GSK1322322 Versus Linezolid in the Treatment of Acute Bacterial Skin and Skin Structure Infection

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT01209078
First received: September 14, 2010
Last updated: April 3, 2012
Last verified: April 2012
  Purpose

This study will determine the safety, tolerability and efficacy of GSK1322322 verses Linezolid in subjects with Acute Bacterial Skin and Skin Structure Infection (ABSSSI).


Condition Intervention Phase
Skin Infections, Bacterial
Drug: GSK1322322
Drug: Linezolid
Drug: GSK1322322 placebo
Drug: Linezolid placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double Blind, Double Dummy Multicenter Phase IIa Study to Assess Safety, Tolerability and Efficacy of GSK1322322 Versus Linezolid in the Treatment of Acute Bacterial Skin and Skin Structure Infection

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • GSK1322322 adverse events [ Time Frame: 38 days ] [ Designated as safety issue: No ]
  • GSK1322322 absolute values and changes over time of hematology [ Time Frame: 38 days ] [ Designated as safety issue: No ]
  • GSK1322322 absolute values and changes over time of clinical chemistry [ Time Frame: 38 days ] [ Designated as safety issue: No ]
  • GSK1322322 absolute values and changes over time of vital signs [ Time Frame: 38 days ] [ Designated as safety issue: No ]
  • GSK1322322 absolute values and changes over time of electrocardiogram (ECG) intervals [ Time Frame: 38 days ] [ Designated as safety issue: No ]
  • GSK1322322 absolute values and changes over time of ECG rhythm [ Time Frame: 38 days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinical rate of response at Day 2 in subjects receiving GSK1322322 for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-14 days ] [ Designated as safety issue: No ]
  • Clinical rate of response at Day 2 in subjects receiving linezolid for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-14 days ] [ Designated as safety issue: No ]
  • Clinical and microbiological outcome at end of therapy in subjects receiving GSK1322322 for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-18 days ] [ Designated as safety issue: No ]
  • Clinical and microbiological outcome at end of therapy in subjects receiving linezolid for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-18 days ] [ Designated as safety issue: No ]
  • Therapeutic outcome, combined clinical and microbiological outcome at follow-up. [ Time Frame: 18 days ] [ Designated as safety issue: No ]
  • Clinical rate of response at Day 3 in subjects receiving GSK1322322 for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-18 days ] [ Designated as safety issue: No ]
  • Clinical rate of response at Day 4 in subjects receiving GSK1322322 for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-18 days ] [ Designated as safety issue: No ]
  • Clinical rate of response at the end of therapy in subjects receiving GSK1322322 for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-18 days ] [ Designated as safety issue: No ]
  • linical rate of response at Day 3 in subjects receiving linezolid for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-18 days ] [ Designated as safety issue: No ]
  • linical rate of response at Day 4 in subjects receiving linezolid for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-18 days ] [ Designated as safety issue: No ]
  • Clinical rate of response at the end of therapy in subjects receiving linezolid for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-18 days ] [ Designated as safety issue: No ]
  • Clinical and microbiological outcome at follow-up in subjects receiving GSK1322322 for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-18 days ] [ Designated as safety issue: No ]
  • Clinical and microbiological outcome at follow up in subjects receiving linezolid for suspected Gram positive Acute Bacterial Skin and Skin Structure Infection [ Time Frame: 10-18 days ] [ Designated as safety issue: No ]

Enrollment: 84
Study Start Date: August 2010
Study Completion Date: January 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen 1
GSK1322322 1500mg and Placebo Linezolid given twice a day (BID) for 10 days
Drug: GSK1322322
GSK1322322 1500mg BID
Drug: Linezolid placebo
placebo
Active Comparator: Regimen 2
Linezolid 600mg and placebo GSK1322322 given BID for 10 days
Drug: Linezolid
Linezolid 600mg
Drug: GSK1322322 placebo
Placebo

Detailed Description:

