A Study of Nevirapine Used Alone or in Combination With AZT in HIV-1-Infected Children

February 28, 2011 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

Pharmacokinetics, Safety, Tolerance, and Activity of Nevirapine (BI-RG-587) Alone and in Combination With AZT in Mildly to Moderately Symptomatic HIV-1 Infected Children

Monotherapy phase: To evaluate and compare the safety, tolerance, pharmacokinetics, and preliminary activity of nevirapine administered alone in mildly to moderately symptomatic HIV-infected children ages 2 months to less than 18 years; to evaluate and compare the safety, tolerance, and pharmacokinetics of nevirapine in HIV-infected children ages 1 day to less than 2 months. Combination therapy phase: To evaluate and compare the safety, tolerance, pharmacokinetics, and preliminary activity of nevirapine administered in combination with zidovudine (AZT) in mildly to moderately symptomatic HIV-infected children ages 2 months to less than 18 years.

Compounds with reverse transcriptase inhibitory activity that are more potent and less toxic than the nucleoside analogues are needed. Nevirapine (BI-RG-587) has shown in vitro inhibitory activity against HIV-1reverse transcriptase and has shown a synergistic inhibition of HIV-1 replication when combined with zidovudine (AZT) in a plaque reduction assay.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Compounds with reverse transcriptase inhibitory activity that are more potent and less toxic than the nucleoside analogues are needed. Nevirapine (BI-RG-587) has shown in vitro inhibitory activity against HIV-1 reverse transcriptase and has shown a synergistic inhibition of HIV-1 replication when combined with zidovudine (AZT) in a plaque reduction assay.

Sixty mildly to moderately symptomatic HIV-infected children (five patients in each of four age groups) will receive oral nevirapine at 1 of 3 doses for 168 days. If preliminary activity is demonstrated and toxicity is acceptable after 84 days of treatment in the three oldest age groups (ages 2 months - less than 2 years, ages 2 years - less than 13 years, and ages 13 years - less than 18 years), children ages 1 day - less than 2 months will receive one of the three doses of nevirapine. Additionally, 15 additional patients (five in each of three age groups) will receive zidovudine in combination with nevirapine. At the end of 24 weeks of combination therapy, patients discontinue zidovudine for 2 weeks while remaining on nevirapine, in order for pharmacokinetic sampling to be done. Children will be enrolled sequentially by decreasing age and increasing nevirapine dose.

Study Type

Interventional

Enrollment

35

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 900331079
        • Univ of Southern California / LA County USC Med Ctr
      • Los Angeles, California, United States, 90095
        • UCLA Med Ctr / Pediatrics
    • Connecticut
      • Farmington, Connecticut, United States, 06032
        • Univ of Connecticut Health Ctr / Pediatrics
    • Florida
      • Miami, Florida, United States, 33161
        • Univ of Miami (Pediatric)
    • Massachusetts
      • Springfield, Massachusetts, United States, 01199
        • Baystate Med Ctr of Springfield
      • Worcester, Massachusetts, United States, 01605
        • Univ of Massachusetts Med Ctr / Biotech II
    • New Jersey
      • Newark, New Jersey, United States, 071072198
        • Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 15 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

  • IV gammaglobulin therapy.
  • Medications for PCP prophylaxis (e.g., TMP / SMX, dapsone, aerosolized and IV pentamidine).
  • Fluconazole.

Patients must have:

  • HIV infection. A positive Polymerase Chain Reaction (PCR) is not acceptable as the sole evidence of HIV infection. Three out of five children in each age and dose group must have a serum p24 antigen level of 70 pg/ml or greater and/or a plasma viral titer of 50 TCID/ml or greater prior to study entry.
  • Ability to be followed by their original trial center for the duration of the trial.
  • Consent of parent or guardian.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms and conditions are excluded:

  • Lymphocytic interstitial pneumonitis if steroid-dependent or requiring supplemental oxygen or with a pretreatment paO2 < 70 mm Hg.
  • Opportunistic or serious bacterial infections within 28 days prior to entry.
  • Demonstrated intolerance to zidovudine prior to administration of nevirapine (in patients enrolled in the combination therapy phase of the study).
  • CDC classification of P-2D (secondary infectious diseases) and/or P-2E (secondary cancers).
  • Pre-existing malignancies.

Concurrent Medication:

Excluded:

  • Other approved or investigational antiretroviral agents.
  • All other investigational agents (except fluconazole).
  • Glucocorticoids and steroid hormones.
  • Dicumarol, warfarin, and other anticoagulants.
  • Digitoxin.
  • Valproic acid.
  • Tolbutamide.
  • Doxycycline.
  • Chloramphenicol.
  • Isoniazid.
  • Phenobarbital and other barbiturates.
  • Hepatotoxic drugs.

Patients with prior participation in this trial are excluded.

Prior Medication:

Excluded:

  • More than 6 weeks of prior zidovudine (AZT) therapy or more than 6 weeks of any other antiretroviral therapy.

Excluded within 7 days prior to study entry:

  • AZT (in monotherapy groups only).

Excluded within 4 weeks prior to study entry:

  • Other approved or investigational antiretroviral agents.
  • All other investigational agents.
  • Glucocorticoids and steroid hormones.
  • Dicumarol, warfarin, and other anticoagulants.
  • Digitoxin.
  • Valproic acid.
  • Tolbutamide.
  • Doxycycline.
  • Chloramphenicol.
  • Isoniazid.
  • Phenobarbital and other barbiturates. Active alcohol or drug abuse to impair compliance with the protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Roxane Laboratories

Investigators

  • Study Chair: J Sullivan
  • Study Chair: K Luzuriaga

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Primary Completion (Actual)

June 1, 1995

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Estimate)

March 1, 2011

Last Update Submitted That Met QC Criteria

February 28, 2011

Last Verified

February 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 180
  • 882

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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