A Study to Assess the Safety and Tolerability of E2730 After Multiple Dose and the Food Effect After Single Dose in Healthy Participants

NCT04676685 | Completed Phase 1 FDA Drug

• 1 other identifier: E2730-A001-013
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Volunteers

Keywords

E2730; Healthy participants; Pharmacokinetics

Outcome Measures

Primary Outcomes (24)

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

  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.

  Screening up to Day 32 (approximately 60 days)

• Part A, Cmax: Maximum Observed Plasma Concentration for E2730

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

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

  Time Frame: Day 18: 0-24 hours

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

  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: 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

  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

  Day 18: 0-336 hours

• Part A, PTF: Peak-trough Fluctuation for E2730

  Day 18: 0-24 hours

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

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

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

  Day 18: 0-336 hours

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

  Day 18: 0-336 hours

• Part B, Cmax: Maximum Observed Plasma Concentration for E2730

  Day 1: 0-288 hours; Day 22: 0-288 hours

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

  Day 1: 0-288 hours; Day 22: 0-288 hours

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

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

• Part B, AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to Time of Last Quantifiable Concentration for E2730

  Day 1: 0-288 hours; Day 22: 0-288 hours

• Part B, AUC(0-72h): Area Under the Plasma Concentration-time Curve From Zero Time to 72 Hours After Dosing for E2730

  Day 1: 0-72 hours; Day 22: 0-72 hours

• Part B, AUC(0-inf): Area Under the Plasma Concentration-time Curve From Zero Time Extrapolated to Infinite Time for E2730

  Day 1: 0-288 hours; Day 22: 0-288 hours

• Part B, t1/2: Terminal Elimination Phase Half-life for E2730

  Day 1: 0-288 hours; Day 22: 0-288 hours

• Part A: Geometric Mean Ratio of Cmax Between the Healthy Japanese and non-Japanese Participants for E2730

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

• Part A: Geometric Mean Ratio of AUC(0-24) Between the Healthy Japanese and non-Japanese Participants for E2730

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

• Part B: Geometric Mean Ratio of Cmax Between the Fasted and fed State for E2730

  Day 1: 0-288 hours; Day 22: 0-288 hours

• Part B: Geometric Mean Ratio of AUC(0-t) Between the Fasted and fed State for E2730

  Day 1: 0-288 hours; Day 22: 0-288 hours

• Part B: Geometric Mean Ratio of AUC(0-72h) Between the Fasted and fed State for E2730

  Day 1: 0-72 hours; Day 22: 0-72 hours

• Part B: Geometric Mean Ratio of AUC(0-inf) Between the Fasted and fed State for E2730

  Day 1: 0-288 hours; Day 22: 0-288 hours

Secondary Outcomes (11)

• Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP)

  Baseline, Day 32

• Change From Baseline in Heart Rate (HR)

  Baseline, Day 32

• Placebo Corrected Change From Baseline in SBP and DBP

  Baseline, Day 32

• Placebo Corrected Change From Baseline in HR

  Baseline, Day 32

• Number of Participants With Categorical Outliers for SBP and DBP

  Baseline up to Day 32

Study Arms (6)

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

EXPERIMENTAL

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.

Drug: E2730; Drug: E2730-matched placebo

Part A, Cohort 2: E2730 40 mg or Placebo

EXPERIMENTAL

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.

Drug: E2730; Drug: E2730-matched placebo

Part A, Cohort 3: E2730 60 mg or Placebo

EXPERIMENTAL

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.

Drug: E2730; Drug: E2730-matched placebo

Part A, Cohort 4: E2730 80 mg or Placebo

EXPERIMENTAL

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.

Drug: E2730; Drug: E2730-matched placebo

Part B, E2730 80 mg: Fasted + Fed

EXPERIMENTAL

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.

Drug: E2730

Part B, E2730 80 mg: Fed + Fasted

EXPERIMENTAL

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.

Drug: E2730

Interventions

E2730 DRUG

E2730 capsules.

Part A, Cohort 1: E2730 20 Milligram (mg) or Placebo; Part A, Cohort 2: E2730 40 mg or Placebo; Part A, Cohort 3: E2730 60 mg or Placebo; Part A, Cohort 4: E2730 80 mg or Placebo; Part B, E2730 80 mg: Fasted + Fed; Part B, E2730 80 mg: Fed + Fasted

E2730-matched placebo DRUG

E2730-matched placebo capsules.

Part A, Cohort 1: E2730 20 Milligram (mg) or Placebo; Part A, Cohort 2: E2730 40 mg or Placebo; Part A, Cohort 3: E2730 60 mg or Placebo; Part A, Cohort 4: E2730 80 mg or Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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
• Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
• Evidence of disease that may influence the outcome of the study within 4 weeks before dosing; example, psychiatric disorders and disorders of the gastrointestinal tract, liver, kidney, respiratory system, endocrine system, hematological system, neurological system, or cardiovascular system, or participants who have a congenital abnormality in metabolism
• Any history of gastrointestinal surgery that may affect PK profiles of E2730, example, hepatectomy, nephrectomy, and digestive organ resection
• Any clinically abnormal symptom or organ impairment found by medical history, physical examinations, vital signs, ECG finding, or laboratory test results that require medical treatment at Screening
• A prolonged QT interval of the ECG/Corrected QT interval (QT/QTc) (QTcF greater than \[\>\] 450 milliseconds \[ms\]) demonstrated by a repeated ECG at Screening or Baseline (based on average of triplicate ECGs). A history of risk factors for torsade de pointes (example, heart failure, hypokalemia, family history of long QT Syndrome) or the use of concomitant medications that prolonged the QT/QTc interval
• Persistent systolic BP \>139 or \<90 millimeter of mercury (mmHg) or diastolic BP \>89 or \<50 mmHg at Screening or Baseline

Sponsors & Collaborators

• Eisai Inc.: lead

Study Sites (1)

Collaborative Neuroscience Research, LLC.

Long Beach, California, 90806, United States

Location

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: December 21, 2020
• Study Start: December 16, 2020
• Primary Completion: June 23, 2021
• Study Completion: June 23, 2021
• Last Updated: August 26, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will share

Locations

US (1)