Cubist Pharmaceuticals Inc announced the enrollment of the first patients in a Phase III clinical trial evaluating the safety and efficacy of Cubist's investigational antibiotic Cidecin (daptomycin for injection) in the treatment of infective endocarditis (IE) and bacteremia caused by Staphylococcus aureus.
All patients with staphylococcal bacteremia, or the presence of bacteria in the blood, are at risk for serious complications, including deep tissue infections and IE, or infection of the heart valves. Even with prompt treatment, IE caused by S. aureus continues to be associated with significant morbidity and mortality. The primary objective of this study is to evaluate the safety and efficacy of Cidecin in the treatment of IE due to S. aureus; in order to seek a formal indication for endocarditis, Cidecin's clinical success rate must prove to be non-inferior to standard therapy. Secondarily, the study will evaluate the safety and efficacy of Cidecin in the treatment of S. aureus bacteremia not complicated by IE and compares the pharmacoeconomic impact of Cidecin treatment with that of conventional therapy.
The endocarditis/bacteremia study is a multi-center, randomized, open-label trial comparing Cidecin, dosed 6 mg/kg once daily via intravenous (IV) infusion, with conventional IV therapy (nafcillin, 2g every 4 hours or vancomycin, 1g every 12 hours). Subjects can be enrolled in the study based on a single positive S. aureus blood culture. Those with confirmed IE will be treated for an appropriate duration (typically 4 weeks); all others will be treated for bacteremia, also for an appropriate duration of therapy (typically 10 to 14 days). Data from both patient populations will be collected and analyzed.
"From what we are hearing, the start of this trial seems to be generating excitement in the infectious disease (ID) community," said Robert D. Arbeit, Executive Medical Director at Cubist. "Not only is it an unusual trial design, making extensive use of modern diagnostic technologies, but it is also the first antibiotic trial in over a decade seeking formal regulatory approval for endocarditis. At present, there are relatively few FDA-approved treatments for endocarditis and ID physicians recognize the need for new validated therapies, particularly in light of the increasing incidence of disease caused by resistant organisms. If successful, this study would become an important component of our ongoing package insert development program, should Cidecin gain regulatory approval."
Cubist intends to continue the study until 200 subjects with confirmed IE have been enrolled. Several interim analyses of the data will be performed, the first of which will occur after approximately 30 evaluable IE subjects have been enrolled. At that time, a Data Monitoring Committee (DMC) will convene to examine the data and determine Cidecin's clinical performance in the initial group of subjects.