Safety and Effectiveness of World Health Organization Dosing Guidelines of Lopinavir/Ritonavir for Children
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.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II/III Trial of Lopinavir/Ritonavir Dosed According to the WHO Pediatric Weight Band Dosing Guidelines|
- Safety, as determined by non-occurrence of any recurring Grade 3 or non-life-threatening Grade 4 toxicity, or a single life-threatening Grade 4 toxicity [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
- Area under the curve (AUC), as determined by a non-compartmental analysis of 12-hour pharmacokinetic sampling for lopinavir/ritonavir [ Time Frame: Measured after 4 weeks of treatment ] [ Designated as safety issue: No ]
- Maximum and minimum concentrations and half-life of lopinavir/ritonavir [ Time Frame: Measured at study completion ] [ Designated as safety issue: No ]
- Proportion of participants with an AUC of less than 10% of adults [ Time Frame: Measured after 4 weeks of treatment ] [ Designated as safety issue: No ]
- Number and percent of participants experiencing adverse events of Grade 3 or greater [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
- Adherence, defined as proportion of doses taken [ Time Frame: Measured at study completion ] [ Designated as safety issue: Yes ]
|Study Start Date:||November 2010|
|Estimated Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
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
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 by weight. This study will evaluate the pharmacokinetics, safety, and tolerance of LPV/r dosed according to these guidelines.
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 the infant can swallow pills. Dosing will be calculated using the WHO schedule. At all study visits, infant 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 infant 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.
|Contact: Jorge A. Pinto, MD, DSc||(55 31) 3409 firstname.lastname@example.org|
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|Study Chair:||Jorge A. Pinto, MD||Federal University of Minas Gerais|