The Safety and Effectiveness of BI-RG-587 in HIV-Infected Patients
|Study Design:||Primary Purpose: Treatment|
|Official Title:||An Open Label, Staggered Rising Dose Cohort Study Assessing Safety, Tolerance, and Activity of BI-RG-587 in Patients With HIV Infection (CD4+ Cell Count < 400 Cells/mm3)|
A compound free of the toxic effects of nucleoside chain terminators such as zidovudine (AZT) may have an advantage over currently available treatments for HIV infection. Such a compound has further advantages if it is active against AZT-resistant isolates. Nevirapine (BI-RG-587) has shown in vitro inhibitory activity against HIV-1 reverse transcriptase (RT). The molecular mechanism of the RT inhibitory effect is hypothesized to be non-competitive inhibition due to its binding to an RT site distinct from those for the RNA template primer, the deoxynucleotide triphosphate or the RNase H catalytic site.
This is a staggered dose escalation cohort trial which examines the safety, tolerance, pharmacokinetics and activity of Nevirapine (BI-RG-587) in patients with HIV infection. Groups of 10 patients must have completed 4 weeks of therapy without requiring dose interruption before the next dosage level can be initiated. All 10 patients must be enrolled at a lower dosage level before the next dosage level can be initiated. Patients discontinue antiretroviral therapy, after signing informed consent, 28 days prior to receipt of a first dose of Nevirapine. Screening lab tests, including p24 antigen and plasma viremia, and CD4+ cell count determination are performed 21 days prior to drug dosing in Part I. Patients are notified of screening laboratory measures that exclude them from study participation. Upon such notification patients have the option to resume prior antiretroviral therapy or to repeat those values in one week. Part II consists of two 8-hour intensive blood sampling periods plus frequent trough value blood samplings. Safety, trough value blood sampling, and activity assessments are performed in Part III. An assessment of dose-tolerance and of activity is made in Study Week 12 in order that patients may continue Nevirapine chronic therapy for an additional 12 weeks. The Final Visit in Part IV takes place on Study Week 24 to complete the trial. Patients who complete 24 weeks are offered the option to continue on Nevirapine chronic therapy at the initial or an altered dose on a separate open-label protocol.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00000962
|United States, California|
|Univ of California / San Diego Treatment Ctr|
|San Diego, California, United States, 921036325|
|United States, Massachusetts|
|Univ of Massachusetts Med Ctr|
|Worcester, Massachusetts, United States, 01655|
|United States, Minnesota|
|Univ of Minnesota|
|Minneapolis, Minnesota, United States, 55455|