A Phase I Double-Blind, Randomised, Placebo-Controlled, Multiple Ascending Dose Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of UE2343 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Assess the Pharmacokinetic (PK) Plasma Parameter Area Under the Curve (AUC) of UE2343 after a single dose
研究概览
简要总结
The purpose of this study is to determine whether the drug UE2343, a potential treatment for Alzheimer's Disease (AD), is effective by assessing safety, tolerability, pharmacokinetics and pharmacodynamics in a Multiple Ascending Dose Study. Protocol amendments to the study will examine any food effect and determine if the drug penetrates the Blood-Brain Barrier.
详细描述
Part 1 of this study is a double-blind, randomised, placebo-controlled, multiple ascending dose study to assess the safety, tolerability, PK and PD in healthy participants dosed twice daily at levels of 10, 20 and 35mg for 10 days.This part of the study will recruit 3 groups of 8 participants each.
Part 2 is a cross-over study to assess the effects of food on the PK of UE2343 in healthy participants dosed with two single doses at a level decided from Part 1. This part of the study will recruit a total of 12 participants.
Part 3 seeks to determine the PK of the UE2343 in CSF of healthy participants dosed twice daily for 4 days with a dose level determined from Part 1 and 2. This part of the study will recruit 4 participants.
Strategies to ensure adherence to the study include the requirement that participants remain at the clinical research facility for the duration of their participation in the study; drug accountability checks (i.e. reconciliation of used and unused capsules) by an independent clinical research associate; and administration of the capsules to the participant by a member of the study site team.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Willing to use specified contraception
- •BMI within specified range
- •No clinically significant abnormalities in the results of laboratory evaluations at Screening and Day -1.
排除标准
- •Abnormal medical history, including history of dementia
- •No significant allergic reactions
- •No prior drug or alcohol abuse
- •Use of regular prescribed medication
研究组 & 干预措施
MAD Study
干预措施: UE2343 (Drug)
MAD Study
干预措施: Placebo (Drug)
Fed-Fasted
干预措施: Placebo (Drug)
Fed-Fasted
干预措施: UE2343 (Drug)
CSF
干预措施: UE2343 (Drug)
结局指标
主要结局
Assess the Pharmacokinetic (PK) Plasma Parameter Area Under the Curve (AUC) of UE2343 after a single dose
时间窗: Day 1 and Day 8
Assess PK Parameter Maximum Plasma Concentration (Cmax) of UE2343 in CSF
时间窗: Day 4
Assess the Pharmacokinetic (PK) Plasma Parameter Maximum Plasma Concentration (Cmax) of UE2343 after a single dose
时间窗: Day 1 and Day 8
Assess the Pharmacokinetic (PK) Plasma Parameter Time to Cmax (Tmax) of UE2343 after a single dose
时间窗: Day 1 and Day 8
Assess the Pharmacokinetic (PK) Plasma Parameter Terminal Elimination Half Life (t½) of UE2343 after a single dose
时间窗: Day 1 and Day 8
Assess Safety and Tolerability of UE2343 over 17 days including AEs, 12-lead ECGs, vital signs, Nerve conduction velocity, Labs.
时间窗: Up to Day 17
次要结局
- Assess Pharmacokinetics (PK) Plasma parameter Maximum Plasma Concentration (Cmax) from time of dosing to 12 hours(Day 1 and Day 10)
- Assess Pharmacodynamics (PD) Urine parameter Urinary Free Cortisol (UFF) from baseline to end of study(Days 1, 10, 11 and 12)
- Assess Pharmacokinetics (PK) Plasma parameter Area Under the Curve (AUC) from time of dosing to 12 hours(Day 1 and Day 10)
- Assess Pharmacodynamics (PD) Urine parameter Urinary Free Cortisone (UFE) from baseline to end of study(Days 1, 10, 11 and 12)
- Assess Pharmacodynamics (PD) Urine parameter 5α-tetrahydrocortisol (5αTHF) from baseline to end of study(Days 1, 10, 11 and 12)
- Assess Pharmacodynamics (PD) Urine parameter tetrahydrocortisone (THE) from baseline to end of study(Days 1, 10, 11 and 12)
- Assess Pharmacokinetics (PK) Urine parameters (Amount of drug excreted in urine (Ae) and Ae as a % of dose) from time of dosing to 24 hours(Day 1 and Day 10)
- Assess PK Parameter Maximum Plasma Concentration (Cmax) of UE2343 in CSF compared to the Cmax value obtained in plasma(Day 4)
- Assess Pharmacodynamics (PD) Blood parameter Serum Cortisol from baseline to end of study(Days 1, 10, 11, 12, 13 and 17.)
- Assess Pharmacodynamics (PD) Blood parameter for Adrenal Androgens from baseline to end of study(Days 1, 10, 11, 12, 13 and 17.)
- Assess Pharmacodynamics (PD) Urine parameter 5β-tetrahydrocortisol (5βTHF) from baseline to end of study(Days 1, 10, 11 and 12)
- Assess Pharmacokinetics (PK) Plasma parameter Time to Cmax (Tmax) from time of dosing to 12 hours(Day 1 and Day 10)
- Assess Pharmacokinetics (PK) Plasma parameter Terminal Elimination Half Life (t½) from time of dosing to 12 hours(Day 1 and Day 10)
- Assess Pharmacodynamics (PD) Blood parameter Adrenocorticotropic hormone (ACTH) from baseline to end of study(Days 1, 10, 11, 12, 13 and 17.)