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
Nevirapine
+ Zidovudine
Infections transmises par le sang+14
+ Maladies génito-urinaires
+ Maladies Génitales
Étude thérapeutique
Résumé
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.
Protocole
Cette section fournit des détails sur le plan de l'étude, y compris la manière dont l'étude est conçue et ce qu'elle évalue.35 participants à inclure
Nombre total de participants que l'essai clinique vise à recruter.Traitement
Éligibilité
Les chercheurs recherchent des patients correspondant à une certaine description appelée critères d'éligibilité : état de santé général ou traitements antérieurs du patient.Tout sexe
Le sexe biologique des participants éligibles à s'inscrire.Volontaires sains non autorisés
Indique si les individus en bonne santé et ne présentant pas la condition étudiée peuvent participer.Conditions
Pathologie
Critères
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.
Centres d'étude
Ce sont les hôpitaux, cliniques ou centres de recherche où l'essai est conduit. Vous pouvez trouver le site le plus proche de vous ainsi que son statut.Cette étude comporte 7 sites
Univ of Southern California / LA County USC Med Ctr
Los Angeles, United StatesOuvrir Univ of Southern California / LA County USC Med Ctr dans Google MapsUCLA Med Ctr / Pediatrics
Los Angeles, United StatesUniv of Connecticut Health Ctr / Pediatrics
Farmington, United StatesUniv of Miami (Pediatric)
Miami, United States