Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2609 in Healthy Adult Male Japanese and White Subjects

NCT02207790 | Completed Phase 1

• 1 other identifier: E2609-A001-006
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study is primarily designed to bridge the pharmacokinetics (PK) and safety data for E2609 between Japanese subjects and non-Japanese (ie, white) subjects. To bridge these PK characteristics, the proposed study includes a cohort of white subjects treated for comparison with the cohort of Japanese subjects treated at the same dose. This comparison serves as a key PK bridge in assessing ethnic factors that may contribute to differences in plasma concentrations. Pharmacokinetic assessments in the proposed study will include confirmation of dose proportionality in Japanese subjects. This study will also evaluate safety and tolerability in Japanese subjects.

Conditions

Healthy Subjects

Keywords

Clinical Trial, Phase I; Healthy Volunteers

Outcome Measures

Primary Outcomes (11)

• Pharmacokinetics of E2609: Cmax

  Up to Day 10 (216 hours postdose)

• Pharmacokinetics of E2609: tmax

  Up to Day 10 (216 hours postdose)

• Pharmacokinetics of E2609: AUC(0-24h)+D90

  Up to Day 10 (216 hours postdose)

• Pharmacokinetics of E2609: AUC(0-72h)

  Up to Day 10 (216 hours postdose)

• Pharmacokinetics of E2609: AUC(0-t)

  Up to Day 10 (216 hours postdose)

• Pharmacokinetics of E2609: AUC(0-inf)

  Up to Day 10 (216 hours postdose)

• Pharmacokinetics of E2609: AUC Metabolite Ratio

  Up to Day 10 (216 hours postdose)

• Pharmacokinetics of E2609: t1/2

  Up to Day 10 (216 hours postdose)

• Pharmacokinetics of E2609: CL/F

  Up to Day 10 (216 hours postdose)

• Pharmacokinetics of E2609: V/F

  Up to Day 10 (216 hours postdose)

• To evaluate the safety and tolerability of E2609

  Safety will be assessed by monitoring and recording all adverse events (AEs), serious adverse events (SAEs), regular monitoring of hematology, blood chemistry, urine values, regular measurement of vital signs, ECGs and performance of physical examinations

  Baseline and up to 30 days from last dosing of subject

Secondary Outcomes (6)

• Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): Amax

  Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10

• Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): T(Amax)

  Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10

• Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): AUAC(-24h-0h)

  Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10

• Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): AUAC(0-144h)

  Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10

• Pharmacodynamic effect of E2609: percent change from baseline of plasma (AB[1-x]): Change in AUAC

  Baseline, Day 1, Day 2, Day 3, Day 4, Day 5, Day 7, and Day 10

Study Arms (4)

E2609 low-dose and placebo in healthy Japanese subjects

EXPERIMENTAL

Cohort 1 will consist of Japanese subjects randomized to a low-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).

Drug: E2609; Drug: Placebo

E2609 mid-dose and placebo in healthy Japanese subjects

EXPERIMENTAL

Cohort 2 will consist of Japanese subjects randomized to a mid-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).

Drug: E2609; Drug: Placebo

E2609 high-dose and placebo in healthy Japanese subjects

EXPERIMENTAL

Cohort 3 will consist of Japanese subjects randomized to a high-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).

Drug: E2609; Drug: Placebo

E2609 mid-dose and placebo in healthy White subjects

EXPERIMENTAL

Cohort 4 will consist of White subjects randomized to a mid-dose of E2609 as an orally administered tablet along with subjects receiving matching placebo tablets (matched in number and appearance).

Drug: E2609; Drug: Placebo

Interventions

E2609 DRUG

E2609 high-dose and placebo in healthy Japanese subjects; E2609 low-dose and placebo in healthy Japanese subjects; E2609 mid-dose and placebo in healthy Japanese subjects; E2609 mid-dose and placebo in healthy White subjects

Placebo DRUG

E2609 low-dose and placebo in healthy Japanese subjects, E2609 mid-dose and placebo in healthy Japanese subjects, E2609 high-dose and placebo in healthy Japanese subjects, E2609 mid-dose and placebo in healthy White subjects

E2609 high-dose and placebo in healthy Japanese subjects; E2609 low-dose and placebo in healthy Japanese subjects; E2609 mid-dose and placebo in healthy Japanese subjects; E2609 mid-dose and placebo in healthy White subjects

Eligibility Criteria

• Age: 30 Years - 60 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject must meet all of the following criteria in order to be included in the study.
• Japanese Subjects Only:
• Birth in Japan to Japanese parents and grandparents of Japanese descent
• Have been living outside Japan for less than 5 years
• Lifestyle, including diet, has not changed significantly since leaving Japan
• White Subjects Only:
• A person having origins in any of the original peoples of Europe, the Middle East, or North Africa based on documented subject self-report
• All Subjects:
• Healthy male, 30 to 60 years inclusive, at the time of informed consent
• BMI of 18 to 32 kg/m2 inclusive at Screening
• Subjects must have had a successful vasectomy (confirmed azoospermia) or they and their female partners must not be of childbearing potential or must be practicing highly effective contraception (i.e. condom plus spermicide, condom plus diaphragm with spermicide, intrauterine device starting for at least one menstrual cycle before starting study drug\[s\]) and throughout the study period and for 30 days after study drug discontinuation. No sperm donation is allowed during the study period and for 30 days after study drug discontinuation.

You may not qualify if:

• Subjects who meet any of the following criteria will be excluded from this study:
• Any history of seizures or epilepsy
• Any medical condition which, in the opinion of the investigator has high risk of seizures
• Any history of cerebrovascular disease
• A history of prolonged QTc interval
• Any other clinically significant ECG abnormalities
• History of risk factors for torsade de pointes or the use of medications that prolonged the QT/QTc interval
• Heart rate less than 50 or greater than 100 beats/min
• History of ischemic heart disease
• Persistent systolic blood pressure (BP) greater than 140 mmHg or less than 90 mmHg and diastolic BP greater than 90 mmHg or less than 60 mmHg
• Left bundle branch block
• Evidence of clinically significant disease
• Any laboratory abnormalities considered clinically significant
• Clinically significant illness which requires medical treatment
• Any history of abdominal surgery that may affect study drugs

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: July 31, 2014
• First Posted: August 4, 2014
• Study Start: July 1, 2014
• Primary Completion: August 1, 2014
• Study Completion: October 1, 2014
• Last Updated: November 3, 2015

Record last verified: 2015-11

Locations

US (1)