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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT01209078

Collaborator

(none)

Enrollment

Locations

Arms

5.1

Actual Duration (Months)

Patients Per Site

2.4

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Skin Infections, Bacterial	Drug: GSK1322322 Drug: Linezolid Drug: GSK1322322 placebo Drug: Linezolid placebo	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, 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

Actual Study Start Date :

Aug 17, 2010

Actual Primary Completion Date :

Jan 18, 2011

Actual Study Completion Date :

Jan 18, 2011

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE) [Up to Follow-up (28 Day Follow-up, Day 40)]
An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase (ALT) >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalised ratio >1.5.
Mean Clinical Chemistry Parameters of Albumin and Total Protein at Indicated Time Points [Up to Follow-up (28 Day Follow-up, Day 40)]
Blood samples were obtained for analysis of albumin and total protein at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
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 [Up to Follow-up (28 Day Follow-up, Day 40)]
Blood samples were obtained for analysis of ALT, ALP, AST, FSH, GGT, LDH and creatine kinase at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Mean Clinical Chemistry Parameters of Creatinine, Uric Acid, Direct Bilirubin and Total Bilirubin at Indicated Time Points [Up to Follow-up (28 Day Follow-up, Day 40)]
Blood samples were obtained for analysis of creatinine, uric acid, direct bilirubin and total bilirubin at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
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 [Up to Follow-up (28 Day Follow-up, Day 40)]
Blood samples were obtained for analysis of glucose, sodium, calcium, potassium, chloride, CO2 content /bicarbonate and urea/BUN at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Mean Clinical Chemistry Parameter of Estradiol at Indicated Time Point [Day 1]
Blood samples were obtained for analysis of estradiol at Day 1.
Mean Clinical Chemistry Parameter of High Sensitivity C-Reactive Protein at Indicated Time Points [Up to Follow-up (7 Day Follow-up, Day 19)]
Blood samples were obtained for analysis of high sensitivity C-Reactive protein at Day 1, Day 2, Day 3, Day 4, Day 8, Day 11 and 7 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Mean Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC) and Platelet Count at Indicated Time Points [Up to Follow-up (28 Day Follow-up, Day 40)]
Blood samples were obtained for analysis of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, WBC and platelet count at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Mean Hematology Parameter of Mean Corpuscle Volume (MCV) at Indicated Time Points [Up to Follow-up (28 Day Follow-up, Day 40)]
Blood samples were obtained for analysis of MCV at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Mean Hematology Parameter of Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) at Indicated Time Points [Up to Follow-up (28 Day Follow-up, Day 40)]
Blood samples were obtained for analysis of MCHC at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Mean Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) at Indicated Time Points [Up to Follow-up (28 Day Follow-up, Day 40)]
Blood samples were obtained for analysis of MCH at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Mean Hematology Parameter of Red Blood Cell (RBC) Count and Reticulocyte Count at Indicated Time Points [Up to Follow-up (28 Day Follow-up, Day 40)]
Blood samples were obtained for analysis of RBC count and reticulocyte at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Mean Vital Sign Value of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points [Up to Day 11]
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three BP measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single BP was obtained at all other time points during the study.
Mean Vital Sign Value of Heart Rate (HR) at Indicated Time Points [Up to Day 11]
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three HR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single HR was obtained at all other time points during the study.
Mean Vital Sign Value of Respiratory Rate (RR) at Indicated Time Points [Up to Day 11]
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three RR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single RR was obtained at all other time points during the study.
Mean Change From Baseline in SBP and DBP at Indicated Time Points [Day 1 (Baseline) up to Day 11]
