A Two-Part Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2006 in Healthy Japanese and White Subjects

Healthy Volunteers Clinical Trial

Official title:

A Two-Part, Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2006 in Healthy Japanese and White Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02039089
• Other study ID #: E2006-A001-003
• Status: Completed
• Phase: Phase 1
• First received: January 10, 2014
• Last updated: November 2, 2015
• Start date: January 2014
• Est. completion date: May 2014

Study information

• Verified date: November 2015
• Source: Eisai Inc.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: May 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 20 Years to 55 Years

Eligibility

Inclusion Criteria

Subjects have to meet all of the following criteria to be included into this study:

1. 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.

2. 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.

3. 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.

4. Who report typical sleep latency of less than or equal to 30 minutes.

5. With typical total sleep time greater than or equal to 420 minutes.

6. 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:

1. Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing.

2. 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.

3. 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).

4. Any history of abdominal surgery that may affect PK profiles of E2006 (eg, hepatectomy, nephrotomy, digestive organ resection).

5. 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.

6. 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.

7. 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.

8. 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).

9. Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS).

10. Known history of clinically significant drug allergy at screening.

11. Known history of food allergies or presently (at Screening or Baseline) experiencing significant seasonal or perennial allergy.

12. Active viral hepatitis (A, B or C) as demonstrated by positive serology at Screening. Subjects with HIV infection as confirmed verbally.

13. 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.

14. Habitually consumes more than 400 mg caffeine per day. Caffeine consumption must be discontinued for at least 24 hours before Baseline check-in.

15. 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.

16. Intake of herbal preparations containing St. John's Wort within 4 weeks before dosing.

17. Use of prescription drugs within 4 weeks before dosing.

18. Intake of over-the-counter medications within 2 weeks before dosing.

19. Currently enrolled in another clinical study or used any investigational drug or device within 30 days preceding initial dose of study drug.

20. Receipt of blood products within 4 weeks, donation of blood within 8 weeks, or donation of plasma within 1 week of dosing.

21. Engagement in strenuous exercise within 2 weeks before Screening and check-in (eg, marathon running, weight lifting).

22. Diagnosis of a sleep disorder (eg, insomnia, obstructive sleep apnea, restless leg syndrome, Periodic Limb movements in Sleep, narcolepsy, circadian rhythm disorder).

23. Performed shift work within 2 weeks before Screening.

24. Had taken an airline flight across 3 or more time zones in the 7 days before Screening.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• E2006 2.5 mg

• E2006 10 mg

• E2006 25 mg

• Placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Eisai Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	Adverse events (AEs ) as a measure of safety and tolerability		Up to 49 days	Yes
Primary	Suicidality as a measure of safety and tolerability	Measured by the columbia suicide severity rating scale (C-SSRS)	Up to 49 days	Yes
Primary	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	No
Primary	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	No
Primary	Laboratory assessments as a measure of safety and tolerability		Up to 49 days	No