Effect of Moderate Liver Impairment on the Pharmacokinetics of Saquinavir After Administration of Saquinavir/Ritonavir 1000/100mg BID in HIV Patients
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 16
- 主要终点
- Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 Hours After Dosing (AUC 0-12h) of Saquinavir (SQV) and Ritonavir (RTV)
研究概览
简要总结
This 2 arm study will assess the effect of moderate liver impairment on the pharmacokinetics of saquinavir and ritonavir at steady state following administration of saquinavir/ritonavir 1000mg/100mg po bid in HIV patients. Saquinavir/ritonavir will be administered concomitantly with 2 to 3 active nucleoside reverse transcriptase inhibitors. The study will compare a group of HIV patients without known liver disease and a group with moderate liver disease. The anticipated time on study treatment is <3 months, and the target sample size is <100 individuals.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- 否
入选标准
- •adult patients, 18-65 years of age;
- •HIV infection;
- •normal liver function, or moderate liver disease (Child-Pugh grade B);
- •antiretroviral therapy naive and eligible to take antiretroviral treatment as per treatment guidelines, or treatment experienced for at least 4 weeks prior to first dosing.
排除标准
- •severe ascites at screening, or Child-Pugh grade C;
- •acute infection or current malignancy requiring treatment;
- •taking any inhibitor of CYP3A4 (with the exception of anti-HIV drugs) within 14 days prior to first dosing;
- •taking any inducer of CYP3A4 (with the exception of anti-HIV drugs) within 4 weeks prior to pharmacokinetic evaluation (day 14 or 28);
- •evidence of resistance to saquinavir.
研究组 & 干预措施
1
干预措施: Ritonavir (Drug)
1
干预措施: saquinavir [Invirase] (Drug)
2
干预措施: Ritonavir (Drug)
2
干预措施: saquinavir [Invirase] (Drug)
结局指标
主要结局
Area Under the Plasma Concentration-Time Curve From Time of Administration to 12 Hours After Dosing (AUC 0-12h) of Saquinavir (SQV) and Ritonavir (RTV)
时间窗: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
Area Under the Plasma Concentration-Time Curve (AUC) is a measure of the plasma concentration of the drug over time. It is used to characterize drug absorption. The pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the area under the plasma concentration-time curve from 0 to 12 hours after dosing (AUC (0-12h) of SQV and RTV The AUC (0-12hours) was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
Maximum Observed Plasma Concentration (Cmax) of SQV and RTV
时间窗: Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14
The plasma concentration (Cmax) is defined as maximum observed analyte concentration. The pharmacokinetic profile for following 14 days of administration with SQV/RTV 1000/100 mg BID included determining the maximum observed plasma concentration (C max) of SQV and Ritonavir RTV The Cmax was analyzed for SQV and RTV by non-compartmental methods, using WinNonlin.
次要结局
- Time of Maximum Plasma Concentration (Tmax) of SQV and RTV(Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14)
- Terminal Half-life (T1/2) of SQV and RTV(Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post-dose on Day 14)
- Number of Participants With Abnormal Electrocardiogram (ECG) Findings(Up to Day 35)
- Volume of Distribution (Vd) of SQV and RTV(Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14)
- Cluster of Differentiation 4 (CD4 ) Count(Screening (Day -35 to -1), pre-dose on Day 8, Day 14 and at follow up (Day 28-Day 35))
- Number of Participants With the Indicated Grade 3 and Grade 4 Laboratory Parameters(Up to Day 35)
- Number Participants With Abnormal Vital Signs(Up to Day 35)
- Minimum Observed Plasma Concentration (Cmin) of SQV and RTV(Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14)
- Plasma Clearance After Oral Administration (CL/F) of SQV and RTV(Pre-dose and at 0.5 hr, 1hr, 2hrs, 3hrs, 4hrs, 5hrs, 6hrs, 8hrs, 10hrs, and 12 hrs post dose on Day 14)