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three BP measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single BP was obtained at all other time points during the study. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 2, Day 3, Day 4, Day 8 and Day 11) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Mean Change From Baseline in HR at Indicated Time Points [Day 1 (Baseline) up to Day 11]
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three HR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single HR was obtained at all other time points during the study. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 2, Day 3, Day 4, Day 8 and Day 11) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Mean Change From Baseline in RR at Indicated Time Points [Day 1 (Baseline) up to Day 11]
Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three RR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single RR was obtained at all other time points during the study. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 2, Day 3, Day 4, Day 8 and Day 11) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Mean Electrocardiogram (ECG) Values at Indicated Time Points [Up to Day 11]
12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart. The mean PR interval, RR interval, QRS duration, uncorrected QT interval (UncQT) and QTcB (QT corrected by Bazett's formula) and QTcF (corrected by Friedericia's formula) was calculated from automated ECG readings. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour). The mean value recorded pre-dose on Day 1 was classified as Baseline.
Mean Change From Baseline in ECG Values at Indicated Time Points [Day 1 (pre-dose, Baseline) up to Day 11]
12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart. The mean PR interval, RR interval, QRS duration, uncorrected QT interval (UncQT) and QTcB (QT corrected by Bazett's formula) and QTcF (corrected by Friedericia's formula) was calculated from automated ECG readings. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour). Mean value recorded pre-dose on Day 1 was classified as Baseline. Change from Baseline was calculated by subtracting the Baseline value from individual post-Baseline (Day 1 post-dose, Day 4, Day 8 and Day 11) values.
Mean ECG Rhythms at Indicated Time Points [Up to Day 11]
12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rhythm and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart and the mean of the three measurements was calculated. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour).
Mean Change From Baseline in ECG Rhythms at Indicated Time Points [Day 1 (pre-dose, Baseline) up to Day 11]
12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rhythm and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart and the mean of the three measurements was calculated. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour). The value recorded pre-dose on Day 1 was the Baseline. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 1 post-dose, Day 4, Day 8 and Day 11) values.
Number of Participants With Abnormal Transition From Baseline in Clinical Chemistry Values Relative to Normal Range [Day 1 (pre-dose, Baseline) up Follow-up (28 Day Follow-up, Day 40)]
The parameters of clinical chemistry included albumin, total protein, ALT, ALP, AST, GGT, LDH and creatine kinase, creatinine, uric acid, direct bilirubin, total bilirubin, glucose, sodium, calcium, potassium, chloride, CO2 content /bicarbonate and urea/BUN and high sensitivity C-Reactive protein. The assessments were done at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline was defined as the assessment done on Day 1 (pre-dose). Data is reported for number of participants with abnormal transition from Baseline 'to high' or 'to low' relative to normal range. Only those parameters for which at least one value of abnormal transition was reported are summarized.
Number of Participants With Abnormal Transition From Baseline in Hematology Values Relative to Normal Range [Day 1 (pre-dose, Baseline) up Follow-up (28 Day Follow-up, Day 40)]
The parameters of clinical chemistry included basophils, eosinophils, lymphocytes, monocytes, total neutrophils, WBC count, platelet count, MCV, hemoglobin, MCHC, MCH, RBC count and reticulocyte count. The assessments were done at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline was defined as the assessment done on Day 1 (pre-dose). Data is reported for number of participants with abnormal transition from Baseline 'to high' or 'to low' relative to normal range. Only those parameters for which at least one value of abnormal transition was reported are summarized.

