Phase III Data Show Safety of Fidaxomicin for C. difficile

SAN FRANCISCO — Fidaxomicin appears to be just as safe as vancomycin for the treatment of Clostridium difficile infection, results from a multicenter randomized trial showed.

The finding comes from the first phase III study of fidaxomicin (Dificid), a first-in-class macrocyclic antibiotic for the treatment of C. difficile. A second phase III trial that is underway is expected to be completed by the end of the year, Pamela Sears, Ph.D., said in an interview during a poster session at the annual meeting of the Interscience Conference on Antimicrobial Agents and Chemotherapy.

The drug's safety profile is “very similar to oral vancomycin, which is a very safe drug,” said Dr. Sears, executive director of biology and preclinical trials at Optimer Pharmaceuticals Inc., San Diego, which developed the drug.

Dr. Sears and her associates said fidaxomicin has “potent bactericidal activity against C. difficile infection with a prolonged postantibiotic effect but minimal activity against much of the other commensal gut flora. The narrow spectrum of activity allows fidaxomicin to kill C. difficile while sparing much of the normal gut flora. Importantly, fidaxomicin is also minimally absorbed from the gastrointestinal tract.”

In a multicenter trial supported by Optimer, the researchers compared two regimens for C. difficile: fidaxomicin 200 mg twice a day (300 patients) and vancomycin 125 mg four times a day (323 patients). Both agents were taken for 10 days. The mean age of the patients was 62 years. At baseline and after 10 days of therapy, the researchers collected plasma and urine samples, obtained 12-lead electrocardiograms, and conducted physical exams.

Any treatment-emergent event occurred in 62% of patients in the fidaxomicin group and in 60% of patients in the vancomycin group. Gastrointestinal disorders were most common (25% vs. 22%), followed by infections (21% vs. 20%, primarily urinary tract infections and pneumonia) and general disorders and administration site conditions (15% vs. 16%, primarily fever, chills, edema, and fatigue).

The incidence of serious adverse events also was similar between groups: 25% in the fidaxomicin group, compared with 24% among the vancomycin group. The most common serious adverse events were infections, including C. difficile, pneumonia, sepsis, or bacteremia (7% vs. 9%, respectively), and GI disorders (4% vs. 3%). Fewer than 3% of patients in both groups developed abnormal liver, blood, and renal tests while on therapy, and mortality was similar in both groups (5% vs. 7%). No death was considered to be related to the study drug.

A limitation of the study was that it did not compare fidaxomicin with metronidazole. For C. difficile, vancomycin “appears to be the marketed compound that performs the best, but most people use metronidazole. We may explore that comparison in phase IV,” she said.

Dr. Sears expects Optimer to file for new drug approval with the Food and Drug Administration by early 2011.

Any treatment-emergent event occurred in 62% of patients on fidaxomicin and 60% of those on vancomycin.

Source DR. SEARS