A Phase II/III Trial of Lopinavir/Ritonavir Dosed According to the WHO Pediatric Weight Band Dosing Guidelines
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|ClinicalTrials.gov Identifier: NCT01172535|
Recruitment Status : Completed
First Posted : July 29, 2010
Results First Posted : December 21, 2015
Last Update Posted : December 21, 2015
|Condition or disease||Intervention/treatment||Phase|
|HIV||Drug: Lopinavir/ritonavir||Phase 2 Phase 3|
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
10-16.9 kg: 11 liquid, 22 tablet
17-19.9 kg: 11 tablet
20-24.9 kg: 11 tablet
Participation in this study will last 6 months. Infant participants and their caretakers will need to attend study visits at entry and Weeks 2, 4, 12, and 24. At entry, participants will be given LPV/r either in liquid or tablet form, depending on whether they can swallow pills. Dosing will be calculated using the WHO schedule. At all study visits, participants will undergo a physical exam and caretakers will be asked about how well the child is taking the study medications. In addition, at Weeks 4, 12, and 24, blood samples will be taken from the participant to determine health and levels of the medication in the body. The visit on Week 4 will also require pharmacokinetic testing, which means the child will need to be monitored at the hospital for 12 hours and complete six additional blood drawls. All other study visits will last 1 to 2 hours.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||97 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II/III Trial of Lopinavir/Ritonavir Dosed According to the WHO Pediatric Weight Band Dosing Guidelines|
|Study Start Date :||November 2010|
|Actual Primary Completion Date :||December 2013|
|Actual Study Completion Date :||December 2013|
Participants will receive lopinavir/ritonavir in addition to two nucleoside reverse transcriptase inhibitors (NRTIs) chosen by their doctors.
Heat-stable tablets of 100 mg lopinavir, 25 mg ritonavir, or liquid formulation of 80 mg lopinavir, 20 mg ritonavir, dosed according to World Health Organization (WHO) pediatric weight band dosing guidelines
- Lopinovir/Ritonavir Area Under the Concentration-time Curve (AUC0-24) [ Time Frame: 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
- Maximum Concentration of Lopinavir/Ritonavir (Cmax) [ Time Frame: 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
- Minimum Concentration of Lopinavir/Ritonavir (Cmin) [ Time Frame: 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
- Clearance of Lopinavir/Ritonavir (CL/F) [ Time Frame: 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 [ Time Frame: 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)
- Number of Participants Experiencing Adverse Events of Grade 3 or 4 [ Time Frame: 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
- Proportion of Participants Tolerating LPV/r [ Time Frame: 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.
- Adherence [ Time Frame: Measured at week 4, week 12, and study completion (week 24) ]Adherence, defined as proportion of doses taken (note: proportion could be greater than 1.0 for reasons such as tablets having to be taken twice due to first one being spit out or imprecise measurement of liquid doses)
- Treatment Efficacy (HIV Viral Load) [ Time Frame: Measured at entry and study completion (week 24) ]Having HIV viral load <400 copies/mL at the week 24 visit
- Treatment Efficacy (CD4%) [ Time Frame: Measured at entry and study completion (week 24) ]Having CD4%≥25 at the week 24 visit.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01172535
|Study Chair:||Jorge A. Pinto, MD||Federal University of Minas Gerais|