Patient enrollment has begun for the first of what will be a number ofstudies assessing the effectiveness of various three-drugcombinations against HIV.
The 48-week, 225-patient trial will be conducted at 20 sites in theU.S. by Parexel International Corp., a contract research organizationbased in Waltham, Mass. Fifteen pharmaceutical companies areparticipating in the study under an umbrella organization called theInter-Company Collaboration for AIDS Drug Development (ICC).
The first study will compare AZT (Burroughs Wellcome Co.'sRetrovir), ddC (Hoffmann-La Roche Inc.'s HIVID) and a placebowith AZT, ddC and saquinavir (Roche's Invirase); and AZT, ddCand nevirapine, an investigational non-nucleoside analog reversetranscriptase inhibitor being developed by Boehringer IngelheimInternational GmbH. AZT and ddC are approved products, whilesaquinavir is an investigational protease inhibitor.
"The next study will probably start about the time the first one iscompletely enrolled," which is expected to be in about two months,Linda Distlerath, who chairs ICC's communications committee, toldBioWorld. The next study, she said, is expected to involve Bristol-Myers Squibb Co.'s d4t (Zerit or stavudine); ddI, Bristol-Myers'Videx; and 3TC, a nucleoside analog being developed by Glaxo plcand BioChem Pharma Inc.
Patients can be male or female. They must be at least 13 years old,have CD4 counts of 200 to 500 and must not have received priorantiretroviral therapy. Primary endpoints are measures of CD4 andplasma RNA levels, Distlerath said. Secondary endpoints are adverseevents and development of viral resistance.
Those enrolled early in the trial will continue their treatment until thelast patients have completed their 48-week regimen, said SteveReich, Parexel's senior vice president, medical affairs. "It will take amatter of weeks [after that] before the official results are known," hetold BioWorld.
Distlerath said those already receiving retroviral therapy areexcluded from the study because they probably have developedresistance. "The whole concept of these protocols is to rapidlyidentify promising three-drug combinations worthy of further study,"she said.
The first trial will be conducted at centers in the U.S., but discussionsalready are under way about expanding to sites in Europe.
Distlerath, who's also senior director of public affairs for MerckResearch Laboratories, said the combinations were chosen, and willbe chosen, based on synergies seen in vitro, prevention of resistancein vitro, the lack of overlapping toxicities and certain logisticalconcerns, such as availability.
Merck & Co. Inc., of Whitehouse Station, N.J., initiated thediscussions that resulted in the April 1993 formation of the ICC.Current participants, in addition to all other companies citedpreviously, are AB Astra, of Sweden; Aji Pharma USA, a unit ofJapanese firm Ajinomoto Co.; DuPont Merck, of Wilmington, Del.;Gilead Sciences Inc., of Foster City, Calif.; Hoechst AG, ofGermany; Pfizer Inc., of New York; Miles Laboratories, a U.S. unitof German firm Bayer AG; Sigma-Tau, of Italy; and SmithKlineBeecham plc, of the U.K. n
-- Jim Shrine
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