Oscient Pharmaceuticals Corporation's recently completed phase II trial of its investigational new drug, Ramoplanin, for the treatment of Clostridium difficile-associated diarrhoea (CDAD) has yielded encouraging preliminary results. Pending the completion of full analysis of the phase II data and the outcome of planning discussions with the FDA, the Company expects to commence the Phase III study by the end of this year.
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 per cent in the Ramoplanin 400 mg arm and 78 per cent 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 per cent. 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 per cent and 85.7 per cent, respectively, release from Oscient Pharmaceuticals said.
"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, 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," Dale Gerding added.
Patients were enrolled, regardless of the severity of their CDAD disease, in 24 US 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 programme," he concluded.
Clostridium difficile-associated diarrhoea is the most common type of infectious, hospital-acquired diarrhoea. 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.