Pharmacokinetics of Once Daily Darunavir/Ritonavir in HIV-infected Children

Study Overview
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Brief Summary
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Darunavir/ritonavir is one of the preferred antiretroviral agents as part of combination antiretroviral therapy for treatment of HIV-infected adults according to international guidelines. For children 3-12 years old, FDA has approved once daily dosing of darunavir/ritonavir. Dosing recommendations for children 6-12 years old have been approved based on a modelling and simulation procedure by the company. This pharmacokinetic study is designed to validate the proposed dosing recommendation for once daily darunavir/ritonavir in HIV-infected children aged 6-12 years old.

Detailed Description
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The EMA and FDA recommended weight band dosing for once daily DRV/r dosing in children 3 -12 years of age has been derived from pharmacokinetic modelling. Results from population pharmacokinetic modelling and simulation in these children predict similar DRV plasma exposures compared to treatment-naïve adults, but has not been formally studied in the target population. Although no clinical trial was conducted to collect exposure-safety data, the predicted exposures from the once daily dosing is supported by exposures observed in a paediatric clinical trial where twice-daily dosing was administered. To validate the weight band based dosing recommendations, we want to evaluate the pharmacokinetics of DRV/r administered once daily, using DRV tablets, in HIV-infected children. Darunavir/ritonavir is one of the preferred antiretroviral agents as part of combination antiretroviral therapy for treatment of HIV-infected adults according to international guidelines. For children 3-12 years old, FDA has approved once daily dosing of darunavir/ritonavir. Dosing recommendations for children 6-12 years old have been approved based on a modelling and simulation procedure by the company. This pharmacokinetic study is designed to validate the proposed dosing recommendation for once daily darunavir/ritonavir in HIV-infected children aged 6-12 years old.

Official Title
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Once Daily Darunavir/Ritonavir in HIV-infected Children 6-12 Years Old: a Pharmacokinetic Validation of Model Based Dosing Recommendations

Conditions
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Human Immunodeficiency Virus, Children

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Parents/carers are able and willing to sign the informed consent form prior to screening evaluations Subject is HIV infected Subject is at least 6 and less than 12 years at day of screening Subject has a body weight of at least 15kg Subject is able to swallow tablets Subject has an undetectable viral load (<50 copies/mL) for the last 6 months prior to screening (at least 2 measurements) ART regimen consists of darunavir/ritonavir and 2 NRTIs Exclusion Criteria: Inability to understand the nature and extent of the trial and the procedures required Documented history of sensitivity/idiosyncrasy to darunavir or ritonavir medicinal products or its excipients Relevant history or current condition that might interfere with drug absorption, distribution, metabolism or excretion Abnormal renal or liver function (grade 3 or above) Participation in a drug trial within 60 days prior to the first dose Hemoglobin < 10 g/dL (6.0 mmol/L) Children who have previously failed virologically on a PI containing regimen (where virological failure is defined as two successive HIV-1 RNA results >1,000 c/mL more than 24 weeks after starting cART, i.e. changes for toxicity or convenience are not counted as failure) Acute illness Receiving concomitant therapy except for prophylaxis for opportunistic infections; some treatments may be allowed, but must first be discussed with the principal investigator or project manager.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 12 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The exposure of darunavir, compared to the target exposure (AUC0-24) in adults |  | 24 hours |