Healthy Volunteers
Conditions
Keywords
E2730, Healthy participants, Pharmacokinetics
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.
Interventions
DRUGE2730
E2730 capsules.
DRUGE2730-matched placebo
E2730-matched placebo capsules.
Sponsors
Eisai Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
1. 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 2. 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 3. Body mass index (BMI) \>=18 and \<30 kilograms per meter square (kg/m\^2) at Screening
Exclusion criteria
1. 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 2. 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 3. Males who have not had a successful vasectomy (confirmed azoospermia) if their female partners meet the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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 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 Cmax Between the Fasted and fed State for E2730 | Day 1: 0-288 hours; Day 22: 0-288 hours | — |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | 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, 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 | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Change From Baseline in QT Interval by Fridericia (QTcF) | Baseline, Day 32 | — |
| Change From Baseline in PR Interval of the ECG (PR), QRS Interval of the ECG (QRS) | Baseline, Day 32 | — |
| Placebo Corrected Change From Baseline in QTcF, PR and QRS | Baseline, Day 32 | — |
| Number of Participants With Categorical Outliers for QTcF, HR, PR, and QRS | Baseline, Day 32 | — |
| Number of Participants With T-wave Morphology Changes | Baseline up to Day 32 | The T-wave morphology categories includes the following: Normal T-wave (Any positive T-wave not meeting any criterion); Flat T-wave (T amplitude less than (\<) 1 millimeter \[mm\] \[either positive or negative\] including flat isoelectric line); Notched T-wave (+) (Presence of notch(es) of at least 0.05 millivolt \[mV\] amplitude on ascending or descending arm of the positive T-wave); Biphasic (T-wave that contains a second component with an opposite phase that is at least 0.1 mV deep (both positive/negative and negative/positive and polyphasic T-waves included); Normal T-wave (-) (T amplitude that is negative, without biphasic T-wave or notches); Notched T-wave (-) (Presence of notch(es) of at least 0.05 mV amplitude on descending or ascending arm of the negative T-wave). |
| Number of Participants With Presence of Abnormal U-wave | Baseline up to Day 32 | — |
| Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) | Baseline, Day 32 | — |
Countries
United States
Outcome results
None listed