Intensive Pharmacokinetic Studies of Antiretroviral Drug Combinations in Children
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 75
- 试验地点
- 23
- 主要终点
- Predosage concentration (C0 and C12) and area under the concentration-time curve (AUC)
研究概览
简要总结
Limited data exist about combination anti-HIV treatment regimens in children, including how those drugs are cleared by the body in children. The purpose of this study is to measure the blood levels of the following combinations of anti-HIV drugs in HIV infected chilren: tenofovir disoproxil fumurate (TDF) and efavirenz (EFV) or nevirapine (NVP); TDF and darunavir (DRV) with or without EFV; and TDF and ritonavir (RTV) with or without EFV.
详细描述
Because all of the available non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) are metabolized by and affect hepatic cytochrome enzymes, combinations of two or more of these drugs produce complex pharmacokinetic (PK) interactions. However, little data exist regarding PK of anti-HIV drug combinations in the pediatric population. The purpose of this study is to assess steady-state PK of the following anti-HIV regimens: TDF and EFV or NVP; TDF and DRV with or without EFV; and TDF and RTV with or without EFV. In addition, this study will evaluate how age, length of treatment, adverse effects, and genes affect children's response to different anti-HIV combinations.
This study will last between 1 and 7 weeks. Participants in this study will be grouped based on the treatment regimen they are receiving or about to initiate. There are three groups in this study. Group D participants will receive TDF and EFV or NVP; Group E participants will receive TDF and DRV with or without EFV; and Group F participants will receive TDF and RTV with or without EFV. The inclusion of EFV or NVP will be dependent on each participant's prescribed regimen. Participants within each group will be stratified by age and how long they have been receiving their anti-HIV regimens. Antiretrovirals will not be provided by this study.
Most participants will have two study visits. The first visit will occur at study entry. Medical history, a physical exam, and blood collection will occur. The second visit will occur within 35 days of study entry and will take approximately 24 hours. Blood collection for PK studies, a physical exam, and medical history will be done at this visit. Urine collection will occur at all visits for female participants.
Participants will undergo PK testing at least 14 days after initiating their study regimens. Participants will be given a dose of their anti-HIV medications with food. A blood sample will be taken before dosing. Blood samples will also be taken at 1, 2, 4, 6, 8, 12, and 24 hours after dosing. Participants in Groups E and F may need to repeat PK testing within 6 weeks of initial PK testing at the discretion of the investigator.
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
- 8 Years 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •HIV infected
- •Currently receiving or about to initiate one of the following anti-HIV regimens: TDF with EFV or NVP, TDF and DRV/r with or without EFV, or TDF with ATV/r with or without EFV
- •Body surface area at least 0.85 m2
- •Parent or guardian willing and able to provide signed informed consent
- •Willing to use acceptable forms of contraception
排除标准
- •Liver disease that may affect the metabolism of study drugs
- •Certain abnormal laboratory values
- •Require certain medications
- •Treatment with any anti-HIV or nonantiretroviral drug that could interact with drugs under PK study in the 14 days prior to study entry
- •Any clinical or laboratory toxicity of Grade 4 or higher at screening. More information on this criterion can be found in the protocol.
- •Pregnant or breastfeeding
研究组 & 干预措施
D
TDF and EFV or NVP throughout study
干预措施: Efavirenz (Drug)
D
TDF and EFV or NVP throughout study
干预措施: Nevirapine (Drug)
D
TDF and EFV or NVP throughout study
干预措施: Tenofovir disoproxil fumarate (Drug)
D
TDF and EFV or NVP throughout study
干预措施: Pharmacokinetic Study (Procedure)
E
TDF and DRV with or without EFV throughout study
干预措施: Darunavir (Drug)
E
TDF and DRV with or without EFV throughout study
干预措施: Efavirenz (Drug)
E
TDF and DRV with or without EFV throughout study
干预措施: Ritonavir (Drug)
E
TDF and DRV with or without EFV throughout study
干预措施: Tenofovir disoproxil fumarate (Drug)
E
TDF and DRV with or without EFV throughout study
干预措施: Pharmacokinetic Study (Procedure)
F
TDF and ATV and RTV with or without EFV throughout study
干预措施: Atazanavir (Drug)
F
TDF and ATV and RTV with or without EFV throughout study
干预措施: Efavirenz (Drug)
F
TDF and ATV and RTV with or without EFV throughout study
干预措施: Ritonavir (Drug)
F
TDF and ATV and RTV with or without EFV throughout study
干预措施: Tenofovir disoproxil fumarate (Drug)
F
TDF and ATV and RTV with or without EFV throughout study
干预措施: Pharmacokinetic Study (Procedure)
结局指标
主要结局
Predosage concentration (C0 and C12) and area under the concentration-time curve (AUC)
时间窗: Over the dosing interval
次要结局
未报告次要终点