A Double-blind, Randomized, Placebo-controlled Study in Healthy Volunteers to Investigate the Safety, Tolerability and Pharmacokinetics of Oral AZD5055 Following Single and Multiple Ascending Doses
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 63
- 试验地点
- 1
- 主要终点
- Part 2: Number of participants with AEs
研究概览
简要总结
This is a phase I, First-in-Human study in healthy participants, performed at a single study center, consisting of 2 parts: Part 1 is a single ascending dose (SAD) study and Part 2 is a multiple ascending dose (MAD) study.
详细描述
Part 1: This is a double-blind, randomized, placebo-controlled study consisting of 2 parts. Part 1: SAD and Part 2: MAD.
Part 1 will be a double-blind, randomized, placebo-controlled study, with a sequential SAD design. Three dose levels of AZD5055 are planned to be investigated in 3 cohorts. Depending on evaluation of data from the preceding cohorts, 2 additional cohorts/dose levels may be added at the discretion of the SRC.
Part 1 will comprise of:
- A Screening Period of a maximum of 6 weeks.
- A Treatment Period during which subjects will be resident at the Clinical Unit from 1 day before IMP administration (Day 1) until at least 72 hours after IMP administration (Day 4). Subjects will receive a single oral dose of AZD5055 or placebo on Day 1.
- A Follow up Visit within 6 ± 1 day after the IMP dose.
Part 2 will be a double-blind, randomized, placebo-controlled study with a MAD design. Subjects will receive AZD5055 on Day 1 and Day 3 to Day 16, with no dosing on Day 2. Subjects will be naïve, ie, will not have participated in Part 1 of this study. Three dose levels of AZD5055 are planned to be investigated in 3 cohorts. Depending on evaluation of data of the preceding cohorts, up to 2 additional dose levels/cohorts may be added or expanded at the discretion of the SRC.
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
- 18 Years 至 55 Years（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
Part 1 (single ascending doses [SAD])
Healthy participants will be randomized to a single dose of AZD5055 or placebo.
干预措施: AZD5055 (Drug)
Part 1 (single ascending doses [SAD])
Healthy participants will be randomized to a single dose of AZD5055 or placebo.
干预措施: Placebo (Drug)
Part 2 (multiple ascending doses [MAD])
Healthy participants will be randomized to repeated dosing with AZD5055 or placebo
干预措施: AZD5055 (Drug)
Part 2 (multiple ascending doses [MAD])
Healthy participants will be randomized to repeated dosing with AZD5055 or placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Part 2: Number of participants with AEs
时间窗: Until follow-up (45 days post-last dose) (approximately up to 89 days)
To investigate the safety and tolerability of AZD5055 by assessment of AEs (non-serious and serious) following administration of MAD
Part 1: Number of participants with adverse events (AEs)
时间窗: Until Follow-up (7 days post dose) (approximately up to 53 days)
To investigate the safety and tolerability of AZD5055 by assessment of AEs (non-serious and serious) following administration of SAD
次要结局
- Part 1: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)(Day 1: profile 0-72 hours after dose)
- Part 2: Maximum observed plasma (peak) drug concentration (Cmax)(Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose)
- Part 1: Time to reach maximum observed concentration (tmax)(Day 1: profile 0-72 hours after dose)
- Part 1: Maximum observed plasma (peak) drug concentration (Cmax)(Day 1: profile 0-72 hours after dose)
- Part 1: Area under plasma concentration time curve from zero to infinity (AUCinf)(Day 1: profile 0-72 hours after dose)
- Part 2: Area under the plasma concentration curve from zero to the last quantifiable concentration (AUClast)(Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose)
- Part 1: Partial area under the plasma concentration-time curve from 0 to time 24 hours post dose [AUC(0-24)](Day 1: profile 0-72 hours after dose)
- Part 2: Area under plasma concentration time curve from zero to infinity (AUCinf)(Day 1: profile 0-48 hours after dose)
- Part 2: Time to reach maximum observed concentration (tmax)(Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose)
- Part 1: Mean residence time of the unchanged drug in the systemic circulation (MRTinf)(Day 1: profile 0-72 hours after dose)
- Part 2: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)(Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose)
- Part 1: Apparent volume of distribution following extravascular administration based on terminal phase (Vz/F)(Day 1: profile 0-72 hours after dose.)
- Part 1: Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)](Day 1: profile 0-72 hours after dose)
- Part 1: Cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)](Day 1: profile 0-72 hours after dose)
- Part 2: Accumulation ratio (Rac)(Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose)
- Part 2: Area under plasma concentration-time curve in the dose interval (repeat dose only) (AUC[0-1τ])(Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose)
- Part 2: Partial area under the plasma concentration-time curve from 0 to time 12 hours post dose [AUC(0-12)](Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose)
- Part 2: Half-life associated with terminal slope (λz) of a semi logarithmic concentration-time curve (t½λz)(Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose)
- Part 2: Apparent volume of distribution following extravascular administration based on terminal phase (Vz/F)(Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose)
- Part 1: Partial area under the plasma concentration-time curve from 0 to time 12 hours post dose [AUC(0-12)](Day 1: profile 0-72 hours after dose)
- Part 1: Half-life associated with terminal slope (λz) of a semi logarithmic concentration-time curve (t½λz)(Day 1: profile 0-72 hours after dose)
- Part 1: Apparent total body clearance of drug from plasma after extravascular administration (CL/F)(Day 1: profile 0-72 hours after dose)
- Part 2: Partial area under the plasma concentration-time curve from 0 to time 24 hours post dose [AUC(0-24)](Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose)
- Part 2: Mean residence time of the unchanged drug in the systemic circulation (MRTinf)(Day 1: profile 0-48 hours after dose)
- Part 2: Cumulative percentage of dose excreted unchanged in urine from time t1 to time t2 [fe(t1-t2)](Day 1-3 and Day 16-19)
- Part 1: Renal clearance of drug from plasma (CLR)(Day 1: profile 0-72 hours after dose)
- Part 2: Cumulative amount of unchanged drug excreted into urine from time t1 to time t2 [Ae(t1-t2)](Day 1-3 and Day 16-19)
- Part 2: Renal clearance of drug from plasma (CLR)(Day 1-3 and Day 16-19)
- Part 2: Temporal change parameter in systemic exposure (TCP)(Day 1: profile 0-48 hours after dose, Day 16; profile 0-72 hours after dose)
- Part 1: Accumulation ratio (Rac)(Day 1: profile 0-72 hours after dose)
- Part 1: Temporal change parameter in systemic exposure (TCP)(Day 1: profile 0-72 hours after dose)