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

NCT02039089 | Completed Phase 1

• 1 other identifier: E2006-A001-003
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (7)

• 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

  Up to 49 days

Study Arms (3)

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).

Drug: E2006 2.5 mg; Drug: E2006 10 mg; Drug: E2006 25 mg

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.

Drug: E2006 10 mg

3

PLACEBO COMPARATOR

E2006-matched placebo tablets

Drug: Placebo

Interventions

E2006 25 mg DRUG

1

E2006 10 mg DRUG

1; 2

Placebo DRUG

3

Eligibility Criteria

• Age: 20 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects have to meet all of the following criteria to be included into this study:
• 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.
• 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.
• 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.
• Who report typical sleep latency of less than or equal to 30 minutes.
• With typical total sleep time greater than or equal to 420 minutes.
• Body mass index (BMI) greater than or equal to 18 and less than or equal to 28 kg/m2 at Screening.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from this study:
• Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing.
• 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.
• 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).
• Any history of abdominal surgery that may affect PK profiles of E2006 (eg, hepatectomy, nephrotomy, digestive organ resection).
• 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.
• 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.
• 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.
• 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).
• Any lifetime suicidal behavior (per the Suicidal Behavior Section of the C-SSRS).
• Known history of clinically significant drug allergy at screening.
• Known history of food allergies or presently (at Screening or Baseline) experiencing significant seasonal or perennial allergy.
• Active viral hepatitis (A, B or C) as demonstrated by positive serology at Screening. Subjects with HIV infection as confirmed verbally.
• 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.
• Habitually consumes more than 400 mg caffeine per day. Caffeine consumption must be discontinued for at least 24 hours before Baseline check-in.

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

Unknown Facility

Glendale, California, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 10, 2014
• First Posted: January 17, 2014
• Study Start: January 1, 2014
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: November 3, 2015

Record last verified: 2015-11

Locations

US (1)