACT-541468 from Day 5 to Day 8 + single dose of midazolam on Day 8, fasted). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Midazolam | Drug | 2 mg/mL oral solution |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum plasma concentration (Cmax) of ACT-541468 | Cmax is directly determined from the plasma concentrations-time curves of ACT-541468 | PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only |
| Time to reach Cmax (tmax) of ACT-541468 | Tmax is directly determined from the plasma concentrations-time curves of ACT-541468 | PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only |
| Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468 | AUC is calculated from time zero to 24 hours post dose | PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only |
| Terminal half-life (t1/2) of ACT-541468 | t1/2 is calculated from the plasma concentrations-time curves of ACT-541468 | PK blood samples on Day 2, Day 4 and Day 8: before administration of ACT-541468 and up to 24 hours post-dose, and on Day 6 and Day 7: before ACT-541468 administration only |
| Maximum plasma concentration (Cmax) of midazolam | Cmax is directly obtained from the plasma concentrations-time curves of midazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose |
| Time to reach Cmax (tmax) of midazolam |
| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects with treatment-emergent adverse events and serious adverse events | From baseline to end-of-study, i.e.,maximum 5 days after Day 8 | |
| Maximum plasma concentration (Cmax) of ACT-541468 metabolites | PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Marie-Laure Boof, PhD | Actelion | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigator Site | Kiel | 24105 | Germany |
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| ID | Term |
|---|---|
| D008874 | Midazolam |
| C000634383 | daridorexant |
| ID | Term |
|---|---|
| D001569 | Benzodiazepines |
| D001552 | Benzazepines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| ACT-541468 |
| Drug |
Hard gelatin capsules for oral use at a strength of 25 mg |
|
Tmax is directly obtained from the plasma concentrations-time curves of midazolam
| PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose |
| Area under the plasma concentration-time curve [AUC(0-24)] of midazolam | AUC is calculated from time zero to 24 hours post dose | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose |
| Terminal half-life (t1/2) of midazolam | t1/2 is calculated from the plasma concentrations-time curves of midazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose |
| Maximum plasma concentration (Cmax) of 1-hydroxymidazolam | Cmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose |
| Time to reach Cmax (tmax) of 1-hydroxymidazolam | Tmax is directly determined from the plasma concentrations-time curves of 1-hydroxymidazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose |
| Area under the plasma concentration-time curve [AUC(0-24)] of 1-hydroxymidazolam | AUC is calculated from time zero to 24 hours post dose | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose |
| Terminal half-life (t1/2) of 1-hydroxymidazolam | t1/2 is calculated from the plasma concentrations-time curves of 1-hydroxymidazolam | PK blood samples on Day 1, Day 2, Day 8: before administration of midazolam and up to 24 hours post dose |
| Time to reach Cmax (tmax) of ACT-541468 metabolites | PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose |
| Area under the plasma concentration-time curve [AUC(0-24)] of ACT-541468 metabolites | PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose |
| Terminal half-life (t1/2) of ACT-541468 metabolites | PK blood samples on Day 8, before administration of ACT-541468 and up to 24 hours post dose |
| D006571 | Heterocyclic Compounds |