A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, and Pharmacokinetics of E6742 in Japanese Healthy Adult Subjects
Overview
- Phase
- Phase 1
- Intervention
- E6742
- Conditions
- Healthy Volunteers
- Sponsor
- Eisai Co., Ltd.
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- AUC(0-12h): Area Under the Plasma Concentration-time Curve From Zero Time to 12 Hours Postdose for E6742 and its Metabolite (ER-001132963) on Day 1
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The primary purpose of the study is to evaluate the safety, tolerability and pharmacokinetics (PK) of multiple ascending oral doses of E6742 in Japanese healthy adult participants.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Non-smoking, male or female Japanese, greater than or equal to (\>=) age 20 years and less than or equal to (\<=) 55 years old at the time of informed consent
- •Body mass index (BMI) \>=18.5 and less than (\<) 25.0 kilogram per meter square (kg/m\^2) at Screening
Exclusion Criteria
- •Females who are breastfeeding or pregnant at Screening or Baseline
- •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
- •An intrauterine device (IUD) or intrauterine hormone-releasing system (IUS)
- •A contraceptive implant
- •An oral contraceptive
- •Have a vasectomized partner with confirmed azoospermia
- •Do not agree to use a highly effective method of contraception (as described above) throughout the entire study period and for 28 days after study drug discontinuation
- •Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (that is, not of childbearing potential or practicing highly effective contraception throughout the study period and for 5 times the half-life of the study drug plus 90 days after study drug discontinuation)
Arms & Interventions
Cohort 2: E6742 200 mg or Placebo
Participants will receive E6742 200 mg or E6742-matched placebo, tablets, orally, twice daily for 6 days under fasted conditions and once on Day 7 in the morning.
Intervention: E6742
Cohort 2: E6742 200 mg or Placebo
Participants will receive E6742 200 mg or E6742-matched placebo, tablets, orally, twice daily for 6 days under fasted conditions and once on Day 7 in the morning.
Intervention: Placebo
Cohort 3: E6742 400 mg or Placebo
Participants will receive E6742 400 mg or E6742-matched placebo, tablets, orally, twice daily for 6 days under fasted conditions and once on Day 7 in the morning.
Intervention: E6742
Cohort 3: E6742 400 mg or Placebo
Participants will receive E6742 400 mg or E6742-matched placebo, tablets, orally, twice daily for 6 days under fasted conditions and once on Day 7 in the morning.
Intervention: Placebo
Cohort 1: E6742 100 milligram (mg) or Placebo
Participants will receive E6742 100 mg or E6742-matched placebo, tablets, orally, twice daily for 6 days under fasted conditions and once on Day 7 in the morning.
Intervention: E6742
Cohort 1: E6742 100 milligram (mg) or Placebo
Participants will receive E6742 100 mg or E6742-matched placebo, tablets, orally, twice daily for 6 days under fasted conditions and once on Day 7 in the morning.
Intervention: Placebo
Outcomes
Primary Outcomes
AUC(0-12h): Area Under the Plasma Concentration-time Curve From Zero Time to 12 Hours Postdose for E6742 and its Metabolite (ER-001132963) on Day 1
Time Frame: Day 1: 0-12 hours
AUC Metabolite to E6742 Ratio Following Molecular Weight Correction to E6742 Equivalents on Day 1
Time Frame: Day 1: 0-12 hours
Cmax: Maximum Observed Plasma Concentration for E6742 and its Metabolite (ER-001132963) on Day 1
Time Frame: Day 1: 0-12 hours
Incidence of Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Baseline up to 28 days after the last dose of study drug (approximately Day 35)
Safety assessments will consist of monitoring and recording all adverse events (AEs) and SAEs; laboratory evaluation for hematology, blood chemistry, and urine values; periodic measurement of vital signs and electrocardiograms (ECGs); and the performance of physical examinations.
tss,max: Time at Which the Highest Drug Plasma Concentration Occurs at Steady State for E6742 and its Metabolite (ER-001132963) on Day 7
Time Frame: Day 7: 0-168 hours
Css,av: Average Steady State Plasma Concentration for E6742 and its Metabolite (ER-001132963) on Day 7
Time Frame: Day 7: 0-168 hours
AUC(0-t): Area Under the Plasma Concentration-time Curve From Zero Time to Time of Last Quantifiable Concentration for E6742 and its Metabolite (ER-001132963) on Day 7
Time Frame: Day 7: 0-168 hours
tmax: Time at Which the Highest Drug Plasma Concentration Occurs for E6742 and its Metabolite (ER-001132963) on Day 1
Time Frame: Day 1: 0-12 hours
Css,max: Maximum Observed Plasma Concentration at Steady State for E6742 and its Metabolite (ER-001132963) on Day 7
Time Frame: Day 7: 0-168 hours
AUC(0-12hr): Area Under the Plasma Concentration-time Curve Within a Dosing Interval at Steady State for E6742 and its Metabolite (ER-001132963) on Day 7
Time Frame: Day 7: 0-12 hours
t1/2: Terminal Elimination Phase Half-life for E6742 and its Metabolite (ER-001132963) on Day 7
Time Frame: Day 7: 0-168 hours
CLss/F: Apparent Total Clearance at Steady State for E6742 on Day 7
Time Frame: Day 7: 0-168 hours
Vss/F: Apparent Volume of Distribution at Steady State for E6742 on Day 7
Time Frame: Day 7: 0-168 hours
PTF: Peak-trough Fluctuation for E6742 and its Metabolite (ER-001132963) on Day 7
Time Frame: Day 7: 0-168 hours
Accumulation Ratio for Cmax and AUC for E6742 and its Metabolite (ER-001132963) on Day 7
Time Frame: Day 7: 0-168 hours
Metabolite to E6742 AUC Ratio Following Molecular Weight Correction to E6742 Equivalents on Day 7
Time Frame: Day 7: 0-168 hours
AUC(0-12hr)ss: Area Under the Plasma Concentration-time Curve Within a Dosing Interval at Steady State for E6742 and its Metabolite (ER-001132963) on Day 7
Time Frame: Day 7: 0-12 hours
Secondary Outcomes
- Change From Baseline in Corrected QT Interval (QTc) for E6742(Day 1 and 7: 0-12 hours)