A Two-Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2006 in Healthy Japanese and White Subjects
Study Details
Study Description
Brief Summary
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.
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: 1 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). |
Drug: E2006 2.5 mg
Drug: E2006 10 mg
Drug: E2006 25 mg
|
Experimental: 2 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. |
Drug: E2006 10 mg
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Placebo Comparator: 3 E2006-matched placebo tablets |
Drug: Placebo
|
Outcome Measures
Primary Outcome Measures
- Pharmacokinetic (PK) profiles of E2006 [Up to 49 days]
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).
- Pharmacodynamic (PD) profile of E2006 [Up to 49 days]
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.
- Adverse events (AEs ) as a measure of safety and tolerability [Up to 49 days]
- Suicidality as a measure of safety and tolerability [Up to 49 days]
Measured by the columbia suicide severity rating scale (C-SSRS)
- Vital signs as a measure of safety and tolerability [Up to 49 days]
Vital sign measurements will include systolic and diastolic blood pressure (BP) and pulse rate
- Electrocardiogram (ECG) as a measure of safety and tolerability [Up to 49 days]
Twelve-lead ECGs will be obtained as a measure of safety and tolerability
- Laboratory assessments as a measure of safety and tolerability [Up to 49 days]
Eligibility Criteria
Criteria
Inclusion Criteria
Subjects have to meet all of the following criteria to be included into this study:
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Non-smoking, male or female subjects age greater than or equal to 20 years and less than or equal to 55 years old at the time of informed consent.
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Japanese subjects must have been born in Japan of Japanese parents and Japanese grandparents, must have lived no more than 5 years outside of Japan, and must not have changed their life style or habits, including diet, while living outside of Japan.
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Who report habitual time in bed greater than 7 hours, with lights-out 21:00 to 24:00 hours and lights-on 06:00 to 09:00 hours.
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Who report typical sleep latency of less than or equal to 30 minutes.
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With typical total sleep time greater than or equal to 420 minutes.
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Body mass index (BMI) greater than or equal to 18 and less than or equal to 28 kg/m2 at Screening.
Exclusion Criteria
Subjects who meet any of the following criteria will be excluded from this study:
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Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing.
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Any subject that has a known history of malaria or has traveled to a country with known malarial risk (ie, countries designated as 'high' or 'moderate' risk according to the list available at http://www.cdc.gov/malaria) within the last year.
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Evidence of disease that may influence the outcome of the study within 4 weeks before dosing (eg, psychiatric disorders, disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or subjects who have a congenital abnormality in metabolism).
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Any history of abdominal surgery that may affect PK profiles of E2006 (eg, hepatectomy, nephrotomy, digestive organ resection).
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Any clinically abnormal symptom or organ impairment found by medical history, physical examination, vital sign and, ECG assessments, or laboratory test results that requires medical treatment.
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A QTcF interval greater than 450 ms demonstrated on a repeated ECGs (repeated if initial ECG indicates QT greater than 450 ms) at Screening or Baseline.
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A history or a family history of congenital QT prolongation or with a history of risk factors for torsade de pointes (eg, heart failure, hypokalemia, family history of long QT Syndrome), or use of concomitant medications that prolong the QT/QTc interval.
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Any suicidal ideation with intent with or without a plan at Baseline or within 6 months of Baseline (ie, answering "Yes" to questions 4 or 5 on the Suicidal Ideation Section of the C-SSRS).
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Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS).
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Known history of clinically significant drug allergy at screening.
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Known history of food allergies or presently (at Screening or Baseline) experiencing significant seasonal or perennial allergy.
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Active viral hepatitis (A, B or C) as demonstrated by positive serology at Screening. Subjects with HIV infection as confirmed verbally.
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History of drug or alcohol dependency or abuse within the 2 years before Screening, or those who have a positive urine drug test or breath (or urine) alcohol test at Screening or Baseline.
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Habitually consumes more than 400 mg caffeine per day. Caffeine consumption must be discontinued for at least 24 hours before Baseline check-in.
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Intake of nutritional supplements, juice, and herbal preparations or other foods or beverages that may affect the various drug metabolizing enzymes and transporters (eg, alcohol, grapefruit, grapefruit juice, grapefruit-containing beverages, apple or orange juice, vegetables from the mustard green family [eg, kale, broccoli, watercress, collard greens, kohlrabi, brussel sprouts, mustard], charbroiled meats) within 1 week before dosing.
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Intake of herbal preparations containing St. John's Wort within 4 weeks before dosing.
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Use of prescription drugs within 4 weeks before dosing.
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Intake of over-the-counter medications within 2 weeks before dosing.
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Currently enrolled in another clinical study or used any investigational drug or device within 30 days preceding initial dose of study drug.
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Receipt of blood products within 4 weeks, donation of blood within 8 weeks, or donation of plasma within 1 week of dosing.
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Engagement in strenuous exercise within 2 weeks before Screening and check-in (eg, marathon running, weight lifting).
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Diagnosis of a sleep disorder (eg, insomnia, obstructive sleep apnea, restless leg syndrome, Periodic Limb movements in Sleep, narcolepsy, circadian rhythm disorder).
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Performed shift work within 2 weeks before Screening.
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Had taken an airline flight across 3 or more time zones in the 7 days before Screening.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Glendale | California | United States |
Sponsors and Collaborators
- Eisai Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- E2006-A001-003