Open-Label, Single-Sequence Study to Evaluate the Effects of Darunavir/Ritonavir and/or Etravirine on the Pharmacokinetics of GSK3640254 and the Effects of GSK3640254 on the Pharmacokinetics of Darunavir/Ritonavir and/or Etravirine in Heathy Adults
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- Cohort 1: Cmax of RTV
研究概览
简要总结
This is an open-label, single-sequence, multiple-dose, 3 cohort study to investigate the effects of DRV/RTV and/or ETR on the pharmacokinetics (PK) of GSK3640254 and the effects of GSK3640254 on the PK of DRV/RTV and/or ETR. This study will aid in understanding these interactions and resulting changes in exposure (if any) when given in combination with GSK3640254.
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
- None
盲法说明
This is an open-label study.
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: GSK3640254 then DRV/RTV then GSK3640254 + DRV/RTV
Cohort 1 will include 3 periods. In Period 1 GSK3640254 will be administered (Treatment A). In Period 2 DRV/RTV will be administered (Treatment B). In Period 3 GSK3640254 (Treatment A) and DRV/RTV (Treatment B) will be administered.
干预措施: GSK3640254 (Drug)
Cohort 1: GSK3640254 then DRV/RTV then GSK3640254 + DRV/RTV
Cohort 1 will include 3 periods. In Period 1 GSK3640254 will be administered (Treatment A). In Period 2 DRV/RTV will be administered (Treatment B). In Period 3 GSK3640254 (Treatment A) and DRV/RTV (Treatment B) will be administered.
干预措施: Darunavir/Ritonavir (DRV/RTV) (Drug)
Cohort 2: GSK3640254 then ETR then GSK3640254 + ETR
Cohort 2 will include 3 periods. In Period 1 GSK3640254 will be given (Treatment A). In Period 2 ETR will be given (Treatment C). In Period 3 GSK3640254 (Treatment A) and ETR (Treatment C) will be administered.
干预措施: GSK3640254 (Drug)
Cohort 2: GSK3640254 then ETR then GSK3640254 + ETR
Cohort 2 will include 3 periods. In Period 1 GSK3640254 will be given (Treatment A). In Period 2 ETR will be given (Treatment C). In Period 3 GSK3640254 (Treatment A) and ETR (Treatment C) will be administered.
干预措施: Etravirine (ETR) (Drug)
Cohort 3: GSK3640254 then GSK3640254 + DRV/RTV + ETR
Cohort 3 will include 2 periods. In Period 1 GSK3640254 will be administered (Treatment A). In Period 2 GSK3640254 (Treatment A), DRV/RTV (Treatment B), and ETR (Treatment C) will be administered.
干预措施: GSK3640254 (Drug)
Cohort 3: GSK3640254 then GSK3640254 + DRV/RTV + ETR
Cohort 3 will include 2 periods. In Period 1 GSK3640254 will be administered (Treatment A). In Period 2 GSK3640254 (Treatment A), DRV/RTV (Treatment B), and ETR (Treatment C) will be administered.
干预措施: Darunavir/Ritonavir (DRV/RTV) (Drug)
Cohort 3: GSK3640254 then GSK3640254 + DRV/RTV + ETR
Cohort 3 will include 2 periods. In Period 1 GSK3640254 will be administered (Treatment A). In Period 2 GSK3640254 (Treatment A), DRV/RTV (Treatment B), and ETR (Treatment C) will be administered.
干预措施: Etravirine (ETR) (Drug)
结局指标
主要结局
Cohort 1: Cmax of RTV
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Cohort 1: Area Under the Plasma Concentration-time Curve From Time Zero to the End of the Dosing Interval at Steady State (AUC[0-tau]) of GSK3640254
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 16 Hours, 24 Hours post-dose in Treatment Periods 1 and 3
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Cohort 1: Cmax of DRV
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Cohort 2: AUC(0-tau) of GSK3640254
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 16 Hours, 24 Hours post-dose in Treatment Periods 1 and 3
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Cohort 2: Cmax of GSK3640254
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 16 Hours, 24 Hours post-dose in Treatment Periods 1 and 3
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Cohort 2: AUC(0-tau) of ETR
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Cohort 3: AUC(0-tau) of GSK3640254
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 16 Hours, 24 Hours post-dose in Treatment Periods 1 and 2
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Cohort 3: Cmax of GSK3640254
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 16 Hours, 24 Hours post-dose in Treatment Periods 1 and 2
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Cohort 1: Maximum Observed Concentration (Cmax) of GSK3640254
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 16 Hours, 24 Hours post-dose in Treatment Periods 1 and 3
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Cohort 1: AUC(0-tau) of DRV
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Cohort 1: AUC(0-tau) of RTV
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
Cohort 2: Cmax of ETR
时间窗: Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3
Blood samples were collected at indicated time points. Pharmacokinetic analysis was conducted using standard non-compartmental methods.
