If this is not your name, click here.
| | If this is not your name, click here. | | |
| | Contact Us | Order Now | Journals | Bookstore | Register a colleague | | |
| |  Capravirine Demonstrates Anti-HIV Activity, Good Tolerability SAN FRANCISCO, CA -- January 31, 2000 -- Agouron Pharmaceuticals, Inc. reported that the investigational drug capravirine (formerly AG1549), showed antiretroviral activity and was well-tolerated in a short course monotherapy trial of HIV-infected patients. In a second trial to examine pharmacokinetics, capravirine achieved target antiretroviral concentrations in plasma when administered in combination with HIV protease inhibitors. Capravirine, which demonstrates a novel HIV resistance profile in preclinical studies, is a member of the class of agents known as non-nucleoside reverse transcriptase inhibitors (NNRTIs). In preclinical studies, capravirine demonstrates potent antiviral activity against wild-type HIV as well as HIV strains with mutations in reverse transcriptase, including K103N, that confer broad viral resistance to other, commercially available reverse transcriptase inhibitors. Investigators will present results from both clinical trials this week at the 7th Conference on Retroviruses and Opportunistic Infections in San Francisco, California. Results of the capravirine monotherapy trial will be presented by Jose Hernandez, MD, Immunity Care and Research, LLC., Plantation, Florida. Capravirine was administered orally for 10 days to antiretroviral naive HIV-infected patients at doses of either 700, 1400, or 2100 mg twice daily (BID) or 700 or 1400 mg three times daily (TID). A control arm was treated with standard doses of the HIV protease inhibitor nelfinavir (NFV) plus AZT and 3TC. Six patients were entered into each arm, and daily plasma HIV RNA levels were measured by the AMPLICOR(TM) HIV-1 Monitor Assay. Over the course of the study, comparable decreases in HIV RNA were exhibited across all study arms, with mean decreases ranging from 1.1 log10 for the 700 mg TID arm to 1.69 log10 for the 2100 mg BID arm. A mean decrease of 1.65 log10 was observed in the NFV/AZT/3TC control arm. BID and TID capravirine monotherapy treatment arms showed similar reductions in plasma HIV RNA and were well-tolerated. The most commonly reported drug-related adverse events were nausea, vomiting, and headache. Mark Jacobs, MD, HIVCare at St. Francis Memorial Hospital, San Francisco, California will report results from a second trial that examined the pharmacokinetic interaction of capravirine with the HIV protease inhibitors nelfinavir or indinavir. Forty patients on stable anti-HIV therapy with standard doses of either nelfinavir (29) or indinavir (11) plus either AZT or d4T were treated with capravirine for 28 days at doses ranging from 175 to 1800 mg BID (indinavir at 175 mg BID only). Capravirine co-administered with these HIV protease inhibitors was well-tolerated and achieved the target antiviral concentrations in blood that exhibited antiretroviral activity in preclinical studies. Dr. Hernandez said, "These are the first clinical data to be reported for capravirine, which exhibits a unique HIV resistance profile preclinically. The results in decreasing viral load and achieving target antiviral concentrations will open the pathway to further clinical development." Related Link: Agouron Pharmaceuticals, Inc.
|
