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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

Page last updated: August 23, 2015

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