A Randomized, Double-blind, Placebo-controlled, Single-Ascending Dose Study to Assess Safety, Tolerability, and Pharmacokinetics of E2307 in Healthy Young and Elderly Japanese Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 24
- 主要终点
- Plasma PK of E2307: Vz/F (apparent volume of distribution at terminal phase)
研究概览
简要总结
This study will be a single-center, single dose, randomized, double-blind, placebo-controlled study in healthy Japanese male subjects. The study will consist of 2 parts: Part A (young subjects) and Part B (elderly subjects). In Part A sequential cohorts of subjects will be treated with single ascending doses of E2307. The maximum tolerated dose (MTD) will be determined in Part A. Part B will be initiated after Part A is completed. In Part B one cohort of healthy elderly subjects will be treated with a single dose of E2307 at one dose level below the MTD. In part A, a total of 56 subjects will be enrolled into 7 cohorts sequentially and randomized 3:1 to receive either E2307 (1 mg, 3 mg, 10 mg, 30 mg, 100 mg, 200 mg, or 300 mg) or placebo. In part B, a total of 8 subjects will be randomized, 6 subjects to a single dose of E2307 and 2 subjects to placebo.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 20 Years 至 85 Years（Adult, Older Adult）
- 性别
- Male
- 接受健康志愿者
- 是
入选标准
- •Parts A and B
- •Provide written informed consent
- •Willing and able to comply with all aspects of the protocol
- •Part A: Young cohort
- •Non-smoking, male subjects age >=20 years and less than 55 years old at the time of informed consent
- •Part B: Elderly Cohort
- •Non-smoking, male subjects age >=65 years and less than 85 years old at the time of informed consent
排除标准
- •Subjects who meet any of the following criteria will be excluded from this study:
- •Clinically significant illness that requires medical treatment within 8 weeks or a clinically significant infection that requires medical treatment within 4 weeks of dosing
- •Any history of abdominal surgery that may affect PK profiles of E2307 (eg. hepatectomy, nephrectomy, digestive organ resection)
- •Known history of clinically significant drug allergy (at Screening)
研究组 & 干预措施
Part A: 1 mg E2307 (young cohort)
E2307 (1 x 1 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)
干预措施: E2307 (Drug)
Part A: 1 mg E2307 (young cohort)
E2307 (1 x 1 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)
干预措施: E2307 Matching Placebo (Drug)
Part A: 3 mg E2307 (young cohort)
E2307 (3 x 1 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)
干预措施: E2307 (Drug)
Part A: 3 mg E2307 (young cohort)
E2307 (3 x 1 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)
干预措施: E2307 Matching Placebo (Drug)
Part A: 10 mg E2307 (young cohort)
E2307 (1 x 10 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)
干预措施: E2307 (Drug)
Part A: 10 mg E2307 (young cohort)
E2307 (1 x 10 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)
干预措施: E2307 Matching Placebo (Drug)
Part A: 30 mg E2307 (young cohort)
E2307 (3 x 10 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)
干预措施: E2307 (Drug)
Part A: 30 mg E2307 (young cohort)
E2307 (3 x 10 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)
干预措施: E2307 Matching Placebo (Drug)
Part A: 100 mg E2307 (young cohort)
E2307 (1 x 100 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)
干预措施: E2307 (Drug)
Part A: 100 mg E2307 (young cohort)
E2307 (1 x 100 mg E2307 capsule) or placebo (1 x 1 E2307 matching placebo capsule)
干预措施: E2307 Matching Placebo (Drug)
Part A: 200 mg E2307 (young cohort)
E2307 (2 x 100 mg E2307 capsules) or placebo (2 x 1 E2307 matching placebo capsules)
干预措施: E2307 (Drug)
Part A: 200 mg E2307 (young cohort)
E2307 (2 x 100 mg E2307 capsules) or placebo (2 x 1 E2307 matching placebo capsules)
干预措施: E2307 Matching Placebo (Drug)
Part A: 300 mg E2307 (young cohort)
E2307 (3 x 100 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)
干预措施: E2307 (Drug)
Part A: 300 mg E2307 (young cohort)
E2307 (3 x 100 mg E2307 capsules) or placebo (3 x 1 E2307 matching placebo capsules)
干预措施: E2307 Matching Placebo (Drug)
Part B: Elderly cohort
One dose level below MTD from Part A
干预措施: E2307 (Drug)
结局指标
主要结局
Plasma PK of E2307: Vz/F (apparent volume of distribution at terminal phase)
时间窗: Up to 12 days
Vz/F are calculated for E2307 only
Plasma PK of E2307: AUC ratio (AUC ratio of metabolite to parent)
时间窗: Up to 12 days
Urine PK of E2307: Ae (cumulative amount of drug excreted in urine up to 264 hours postdose)
时间窗: Up to 12 days
Urine PK of E2307: CLR (renal clearance)
时间窗: Up to 12 days
Plasma PK of E2307: t1/2 (terminal elimination phase half-life)
时间窗: Up to 12 days
Number of adverse events/serious adverse events
时间窗: Up to 30 days
Plasma pharmacokinetics (PK) of E2307: Cmax (maximum observed concentration)
时间窗: Up to 12 days
Plasma PK of E2307: tmax (time at which the highest drug concentration occurs)
时间窗: Up to 12 days
Plasma PK of E2307: AUC(0-t) [area under the concentration (AUC)-time curve from zero time to time of last quantifiable concentration]
时间窗: Up to 12 days
Plasma PK of E2307: AUC(0-inf) [area under the concentration-time curve from zero time extrapolated to infinite time]
时间窗: Up to 12 days
Plasma PK of E2307: CL/F (apparent total clearance following oral administration)
时间窗: Up to 12 days
CL/F are calculated for E2307 only
次要结局
- Mean difference in change of mean blood pressure (BP) between E2307 and placebo(24 hours predose and continue until 24 hours postdose (Day 2))
- QT interval assessment using Holter monitoring(24 hours predose through Day 2 (at 24 hours postdose))