Clinical Trials/NCT04676685

NCT04676685

Completed

Phase 1

A Randomized, Double-Blind, Placebo-Controlled, Multiple-Ascending Dose and Single Dose Food Effect Study to Assess the Safety, Tolerability, and Pharmacokinetics of E2730 in Healthy Subjects

Eisai Inc.1 site in 1 country32 target enrollmentDecember 16, 2020

ConditionsHealthy Volunteers

InterventionsE2730 E2730-matched placebo

DrugsE2730 E2730-matched placebo

Overview

Phase: Phase 1
Intervention: E2730
Conditions: Healthy Volunteers
Sponsor: Eisai Inc.
Enrollment: 32
Locations: 1
Primary Endpoint: Part A, tmax: Time at Which the Highest Drug Plasma Concentration Occurs for E2730
Status: Completed
Last Updated: 4 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The primary purpose of the study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of E2730 of multiple ascending oral doses in healthy adult participants and to assess the differences in PK, safety, and tolerability of E2730 between healthy Japanese and non-Japanese participants following multiple doses. This study will also determine the effect of food on PK of E2730.

Registry

clinicaltrials.gov

Start Date

December 16, 2020

End Date

June 23, 2021

Last Updated

4 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Eisai Inc.

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Non-smoking, healthy male or female, age greater than or equal to (\>=) 18 years and \<55 years old at the time of informed consent. To be considered non-smokers, Participants must have discontinued smoking for at least 4 weeks before dosing
•Japanese Participants 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
•Body mass index (BMI) \>=18 and \<30 kilograms per meter square (kg/m\^2) at Screening

Exclusion Criteria

•Females who are breastfeeding or pregnant at Screening or Baseline (as documented by a positive beta-human chorionic gonadotropin \[β-hCG\] test). A separate baseline assessment is required if a negative screening pregnancy test was obtained more than 72 hours before the first dose of study drug
•Females of childbearing potential who:
•Within 28 days before study entry, did not use a highly effective method of contraception, which includes any of the following:
•Total abstinence (if it is their preferred and usual lifestyle)
•An intrauterine device or intrauterine hormone-releasing system (IUS)
•A contraceptive implant
•An oral contraceptive (Participant must have been on a stable dose of the same oral contraceptive product for at least 28 days before dosing and must agree to stay on the same dose of the oral contraceptive throughout the study and for 28 days after study drug discontinuation)
•Have a vasectomized partner with confirmed azoospermia
•Do not agree to use a highly effective method of contraception throughout the entire study period and for 28 days after study drug discontinuation
•Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the exclusion criteria above (that is, the female partners are of childbearing potential and are not willing to use a highly effective contraceptive method throughout the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation)

Arms & Interventions

Part A, Cohort 4: E2730 80 mg or Placebo

Healthy Japanese and non-Japanese participants will receive E2730 80 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.

Intervention: E2730

Part A, Cohort 4: E2730 80 mg or Placebo

Healthy Japanese and non-Japanese participants will receive E2730 80 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.

Intervention: E2730-matched placebo

Part B, E2730 80 mg: Fasted + Fed

Participants will receive a single treatment of E2730 (80 mg capsule) in fasted condition on Day 1 treatment period 1 followed by E2730 80 mg capsule in fed condition on Day 1 of treatment period 2. A washout period of at least 21 days will be maintained between the 2 treatments.

Intervention: E2730

Part A, Cohort 1: E2730 20 Milligram (mg) or Placebo

Healthy Japanese and non-Japanese participants will receive E2730 20 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.

Intervention: E2730

Part A, Cohort 1: E2730 20 Milligram (mg) or Placebo

Healthy Japanese and non-Japanese participants will receive E2730 20 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.

Intervention: E2730-matched placebo

Part A, Cohort 2: E2730 40 mg or Placebo

Healthy Japanese and non-Japanese participants will receive E2730 40 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.

Intervention: E2730

Part A, Cohort 2: E2730 40 mg or Placebo

Healthy Japanese and non-Japanese participants will receive E2730 40 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.

Intervention: E2730-matched placebo

Part A, Cohort 3: E2730 60 mg or Placebo

Healthy Japanese and non-Japanese participants will receive E2730 60 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.

Intervention: E2730

Part A, Cohort 3: E2730 60 mg or Placebo

Healthy Japanese and non-Japanese participants will receive E2730 60 mg or E2730-matched placebo, capsules, orally, once daily for 18 days under fasted conditions.

Intervention: E2730-matched placebo

Part B, E2730 80 mg: Fed + Fasted

Participants will receive a single treatment of E2730 80 mg capsule in fed condition on Day 1 of treatment period 1 followed by E2730 80 mg capsule in fasted condition on Day 1 of treatment period 2. A washout period of at least 21 days will be maintained between the 2 treatments.

Intervention: E2730

Outcomes

Primary Outcomes

Part A, tmax: Time at Which the Highest Drug Plasma Concentration Occurs for E2730

Time Frame: Day 1: 0-24 hours; Day 18: 0-336 hours

Part A, Css,av: Average Steady State Plasma Concentration at Steady State for E2730

Time Frame: Time Frame: Day 18: 0-24 hours

Part A, Rac: Accumulation Ratio for Cmax and AUC for E2730

Time Frame: Day 1: 0-24 hours; Day 18: 0-24 hours

Part B, AUC(0-24h): Area Under the Plasma Concentration-time Curve From Zero Time to 24 Hours After Dosing for E2730

Time Frame: Day 1: 0-24 hours; Day 22: 0-24 hours

Number of Participants With Treatment-emergent Adverse Events (TEAEs)

Time Frame: Screening up to Day 32 (approximately 60 days)

Safety assessments will consist of monitoring and recording all adverse events (AEs); laboratory evaluation for hematology, clinical chemistry, and urinalysis; periodic measurement of vital signs, electrocardiograms (ECGs), electroencephalogram (EEGs), corrected QT (QTc) interval and blood pressure.

Part A, Css,min: Minimum Observed Plasma Concentration at Steady State for E2730

Time Frame: Time Frame: Day 18: 0-24 hours

Part A, AUC(0-24h): Area Under the Plasma Concentration-time Curve From Zero Time to 24 Hours After Dosing for E2730

Time Frame: Day 1: 0-24 hours; Day 18: 0-24 hours

Part A, t1/2: Terminal Elimination Phase Half-life Following Last day of Dosing for E2730

Time Frame: Day 18: 0-336 hours

Part A, CLss/F: Apparent Total Clearance Following Extravascular Administration at Steady State for E2730

Time Frame: Day 18: 0-336 hours

Part A, Cmax: Maximum Observed Plasma Concentration for E2730

Time Frame: Day 1: 0-24 hours; Day 18: 0-336 hours

Part A, Vz/F: Apparent Volume of Distribution at Terminal Phase

Time Frame: Day 18: 0-336 hours

Part B, Cmax: Maximum Observed Plasma Concentration for E2730