Sarawak MediChem Pharmaceuticals, Inc.
SARAWAK MEDICHEM PHARMACEUTICALS BEGINS PHASE 1B CLINICAL TRIAL OF PLANT-BASED ANTI-HIV AGENT 11:15 a.m. Sep 30, 1998 Eastern
LEMONT, Ill., Sept. 30 /PRNewswire/ -- Sarawak MediChem Pharmaceuticals, Inc., has begun screening volunteers for a 32-patient Phase 1B clinical trial of (+)-calanolide A, an anti-AIDS compound discovered in the rain forest of Sarawak, Malaysia. The six-month trial will be performed at six research centers in the United States and will evaluate the safety, pharmacokinetics and effects of two doses of (+)-calanolide A on surrogate markers in HIV-positive patients with no previous antiretroviral therapy. It will be a randomized, sequential, double-blind, placebo-controlled study.
As well as assessing safety and pharmacokinetics, Sarawak MediChem researchers intend to evaluate the effect of (+)-calanolide A on viral load and viral resistance, and compare the effect of the treatment on changes from baseline CD4+ cell count (see note).
After treatment, subjects who participate in the trial may elect to receive an open-label, six-month course of approved anti-HIV drugs to be selected by and administered under the care of the subject's physician.
Results of a Phase 1A trial with healthy volunteers, who received escalating single doses or multiple doses, showed (+)-calanolide A to be well-tolerated. It was absorbed and circulated in the bloodstream, resulting in higher blood concentrations than anticipated from animal data. The most frequent adverse effects were dizziness, oily aftertaste, headache, belching and nausea, which were mild to moderate. Pharmacokinetic analyses suggest once or twice daily dosing.
(+)-Calanolide A was isolated from the bintangor tree (Calophyllum lanigerum) by the National Cancer Institute (NCI), after a team of botanists from the University of Illinois and the Arnold Arboretum, under the auspices of the NCI, collected plant samples from the Malaysian rain forest. With the plant source proving to be rare, MediChem Research, Inc., synthesized the compound.
In vitro studies have shown (+)-calanolide A, a non-nucleoside reverse transcriptase inhibitor (NNRTI), to be active against HIV-1, including strains resistant to AZT, Nevirapine and other NNRTIs. It has also exhibited synergistic anti-HIV activity when used in combination in vitro with nucleoside analogs such as AZT, ddC, ddI, d4T and 3TC; with non-nucleoside inhibitors such as Nevirapine; and with protease inhibitors such as Saquinavir and Nelfinavir. Animal studies have shown the compound to penetrate into viral reservoir sites by crossing the blood-brain barrier into the brain and accumulating in the lymph nodes.
Sarawak MediChem Pharmaceuticals, Inc., is a joint venture between MediChem Research, Inc., and the State of Sarawak, Malaysia, to advance the clinical development of (+)-calanolide A. Formed in 1987, MediChem Research is a privately held biotechnology firm specializing in custom organic synthesis. It holds a patent for the total synthesis of (+)-calanolide A. It also has a worldwide exclusive license to the National Cancer Institute patent on the structure of the compound, as well as to the rights held by the government of Sarawak. For more information, visit MediChem's and Sarawak MediChem Pharmaceuticals' web sites at www.medichem.com and www.sarawak-medichem.com.
A non-scientific version of this press release can be made available by calling 708-383-3939.
NOTE: The 4 in CD4+ is a subscript and the + is a superscript. SOURCE Sarawak MediChem Pharmaceuticals, Inc.
Copyright 1998, PR Newswire