A Study to Assess Safety, Tolerability, and Pharmacokinetics of E2307 in Healthy Young and Elderly Japanese Subjects

Overview

This study will be a single-center, single dose, randomized, double-blind, placebo-controlled study in healthy Japanese male subjects. The study will consist of 2 parts: Part A (young subjects) and Part B (elderly subjects). In Part A sequential cohorts of subjects will be treated with single ascending doses of E2307. The maximum tolerated dose (MTD) will be determined in Part A. Part B will be initiated after Part A is completed. In Part B one cohort of healthy elderly subjects will be treated with a single dose of E2307 at one dose level below the MTD. In part A, a total of 56 subjects will be enrolled into 7 cohorts sequentially and randomized 3:1 to receive either E2307 (1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 200 mg, or 300 mg) or placebo. In part B, a total of 8 subjects will be randomized, 6 subjects to a single dose of E2307 and 2 subjects to placebo.

Full Title of Study: “A Randomized, Double-blind, Placebo-controlled, Single-Ascending Dose Study to Assess Safety, Tolerability, and Pharmacokinetics of E2307 in Healthy Young and Elderly Japanese Subjects”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Investigator)
  • Study Primary Completion Date: February 2015

Interventions

  • Drug: E2307
  • Drug: E2307 Matching Placebo

Arms, Groups and Cohorts

  • Experimental: Part A: 1 mg E2307 (young cohort)
    • E2307 (1 x 1 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)
  • Experimental: Part A: 3 mg E2307 (young cohort)
    • E2307 (3 x 1 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)
  • Experimental: Part A: 10 mg E2307 (young cohort)
    • E2307 (1 x 10 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)
  • Experimental: Part A: 30 mg E2307 (young cohort)
    • E2307 (3 x 10 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)
  • Experimental: Part A: 100 mg E2307 (young cohort)
    • E2307 (1 x 100 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)
  • Experimental: Part A: 200 mg E2307 (young cohort)
    • E2307 (2 x 100 mg E2307 capsules) or placebo (2 x 1 E2307 matching placebo capsules)
  • Experimental: Part A: 300 mg E2307 (young cohort)
    • E2307 (3 x 100 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)
  • Experimental: Part B: Elderly cohort
    • One dose level below MTD from Part A

Clinical Trial Outcome Measures

Primary Measures

  • Number of adverse events/serious adverse events
    • Time Frame: Up to 30 days
  • Plasma pharmacokinetics (PK) of E2307: Cmax (maximum observed concentration)
    • Time Frame: Up to 12 days
  • Plasma PK of E2307: tmax (time at which the highest drug concentration occurs)
    • Time Frame: Up to 12 days
  • Plasma PK of E2307: AUC(0-t) [area under the concentration (AUC)-time curve from zero time to time of last quantifiable concentration]
    • Time Frame: Up to 12 days
  • Plasma PK of E2307: AUC(0-inf) [area under the concentration-time curve from zero time extrapolated to infinite time]
    • Time Frame: Up to 12 days
  • Plasma PK of E2307: t1/2 (terminal elimination phase half-life)
    • Time Frame: Up to 12 days
  • Plasma PK of E2307: CL/F (apparent total clearance following oral administration)
    • Time Frame: Up to 12 days
    • CL/F are calculated for E2307 only
  • Plasma PK of E2307: Vz/F (apparent volume of distribution at terminal phase)
    • Time Frame: Up to 12 days
    • Vz/F are calculated for E2307 only
  • Plasma PK of E2307: AUC ratio (AUC ratio of metabolite to parent)
    • Time Frame: Up to 12 days
  • Urine PK of E2307: Ae (cumulative amount of drug excreted in urine up to 264 hours postdose)
    • Time Frame: Up to 12 days
  • Urine PK of E2307: CLR (renal clearance)
    • Time Frame: Up to 12 days

Secondary Measures

  • Mean difference in change of mean blood pressure (BP) between E2307 and placebo
    • Time Frame: 24 hours predose and continue until 24 hours postdose (Day 2)
  • QT interval assessment using Holter monitoring
    • Time Frame: 24 hours predose through Day 2 (at 24 hours postdose)

Participating in This Clinical Trial

Inclusion Criteria

Parts A and B 1. Provide written informed consent 2. Willing and able to comply with all aspects of the protocol Part A: Young cohort 3. Non-smoking, male subjects age >=20 years and less than 55 years old at the time of informed consent Part B: Elderly Cohort 4. Non-smoking, male subjects age >=65 years and less than 85 years old at the time of informed consent 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 history of abdominal surgery that may affect PK profiles of E2307 (eg. hepatectomy, nephrectomy, digestive organ resection) 3. Known history of clinically significant drug allergy (at Screening)

Gender Eligibility: Male

Minimum Age: 20 Years

Maximum Age: 85 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Eisai Co., Ltd.
  • Provider of Information About this Clinical Study
    • Sponsor

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