Evaluation of the Pharmacokinetics and Tolerability of Increased Dosage of Lopinavir/Ritonavir(LPV/r) in Individuals Experiencing Viremia on Standard Dose LPV/r Using LPV/r Tablet Formulation
试验速览
- 阶段
- 4 期
- 状态
- 终止
- 试验地点
- 2
- 主要终点
- To evaluate the pharmacokinetic parameters of higher doses of LPV/r
研究概览
简要总结
This study will look to see if increasing the standard dose of Kaletra is tolerated and if it will lower viral loads to undetectable levels. This study will also look at the pharmacokinetic data (amount of Kaletra in blood at different times).
详细描述
There are several reasons for low level viremia in patients on Kaletra (LPV/r), including poor adherence, incomplete absorption, cellular drug pumps or resistance mutations. Increasing exposure to protease inhibitors via boosting with ritonavir increases minimum blood concentrations, and is a strategy which has been shown to improve suppression of virologic replication. Little is known about the pharmacokinetics (PK), tolerability and safety of increased doses of LPV/r. The objectives of this 24-week single arm pilot study are to assess the PK parameters, safety, tolerability, change in viral load and CD4 counts on increased dose (600/150 and 800/200 mg) LPV/r in participants with low level viremia on standard dose LPV/r-based ART. Participants will undergo six PK samplings over 12 hours on standard dose LPV/r. The dose will be increased to 3 tabs (600/150) BID and blood will be sampled for PK after two weeks. If tolerated at 8 weeks, the dose will be increased to 4 tabs (800/200 mg) BID and final PK sampling will be performed after two weeks. There will be a one time, optional, optimization of background regimen of NRTIs two weeks after the first dose escalation.
Major Eligibility Criteria:
- CD4 count: > 50
- Viral load: 200-75,000 on two most recent measures
- Current treatment: > 16 weeks standard dose (400/100mg BID) LPV/r-based ART (no other PI or NNRTI allowed
- Prior treatment experience and resistance profile: Up to 20-fold resistance to LPV/r
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 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
- •CD4 Count >50
- •Viral load 200-75,000 on two most recent measures
- •More than 16 weeks on standard dose Kaletra (LPV/r)
- •May be initial PI regimen or prior PI usage
- •Up to 50-fold resistance to LPV/r
排除标准
- •Age < 18 years old
结局指标
主要结局
To evaluate the pharmacokinetic parameters of higher doses of LPV/r
次要结局
- To evaluate change in CD4 count after increased dose LPV/r
- To evaluate plasma HIV-1 RNA change after increasing the dose of LPV/r
- To compare the tolerability and laboratory safety profile of LPV/r 3 and 4 tablets BID