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Preliminary Results From Ramoplanin Study Announced
The three-arm, open-label, non-inferiority study compared Ramoplanin 200 mg twice daily (n=28), Ramoplanin 400 mg twice daily (n=29) and vancomycin 125 mg four times daily (n=29) to treat CDAD. The response rates at the test-of-cure visit (7-14 days post therapy), the primary endpoint of the trial, were 71% in the Ramoplanin 400 mg arm and 78% in the vancomycin arm. Although response rates for these two arms were comparable, non-inferiority was not statistically demonstrated because the observed response rates of all arms, including the vancomycin arm, were lower than the previously published vancomycin response rates. The trial was designed and powered based on published data in the scientific literature that suggested the vancomycin response rate would be approximately 95%. There was a dose response relationship in the Ramoplanin arms with a higher response rate seen with the 400 mg dose of Ramoplanin. Additionally, Ramoplanin 400 mg and vancomycin had response rates at end of therapy (a secondary endpoint) of 85.2% and 85.7%, respectively.
"The positive results of this Phase II trial of a novel, non-absorbable agent to treat this increasingly frequent hospital infection are encouraging," stated Dale Gerding, M.D., Professor, Department of Medicine, Loyola University of Chicago Stritch School of Medicine. "At the most clinically relevant time point, the end of therapy visit, response rates for Ramoplanin and vancomycin were comparable."
Patients were enrolled, regardless of the severity of their CDAD disease, in 24 U.S. sites. Per protocol, patients were dosed for ten days, at which point end of therapy assessments were recorded. The test-of-cure visit occurred one to two weeks after the end of therapy and patients were followed for an additional one to two weeks, or up to 28 days after the last dose of study drug. Vancomycin was chosen as the comparator drug because it is the only FDA-approved product for treating CDAD. Relapse rates were similar for all three arms. Eighty-seven patients were enrolled in the study and 86 received study drug. Three patients withdrew from the vancomycin arm prior to completion for treatment failure, while one patient in each Ramoplanin arm withdrew. The adverse events profiles and laboratory test results were similar for both drugs. The Company plans to submit full results at a scientific meeting this fall.
"We are encouraged by the top-line data from the Phase II trial as we advance Ramoplanin toward Phase III development," stated Steven M. Rauscher, President and CEO of Oscient Pharmaceuticals. "The association between vancomycin use and generation of vancomycin resistance among bacteria create the need for a novel treatment for this condition. These data will be used to select a dose of Ramoplanin for the planned Phase III program."
About Clostridium difficile-Associated Diarrhea
Clostridium difficile-associated diarrhea is the most common type of infectious, hospital-acquired diarrhea, with approximately 400,000 cases per year reported in the U.S. C. difficile, a spore-forming bacteria, is readily spread from person to person, especially in hospitals and nursing homes. Spore-forming bacteria are difficult to control and can persist in the environment long after patients have been discharged. Under certain conditions, such as antibiotic exposure and gastrointestinal surgery, C. difficile can colonize the gut and release toxins, leading to bowel inflammation and severe diarrhea. If untreated, pseudomembranous colitis (severe inflammation of the colon) and toxic megacolon may ensue leading to colectomy (removal of part of the colon) in some cases. CDAD may be life-threatening, especially in elder or immunocompromised populations. Current therapies for the treatment of CDAD include metronidazole and oral vancomycin, although these agents are associated with a 15-20% relapse rate.
Oscient Pharmaceuticals' Ramoplanin is an investigational new drug in clinical development. Ramoplanin, which has Fast Track status from the FDA, is currently being studied for the treatment of Clostridium difficile-associated diarrhea (CDAD). Existing preclinical data suggest Ramoplanin may have potential in controlling several antibiotic-resistant, Gram-positive bacteria such as vancomycin-resistant enterococci (VRE), methicillin-resistant Staphylococcus aureus and vancomycin-resistant Staphylococcus aureus. The antibiotic has also been shown to be bactericidal in vitro against Clostridium difficile. Because it is not absorbed systemically from the GI tract following oral dosing and exerts its bactericidal activity in the GI tract, Ramoplanin represents a potential new method for managing certain pathogens commonly found in the hospital.
Source: Oscient Pharmaceuticals