Comparison of Liquid Kaletra and Low Dose Kaletra Tablets

Study Overview
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Brief Summary
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Kaletra (a combination drug with lopinavir and ritonavir) is one of a few effective medications that are approved and available for young children who are HIV+. The liquid form is reported to have a very nasty taste and presents difficulties for the children who must take the medication twice a day and for their parents who must enforce the medication regimen. The children are often well into their teens before they weigh enough to be able to take the adult dose tablet (200mg/50mg). A new smaller dose tablet (100mg/25mg) is now available. However, it is not known if the liquid and tablet act the same in children. The purpose of this study is to switch children from the baseline treatment with the liquid to the study intervention treatment with 100mg/25mg tablet form of Kaletra. The study will compare children pre-switch and post-switch in terms of how well their HIV is controlled . Comparisons of parent and child satisfaction will also be made. Eight to 10 HIV+ children currently well managed with a medications including liquid Kaletra will be invited to switch from the liquid to the low dose Kaletra tablet. The parent and/or child will complete a satisfaction survey for the liquid Kaletra and lab values will be taken from the chart. At the time of the switch and 1, 3 and 6 months post switch blood tests will be drawn and the parent and/or child will complete the satisfaction survey. In addition, at the switch and 1 month post switch, a day will be spent in clinic with 5 blood draws to see how much of the drug is in the blood stream at different times after the medicine is taken.

Official Title
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Comparison of Liquid Kaletra and Low Dose Kaletra Tablets in HIV-Positive Children

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Low dose Kaletra tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HIV+ children aged 3-18. Baseline treatment includes liquid Kaletra currently on a stable (on same regimen > 3 months, Viral Load< 5,000), Highly Active Antiretroviral Therapy (HAART) regimen able to take pills or willing to undergo pill training prior to enrollment weight must be greater than or equal to 15kg Exclusion Criteria: Unable to swallow pills Concomitant treatment with Rifampin or St. John's Wort which have been shown to decrease plasma concentrations of lopinavir. Concurrent use of drugs primarily metabolized by CYP3A, which metabolizes ritonavir: Astemizole, Cisapride, Dihydroergotamine, Ergonovine, Ergotamine, Flecainide, Lovastatin, Methylergonovine, Midazolam, Pimozide, Propafenone, Simvastatin, terfenadine, Triazolam Baseline treatment does NOT include Kaletra

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Low dose Kaletra tablets<br>Patients will serve as their own controls as they are switched from the baseline treatment with liquid Kaletra to the study intervention treatment with Low Dose Tablet Kaletra (100mg/25mg) | Drug: Low dose Kaletra tablets<br>* Lopinavir/Ritonavir tablets 100mg/25mg<br>* Other names: lopinavir/ritonavir 100mg/25mg;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Absolute CD4 and CD4 % | Number of participants who had no clinically significant deterioration in absolute CD4 and % CD4 count for the duration of the study. Absolute CD4 and Percent CD4 counts were determined by single or dual platform analysis performed on blood samples by Phoenix Children's Hospital Laboratory, Sonora Quest Laboratory or Labcorp Laboratory. Clinically significant change was determine to be a deterioration in both Absolute CD4 to less than 500 and %CD4 to less than 25%. | Baseline, 4 weeks, 12 weeks, 26 weeks | 
| Lopinavir (Lpv) and Ritonavir (Rtv) Maximumu Plasma Concentration (CMax) Liquid | Cmax values at baseline (participants are taking liquid Kaletra as part of baseline treatment). Time points for data collection: 0, 2hrs post dose, 4 hrs post dose, 8 hrs post dose. | Baseline | 
| Lopinavir and Ritonavir Area Under the Curve (AUC) Liquid Kaletra | Area under the curve values for lopinavir at baseline when participants are taking liquid Kaletra as part of their baseline treatment. Time points for data collection: 0, 2 hrs post, 4 hrs post, 6 hrs post, 8 hrs post. | Baseline | 
| Lopinavir AUC Ratio of Baseline:Week 4 | Ratio of AUC at baseline (liquid)to week 4 (reduced dose tablet). AUC data were collected at 0, 2, 4, 6, and 8 hours post dose. | Baseline, week 4 | 
| Viral Load (VL) | Number of participants who maintained their Viral load undetectable (< 20 copies/ml) for the duration of the study | Baseline, Week 4, Week 12 and Week 24 | 
| Lopinavir (Lpv) and Ritonavir (Rtv) Cmax at 4 Weeks | Lpv and rtv Cmax at 4 weeks when participants are receiving study intervention, low dose Kaletra. Time points for data collection: 0, 2hrs, 4hrs, 6hrs, 8hrs | 4 weeks | 
| Lopinavir and Ritonavir AUC on Low Dose Tablet | Lopinavir and Ritonavir AUC at 4 weeks when participants are receiving the study intervention, low dose tablet formulation of Kaletra. Data collection points for AUC were 0, 2, 4, 6, and 8 hours post dose. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Satisfaction | Patient Satisfaction Survey. Eight item Likert scale of patient satisfaction with their HIV treatment regimen for patients 7 years of age and older. Items scores are summed to compute a total score. Total scores are reported with a minimum of 0 and a maximum of 32, with higher scores indicating higher satisfaction. | Baseline, 1 month | 
| Symptoms Across All Patients | Cumulative tally of symptoms for each patients across all visits. Targetted symptoms were asked for at each visit and patients and parents were encouraged to report additional symptoms that were experienced. Each patient got a score for the total number of symptoms at each visit. Scores were totalled, but it the same symptoms occurred continuously it was counted as 1 symptom. | Baseline, 1 month, 3 months, 6 months | 
| Parent Satisfaction | Parent Satisfaction Survey. Eight item Likert scale of parent/guardian satisfaction with the child's HIV treatment regimen. Item scores are summed to compute a total score. Total scores are reported with a minimum of 0 and a maximum of 32, with higher scores indicating higher satisfaction. | Baseline, 4 week, 12 weeks and 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIV, Kaletra, treatment Experienced