Efficacy and Safety of Ceftaroline Versus Linezolid in Subjects With Complicated Skin and Skin Structure Infections

A Phase 2, Multicenter, Randomized, Open-label, Comparative Study to Evaluate the Efficacy and Safety of Intramuscular Ceftaroline Versus Intravenous Linezolid in Adult Subjects With Complicated Skin and Skin Structure Infections

The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of complicated skin and skin structure infections in adults.

Study Overview

• Status: Completed
• Conditions: Bacterial Infection
• Intervention / Treatment: Drug: ceftaroline; Drug: linezolid; Drug: Aztreonam

Detailed Description

The purpose of this study is to determine whether ceftaroline is effective and safe in the treatment of complicated skin and skin structure infections in adults. The primary focus is bacterial infection.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Buena Park, California, United States, 96020
      • Investigational site
    • Long Beach, California, United States, 90813
      • Investigational site
    • Los Angeles, California, United States, 90015
      • Investigational site
    • Rolling Hills Estate, California, United States, 90274
      • Investigational site
    • San Diego, California, United States, 92114
      • Investigational site
  • Florida
    • Atlantis, Florida, United States, 33462
      • Investigational site
  • Georgia
    • Columbus, Georgia, United States, 31904
      • Investigational site
    • Savannah, Georgia, United States, 31405
      • Investigational site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55422
      • Investigational site
  • Montana
    • Butte, Montana, United States, 59701
      • Investigational site
  • New Jersey
    • Somers Point, New Jersey, United States, 08244
      • Investigational site
  • Ohio
    • Columbus, Ohio, United States, 43215
      • Investigational site
    • Toledo, Ohio, United States, 43608
      • Investigational site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Complicated skin and skin structure infection (cSSSI)
• Require initial hospitalization, or treatment in an emergency room or urgent care setting

Exclusion Criteria:

• Hypersensitivity or allergic reaction to any ß-lactam, ceftaroline, linezolid, aztreonam, or to their components
• Concomitant use of adrenergic or serotonergic agent
• Uncomplicated skin and skin structure infection
• Concomitant therapy with any drug known to exhibit a contraindicated drug-drug interaction
• More than 24 hours of treatment with an antimicrobial within 96 hours before randomization
• Known or suspected endocarditis, osteomyelitis, or septic arthritis
• Severely impaired renal function
• Evidence of significant hepatic, hematologic, or immunologic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ceftaroline; Intramuscular every 12 hours	Drug: ceftaroline; 600 mg injected every 12 hours for at least 5 but not more than 14 days; Other Names: ceftaroline for injection; ceftaroline fosamil
Active Comparator: linezolid plus optional aztreonam; Intravenous every 12 hours	Drug: linezolid; 600 mg parenteral infused over 60 minutes for a minimum of 5 days and a maximum of 14 days; Other Names: Zyvox; Zyvoxid; CAS number 165800-03-3; Drug: Aztreonam; 1000 mg infused over 60 minutes every 24 hours may be started with linezolid or added later (up to 72 hours after the first dose of linezolid) for subjects with a gram-negative infection indicated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Response at the Test of Cure (TOC) Visit in the Modified Intent-to-treat (MITT) Population	The coprimary efficacy outcome measures were the per-subject clinical cure rate at the Test of Cure (TOC) Visit in the Clinically Evaluable (CE) and (Modified-Intent-to-Treat) MITT Populations. Subjects were considered clinically cured at the Test of Cure (TOC) Visit if they had total resolution of all signs and symptoms of the baseline infection, or improvement of the infection to such an extent that no further antimicrobial therapy was necessary.	Test of Cure Visit (8 to 15 days after end of therapy)
Clinical Response at the Test-of-Cure (TOC) Visit in the Clinically Evaluable (CE) Population	The coprimary efficacy outcome measures were the per-subject clinical cure rate at the TOC Visit in the CE and MITT Populations. Subjects were considered clinically cured at the TOC Visit if they had total resolution of all signs and symptoms of the baseline infection, or improvement of the infection to such an extent that no further antimicrobial therapy was necessary.	Test of Cure Visit (8 to 15 Days after end of therapy)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure Rate at the TOC Visit in the cMITT Population	Evaluate per-subject the clinical response at the Test-of-Cure (TOC) Visit in the Clinical Modified Intent-to-treat (cMITT) Population.	TOC Visit (8 to 15 days after end of therapy)
Clinical Response at the End-of-Therapy (EOT) Visit in the MITT, cMITT and CE Populations.	Evaluate per-subject the clinical response at the End-of-therapy (EOT) Visit in the MITT, cMITT and CE populations.	End-of-therapy (EOT) visit
The Microbiological Response at the TOC Visit in the mMITT and ME Populations.	Evaluate per-subject the microbiological response at the TOC Visit in the Microbiological Modified Intent-to-treat (mMITT) and Microbiologically Evaluable (ME) populations.	TOC Visit (8 to 15 days after end of therapy)
Clinical and Microbiological Response by Pathogen at the TOC Visit in the mMITT and ME Populations	Evaluate the clinical and microbiological response by pathogen at the TOC Visit in the mMITT and ME populations.	TOC Visit (8 to 15 days after end of therapy)
Clinical Relapse at the Late Follow-up Visit	Evaluate Clinical relapse rate at Late Follow-up (LFU) (21 to 45 days after the final dose of study drug)in those subjects clinically cured at the TOC visit.	Late Follow-up (LFU) Visit (21 to 35 days after end of therapy)
The Microbiological Reinfection or Recurrence at the Late Follow-up (LFU) Visit	Evaluate per-subject reinfection or recurrence rate at the LFU Visit in those subjects who had a favorable microbiological outcome (eradication or presumed eradication) at the TOC Visit.	LFU Visit (21 to 35 days after end of therapy)
The Safety of Ceftaroline Fosamil	Evaluate safety of Ceftaroline fosamil IM in adults with complicated skin and skin structure infection (cSSSI)	First dose of study drug through LFU Visit or 30 days after the last dose of study drug

Collaborators and Investigators

• Sponsor: Forest Laboratories
• Investigators: Study Director: Medical Monitor Cerexa, Forest Laboratories

Study record dates

Study Major Dates

• Study Start: February 1, 2008
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: March 3, 2008
• First Submitted That Met QC Criteria: March 3, 2008
• First Posted (Estimate): March 11, 2008

Study Record Updates

• Last Update Posted (Actual): March 14, 2017
• Last Update Submitted That Met QC Criteria: February 2, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Keywords: Abscess; bacterial infection; Wound infection; linezolid; Gram-negative bacterial infection; ceftaroline; Cellulitis; clinical response; complicated skin and skin structure infections; microbiological response; Deeper soft tissue; Significant surgical intervention; Gram-positive bacterial infection; cephalosporin; broad-spectrum activity
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Disease Attributes; Bacterial Infections and Mycoses; Skin Diseases, Infectious; Infections; Communicable Diseases; Bacterial Infections; Skin Diseases, Bacterial; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Bacterial Agents; Protein Synthesis Inhibitors; Linezolid; Ceftaroline fosamil; Aztreonam; Cephalosporins
• Other Study ID Numbers: P903-19