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

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

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