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

This study has been completed.
Sponsor:
Collaborator:
Roxane Laboratories
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001111
First received: November 2, 1999
Last updated: February 28, 2011
Last verified: February 2011
  Purpose

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.


Condition Intervention
HIV Infections
Drug: Nevirapine
Drug: Zidovudine

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 35
Primary Completion Date: June 1995 (Final data collection date for primary outcome measure)
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.

  Eligibility

Ages Eligible for Study:   up to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001111

Locations
United States, California
Univ of Southern California / LA County USC Med Ctr
Los Angeles, California, United States, 900331079
UCLA Med Ctr / Pediatrics
Los Angeles, California, United States, 90095
United States, Connecticut
Univ of Connecticut Health Ctr / Pediatrics
Farmington, Connecticut, United States, 06032
United States, Florida
Univ of Miami (Pediatric)
Miami, Florida, United States, 33161
United States, Massachusetts
Baystate Med Ctr of Springfield
Springfield, Massachusetts, United States, 01199
Univ of Massachusetts Med Ctr / Biotech II
Worcester, Massachusetts, United States, 01605
United States, New Jersey
Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
Newark, New Jersey, United States, 071072198
Sponsors and Collaborators
Roxane Laboratories
Investigators
Study Chair: J Sullivan
Study Chair: K Luzuriaga
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00001111     History of Changes
Other Study ID Numbers: ACTG 180, 882
Study First Received: November 2, 1999
Last Updated: February 28, 2011
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Antiviral Agents
Zidovudine
Nevirapine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Nevirapine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on September 22, 2014