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

Information source: Cubist Pharmaceuticals Holdings LLC
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Complicated Skin and Skin Structure Infections; S. Aureus Bacteremia; Renal Impairment

Intervention: Vancomycin (Drug); Daptomycin (Drug); Semi-Synthetic Penicillin (Drug)

Phase: Phase 4

Status: Terminated

Sponsored by: Cubist Pharmaceuticals

Official(s) and/or principal investigator(s):
Ellie Hershberger, Pharm.D., Study Director, Affiliation: Cubist Pharmaceuticals Holdings LLC


This is a multicenter, randomized, evaluator-blinded, comparator-controlled study. Participants were to be randomized (1: 1) to daptomycin or comparator, stratified by degree

of renal impairment (creatinine clearance [CLcr] 30 - 50 milliliters per minute [mL/min]

[moderate impairment] and <30 mL/min [severe impairment]) and by type of infection (bacteremia and complicated skin and skin structure infections [cSSSI]) to create 4 cohorts defined as follows:

- Cohort 1: Bacteremia and CLcr <30 mL/min

- Cohort 2: Bacteremia and CLcr 30 - 50 mL/min

- Cohort 3: cSSSI and CLcr <30 mL/min

- Cohort 4: cSSSI and CLcr 30 - 50 mL/min

Participants will be treated and evaluated for safety and microbiological and clinical efficacy in accordance with their type of infection and degree of renal impairment. Peak and trough samples will be collected to assess exposure to daptomycin for participants on Day 1 and following the 5th dose.

Clinical Details

Official title: A Prospective, Multicenter, Randomized, Evaluator-blinded, Comparator-controlled Study to Describe the Safety and Efficacy of Daptomycin for the Treatment of Complicated Skin and Skin Structure Infections (cSSSI) and Staphylococcus Aureus Bacteremia Among Subjects With Moderate or Severe Renal Impairment

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Number of Participants With Treatment-emergent Creatine Phosphokinase (CPK) Elevations Through End of Therapy/Early Termination (EOT/ET)

Secondary outcome: Overall Therapeutic Outcome at Test of Cure (TOC)/Safety Visit


Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.


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


- 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


- 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


- 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


- 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

Locations and Contacts

Azusa, California, United States

Los Angeles, California, United States

Torrance, California, United States

Washington, District of Columbia, United States

Decatur, Georgia, United States

Somers Point, New Jersey, United States

Winston-Salem, North Carolina, United States

Columbus, Ohio, United States

West Reading, Pennsylvania, United States

Mission, Texas, United States

Additional Information

Starting date: April 2010
Last updated: April 28, 2015

Page last updated: August 23, 2015

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