A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2027 in Healthy Subjects
Overview
- Phase
- Phase 1
- Intervention
- E2027
- Conditions
- Healthy Subjects
- Sponsor
- Eisai Inc.
- Enrollment
- 74
- Locations
- 1
- Primary Endpoint
- Maximum drug concentration (Cmax)
- Status
- Completed
- Last Updated
- 7 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacodynamics (PD) and pharmacokinetics (PK) of multiple ascending oral doses of E2027 in healthy participants.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
E2027
Four sequential cohorts of healthy participants (≥50 years and ≤85 years old) will be treated with multiple ascending doses of E2027 up to the maximum tolerated dose (MTD). A total of 6 participants per cohort will be randomized to E2027.Proposed doses of E2027 are: * Part A Cohort 1: 50 mg (1 × 50 mg capsule) * Cohort 2: 100 mg (2 × 50 mg capsules) * Cohort 3: 200 mg (4 × 50 mg capsules) * Cohort 4: 400 mg (8 × 50 mg capsules) * Cohort 6: 25 mg (5 × 5 mg capsules) Part B * Cohort 5: 400 mg (8 × 50 mg capsule) Part C: • Cohort 7: 50 mg (1 × 50 mg capsules) Part D: * Cohort 8: 5 mg (1 × 5 mg capsules) * Cohort 9: 10 mg (2 × 5 mg capsules)
Intervention: E2027
Placebo
Four sequential cohorts of healthy participants (≥50 years and ≤85 years old) will be treated with multiple ascending doses of E2027 matched placebo up to the MTD. A total of 2 participants per cohort will be randomized to E2027 matched placebo.
Intervention: E2027 matched placebo
Outcomes
Primary Outcomes
Maximum drug concentration (Cmax)
Time Frame: Day 1 and Day 14
Blood samples will be collected on Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours; Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours); and Day 15 (24 hours postdose from Day 14).
Mean predose drug concentration (Cmin)
Time Frame: Predose on Days 2, 4, 6, 8, 10, 12, 13, and 14
Mean ratio of cerebrospinal fluid (CSF) : plasma concentrations
Time Frame: Day -2 (time-matched to the Day 13 lumbar puncture [LP]) and Day 13 (predose)
Mean time to reach maximum (peak) drug concentration (tmax)
Time Frame: Day 1 and Day 14
Blood samples will be collected on Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18 and 24 hours; Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours); and Day 15 (24 hours postdose from Day 14).
Mean apparent volume of distribution at steady state (Vss/F)
Time Frame: Day 14
Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).
Mean area under the concentration-time curve from zero time to 24 hours postdose (AUC(0-24h))
Time Frame: Day 1 and Day 14
Blood samples will be collected on Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18 and 24 hours; Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours); and Day 15 (24 hours postdose from Day 14).
Mean terminal elimination half-life (t1/2)
Time Frame: Day 14
Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).
Mean apparent clearance at steady state (CLss/F)
Time Frame: Day 14
Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).
Mean area under the concentration-time curve from zero time extrapolated to infinity (AUC(0-inf))
Time Frame: Day 14
Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).
Average steady state drug concentration (Css,av)
Time Frame: Day 14
Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).
Mean accumulation ratio (Rac) (Day 14: Day 1) for AUC(0-24h), Cmax and Cmin
Time Frame: Day 1 and Day 14
Day 1 at predose and postdose 0.5 (30 minutes), 1, 1.5, 2, 3, 4, 5, 6, 8, 12, 18 and 24 hours; Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours); and Day 15 (24 hours postdose from Day 14)
Mean peak-trough fluctuation ratio (PTF)
Time Frame: Day 14
Blood samples will be collected on Day 14 (at predose and postdose 0.5, 1, 1.5, 2, 3, 4, 5, 6, 8, 12, and 18 hours) and Day 15 (24 hours postdose from Day 14).
Secondary Outcomes
- Percentage change from Baseline in pharmacodynamic measure(Day -2 (baseline with no drug) to Day 13 (on drug))
- Change from baseline in Observed Fridericia's Correction Formula (QTcF)(Days -1, 1, and 14)