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

Eisai Co., Ltd.24 enrolled

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Healthy Subjects

Interventions

Eligibility

Sex: MALEMin age: 20 YearsMax age: 85 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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)

CL/F are calculated for E2307 only

Time frame: Up to 12 days

Plasma PK of E2307: Vz/F (apparent volume of distribution at terminal phase)

Vz/F are calculated for E2307 only

Time frame: Up to 12 days

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 Outcomes

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)

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes