A Pharmacokinetics Study Comparing Lopinavir Plasma Exposure When Given as Lopinavir/Ritonavir (1:1) in the Presence of Rifampicin and Lopinavir/Ritonavir (4:1) Without Rifampicin in HIV and TB Co-infected Children in South Africa.
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 96
- 试验地点
- 10
- 主要终点
- Modelled C0/morning trough
研究概览
简要总结
The purpose of this study is to determine the lopinavir levels in blood of HIV and TB infected children (3-15kg) when given lopinavir/ritonavir in a 1:1 ratio with rifampicin containing TB regimen and its safety.
详细描述
This is a multicentre, open label, non-randomized, prospective, noninferiority study to compare the pharmacokinetics of lopinavir administered with superboosting (LPV/r 1:1) and concurrent RIF treatment or with standard boosting (LPV/r 4:1) without concurrent RIF treatment, and to assess the safety, tolerance, and virological effect of superboosting in HIV-TB co-infected infants and children weighing >3 kg and ≤15 kg.
LPV/r will be administered as the liquid 80/20 mg/mL formulation (4:1 standard boosting ratio). During anti-TB treatment, additional RTV liquid formulation will be provided to deliver a 1:1 superboosting ratio of LPV to RTV. Actual doses for antiretrovirals and anti-TB drugs will be based on the South African (SA) weight band dosing recommendations and provided as per the site standard of care.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 2 Weeks 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Documentation of a confirmed diagnosis of HIV-1 infection following SA clinical guidelines
- •Weight >3kg ≤15 kg at enrolment
- •> 42 weeks gestational age
- •On LPV/r-based therapy or about to start a LPV/r-based antiretroviral combination therapy with 2 NRTIs [ABC+3TC or AZT+3TC or d4T+3TC]
- •Clinical diagnosis of TB requiring RIF-based therapy
- •Parent or legal guardian able and willing to provide written informed consent and able to attend study visits.
排除标准
- •For neonates, less than 42 weeks gestation and 14 days old
- •Concomitant/chronic treatment with potent enzyme-inducing/inhibiting drugs other than those in the study treatments . See Appendix E (minor inducers/inhibitors and drugs used as part of management of the condition are allowed eg. Steroids)
- •Anticipation at the start that anti-TB treatment duration will be longer than 9 months
- •Any other condition/finding that, in the investigator's opinion, would compromise the child's participation in this study eg. alanine transferase (ALT) more than 10 times upper limit of normal (ULN), or chronic renal, hepatic or gastrointestinal disease such as malabsorption.
- •Children with known malignancies and contraindications to taking LPV/r
- •Treatment with experimental drugs for any indication within 30 days prior to study entry; participation in another study may be approved by the study team.
结局指标
主要结局
Modelled C0/morning trough
时间窗: Predose
Proportions of children treated with modelled lopinavir morning C0/morning trough \<1mg/L at each of the intensive PK evaluations.
次要结局
- ALT(baseline, PK1, PK2, PK3)
- C0/morning trough(Predose)
- ECG(baseline, 2 weeks after LPV/r 1:1, PK1)