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

HIV Infections Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00273975
• Other study ID #: 1100.1368
• Status: Completed
• Phase: Phase 2
• First received: January 9, 2006
• Last updated: October 30, 2013
• Start date: January 2002
• Est. completion date: December 2004

Study information

• Verified date: October 2013
• Source: Boehringer Ingelheim
• Contact: n/a
• Is FDA regulated: No
• Health authority: South Africa: Medicines Control Council
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 123
• Est. completion date: December 2004
• Est. primary completion date: December 2004
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Months to 16 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Nevirapine

• Lamivudine

• Zidovudine

Locations

Country	Name	City	State
South Africa	Groote Schuur Hospital	Cape Town
South Africa	Boehringer Ingelheim Investigational Site	Pretoria
South Africa	Boehringer Ingelheim Investigational Site	Soweto
South Africa	Boehringer Ingelheim Investigational Site	Tygerberg

Sponsors (1)

Lead Sponsor	Collaborator
Boehringer Ingelheim

Country where clinical trial is conducted

South Africa, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the concentration-time curve over one dosing interval (AUCt)		1, 3 and 6 hours on Day 28	No
Primary	Maximum observed concentration (Cmax)		1, 3 and 6 hours on Day 28	No
Primary	Minimum observed concentration (Cmin)		1, 3 and 6 hours on Day 28	No
Primary	Oral clearance (Dose/AUC) at steady state		1, 3 and 6 hours on Day 28	No
Secondary	Change in HIV-1 RNA count		week 2, 4, 8, 12, 18, 24, 30, 36, 42,48	No
Secondary	Virologic Response		48 weeks	No
Secondary	Time to Virologic Suppression		48 weeks	No
Secondary	Virologic Failure		48 weeks	No
Secondary	Time to Virologic Failure		48 weeks	No
Secondary	Treatment Failure		48 weeks	No
Secondary	Time to Treatment Failure		48 weeks	No
Secondary	Change in CD4+ cell count		week 2, 4, 8, 12, 18, 24, 30, 36, 42,48	No
Secondary	Change in CD4+ percent		week 2, 4, 8, 12, 18, 24, 30, 36, 42,48	No
Secondary	Occurrence of Adverse Events		48 weeks	No
Secondary	Occurrence of Rash		48 weeks	No

External Links

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