Phase 2 Safety and Efficacy Study of Daptomycin in Complicated Skin and Skin Structure Infections

multicenter, randomized (1:1), semi-single blind study comparing the safety and efficacy of HDSD daptomycin (10 mg/kg q24h for 4 days) with that of comparator (vancomycin +/- SSP for 7-14 days) in patients with cSSSI due to Gram-positive bacteria. Patients will be randomized on a 1:1 basis to receive either daptomycin 10 mg/kg i.v. q24h for 4 days or vancomycin 1 g. q12h for up to 14 days.

The main criteria for evaluation will be:

• Efficacy
• Safety
• Microbiologic eradication

Inclusion criteria

• Informed consent obtained
• Male or female ≥18 years of age
• If female of childbearing potential, willing to practice reliable birth control measures and documented negative pregnancy test
• Skin and skin structure infections of a complicated nature that require intravenous antibiotic treatment
• Gram-positive infecting pathogen
• Physician determination that vancomycin would be the initial treatment of choice
• At least three clinical signs and symptoms associated with the cSSSI:

• Pain;
• Tenderness to palpation;
• Elevated Temperature;
• Elevated White blood count;
• Swelling and/or induration;
• Erythema (>1 cm beyond edge of wound or abscess);
• Pus formation;
• Creatinine clearance of ≥50 mL/min.

Exclusion criteria

• MSSA
• Known or suspected bacteremia, osteomyelitis, or endocarditis
• Primary study infection of an uncomplicated nature such as furuncles, simple abscesses, cellulitis not requiring i.v., perirectal abscess, hidradenitis suppurativa, third degree burn infections or other minor infections;
• Conditions where required surgery (in and of itself) constitutes curative treatment of the infection (e.g., amputation);
• Necrotizing infections or concomitant gangrene;
• Myositis with or without skin and skin structure infections;
• Hemodialysis or peritoneal dialysis;
• BMI ≥40 kg/m2;
• Previous antibiotics exceeding 24 hours within the 48 hours prior to the first dose of study drug
• Patients admitted for rhabdomyolysis including drug overdose
• Neutropenic patients with absolute neutrophil count ≤500 cells/mm3
• Known HIV-infected patients with CD4 count ≤200 cells/ mm3;
• Baseline CPK values ≥2 X ULN (upper limit of normal);
• Has received an investigational drug within 30 days of study entry;
• Known to be allergic or intolerant to study medications;
• unlikely to comply with study procedures
• Is expected to receive HMG CoA Reductase Inhibitors from enrollment through End of Treatment