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This study will be a single-center, multiple-dose, randomized, double-blind, placebo-controlled, parallel-group study in healthy male and female subjects. The study will consist of 2 parts: Part A (3 cohorts of healthy Japanese subjects dosed in the evening) and Part B (one cohort of healthy white subjects dosed in the evening). The cohorts will be conducted sequentially. Part A will be started first with the 2.5-mg dose cohort, followed by the 10-mg dose cohort and then the 25-mg dose cohort. Part B will be conducted in parallel with the 10-mg cohort of Part A, with the possibility of overlap.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Part A: dose escalation of E2006 in Japanese subjects from 2.5 mg (1 x 2.5-mg tablet) up to 10 mg (1 x 10-mg tablet) then to 25 mg (2 x 10-mg tablet, 1 x 5-mg tablet). |
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| 2 | Experimental | Part B: E2006 10 mg for White subjects that will be group matched to the Japanese subjects in the 10 mg period in Part A. |
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| 3 | Placebo Comparator | E2006-matched placebo tablets |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| E2006 2.5 mg | Drug |
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| E2006 10 mg |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic (PK) profiles of E2006 | The primary PK parameters are Cmax, tmax, AUC(0-T), AUC(0-24h), and t1/2, derived by non-compartmental analyses using the plasma concentration of E2006 and metabolites (as data permit). | Up to 49 days |
| Pharmacodynamic (PD) profile of E2006 | acute effects of E2006 on sleepiness in the hour before bedtime as well as next-day residual sleepiness throughout the daytime hours subsequent to each dose using the KSS and PVT. Effects of E2006 on nighttime sleep will be evaluated using PSG. High-precision QT analyses (HPQT) will be performed using data from 24-hour Holter recordings. The time points of Holter readings will be corresponding to the PK time points. | Up to 49 days |
| Adverse events (AEs ) as a measure of safety and tolerability | Up to 49 days | |
| Suicidality as a measure of safety and tolerability | Measured by the columbia suicide severity rating scale (C-SSRS) | Up to 49 days |
| Vital signs as a measure of safety and tolerability | Vital sign measurements will include systolic and diastolic blood pressure (BP) and pulse rate | Up to 49 days |
| Electrocardiogram (ECG) as a measure of safety and tolerability | Twelve-lead ECGs will be obtained as a measure of safety and tolerability | Up to 49 days |
| Laboratory assessments as a measure of safety and tolerability |
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Inclusion Criteria
Subjects have to meet all of the following criteria to be included into this study:
Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from this study:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Glendale | California | United States |
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| E2006 25 mg | Drug |
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| Placebo | Drug |
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| Up to 49 days |