次要结局
- Cohort 2: Ctau of ETR(Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3)
- Cohort 2: Ctau of GSK3640254(Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 16 Hours, 24 Hours post-dose in Treatment Periods 1 and 3)
- Cohort 2: Tmax of GSK3640254(Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 16 Hours, 24 Hours post-dose in Treatment Periods 1 and 3)
- Cohort 1: Number of Participants With Serious Adverse Events (SAEs) and Non-serious Adverse Events (Non-SAEs)(Up to Day 35)
- Cohort 2: Number of Participants With SAEs and Non-SAEs(Up to Day 36)
- Cohort 1: Plasma Concentration at the End of the Dosing Interval (Ctau) of DRV(Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3)
- Cohort 1: Time of Maximum Observed Concentration (Tmax) of DRV(Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3)
- Cohort 1: Ctau of RTV(Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3)
- Cohort 1: Tmax of RTV(Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3)
- Cohort 1: Ctau of GSK3640254(Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 16 Hours, 24 Hours post-dose in Treatment Periods 1 and 3)
- Cohort 1: Tmax of GSK3640254(Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours, 16 Hours, 24 Hours post-dose in Treatment Periods 1 and 3)
- Cohort 2: Tmax of ETR(Pre-dose and 0.5 Hours, 1 Hour, 1.5 Hours, 2 Hours, 3 Hours, 4 Hours, 6 Hours, 8 Hours, 12 Hours post-dose in Treatment Periods 2 and 3)
- Cohort 3: Number of Participants With SAEs and Non-SAEs(Up to Day 26)
- Cohort 1: Number of Participants With AEs Leading to Discontinuations and Deaths(Up to Day 35)
- Cohort 2: Number of Participants With AEs Leading to Discontinuations and Deaths(Up to Day 36)
- Cohort 3: Number of Participants With AEs Leading to Discontinuations and Deaths(Up to Day 26)
- Cohort 1: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters(Baseline (Pre-dose, Day-1) and up to Day 35)
- Cohort 2: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters(Baseline (Pre-dose, Day-1) and up to Day 36)
- Cohort 3: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Hematology Parameters(Baseline (Pre-dose, Day-1) and up to Day 26)
- Cohort 1: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Bilirubin and Direct Bilirubin(Baseline (Pre-dose, Day-1) and up to Day 35)
- Cohort 1: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Calcium, Creatine Kinase, Creatinine, Phosphate, Potassium and Sodium(Baseline (Pre-dose, Day-1) and up to Day 35)
- Cohort 1: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Glucose, Triglycerides, Lipase, Urate and Cholesterol(Baseline (Pre-dose, Day-1) and up to Day 35)
- Cohort 3: Number of Participants With Vital Sign Values of PCI Criteria(Up to Day 26)
- Cohort 2: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Bilirubin and Direct Bilirubin(Baseline (Pre-dose, Day-1) and up to Day 36)
- Cohort 2: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Calcium, Creatine Kinase, Creatinine, Phosphate, Potassium and Sodium(Baseline (Pre-dose, Day-1) and up to Day 36)
- Cohort 2: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Glucose, Triglycerides, Lipase, Urate and Cholesterol(Baseline (Pre-dose, Day-1) and up to Day 36)
- Cohort 3: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Alanine Aminotransferase, Albumin, Alkaline Phosphatase, Amylase, Aspartate Aminotransferase, Bilirubin and Direct Bilirubin(Baseline (Pre-dose, Day-1) and up to Day 26)
- Cohort 1: Number of Participants With Clinically Significant Abnormal Electrocardiogram (ECG) Findings(Day 1 (2,4,6 Hours), Day 7 and Day 11 in Treatment Period 1; Day 12 (2,4,6 Hours), Day 21 in Treatment Period 2; Day 22 (2,4,6 Hours), Day 26 and Day 35 in Treatment Period 3)
- Cohort 3: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Calcium, Creatine Kinase, Creatinine, Phosphate, Potassium and Sodium(Baseline (Pre-dose, Day-1) and up to Day 26)
- Cohort 3: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Clinical Chemistry Parameters: Glucose, Triglycerides, Lipase, Urate and Cholesterol(Baseline (Pre-dose, Day-1) and up to Day 26)
- Cohort 1: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Urinalysis Parameters(Baseline (Pre-dose, Day-1) and up to Day 35)
- Cohort 2: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Urinalysis Parameters(Baseline (Pre-dose, Day-1) and up to Day 36)
- Cohort 3: Number of Participants With Grade Increase Post-Baseline Relative to Baseline in Urinalysis Parameters(Baseline (Pre-dose, Day-1) and up to Day 26)
- Cohort 1: Number of Participants With Vital Sign Values of Potential Clinical Importance (PCI) Criteria(Up to Day 35)
- Cohort 2: Number of Participants With Vital Sign Values of PCI Criteria(Up to Day 36)
- Cohort 2: Number of Participants With Clinically Significant Abnormal ECG Findings(Day 1 (2,4,6 Hours), Day 7 and Day 11 in Treatment Period 1; Day 12 (2,4,6 Hours), Day 21 in Treatment Period 2; Day 22 (2,4,6 Hours), Day 26 and Day 36 in Treatment Period 3)
- Cohort 3: Number of Participants With Clinically Significant Abnormal ECG Findings(Day 1 (2,4,6 Hours) in Treatment Period 1; Day 8 (2,4,6 Hours), Day 9 (2,4,6 Hours), Day 26 in Treatment Period 2)