A Phase II/III Trial of Lopinavir/Ritonavir Dosed According to the WHO Pediatric Weight Band Dosing Guidelines
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 97
- 试验地点
- 19
- 主要终点
- Maximum Concentration of Lopinavir/Ritonavir (Cmax)
研究概览
简要总结
Treatment of children and infants with HIV requires modification of medication dosing according to a child's specific weight. For lopinavir/ritonavir (LPV/r), a second line treatment option that is increasingly necessary due to infant drug resistance, this dosing is often complicated and impractical in busy clinical settings. To address this, the World Health Organization (WHO) has released a simplified dosing table based on infant weight bands. This study will evaluate the absorption, safety, and tolerance of LPV/r in infants when dosed according to the new WHO guidelines.
详细描述
Because of previous exposure to nevirapine or other non-nucleoside reverse transcriptase inhibitors (NNRTIs), either by direct treatment or through their mothers in pregnancy, infants must often receive an alternate antiretroviral regimen that includes LPV/r. Dosing of LPV/r is currently based on a child's specific weight, and calculations of proper dosages are often too complicated to be practical in busy clinics, particularly those in limited resource settings. In order to simplify medication delivery and reduce prescribing errors, the WHO has released a dosing schedule for LPV/r based on groupings of infants and children by weight. This study will evaluate the pharmacokinetics, safety, and tolerance of LPV/r dosed according to these guidelines. The following strata were used to guide accrual:
Number of Participants to be Enrolled by Weight Band:
3-4.9 kg: 11 liquid
5-6.9 kg: 11 liquid
7-9.9 kg: 17 liquid
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
- 4 Weeks 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Weight equal to or greater than 3 kg, but less than 25 kg, at the time of enrollment
- •Confirmed diagnosis of HIV-1 infection
- •Lopinavir/ritonavir (LPV/r)-treatment naïve and LPV/r-treatment eligible as defined by country-specific guidelines or the WHO pediatric treatment guidelines and confirmed by investigator
- •Willingness to take two nucleoside reverse transcriptase inhibitos (NRTIs), in accordance with appropriate national or international treatment guidelines
- •Demonstrated ability and willingness to swallow tablets for children larger than 10 kg. This can be assessed before inclusion (for example, a test trial with similar size solid tablet such as tic-tac).
- •Participants in the weight band between 10 and 16.9 kg that are unable to swallow tablets will receive liquid formulation
- •Parent or legal guardian able and willing to provide written informed consent
排除标准
- •Planned concurrent use of non-nucleoside reverse transcriptase inhibitors (NNRTIs), integrase inhibitors, or an entry inhibitor
- •Planned concurrent protease inhibitor (PI) use, other than LPV/r
- •Prior treatment with LPV/r. Prior treatment with other PIs is allowed.
- •Results of certain laboratory tests indicating adverse events of Grade 3 or greater
- •Results of a lipase test indicating adverse event of Grade 2 or greater or clinical evidence of pancreatitis within 30 days prior to study entry
- •Tuberculosis co-treatment with rifampicin-containing regimen
- •Treatment with any enzyme-inducing antiepileptic drugs, such as henobarbital, phenytoin or carbamazepine
- •Clinical condition requiring the use of a prohibited medication (see protocol for more details)
- •Clinically unstable child requiring acute treatment for a serious opportunistic infection
- •Chemotherapy for active malignancy
- •Any clinically significant diseases (other than HIV-1 infection) or clinically significant findings during the screening medical history or physical examination that, in the investigator's opinion, would compromise participation in this study
- •Treatment with experimental drugs for any indication within 30 days prior to study entry
- •Known history of cardiac conduction abnormality and/or underlying structural heart disease, including congenital long QT
研究组 & 干预措施
Lopinavir/ritonavir
Participants will receive lopinavir/ritonavir in addition to two nucleoside reverse transcriptase inhibitors (NRTIs) chosen by their doctors.
干预措施: Lopinavir/ritonavir (Drug)
结局指标
主要结局
Maximum Concentration of Lopinavir/Ritonavir (Cmax)
时间窗: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Maximum concentration of lopinavir/ritonavir, as determined by analysis of 12-hour pharmacokinetic sampling
Lopinovir/Ritonavir Area Under the Concentration-time Curve (AUC0-24)
时间窗: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Area under the curve over 24 hours (AUC0-24), as determined by a non-compartmental analysis of 12-hour pharmacokinetic sampling for lopinavir/ritonavir
Clearance of Lopinavir/Ritonavir (CL/F)
时间窗: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Clearance of lopinavir/ritonavir, as determined by analysis of 12-hour pharmacokinetic sampling
Proportion of Participants With an AUC of Less Than 10% of Adults
时间窗: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Proportion of participants with an AUC less that 10% of adults (AUC0-24 \<104 mcg\*hr/mL)
Minimum Concentration of Lopinavir/Ritonavir (Cmin)
时间窗: Measured at 4 weeks of treatment prior to the observed dose and at 2, 4, 6, 8, and 12 hours post-dose
Minimum concentration of lopinavir/ritonavir, as determined by analysis of 12-hour pharmacokinetic sampling
Proportion of Participants Tolerating LPV/r
时间窗: Measured at study completion (week 24)
Participants were considered to have tolerated medication if they did not stop treatment before the 24 week PK visit for any reason other than completing treatment or death not related to treatment.
Number of Participants Experiencing Adverse Events of Grade 3 or 4
时间窗: Measured at study visits through end of study (weeks 2, 4, 12, 24)
Adverse events were graded by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 1.0, dated December, 2004, Clarification August 2009, which is available on the RSC web site (http://rsc.tech-res.com/safetyandpharmacovigilance/). Grade 1 = mild, Grade 2 = moderate, Grade 3 = severe, Grade 4 = potentially life-threatening, Grade 5 = death
次要结局
- Treatment Efficacy (HIV Viral Load)(Measured at entry and study completion (week 24))
- Adherence(Measured at week 4, week 12, and study completion (week 24))
- Treatment Efficacy (CD4%)(Measured at entry and study completion (week 24))