Phase IIB, Randomized, Multicenter, Parallel Group, Study to Evaluate the Safety, Pharmacokinetics and Antiviral Effect of Four Blinded Dosing Regimens of GW640385X/Ritonavir Compared to Open-label Current PI Therapy in HIV-1 Infected, Protease Inhibitor Experienced Adults for 2 Weeks With Long-term Assessment (>48 Weeks) of Safety, Pharmacokinetic and Antiviral Activity of Selected 385/RTV Dosing Regimen(s) vs. a Ritonavir-boosted, Protease Inhibitor Containing Regimen
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 130
- 试验地点
- 70
- 主要终点
- Change in laboratory parameters
研究概览
简要总结
This is a two phase study (randomised and non-randomised phase). The randomised phase will initially examine 4 blinded doses of GW640385 boosted with rtv (with continuation of current background therapy) in comparison to an ongoing, open-labeled rtv-boosted protease inhibitor (PI) regimen for 15 days. At the Day 15 visit, all subjects will optimize background therapy. Additionally, subjects receiving the lowest dose of GW640385 will be re-randomised to one of the higher doses and subjects in the control arm will receive a new rtv-boosted PI based on resistance testing at screening. Subjects will remain in the randomized phase on one of these 4 continuing treatment arms for at least 48 weeks. An interim analysis will occur during the randomised phase to select for a dose of GW640385 to evaluate further in Phase III studies. After dose selection subjects will move to the non-randomised phase of the study. In the non-randomised phase subjects who are receiving GW640385 will be assigned to final selected dose for assessment of long term safety, tolerability, pharmacokinetics, and antiviral activity.
详细描述
A Phase IIB, Randomized, Multicenter, Parallel Group Study to Evaluate the Short-Term Safety, PK and Antiviral Activity of Four Dosing Regimens of GW640385/rtv Therapy Compared to Open-label Current Protease Inhibitor (PI) Therapy in HIV-1, PI-Experienced Adults for 2 wks with Long-Term Evaluation (>48 wks) of Safety, PK and Antiviral Activity of Selected GW640385/rtv Dosing Regimen(s) vs. a RTV-boosted, PI Containing Regimen
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
- None
入排标准
- 年龄范围
- 18 Years 至 —(Adult, Older Adult)
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •18+ years of age (or =16 years of age for non-EU countries, according to local requirements).
- •HIV-1 infected subjects.
- •Females must be of either non-childbearing potential or have a negative pregnancy test at Screening and agree to use a protocol approved method of contraception.
- •Plasma HIV-1 RNA (viral load) =1,000 copies/mL at Screening.
- •Evidence of at least 2 multi-PI resistant mutations at Screening or within 3 months of Screening.
- •Subjects must have been receiving the same anti-HIV medicines that they are on currently for at least 8 weeks prior to Screening; these anti-HIV medicines will include a single protease inhibitor (PI) in combination with a low dose of ritonavir (i.e., a ritonavir-boosted PI). However, the current PI cannot be tipranavir.
- •Able to understand and follow protocol requirements, instructions and protocol-stated restrictions.
- •Be willing and able to provide signed and dated written informed consent prior to study entry.
排除标准
- •Subjects cannot change their anti-HIV medicines between Screening and Day 1 Visit.
- •Subjects can not be receiving dual ritonavir-boosted PIs, non-nucleoside reverse transcriptase inhibitors (NNRTIs) or Tipranavir at Screening.
- •Active CDC Class C disease at screening.
- •Pregnant or breastfeeding women.
- •Protocol-specified laboratory abnormalities at Screening.
结局指标
主要结局
Change in laboratory parameters
Time averaged change in plasma HIV-1 RNA over 16 wks
Proportion of subjects achieving the target pharmacokinetic (PK) GW640385 drug levels
次要结局
- Immunologic measures
- The incidence of adverse events
- Changes in laboratory measurements
- HIV viral resistance assessment
- ECG measurements
- Assessments of HIV viral load changes
- GW640385 and RTV pharmacokinetic measurements
