Development of Alinia in Treating Clostridium Difficile-Associated Disease

TAMPA, Fla. -- Romark Laboratories announced another advance in its development of Alinia (nitazoxanide) for treating Clostridium difficile-associated disease (CDAD). A recently completed clinical study showed that administration of Alinia does not interact with warfarin, a drug that is commonly used by patients affected by CDAD.

Clostridium difficile is a leading cause of diarrhea and colitis contracted in hospitals or nursing homes and associated with the use of antibiotics. The disease often affects elderly and debilitated patients and can be quite serious. Recent reports from public health officials at the Centers for Disease Control and Prevention indicate that CDAD has become more common and that new toxigenic strains of C. difficile are responsible for geographically dispersed outbreaks.

The only two treatments available in the United States are metronidazole and vancomycin. Metronidazole has been the standard of care for CDAD, but the rate of response to metronidazole is reported to have declined significantly in recent years. Vancomycin is typically reserved because of its cost and the risk of selecting vancomycin-resistant bacteria.

Romark recently completed a randomized double-blind clinical study demonstrating the effectiveness of Alinia in treating hospitalized patients with CDAD. That study successfully achieved its primary objective with an 89.5 percent response rate at study day 8 in nitazoxanide-treated patients compared to 82.4 percent for metronidazole-treated patients (difference: +7.1 percent, 95 percent confidence interval: -7 percent, +26 percent). Patients treated with nitazoxanide also showed a lower recurrence rate than patients treated with metronidazole, although the differences in recurrence rates were not statistically significant.

Many patients with CDAD, particularly elderly patients, use the drug warfarin to prevent blood clotting and strokes. Warfarin has been described as the most frequently prescribed oral anticoagulant, the fourth most prescribed cardiovascular agent and the overall eleventh most prescribed drug in the United States. A number of other drugs, including metronidazole, alter the metabolism of warfarin, making the patient prone to excessive bleeding. To minimize the risk of warfarin-related bleeding, concomitant administration of warfarin and metronidazole is avoided.

To evaluate the effect of nitazoxanide on the pharmacokinetics and anticoagulant effects of warfarin, Romark conducted a study involving 14 volunteers. Each patient received a single oral dose of 25 mg of warfarin sodium in one study period and the same dose of warfarin with a single 500 mg dose of nitazoxanide followed by continuing administration of nitazoxanide 500 mg twice daily for six days in a second study period. The two study periods were separated by a three-week washout period. Concentration-time profiles of R- and S-warfarin were measured in plasma, and coagulation parameters were monitored throughout the study period. The concentration-time profiles of warfarin metabolites and the effect of warfarin on coagulation parameters were equivalent when warfarin was administered with or without nitazoxanide.

"This is an issue that will be very important to patients with CDAD and their physicians," said Jean-Francois Rossignol, MD, PhD, chairman and chief science officer of Romark. "Drug interactions with warfarin are not uncommon. Furthermore, they can be dangerous and result in significant medical costs. This is an important part of our CDAD development program."

Romark plans to initiate a final clinical trial early in 2006 designed to obtain data required for FDA approval to market Alinia for treating CDAD.

About Alinia
Alinia (nitazoxanide) is indicated in the United States for treatment of diarrhea caused by Giardia lamblia or Cryptosporidium parvum in patients one year of age and older. Alinia has not been shown to be superior to placebo for the treatment of diarrhea caused by Cryptosporidium parvum in HIV-infected or immunodeficient patients. The most common adverse events reported by patients receiving Alinia have been abdominal pain, diarrhea, headache and nausea. In controlled trials, the frequency of these events has been similar to patients receiving a placebo. Alinia is under development in the United States for treatment of Clostridium difficile-associated diarrhea, Crohn's disease and chronic hepatitis C.

About Romark Laboratories
Romark Laboratories is a pharmaceutical company dedicated to the discovery and development of innovative new first-in-class and best-in-class pharmaceutical products.

Source: Romark Laboratories

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