Clinical trial NCT01209078: GSK1322322 Versus Linezolid in the Treatment of Acute Bacterial Skin and Skin Structure Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Skin Infections, Bacterial
Keywords: methicillin-resistant Staphylococcus aureus
linezolid
repeat dose
GSK1322322
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2010-09-24
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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).

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 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

Primary outcomes:
measure: Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Clinical Chemistry Parameters of Albumin and Total Protein at Indicated Time Points
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Clinical Chemistry Parameters of ALT, Alkaline Phosphatase (ALP), Aspartate Aminotransferase (AST), Follicle Stimulating Hormone (FSH), Gamma Glutamyl Transferase (GGT), Lactate Dehydrogenase (LDH) and Creatine Kinase at Indicated Time Points
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Clinical Chemistry Parameters of Creatinine, Uric Acid, Direct Bilirubin and Total Bilirubin at Indicated Time Points
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Clinical Chemistry Parameters of Glucose, Sodium, Calcium, Potassium, Chloride, Carbon Dioxide (CO2) Content /Bicarbonate and Urea/ Blood Urea Nitrogen (BUN) at Indicated Time Points
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Clinical Chemistry Parameter of Estradiol at Indicated Time Point
timeFrame: Day 1
measure: Mean Clinical Chemistry Parameter of High Sensitivity C-Reactive Protein at Indicated Time Points
timeFrame: Up to Follow-up (7 Day Follow-up, Day 19)
measure: Mean Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC) and Platelet Count at Indicated Time Points
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Hematology Parameter of Mean Corpuscle Volume (MCV) at Indicated Time Points
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Hematology Parameter of Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) at Indicated Time Points
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) at Indicated Time Points
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Hematology Parameter of Red Blood Cell (RBC) Count and Reticulocyte Count at Indicated Time Points
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Vital Sign Value of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points
timeFrame: Up to Day 11
measure: Mean Vital Sign Value of Heart Rate (HR) at Indicated Time Points
timeFrame: Up to Day 11
measure: Mean Vital Sign Value of Respiratory Rate (RR) at Indicated Time Points
timeFrame: Up to Day 11
measure: Mean Change From Baseline in SBP and DBP at Indicated Time Points
timeFrame: Day 1 (Baseline) up to Day 11
measure: Mean Change From Baseline in HR at Indicated Time Points
timeFrame: Day 1 (Baseline) up to Day 11
measure: Mean Change From Baseline in RR at Indicated Time Points
timeFrame: Day 1 (Baseline) up to Day 11
measure: Mean Electrocardiogram (ECG) Values at Indicated Time Points
timeFrame: Up to Day 11
measure: Mean Change From Baseline in ECG Values at Indicated Time Points
timeFrame: Day 1 (pre-dose, Baseline) up to Day 11
measure: Mean ECG Rhythms at Indicated Time Points
timeFrame: Up to Day 11
measure: Mean Change From Baseline in ECG Rhythms at Indicated Time Points
timeFrame: Day 1 (pre-dose, Baseline) up to Day 11
measure: Number of Participants With Abnormal Transition From Baseline in Clinical Chemistry Values Relative to Normal Range
timeFrame: Day 1 (pre-dose, Baseline) up Follow-up (28 Day Follow-up, Day 40)
measure: Number of Participants With Abnormal Transition From Baseline in Hematology Values Relative to Normal Range
timeFrame: Day 1 (pre-dose, Baseline) up Follow-up (28 Day Follow-up, Day 40)
Secondary outcomes:
measure: Number of Participants With Clinical Success of Clinical Response
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Percentage of Participants With Clinical Success of Clinical Outcome
timeFrame: Day 11 (end of therapy) and Follow-up (7 Day Follow-up, Day 19)
measure: Percentage of Participants With Microbiological Success of Microbiological Outcome at End of Therapy
timeFrame: Day 11 (end of therapy)
measure: Percentage of Participants With Microbiological Success of Microbiological Outcome at Follow-up
timeFrame: Follow-up (7 Day Follow-up, Day 19)
measure: Percentage of Participants With Therapeutic Success of Therapeutic Outcome
timeFrame: Follow-up (7 day Follow-up, Day 19)
measure: Mean Short Form McGill Pain Questionnaire-2 (SF-MPQ-2) Sub-score of Continuous Pain, Intermittent Pain, Neuropathic Pain and Affective Descriptors at Indicated Time Points
timeFrame: Up to Follow-up (7 Day Follow up, Day 19)
measure: Mean Exudate or Pus Sub-score of SIS at Indicated Time Points
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Total SIS at Indicated Time Points
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Change From Baseline in Total SIS at Indicated Time Points
timeFrame: Day 1 (Baseline ) up to Follow-up (28 Day Follow-up, Day 40)
measure: Mean Change From Baseline in Wound Area at Indicated Time Points
timeFrame: Day 1 (Baseline) up to Follow-up (28 Day Follow-up, Day 40)
measure: Percentage of Participants With Clinical Success at End of Therapy by Pathogen Isolated at Baseline
timeFrame: Up to Follow-up (28 Day Follow-up, Day 40)
measure: Population Pharmacokinetic Parameters of Apparent Total Clearance of GSK1322322 From Plasma After Oral Administration (CL/F)
timeFrame: Day 1 (0.25-1.5 hours post-initial dose, 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose) and Day 8 (pre-morning dose)
Other outcomes:
Locations:
city: Anniston
country: United States
facility: GSK Investigational Site
state: Alabama
city: Chula Vista
country: United States
facility: GSK Investigational Site
state: California
city: La Mesa
country: United States
facility: GSK Investigational Site
state: California
city: Long Beach
country: United States
facility: GSK Investigational Site
state: California
city: Oceanside
country: United States
facility: GSK Investigational Site
state: California
city: Honolulu
country: United States
facility: GSK Investigational Site
state: Hawaii
city: West Reading
country: United States
facility: GSK Investigational Site
state: Pennsylvania
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Corey R, Naderer OJ, O'Riordan WD, Dumont E, Jones LS, Kurtinecz M, Zhu JZ. Safety, tolerability, and efficacy of GSK1322322 in the treatment of acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2014 Nov;58(11):6518-27. doi: 10.1128/AAC.03360-14. Epub 2014 Aug 18.