Trial to Evaluate Steady State Pharmacokinetic Parameters, Efficacy and Safety of Nevirapine in Antiretroviral Drug naïve Pediatric Patients

Study Overview
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Brief Summary
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Trial to evaluate steady state pharmacokinetic parameters of nevirapine 150mg/m2 and nevirapine 4 or 7 mg/kg after 4 weeks, and efficacy and safety of the dosing when administered for 48 weeks in antiretroviral drug naïve paediatric patients.

Detailed Description
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A randomised open label multi-centre trial to evaluate the pharmacokinetic, efficacy and safety parameters of nevirapine 150mg/m2 and nevirapine 4 or 7mg/kg when administered in combination with ZDV and 3TC for 48 weeks in antiretroviral naive pediatric patients. Primary objective: To evaluate steady state pharmacokinetic parameters of nevirapine 150mg/m2 in antiretroviral drug naive pediatric patients. Secondary objective: To assess efficacy and safety of nevirapine 150 mg/m2 and nevirapine 4/7mg/kg after 24 and 48 weeks of treatment Study Hypothesis: Evaluation of recent pharmacokinetic data has suggested that a dose based on body surface area rather than body weight might be a better therapeutic regimen to achieve steady state plasma concentrations. The goal in this study was to determine if a Nevirapine suspension dose of 150 mg/m2 BID, following a two week lead-in of 150 mg/m2 QD, produces plasma nevirapine steady state concentrations of 4 - 6 ?g/mL in all age groups as was observed in adult safety and efficacy trials. Comparison(s): ACTG 245

Official Title
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A Randomised Open Label Multi-centre Trial to Evaluate the Pharmacokinetic, Efficacy and Safety Parameters of Nevirapine 150mg/m2 and Nevirapine 4 or 7 mg/kg When Administered in Combination With AZT and 3TC for 48 Weeks in Antiretroviral naïve Paediatric Patients.

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Nevirapine
* Drug: Lamivudine
* Drug: Zidovudine


Participation Criteria
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Eligibility Criteria
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Inclusion: Male or female patients between 3 months and 16 years of age at day 28 of the study. Evidence of HIV-1 infection Patients who are antiretroviral drug naive Plasma viral load detectable CD4 >=50 cells/cc3 Written informed permission Active assent given by the patient if the child is capable of understanding the given information Reasonable probability for completion of the trial Exclusion: Any significant disease, other than HIV Any acute illness within 2 weeks prior to Day 0 Patients requiring the continued use of inhibitors or inducers of P450 metabolic enzymes Patients requiring systematic treatment with CYP3A4 substrates Patients with malabsorption, severe chronic diarrhea Receipt of any cytotoxic therapy for malignancy Current grade 3 or 4 clinical or laboratory toxicity Pregnancy or breast-feeding Females of childbearing potential not using adequate contraception. allergy or known drug hypersensitivity to any of the study drugs intravenous drug abuse, alcohol or substance abuse

Ages Eligible for Study
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Minimum Age: 3 Months
Maximum Age: 16 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Nevirapine|nan|
|Drug: Lamivudine|nan|
|Drug: Zidovudine|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve over one dosing interval (AUCτ) |  | 1, 3 and 6 hours on Day 28 | 
| Maximum observed concentration (Cmax) |  | 1, 3 and 6 hours on Day 28 | 
| Minimum observed concentration (Cmin) |  | 1, 3 and 6 hours on Day 28 | 
| Oral clearance (Dose/AUC) at steady state |  | 1, 3 and 6 hours on Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in HIV-1 RNA count |  | week 2, 4, 8, 12, 18, 24, 30, 36, 42,48 | 
| Virologic Response |  | 48 weeks | 
| Time to Virologic Suppression |  | 48 weeks | 
| Virologic Failure |  | 48 weeks | 
| Time to Virologic Failure |  | 48 weeks | 
| Treatment Failure |  | 48 weeks | 
| Time to Treatment Failure |  | 48 weeks | 
| Change in CD4+ cell count |  | week 2, 4, 8, 12, 18, 24, 30, 36, 42,48 | 
| Change in CD4+ percent |  | week 2, 4, 8, 12, 18, 24, 30, 36, 42,48 | 
| Occurrence of Adverse Events |  | 48 weeks | 
| Occurrence of Rash |  | 48 weeks |