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

NCT02289599 | Completed Phase 1

• 1 other identifier: E2307-J081-001
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Subjects

Keywords

Healthy Japanese Subjects; E2307; Pharmacokinetics

Outcome Measures

Primary Outcomes (11)

• Number of adverse events/serious adverse events

  Up to 30 days

• Plasma pharmacokinetics (PK) of E2307: Cmax (maximum observed concentration)

  Up to 12 days

• Plasma PK of E2307: tmax (time at which the highest drug concentration occurs)

  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]

  Up to 12 days

• Plasma PK of E2307: AUC(0-inf) [area under the concentration-time curve from zero time extrapolated to infinite time]

  Up to 12 days

• Plasma PK of E2307: t1/2 (terminal elimination phase half-life)

  Up to 12 days

• Plasma PK of E2307: CL/F (apparent total clearance following oral administration)

  CL/F are calculated for E2307 only

  Up to 12 days

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

  Vz/F are calculated for E2307 only

  Up to 12 days

• Plasma PK of E2307: AUC ratio (AUC ratio of metabolite to parent)

  Up to 12 days

• Urine PK of E2307: Ae (cumulative amount of drug excreted in urine up to 264 hours postdose)

  Up to 12 days

• Urine PK of E2307: CLR (renal clearance)

  Up to 12 days

Secondary Outcomes (2)

• Mean difference in change of mean blood pressure (BP) between E2307 and placebo

  24 hours predose and continue until 24 hours postdose (Day 2)

• QT interval assessment using Holter monitoring

  24 hours predose through Day 2 (at 24 hours postdose)

Study Arms (8)

Part A: 1 mg E2307 (young cohort)

EXPERIMENTAL

E2307 (1 x 1 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)

Drug: E2307; Drug: E2307 Matching Placebo

Part A: 3 mg E2307 (young cohort)

EXPERIMENTAL

E2307 (3 x 1 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)

Drug: E2307; Drug: E2307 Matching Placebo

Part A: 10 mg E2307 (young cohort)

EXPERIMENTAL

E2307 (1 x 10 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)

Drug: E2307; Drug: E2307 Matching Placebo

Part A: 30 mg E2307 (young cohort)

EXPERIMENTAL

E2307 (3 x 10 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)

Drug: E2307; Drug: E2307 Matching Placebo

Part A: 100 mg E2307 (young cohort)

EXPERIMENTAL

E2307 (1 x 100 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)

Drug: E2307; Drug: E2307 Matching Placebo

Part A: 200 mg E2307 (young cohort)

EXPERIMENTAL

E2307 (2 x 100 mg E2307 capsules) or placebo (2 x 1 E2307 matching placebo capsules)

Drug: E2307; Drug: E2307 Matching Placebo

Part A: 300 mg E2307 (young cohort)

EXPERIMENTAL

E2307 (3 x 100 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)

Drug: E2307; Drug: E2307 Matching Placebo

Part B: Elderly cohort

EXPERIMENTAL

One dose level below MTD from Part A

Drug: E2307

Interventions

E2307 DRUG

Part A: 1 mg E2307 (young cohort); Part A: 10 mg E2307 (young cohort); Part A: 100 mg E2307 (young cohort); Part A: 200 mg E2307 (young cohort); Part A: 3 mg E2307 (young cohort); Part A: 30 mg E2307 (young cohort); Part A: 300 mg E2307 (young cohort); Part B: Elderly cohort

E2307 Matching Placebo DRUG

Part A: 1 mg E2307 (young cohort); Part A: 10 mg E2307 (young cohort); Part A: 100 mg E2307 (young cohort); Part A: 200 mg E2307 (young cohort); Part A: 3 mg E2307 (young cohort); Part A: 30 mg E2307 (young cohort); Part A: 300 mg E2307 (young cohort)

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Parts A and B
• Provide written informed consent
• Willing and able to comply with all aspects of the protocol
• Part A: Young cohort
• Non-smoking, male subjects age \>=20 years and less than 55 years old at the time of informed consent
• Part B: Elderly Cohort
• Non-smoking, male subjects age \>=65 years and less than 85 years old at the time of informed consent

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 history of abdominal surgery that may affect PK profiles of E2307 (eg. hepatectomy, nephrectomy, digestive organ resection)
• Known history of clinically significant drug allergy (at Screening)

Sponsors & Collaborators

• Eisai Co., Ltd.: lead

Study Sites (1)

Unknown Facility

Kagoshima, Kagoshima-ken, Japan

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: November 10, 2014
• First Posted: November 13, 2014
• Study Start: November 1, 2014
• Primary Completion: February 1, 2015
• Study Completion: July 1, 2015
• Last Updated: January 18, 2016

Record last verified: 2016-01

Locations

JP (1)