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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-003129-16 | EudraCT Number |
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The main objectives of this first-into-man study were to investigate the safety, tolerability and the pharmacokinetic profile of single oral doses of ACT-541468 in healthy male adults. Pharmacodynamic effects (through a battery of Central Nervous System tests) were also assessed.
The study consisted of ascending dose groups; each dose group was investigated in a new group of 8 healthy male subjects (6 on active drug and 2 on placebo). In addition, the study included a biocomparison part (dose group 2), an absolute bioavailability part (dose group 4), and a mass balance / metabolism part (dose group 3).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dose group 1 | Experimental | Six subjects received 5 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo. |
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| Dose group 2 | Experimental | Three subjects received a single oral dose (25 mg) of ACT-541468 formulation A during Period 1 and a single oral dose (25 mg) of ACT-541468 formulation B during Period 2. Three other subjects Subjects received ACT-541468 formulation B during Period 1 and ACT-541468 formulation A during Period 2. Two additional subjects received the matching placebos in both treatment periods. |
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| Dose group 3 | Experimental | Six subjects received 50 mg of ACT-541468 (formulation A) as a single oral dose in combination with a [14C]-ACT-541468 oral tracer for the mass balance and metabolism analyses. Two other subjects received the matching placebos. |
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| Dose group 4 | Experimental | Six subjects received 100 mg of ACT-541468 (formulation A) as a single oral dose in combination with a [14C]-ACT-541468 intravenous tracer for the absolute bioavailability assessment. Two other subjects received the matching placebos. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ACT-541468 (Formulation A) | Drug | Hard gelatin capsules for oral administration formulated at strengths of 5 mg, 25 mg and 100 mg |
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| Measure | Description | Time Frame |
|---|---|---|
| Number of subjects with treatment-emergent adverse events and serious adverse events | Collection of any adverse event at each dose level | Day 8 |
| Measure | Description | Time Frame |
|---|---|---|
| Maximum plasma concentration (Cmax) of ACT-541468 | Cmax was directly derived from the observed plasma concentrations of ACT-541468 for each dose level | From pre-dose up to 168 hours post-dose |
| Time to reach Cmax (tmax) of ACT-541468 |
| Measure | Description | Time Frame |
|---|---|---|
| Change from baseline in saccadic peak velocity (SPV) | At baseline till 10 hours after study drug administration | |
| Change from baseline in body sway | At baseline till 10 hours after study drug administration |
Key inclusion Criteria:
Key exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clemens Muehlan | Actelion | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigator Site | Leiden | 2333 CL | Netherlands |
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| ID | Term |
|---|---|
| C000634383 | daridorexant |
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| Dose group 5 | Experimental | Six subjects received 200 mg of ACT-541468 (formulation A) as a single oral dose and two subjects received the matching placebo. |
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| ACT-541468 (Formulation B) | Drug | Soft gelatin capsules for oral administration formulated at the strength of 25 mg |
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| Placebo (Formulation A) | Drug | Hard capsules matching ACT-541468 Formulation A |
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| Placebo (Formulation B) | Drug | Soft capsules matching ACT-541468 Formulation B |
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| 14C-labeled ACT-541468 | Drug | Tracer at a nominal dose of 250 nCi (corresponding to 2.02 µg ACT-541468) administered either orally or intravenously |
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| Placebo tracer | Drug | Sterile NaCl 0.9% was used as placebo matching the tracer for oral and i.v. administration. |
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tmax was directly derived from the observed plasma concentrations of ACT-541468 for each dose level
| From pre-dose up to 168 hours post-dose |
| Terminal half-life (t1/2) of ACT-541468 | t1/2 was calculated from the terminal rate constant obtained from the plasma concentrations-time curves of ACT-541468, at each dose level | From pre-dose up to 168 hours post-dose |
| Area under the plasma concentration-time curves [AUC(0-inf)] of ACT-541468 | AUC(0-inf) is the area under the plasma concentration-time curves of ACT-541468, calculated from time 0 (pre-dose) to extrapolated infinite time, at each dose level | From pre-dose up to 168 hours post-dose |
| Percentage of dose excreted in feces and urine | Percentage of oral dose of 14C-labeled ACT-541468 excreted in feces (FPE), urine (UPE) and both, as determined in the dose group 3 | From pre-dose up to 168 hours post-dose |
| Absolute bioavailability (F) of ACT-541468 | Absolute bioavailability was determined for dose group 4 and defined as the ratio of AUC(0-inf) after oral administration of ACT-541468 and after intravenous infusion of 14C-labeled ACT-541468 (tracer) | Up to 96 hours post-dose |
| Change from baseline in adaptive tracking | At baseline till 10 hours after study drug administration |
| Chnage from baseline in Bond and Lader visual analog scale (B&L VAS)l | At baseline till 10 hours after study drug administration |