SAN FRANCISCO, Jan. 30 /PRNewswire/ -- Agouron Pharmaceuticals, Inc. today
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."
Registrational clinical trials for capravirine are in progress. Agouron
has exclusive rights to the development and commercialization of capravirine
in North America, Europe, and many other countries. Shionogi & Co., Ltd.
maintains rights to commercialization in Japan, South Korea, and Taiwan.
Agouron Pharmaceuticals, Inc., a wholly owned subsidiary of the Warner-
Lambert Company (NYSE: WLA), is an integrated pharmaceutical company committed
to the discovery, development, manufacturing, and marketing of innovative
therapeutic products engineered to inactivate proteins that play key roles in
cancer, AIDS, and other serious diseases. Agouron employs more than 1200
people of whom approximately 800 are engaged in research and development.
SOURCE Agouron Pharmaceuticals, Inc.
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http://www.prnewswire.com/comp/019650.html or fax,
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CONTACT:
Joy Schmitt, Associate Director, Product
Public Relations, Agouron Pharmaceuticals, Inc., 858-622-3220
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