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| |  Tolevamer Fails in Phase 3 Diarrhea Trial: Presented at ICAAC By John Gever CHICAGO, IL -- September 18, 2007 -- The investigational drug tolevamer was found to be less effective than either vancomycin or metronidazole in a phase 3 clinical study of Clostridium difficile-associated diarrhea (CDAD), researchers reported here at the 47th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). "These are obviously disappointing results," said study leader David M. Davidson, MD, Senior Medical Director, Genzyme Corporation, Waltham, Massachusetts. Genzyme is developing tolevamer and sponsored the trial. However, Dr. Davidson said he was encouraged by significantly lower rates of symptom recurrence in patients treated with tolevamer relative to the other drugs, among patients who had successfully recovered. A total of 574 patients in the United States and Canada were recruited for the randomized, double-blind, multicenter trial. Subjects were at least 18 years old, were experiencing acute diarrhea with presumed or documented C. difficile infection, and their condition was otherwise uncomplicated. Study subjects were assigned to one of three regimens: 3 g of tolevamer 3 times a day for 2 weeks, 125 mg of vancomycin 4 times a day for 10 days, or 375 mg of metronidazole 4 times a day for 10 days. Patients in the tolevamer group received a 9-g loading dose on the first day. Among patients who received at least one dose of study drug and a clinical evaluation, overall clinical success rates were much lower with tolevamer than with vancomycin or metronidazole (46.6%, 81.3%, and 72.0%, respectively, P <.001). Tolevamer was also significantly inferior in a subset of 185 patients with severe CDAD (P <.05). In that subset, vancomycin was significantly more effective than metronidazole (84.8% success vs 64.9%, P =.04). But among patients who did achieve clinical success, recurrence rates were significantly lower with tolevamer than with the other two drugs -- just 3.4% for tolevamer versus 23.4% for vancomycin and 27.1% for metronidazole (P <.001). Recurrence was defined as reappearance of CDAD within 4 weeks after symptoms had initially resolved. Dr. Davidson said Genzyme would decide whether to continue development of tolevamer when another phase 3 trial, now underway in Europe, is completed. Pointing to the less than stellar clinical success rates for vancomycin and metronidazole in the North American trial, he said, "There is definitely an unmet medical need still here."
[Presentation title: Results of a Phase III Trial Comparing Tolevamer, Vancomycin and Metronidazole in Patients With Clostridium Difficile-Associated Diarrhea (CDAD). Abstract K-425a.]
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