Study of Daptomycin Safety and Efficacy for Complicated Skin and Skin Structure Infections (cSSSI) and Bacteremia in Renal Impairment

Inclusion Criteria:

- Written informed consent

- Male or female ≥18 years of age

- Diagnosis of cSSSI or Staphylococcus aureus (S. aureus) bacteremia

- Renal impairment of CLcr of 30 - 50 mL/min or CLcr <30 mL/min per Cockcroft-Gault
equation using actual body weight

- Functioning hemodialysis access and on stable regimen for those receiving dialysis

- In appropriate health for the study with no acute or chronic illnesses that could
adversely impact safety or ability to complete the study

Specific inclusion criteria for cSSSI:

- Presence of a wound infection, major abscess, severe carbunculosis, infected ulcers,
dialysis access site infection, or other type of infection in presence of complicating
factor

- At least 3 of the following symptoms, signs, or laboratory values of a skin infection:
elevated temperature; elevated white blood cell (WBC) count; pain; tenderness;
swelling; erythema greater than 1 centimeter (cm) beyond wound edge; induration; pus
formation

- Evidence of a Gram-positive infecting pathogen as indicated by positive Gram stain or
culture obtained within 96 hours prior to study drug administration

- Infection of sufficient severity to require parenteral antimicrobial therapy

Specific inclusion criteria for S. aureus bacteremia:

• Documented S. aureus bacteremia defined as at least one positive blood culture for S.
aureus obtained within 96 hours prior to the first dose of study medication

Exclusion Criteria:

- Pregnant or lactating females, or unwilling to practice barrier methods of birth
control

- Received an investigational drug (including experimental biologic agents) within 30
days of study entry

- Unable to discontinue use of HMG-CoA reductase inhibitor therapy while on study

- Known allergy or intolerance to daptomycin, penicillin, or vancomycin

- Active intravenous (IV) drug abuse

- Confirmed or suspected osteomyelitis, septic arthritis, meningitis, epidural abscess,
intra-abdominal infection, pneumonia, or infective endocarditis

- Required use of non-study systemic antibacterial agent with activity against target
pathogen

- History of muscular disease

- Neurological disease except stroke >6 months prior to study entry

- Intramuscular injection within 7 days of study drug administration

- Moribund clinical condition (high likelihood of death during next 3 days)

- Shock or hypotension (supine systolic blood pressure <80 millimeters of mercury
[mmHg])

- Body mass index (BMI) <18 or >40 kilograms per meter squared (kg/m^2) [BMI = weight
(kg)/height (m^2)]

- Known human immunodeficiency virus (HIV) infection with CD4 count ≤200
cells/millimeter (mm)^3

- Neutropenic participants with an absolute neutrophil count ≤500 cells/mm^3

- Anticipated to develop neutropenia absolute neutrophil count ≤500 due to prior or
planned chemotherapy

- Alanine aminotransferase (ALT) value >3 × upper limit of normal (ULN)

- Aspartate aminotransferase (AST) value >3 × ULN

- Total bilirubin values ≥ 1.5 x ULN associated with ALT values >3 x ULN

- Creatine phosphokinase (CPK) value >2 × ULN

- Hemoglobin <8 grams per deciliter (gm/dL)

- Unlikely to comply with study procedures or to return for evaluations

- History of rhabdomyolysis

- Prior enrollment into this study

- Infections caused by Gram-positive pathogens known to be resistant to daptomycin or
selected comparator agent

Specific exclusion criteria for cSSSI:

- Minor or superficial skin infections as the primary site of infection

- Cellulitis or erysipelas not associated with complicating factor as primary site of
infection

- Perirectal abscess, hidradenitis suppurativa, concomitant gangrene, myositis, multiple
infected ulcers at distant sites, necrotizing fasciitis, or infected third-degree burn
wounds

- Infections requiring emergency surgery

- Infections suspected or documented to be due exclusively to gram-negative, anaerobic,
or fungal organism

- Confirmed or suspected disorder that could interfere with the evaluations (for
example, primary skin disorders)

- Use of a topical antibiotic at the site of the infection

- Use of systemic antibacterial therapy for the infection for >24 hours within 48 hours
prior to start of study drug unless (a) infecting Gram-positive pathogen resistant to
therapy or (b) therapy administered for 3 or more days with worsening or no
improvement

- Planned surgical treatment that is considered curative of the infection

Specific exclusion criteria for S. aureus bacteremia:

- Has intravascular foreign material at the time the positive blood culture was drawn
(for example., intracardiac pacemaker wires, percutaneous or implanted venous
catheters, vascular grafts) unless material removed within 4 days after first dose of
study medication or approval of medical monitor (exceptions: vascular stents in place
for >6 months, permanent pacemaker attached via epicardial leads, or any dialysis
access device unless this material is felt to be infected)

- Prosthetic heart valve

- Cardiac decompensation or valve damage or both with high likelihood of valve surgery
in the 3 days after randomization

- Polymicrobial blood infection