Clinical trial NCT00273975: Trial to Evaluate Steady State Pharmacokinetic Parameters, Efficacy and Safety of Nevirapine in Antiretroviral Drug naïve Pediatric Patients
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HIV Infections
Lead sponsor: Boehringer Ingelheim
Sponsor class: INDUSTRY
First posted: 2006-01-10
Enrollment: 123
Sex: ALL
Minimum age (years): 3
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: Inclusion:

1. Male or female patients between 3 months and 16 years of age at day 28 of the study.
2. Evidence of HIV-1 infection
3. Patients who are antiretroviral drug naive
4. Plasma viral load detectable
5. CD4 \>=50 cells/cc3
6. Written informed permission
7. Active assent given by the patient if the child is capable of understanding the given information
8. Reasonable probability for completion of the trial

Exclusion:

1. Any significant disease, other than HIV
2. Any acute illness within 2 weeks prior to Day 0
3. Patients requiring the continued use of inhibitors or inducers of P450 metabolic enzymes
4. Patients requiring systematic treatment with CYP3A4 substrates
5. Patients with malabsorption, severe chronic diarrhea
6. Receipt of any cytotoxic therapy for malignancy
7. Current grade 3 or 4 clinical or laboratory toxicity
8. Pregnancy or breast-feeding
9. 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

Primary outcomes:
measure: Area under the concentration-time curve over one dosing interval (AUCτ)
timeFrame: 1, 3 and 6 hours on Day 28
measure: Maximum observed concentration (Cmax)
timeFrame: 1, 3 and 6 hours on Day 28
measure: Minimum observed concentration (Cmin)
timeFrame: 1, 3 and 6 hours on Day 28
measure: Oral clearance (Dose/AUC) at steady state
timeFrame: 1, 3 and 6 hours on Day 28
Secondary outcomes:
measure: Change in HIV-1 RNA count
timeFrame: week 2, 4, 8, 12, 18, 24, 30, 36, 42,48
measure: Virologic Response
timeFrame: 48 weeks
measure: Time to Virologic Suppression
timeFrame: 48 weeks
measure: Virologic Failure
timeFrame: 48 weeks
measure: Time to Virologic Failure
timeFrame: 48 weeks
measure: Treatment Failure
timeFrame: 48 weeks
measure: Time to Treatment Failure
timeFrame: 48 weeks
measure: Change in CD4+ cell count
timeFrame: week 2, 4, 8, 12, 18, 24, 30, 36, 42,48
measure: Change in CD4+ percent
timeFrame: week 2, 4, 8, 12, 18, 24, 30, 36, 42,48
measure: Occurrence of Adverse Events
timeFrame: 48 weeks
measure: Occurrence of Rash
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: Groote Schuur Hospital
city: Pretoria
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Soweto
country: South Africa
facility: Boehringer Ingelheim Investigational Site
city: Tygerberg
country: South Africa
facility: Boehringer Ingelheim Investigational Site
Study officials:
affiliation: B.I. South Africa (Pty.) Ltd.
name: Boehringer Ingelheim Study Coordinator
role: STUDY_CHAIR
References: