GSK1322322 Versus Linezolid in the Treatment of Acute Bacterial Skin and Skin Structure Infection
Condition: Skin Infections, Bacterial
MeSH terms: Infections; Communicable Diseases; Cellulitis; Skin Diseases, Infectious; Bacterial Infections
Intervention: GSK1322322; Linezolid; GSK1322322 placebo; Linezolid placebo
Intervention description: GSK1322322 1500mg BID; Linezolid 600mg; Placebo; placebo
Intervention MeSH terms: Linezolid
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 84.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: methicillin-resistant Staphylococcus aureus; linezolid; repeat dose; GSK1322322

Summary:

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

Eligibility 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