A Double-Blind, Randomized, Placebo-Controlled, Single Dose Escalation First Time in Human Study to Investigate the Safety, Tolerability and Pharmacokinetics of GSK2838232 and to Evaluate the Effect of Food and Ritonavir on GSK2838232 in Healthy Subjects
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 17
- 试验地点
- 1
- 主要终点
- Number of subjects with AEs as a measure of safety and tolerability in cohort 2.
研究概览
简要总结
GSK2838232 is a novel human immune virus (HIV) maturation inhibitor being developed for the treatment of chronic HIV infection. This study is the first administration of GSK2838232 in humans to establish the initial safety, tolerability, and pharmacokinetic profile following single doses of GSK2838232 and to evaluate the effect of food and ritonavir (RTV) on GSK2838232 in healthy subjects. There will be 2 cohorts in this study. In Cohort 1, approximately 8 healthy subjects will be enrolled (6 active and 2 placebo) at each dose visit. There will be four dosing sessions for each subject with subjects randomized to receive placebo in a random sequence. In Cohort 2, approximately 8 healthy subjects will be enrolled (6 active doses and 2 placebo doses at each dose visit). Cohort 2 will have four dosing sessions for each subject with subjects randomized to receive placebo in a random sequence.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 50 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
Cohort 1
Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): ABCD, BACD, BCAD, or BCDA. Where A=Placebo, B= GSK2838232 5mg, C=GSK2838232 10mg, and D=GSK2838232 20mg
干预措施: GSK2838232 (Drug)
Cohort 1
Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): ABCD, BACD, BCAD, or BCDA. Where A=Placebo, B= GSK2838232 5mg, C=GSK2838232 10mg, and D=GSK2838232 20mg
干预措施: Placebo (Drug)
Cohort 2
Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): EGHJ, FEHJ, FGIJ, or FGHK. Where E=Placebo, F= GSK2838232 50mg, G= GSK2838232 100mg, H= GSK2838232 50mg + food, I= Placebo + food, J= GSK2838232 10mg + RTV, K= placebo + RTV.
干预措施: GSK2838232 (Drug)
Cohort 2
Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): EGHJ, FEHJ, FGIJ, or FGHK. Where E=Placebo, F= GSK2838232 50mg, G= GSK2838232 100mg, H= GSK2838232 50mg + food, I= Placebo + food, J= GSK2838232 10mg + RTV, K= placebo + RTV.
干预措施: Placebo (Drug)
Cohort 2
Subject in this cohort will be randomized to one of the four following treatment sequences (1 treatment per visit): EGHJ, FEHJ, FGIJ, or FGHK. Where E=Placebo, F= GSK2838232 50mg, G= GSK2838232 100mg, H= GSK2838232 50mg + food, I= Placebo + food, J= GSK2838232 10mg + RTV, K= placebo + RTV.
干预措施: Ritonavir (Drug)
结局指标
主要结局
Number of subjects with AEs as a measure of safety and tolerability in cohort 2.
时间窗: Up to 12 weeks
AEs will be collected from the start of Study Treatment and until 5 days post last-dose (at follow up).
Absolute values and changes over time of hematology as a measure of safety and tolerability in cohort 2
时间窗: Up to 12 weeks
Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability in cohort 1.
时间窗: Up to 16 weeks
Absolute values and changes over time of clinical chemistry as a measure of safety and tolerability in cohort 2.
时间窗: Up to 12 weeks
Absolute values and changes over time of urinalysis as a measure of safety and tolerability in cohort 2
时间窗: Up to 12 weeks
Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability in cohort 2.
时间窗: Up to 12 weeks
Absolute values and changes over time of hematology as a measure of safety and tolerability in cohort 1.
时间窗: Up to 16 weeks
Number of subjects with adverse events (AEs) as a measure of safety and tolerability in cohort 1
时间窗: Up to 16 weeks
AEs will be collected from the start of Study Treatment and until 5 days post last-dose (at follow up).
Absolute values and changes over time of vital signs as a measure of safety and tolerability in cohort 1
时间窗: Up to 16 weeks.
Vital signs include blood pressure, temperature and heart rate measurement
Real time collection and review of heart rhythm using telemetry as a measure of safety and tolerability in cohort 1.
时间窗: Up to 16 weeks.
Composite of pharmacokinetics (PK) parameters following single dose administration of GSK2838232 in cohort 1
时间窗: PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.
PK parameters include: area under the concentration-time curve from time zero (pre-dose) extrapolated to infinite time (AUC \[0-infinity\]), area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration (AUC \[0-t\]), maximum observed concentration (Cmax), time to maximum observed concentration (Tmax), observed concentration at 24hour post-dose (C24), last observed quantifiable concentration (Ct), lag time before observation of drug concentrations in sampled matrix (tlag), terminal half-life (t1/2), and apparent oral clearance (CL/F).
Absolute values and changes over time of urinalysis as a measure of safety and tolerability in cohort 1.
时间窗: Up to 16 weeks
Absolute values and changes over time of vital signs as a measure of safety and tolerability in cohort 2.
时间窗: Up to 12 weeks
Vital signs include blood pressure, temperature and heart rate measurement
Absolute values and changes over time of ECG intervals and ECG rhythm as a measure of safety and tolerability in cohort 1.
时间窗: Up to 16 weeks.
Real time collection and review of heart rhythm using telemetry as a measure of safety and tolerability in cohort 2.
时间窗: Up to 12 weeks
Composite of pharmacokinetics parameters following single dose administration of GSK2838232 in cohort 2.
时间窗: PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.
PK parameters include: AUC (0-infinity), AUC (0-t), Cmax, Tmax, C24, Ct, tlag, t1/2 and CL/F.
次要结局
- Composite of pharmacokinetics parameters following single dose administration of GSK2838232 with and without food in cohort 2.(PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.)
- Composite of pharmacokinetics parameters following single dose administration of GSK2838232 with co-administration of ritonavir in cohort 2.(PK samples will be collected at pre-dose, 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 6, 8, 12, 24, 36, 48, and 72 hours post dose in each dosing session and at follow up visit.)