A Randomised, Double Blind (Sponsor Unblinded), Placebo-controlled, First Time in Human Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Single and Repeat Oral Doses and the Food Effect of GSK2556286 in Healthy Adult Participants
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 92
- 试验地点
- 1
- 主要终点
- Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK2556286
研究概览
简要总结
This first time in human (FTIH) study assesses the safety, tolerability, and pharmacokinetics (PK) of single and multiple increasing doses of GSK2556286. It also includes food effect cohorts to evaluate how food influences the PK of GSK2556286. The findings will help determine appropriate dosing for future clinical studies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
This is a double-blind study.
入排标准
- 年龄范围
- 18 Years 至 60 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 A: Participants receiving GSK2556286
Participants will be randomized to receive GSK2556286 in any of the 11 cohorts. In each dosing cohort, 6 participants will receive a single dose of GSK2556286. Following initial dosing of cohorts in the fasted state, one cohort will investigate the effect of food administration (high fat meal) on safety, tolerability and PK data of GSK2556286. One cohort may also investigate the effects of a moderate fat meal.
干预措施: GSK2556286 (Drug)
Part A: Participants receiving placebo
Participants will be randomized to receive matching placebo in any of the 11 cohorts. In each dosing cohort, 2 participants will receive a single dose of matching placebo.
干预措施: Placebo (Drug)
Part B: Participants receiving GSK2556286
Participants will be randomized to receive GSK2556286 in any of the 4 cohorts. In each dosing cohort, 6 participants will receive repeat doses of GSK2556286 under either fasting or fed conditions, dependent on the results from Part A.
Appropriate doses and dose regimens for Part B will be selected by the Dose Escalation Committee based on available safety, tolerability and PK data from Part A and/or any preceding repeat dose cohorts from Part B.
干预措施: GSK2556286 (Drug)
Part B: Participants receiving placebo
Participants will be randomized to receive matching placebo in any of the 4 cohorts. In each dosing cohort, 2 participants will receive repeat doses of matching placebo under either fasting or fed conditions, dependent on the results from Part A.
干预措施: Placebo (Drug)
结局指标
主要结局
Part A: Time to maximum observed plasma drug concentration (Tmax) of GSK2556286
时间窗: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: AUC(0-inf) of GSK2556286
时间窗: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Plasma concentrations of GSK2556286
时间窗: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Area under the plasma drug concentration versus time curve from time zero during a dosage interval of time tau (AUC[0-tau)] of GSK2556286
时间窗: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Area under the plasma drug concentration versus time curve from time zero to last time of quantifiable concentration (AUC[0-t]) of GSK2556286
时间窗: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Plasma concentrations of GSK2556286
时间窗: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose. Day 12 and 13: Pre-dose
Part B: AUC(0-t) of GSK2556286
时间窗: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Number of participants with any serious adverse events (SAEs) and non-SAEs
时间窗: Up to Day 15
Part B: Number of participants with any SAEs and non-SAEs
时间窗: Up to Day 28
Part B: Number of participants with AEs (SAEs and non-SAEs) by severity
时间窗: Up to Day 28
Part A: AUC from time zero extrapolated to infinity (AUC[0-inf]) of GSK2556286
时间窗: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Apparent terminal half-life (T1/2) of GSK2556286
时间窗: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part A: Number of participants with AEs (SAEs and non-SAEs) by severity
时间窗: Up to Day 15
Part A: Maximum observed plasma drug concentration (Cmax) of GSK2556286
时间窗: Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Cmax of GSK2556286
时间窗: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Tmax of GSK2556286
时间窗: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
Part B: Trough plasma concentration (Ctau) of GSK2556286
时间窗: Pre-dose on Days 1, 12, 13 and 14
Part B: T1/2 of GSK2556286
时间窗: Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose
次要结局
- Part A: Dose proportionality of GSK2556286 based on AUC(0-t)(Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part A: AUC(0-t) of GSK2556286 under fasted and fed conditions(Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part A: Tmax of GSK2556286 under fasted and fed conditions(Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part B: Dose proportionality of GSK2556286 based on Cmax(Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part A: T1/2 of GSK2556286 under fasted and fed conditions(Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part B: Observed accumulation ratio of GSK2556286 based on AUC (AUC[Ro])(Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part B: Observed accumulation ratio of GSK2556286 based on Cmax (RCmax)(Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part A: AUC(0-inf) of GSK2556286 under fasted and fed conditions(Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part A: Cmax of GSK2556286 under fasted and fed conditions(Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part A: Dose proportionality of GSK2556286 based on AUC(0-inf)(Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part A: Dose proportionality of GSK2556286 based on Cmax(Day 1: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part B: Ctau at the end of the dosing interval to assess steady state of GSK2556286(Pre-dose on Days 1, 12, 13 and 14)
- Part B: Dose proportionality of GSK2556286 based on AUC(0-tau)(Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)
- Part B: Steady state ratio (Rss) of GSK2556286(Day 1 and 14: Pre-dose and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 12, 15, 24, 36, 48 and 72 hours post-dose)