A Randomized, Double-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of E2027 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- Eisai Inc.
- 入组人数
- 74
- 试验地点
- 1
- 主要终点
- Maximum drug concentration (Cmax)
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
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)
干预措施: E2027 (Drug)
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.
干预措施: E2027 matched placebo (Drug)
结局指标
主要结局
Maximum drug concentration (Cmax)
时间窗: 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)
时间窗: Predose on Days 2, 4, 6, 8, 10, 12, 13, and 14
Mean ratio of cerebrospinal fluid (CSF) : plasma concentrations
时间窗: Day -2 (time-matched to the Day 13 lumbar puncture [LP]) and Day 13 (predose)
Mean time to reach maximum (peak) drug concentration (tmax)
时间窗: 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)
时间窗: 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))
时间窗: 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)
时间窗: 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)
时间窗: 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))
时间窗: 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)
时间窗: 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
时间窗: 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)
时间窗: 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).
次要结局
- 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)