Daptomycin in the Treatment of Subjects With Infective Endocarditis or Bacteremia Due to S. Aureus

A Phase 3, Multicenter, Randomized, Open-Label, Comparative Study to Assess the Safety and Efficacy of Daptomycin Compared to Conventional Therapy In the Treatment of Subjects With Infective Endocarditis or Bacteremia Due to Staph Aureus

The purpose of this study is to compare the safety and efficacy of daptomycin, an antibiotic, to standard therapy in subjects who have infective endocarditis or bacteremia due to Staphylococcus aureus (S. aureus).

Even with prompt treatment, Staphylococcus aureus Infective Endocarditis (IE) continues to be associated with significant morbidity and mortality indicating a need for new therapeutic approaches. In vitro, daptomycin is rapidly bactericidal, with concentration-dependent killing, and MIC90 of 0.5 microgram/ml for S. aureus; in clinical studies, daptomycin appears to be well tolerated and can be administered once every 24 hours by i.v. infusion. These characteristics suggest it should be clinically and microbiologically effective in the treatment of serious S. aureus infections, including IE and bacteremia Comparison: standard of care (Vancomycin or Semi-synthetic Penicillin with adjunct gentamicin)

To demonstrate that daptomycin is not inferior to comparator in the treatment of S. aureus bacteremia and IE as assessed by the Independent External Adjudication Committee (IEAC) Outcome at Test of Cure (TOC) in the Intention-to-Treat (ITT) population.

To compare clinical success rates between daptomycin and comparator in the treatment of S. aureus bacteremia and IE as assessed by the IEAC Outcome at End of Treatment (EOT) in the ITT population.

To compare clinical success rates between daptomycin and comparator in the treatment of S. aureus bacteremia and IE as assessed by the IEAC Outcome at EOT and TOC in the Per Protocol (PP) population.

To compare clinical success rates between daptomycin and comparator in the treatment of S. aureus bacteremia and IE as assessed by the IEAC Outcome for each of the diagnoses defined by the IEAC at EOT in the ITT population.

To compare clinical success rates between daptomycin and comparator in the treatment of S. aureus bacteremia and IE as assessed by the IEAC Outcome for each of the diagnoses defined by the Investigator at EOT in the ITT population.

To demonstrate that survival rates are similar between daptomycin and comparator in the ITT population.

Inclusion Criteria: Documented S. aureus bacteremia within 2 calendar days of the first dose of study medication Exclusion Criteria: Subjects with a creatinine clearance of less than 30 ml/min Subjects with pneumonia Pregnant, nursing, or lactating Documented history of allergy or intolerance to penicillin or vancomycin Subjects with osteomyelitis

Fowler VG Jr, Boucher HW, Corey GR, Abrutyn E, Karchmer AW, Rupp ME, Levine DP, Chambers HF, Tally FP, Vigliani GA, Cabell CH, Link AS, DeMeyer I, Filler SG, Zervos M, Cook P, Parsonnet J, Bernstein JM, Price CS, Forrest GN, Fatkenheuer G, Gareca M, Rehm SJ, Brodt HR, Tice A, Cosgrove SE; S. aureus Endocarditis and Bacteremia Study Group. Daptomycin versus standard therapy for bacteremia and endocarditis caused by Staphylococcus aureus. N Engl J Med. 2006 Aug 17;355(7):653-65. doi: 10.1056/NEJMoa053783.

Bhavnani SM, Rubino CM, Ambrose PG, Drusano GL. Daptomycin exposure and the probability of elevations in the creatine phosphokinase level: data from a randomized trial of patients with bacteremia and endocarditis. Clin Infect Dis. 2010 Jun 15;50(12):1568-74. doi: 10.1086/652767.