This is a phase IIa, multicenter, randomized, parallel group, double-blind, double dummy study to assess the safety, tolerability, and efficacy of GSK1322322 when given as 1500mg twice daily over a 10-day period versus linezolid (600mg twice daily for 10 days) in adults with suspected Gram positive Acute Bacterial Skin and Skin Structure Infection who are not currently receiving antibacterial therapy. Subjects will be randomized (2:1) to GSK1322322 or linezolid. This study consists of a screening visit, a 10-day treatment period, and follow-up evaluations 7 and 28 days following the last dose.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subject age 18 years or older at the time of signing the informed consent
  • Male subjects must agree to use one of the contraception methods listed
  • A female is eligible to enter and participate in this study if she is of non-childbearing potential
  • The subject has a diagnosis of ABSSSI defined as one of the following: wound infection with cellulitis that has developed within 30 days of surgery or trauma; abscess with cellulitis, or cellulitis that has developed in no more than 7 days before enrollment with worsening over the past 48 hours OR in the investigator's opinion the patient's condition warrants systemic oral antibiotic therapy
  • The subject has at least 2 additional signs and symptoms of skin infection: purulence, erythema with or without induration, fluctuation, heat/localized warmth, and pain/tenderness
  • The subject has at least 1 systemic marker of infection: Lymphadenopathy, Fever (>38 degrees Celsius), White Blood Cell elevation, or Creatinine Reactive Protein (CRP) >Upper Limit of Normal (ULN)
  • The subject has given written, informed, dated consent to participate in the study
  • QTcB or QTcF < 450 msec; or QTc < 480 msec in subjects with Bundle Branch Block
  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) < 2xULN; and bilirubin < 1.0xULN

Exclusion Criteria:

  • Current or chronic history of liver disease, or known hepatic or biliary abnormalities
  • The subject has been diagnosed with Acquired immune deficiency syndrome (AIDS)
  • Body mass index (BMI) >40 kg/m2
  • The subject has demonstrated a previous hypersensitivity reaction to GSK1322322, or to oxazolidinones
  • The subject has a secondarily infected animal/human bite
  • The subject has a chronic ulcerative lesion that is likely to be polymicrobial or caused by anaerobic organisms and unlikely to have Staphylococcus aureus or Streptococcus pyogenes as the causative agent
  • The subject has an underlying skin disease, such as pre-existing eczematous dermatitis, with clinical evidence of secondary infection
  • The subject has an infection that would normally have a high cure rate after surgical incision alone
  • The subject has a bacterial skin infection which, due to the extent, depth or severity of clinical presentation, in the opinion of the investigator, cannot be appropriately treated by an oral antibiotic
  • The subject has received more than one dose of treatment with a systemic and/or topical antibacterial within 7 days
  • The subject is currently receiving vasopressors
  • The subject is currently receiving adrenergic agents
  • The subject is currently receiving serotonergic reuptake inhibitors
  • The subject is currently receiving monoamine oxidase inhibitors
  • The subject has a documented clinical history of pseudomembranous colitis
  • The subject has known, pre-existing myelosuppression, or a history of myelosuppression with prior linezolid use, or is currently receiving a medication that produces bone marrow suppression
  • The subject has a history of seizures
  • The subject has a history of severe renal failure and is undergoing dialysis
  • The subject has a serious underlying disease that could be imminently life-threatening
  • The subject has been previously enrolled in this study
  • The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product
  • Subject is unable to discontinue the use of prescription drugs listed in the protocol or non-prescription drugs, including vitamins, herbal and dietary supplements prior to the first dose of study medication through the first follow up visit
  • Lactating females or pregnant females as determined by positive urine pregnancy test at screening or prior to dosing
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01209078

Locations
United States, Alabama
GSK Investigational Site
Anniston, Alabama, United States, 36207
United States, California
GSK Investigational Site
Chula Vista, California, United States, 91911
GSK Investigational Site
La Mesa, California, United States, 91942
GSK Investigational Site
Long Beach, California, United States, 90813
GSK Investigational Site
Oceanside, California, United States, 92056
United States, Hawaii
GSK Investigational Site
Honolulu, Hawaii, United States, 96813
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

No publications provided

Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01209078     History of Changes
Other Study ID Numbers: 113414
Study First Received: September 14, 2010
Last Updated: April 3, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by GlaxoSmithKline:
methicillin-resistant Staphylococcus aureus
linezolid
repeat dose
GSK1322322

Additional relevant MeSH terms:
Bacterial Infections
Skin Diseases, Infectious
Infection
Skin Diseases
Linezolid
Oxazolidinones
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Protein Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 17, 2014