A Study of Nevirapine Used Alone or in Combination With AZT in HIV-1-Infected Children
Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: HIV Infections
Intervention: Nevirapine (Drug); Zidovudine (Drug)
Phase: N/A
Status: Completed
Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID) Official(s) and/or principal investigator(s): J Sullivan, Study Chair K Luzuriaga, Study Chair
Summary
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.
Clinical Details
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
Study design: Primary Purpose: 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.
Eligibility
Minimum age: N/A.
Maximum age: 17 Years.
Gender(s): Both.
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.
Locations and Contacts
UCLA Med Ctr / Pediatrics, Los Angeles, California 90095, United States
Univ of Southern California / LA County USC Med Ctr, Los Angeles, California 900331079, United States
Univ of Connecticut Health Ctr / Pediatrics, Farmington, Connecticut 06032, United States
Univ of Miami (Pediatric), Miami, Florida 33161, United States
Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States
Univ of Massachusetts Med Ctr / Biotech II, Worcester, Massachusetts 01605, United States
Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl, Newark, New Jersey 071072198, United States
Additional Information
Click here for more information about Zidovudine Click here for more information about Nevirapine
Related publications: Luzuriaga K, Bryson Y, Krogstad P, Robinson J, Stechenberg B, Lamson M, Cort S, Sullivan JL. Combination treatment with zidovudine, didanosine, and nevirapine in infants with human immunodeficiency virus type 1 infection. N Engl J Med. 1997 May 8;336(19):1343-9. Sullivan J, Luzuriaga K. Nevirapine activity and emergence of resistant virus in pediatric trials. The ACTG 180 Study Team. Int Conf AIDS. 1993 Jun 6-11;9(1):475 (abstract no PO-B26-2042) Luzuriaga K, Bryson Y, McSherry G, Robinson J, Stechenberg B, Scott G, Lamson M, Cort S, Sullivan JL. Pharmacokinetics, safety, and activity of nevirapine in human immunodeficiency virus type 1-infected children. J Infect Dis. 1996 Oct;174(4):713-21.
Last updated: February 28, 2011
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