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 7 mg/kg When Administered in Combination With AZT and 3TC for 48 Weeks in Antiretroviral naïve Paediatric Patients.

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Nevirapine; Drug: Lamivudine; Drug: Zidovudine

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

• Study Type: Interventional
• Enrollment: 123
• Phase: Phase 2

Contacts and Locations

Study Locations

• South Africa
  • Cape Town, South Africa, 7900
    • Groote Schuur Hospital
  • Pretoria, South Africa
    • Boehringer Ingelheim Investigational Site
  • Soweto, South Africa, 2013
    • Boehringer Ingelheim Investigational Site
  • Tygerberg, South Africa, 7505
    • Boehringer Ingelheim Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 months to 16 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Boehringer Ingelheim

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: January 1, 2002
• Primary Completion (Actual): December 1, 2004
• Study Completion: December 1, 2004

Study Registration Dates

• First Submitted: January 9, 2006
• First Submitted That Met QC Criteria: January 9, 2006
• First Posted (Estimate): January 10, 2006

Study Record Updates

• Last Update Posted (Estimate): October 31, 2013
• Last Update Submitted That Met QC Criteria: October 30, 2013
• Last Verified: October 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nevirapine; Lamivudine; Zidovudine
• Other Study ID Numbers: 1100.1368