323   Safety and Efficacy of Capravirine Versus Placebo in HIV-Infected Patients Failing a Nonnucleoside-Reverse- Transcriptase-Inhibitor- Containing Regimen: Results of a Phase II, Double-Blind, Placebo-Controlled Study.

P. Wolfe*, P. Hawley, G. Boccia, N. Clendeninn, L. Paradiso, T. Shaw, and K. Chi-Burris.
Pacific Oaks Res., Beverly Hills and Agouron Pharmaceuticals, Inc., La Jolla, CA.

Background:Capravirine (CPV; AG1549) is a novel nonnucleoside reverse transcriptase inhibitor (NNRTI) that exhibits potent in vitro antiviral activity against HIV variants with RT substitutions, including K103N, that confer broad cross-resistance among the approved NNRTIs. The in vitro resistance profile of CPV suggests that it will reduce plasma HIV RNA levels in patients who have failed regimens that include other NNRTIs.

Methods:This is an ongoing 24-week, phase II, double-blind, placebo-controlled study of capravirine in 75 patients failing a NNRTI-containing regimen to determine if capravirine will reduce plasma HIV RNA levels in these patients compared to placebo. Protease-inhibitor-naive patients with HIV RNA >2000 c/mL were randomized to CPV (1400 or 2100 mg BID) or placebo. All patients received nelfinavir 1250 mg BID and 2 new nucleoside reverse transcriptase inhibitors.

Results:To date among 50 enrolled patients with data available, median baseline HIV RNA was 4.14 log₁₀c/mL and median CD4 cell count was 362/mm³. At week 12, preliminary results show that more than 50% of patients who received capravirine were rescued in the active treatment arms based on HIV RNA <400 c/mL. The most common drug-related adverse events of at least moderate severity were diarrhea, nausea, and vomiting. Among adverse events of any severity, diarrhea, nausea, and vomiting occurred more frequently in the 2100-mg group than in the 1400 mg or placebo groups. To date, four patients have discontinued for treatment failure and seven patients have discontinued for adverse events.

Conclusion:Preliminary efficacy and safety evaluation at 12 weeks of CPV versus placebo shows antiviral activity of CPV and supports the use of CPV 1400 mg BID as the dosage in larger clinical studies.