Pharmacokinetic, Safety and Acceptability Study of the Abacavir/Lamivudine/Lopinavir/Ritonavir/-30/15/ 40/10mg vs. Lopinavir/Ritonavir 40/10mg Pellets Plus Dual Abacavir/Lamivudine-60/30mg Tablets in HIV Infected Children
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 50
- 试验地点
- 3
- 主要终点
- 0 -12 hours Area under the curve plasma concentration versus time for LPV, ABC and 3TC in the 4-in- formulation
研究概览
简要总结
A phase I/II, open label, randomized crossover pharmacokinetic, safety and acceptability study of the Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/ 40/10mg ;4-in-1) Fixed-Dose Combination vs. Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg tablets) in HIV infected Children.
The study is intended to support the adoption of the 4-in-1 by healthcare providers and will provide data that may support its registration in certain countries. The study will be carried out in HIV-infected children in Uganda weighing 3 to 25 kg (inclusive) and unable to swallow tablets and will provide supportive clinical data on the pharmacokinetics, safety, tolerability and acceptability of the 4-in-1.
详细描述
The primary objective is to estimate the population average exposure to LPV, ABC and 3TC provided by the 4-in-1 formulation in HIV-infected children dosed per WHO weight bands.
The secondary objectives:
- To determine the proportion of children overall, and within each weight band, with a lopinavir C12 <1.0 mg/L while receiving the 4-in-1 formulation
- To evaluate and compare the safety and tolerability of the 4-in-1 formulation versus a reference treatment regimen.
- To compare the bioavailability of LPV, ABC and 3TC in the 4-in-1 formulation versus a reference treatment regimen.
- To assess post exposure CD4 and viral load
- To assess the factors that contribute to acceptability of the new 4-in-1 formulation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 4 Weeks 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Children > 4 weeks old and weighing ≥3 and <25 kg at the time of enrolment
- •Past or current documentation of a confirmed diagnosis of HIV infection defined as two positive assays from two different samples. The two results may be in any combination of the following:
- •At any age: HIV-1 DNA PCR positive
- •Documented past HIV-1 RNA viral load > 1,000 copies/mL plasma
- •At any age >18 months of age: HIV-1 antibody reactive on two different rapid tests based on national testing algorithm
- •ARV treatment eligible children with LPV-based treatment indication* as defined by country-specific guidelines or the WHO paediatric treatment guidelines and confirmed by the investigator
- •HIV RNA viral load <1000 copies/mL (suppressed) at the screening visit*
- •Inability to swallow LPV/r tablets
- •Parent or guardian able and willing to provide written informed consent.
- •For lowest weight band (≥3 and ≤ 5.9kgs) ONLY: under treatment for at least 3 weeks but not more than 12 weeks.
- •Does not apply to the youngest children (≥3 and ≤ 5.9kgs)
排除标准
- •Planned or concurrent use of NNRTIs, integrase inhibitors, entry inhibitors, or Protease Inhibitors (PIs) other than LPV/r.
- •Treatment failure with proven resistances to PIs.
- •Contraindication to use of PIs
- •Clinical condition requiring the use of a prohibited medication (see section 7.6) in association with LPV/r, ABC/3TC (Refer to section 7.2- 7.3 of the IB)
- •Pulmonary Tuberculosis and any clinically significant disease or finding during screening that, in the investigator's opinion, would compromise participation in this study.
- •Treatment with experimental drugs (except for LPV/r Pellets) for any indication within 30 days prior to study entry
- •Anticipated transfer of care to a non-participating health facility during the study period
研究组 & 干预措施
4in1 granules
Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/ 40/10mg ;4-in-1) Fixed-Dose Combination in granules formulation administered twice daily for at least 3 weeks, Followed by Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg dispersible tablets) administered twice daily for at least 3 weeks.
干预措施: ABC/3TC/LPV/r granules (30/15/40/10 mgs) (Drug)
4in1 granules
Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/ 40/10mg ;4-in-1) Fixed-Dose Combination in granules formulation administered twice daily for at least 3 weeks, Followed by Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg dispersible tablets) administered twice daily for at least 3 weeks.
干预措施: LPV/r Pellets (40/10mgs) plus ABC/3TC (60/30mgs) (Drug)
LPV/r Pellets Plus ABC/3TC
Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg dispersible tablets) administered twice daily for at least 3 weeks.
Followed by Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/ 40/10mg ;4-in-1) Fixed-Dose Combination in granules formulation administered twice daily for at least 3 weeks
干预措施: ABC/3TC/LPV/r granules (30/15/40/10 mgs) (Drug)
LPV/r Pellets Plus ABC/3TC
Lopinavir/Ritonavir (40/10mg pellets) plus dual Abacavir/Lamivudine (60/30mg dispersible tablets) administered twice daily for at least 3 weeks.
Followed by Abacavir/Lamivudine/ Lopinavir/Ritonavir (30/15/ 40/10mg ;4-in-1) Fixed-Dose Combination in granules formulation administered twice daily for at least 3 weeks
干预措施: LPV/r Pellets (40/10mgs) plus ABC/3TC (60/30mgs) (Drug)
结局指标
主要结局
0 -12 hours Area under the curve plasma concentration versus time for LPV, ABC and 3TC in the 4-in- formulation
时间窗: 0-12 hours
0 -12 hours Area under the curve plasma concentration versus time for LPV, ABC and 3TC in the 4-in- formulation
次要结局
- Plasma concentration at 12 hours for LPV in the 4in1 formulation(12 hours)
- Peak plasma concentration (Cmax) of LPV, ABC and 3TC with the 4-in-1 formulation.(3-5 weeks)
- Concentration time maximum for LPV, ABC and 3TC with the 4-in-1 formulation.(3-5 weeks)
- Clearance function for LPV, ABC and 3TC with the 4-in-1 formulation.(3-5 weeks)
- Geometric mean ratio (GMR) of steady state LPV, ABC and 3TC versus time (0-12) in the 4-in-1 formulation versus the reference treatment regimen(0 - 12 hours)
- Area under curve plasma concentration versus time (0-12) in the 4-in-1 formulation versus the reference treatment regimen.(0 - 12 hours)
- Geometric mean ratio (GMR) of steady state LPV, ABC and 3TC in the 4-in-1 formulation versus the reference treatment regimen.(0 - 12 hours)
- Peak plasma concentration in the 4-in-1 formulation versus the reference treatment regimen.(3-5 weeks)
- Safety: A description of the proportion of children experiencing an Adverse event or Serious Adverse event binomial distribution compared between the two formulations.(6-8 weeks)
- Safety: Summary of the number and percent of subjects with documented Grade 3 or higher adverse events; each summary will be conducted overall and by formulation(6-8 weeks)
- Proportion of children with viral load <1000 copies/ml(6-8 weeks)
- Changes in CD4 counts compared to baseline(6-8 week)
- Changes in CD4 percentage compared to baseline(6-8 weeks)
- Acceptability: Description of factors that affect acceptability of the 4 in1 formulation(6-8 weeks)