Secondary Outcome Measures

Number of Participants With Clinical Success of Clinical Response [Up to Follow-up (28 Day Follow-up, Day 40)]
The clinical response was evaluated by the investigator at end of therapy (within 3 days post therapy; Day 12-14) and Follow-up (7 day Follow-up; Day 16 to 19 and 28 day Follow-up; Day 37 to 40). Clinical response was determined after clinical evaluation of reviewing clinical signs and symptoms. Clinical success was defined as total resolution of all signs and symptoms of infection recorded at Baseline, or improvement to such an extent that no further antimicrobial therapy was necessary, including a pus/exudate skin infection score (SIS) of 0.
Percentage of Participants With Clinical Success of Clinical Outcome [Day 11 (end of therapy) and Follow-up (7 Day Follow-up, Day 19)]
The clinical response was determined by the investigator after clinical evaluation of reviewing clinical signs and symptoms at end of therapy (within 3 days post therapy; visit window of Day 12-14) and 7 day Follow-up ( visit window of Day 16 to 19), and the resulting clinical outcome was assigned, for each participant. Clinical success was defined as total resolution of all signs and symptoms of infection recorded at Baseline, or improvement to such an extent that no further antimicrobial therapy was necessary, including a pus/exudates SIS of 0.
Percentage of Participants With Microbiological Success of Microbiological Outcome at End of Therapy [Day 11 (end of therapy)]
The 'by pathogen' microbiological response was determined by comparing the Baseline (Day 1) culture results to the culture results at the end of therapy (visit window of Day 12-14), and the corresponding microbiological outcome (success or failure) by participant was then assigned. Microbiological success was defined as: elimination of Baseline pathogens (defined as microbiological eradication in microbiological response); clinical outcome was success such that no culture was obtained due to lack of culturable material, secondary to adequate clinical response, and was documented in the electronic case report form (eCRF) (defined as presumed microbiological eradication in microbiological response); new pathogen not previously identified, was identified at end of therapy in a participant who was a 'clinical success' (defined as colonization in microbiological response).
Percentage of Participants With Microbiological Success of Microbiological Outcome at Follow-up [Follow-up (7 Day Follow-up, Day 19)]
The 'by pathogen' microbiological response was determined by comparing the Baseline (Day 1) culture results to culture results at Follow-up (Day 16-19), and corresponding microbiological outcome (success or failure) by participant was then assigned. Microbiological success was defined as: Baseline pathogen was eradicated or presumed eradicated at end of therapy, or Baseline pathogens were present at end of therapy and is absent at Follow-up (microbiological eradication in microbiological response); Baseline pathogen was eradicated or presumed eradicated at end of therapy, or the Baseline pathogens were present at end of therapy and, participant was a 'clinical success', such that no culture was obtained due to lack of culturable material, secondary to adequate clinical response, and was documented in the eCRF (microbiological eradication); a new pathogen, not previously identified at Baseline, was identified at Follow-up in a participant who was a 'clinical success' (colonization)
Percentage of Participants With Therapeutic Success of Therapeutic Outcome [Follow-up (7 day Follow-up, Day 19)]
Therapeutic outcome was combined clinical and microbiological outcome. Therapeutic outcome was a measure of the overall efficacy response, and a therapeutic success referred to participants who had been deemed both a 'clinical success' and a 'microbiological success'. All other combinations (other than 'clinical success' + 'microbiological success') were deemed failures for therapeutic outcome. Therapeutic outcome was determined programmatically, obtained at 7 day Follow-up.
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 [Up to Follow-up (7 Day Follow up, Day 19)]
SF-MPQ-2 is composed of 22 items that describes different quantities of pain and related symptoms. Sub-score of continuous pain represents mean of throbbing pain, cramping pain, gnawing pain, aching pain, heavy pain and tender (mean of items 1, 5, 6, 8, 9 and 10). Sub-score of intermittent pain represents mean of shooting pain, stabbing pain, sharp pain, splitting pain, electric-shock pain and piercing (mean of items 2, 3, 4, 11, 16 and 18). Sub-score of neuropathic pain represents mean of hot-burning pain, cold-freezing pain, pain caused by light touch, itching, tingling or pins and needles, numbness (mean of items 7, 17, 19, 20, 21 and 22). Sub-score of affective descriptors represents mean of tiring-exhaustive, sickening, fearful, punishing-cruel (mean of items 12, 13, 14 and 15). Scores ranged from 0 to 10, where 0 indicated absence of symptom and higher score indicated more severe symptoms. Assessments were done at Day 1, Day 2, Day 3, Day 4, Day 8, Day 11 and 7 Day Follow-up.
Mean Exudate or Pus Sub-score of SIS at Indicated Time Points [Up to Follow-up (28 Day Follow-up, Day 40)]
The SIS consist of 7 items of exudate or pus, crusting, erythema or inflammation, tissue warmth, tissue edema, itching and pain. The exudate or pus sub-score of SIS was rated on a 7-point scale ranging from 0 to 6, where 0 indicated absence of symptom and 6 indicated severe symptom. Assessments were done at Day 1, Day 2, Day 3, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up.
Mean Total SIS at Indicated Time Points [Up to Follow-up (28 Day Follow-up, Day 40)]
The investigator evaluated the infection by grading the infected lesion according to SIS. The SIS consist of 7 items of exudate or pus, crusting, erythema or inflammation, tissue warmth, tissue edema, itching and pain. The items were rated on a 7-point scale ranging from 0 to 6, where 0 indicated absence of symptom and 6 indicated severe symptom. The total score ranged from 0 to 42, where 0 indicated absence of symptoms and higher score indicated more severe symptoms. Assessments were done at Day 1, Day 2, Day 3, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up.
Mean Change From Baseline in Total SIS at Indicated Time Points [Day 1 (Baseline ) up to Follow-up (28 Day Follow-up, Day 40)]
The investigator evaluated the infection by grading the infected lesion according to SIS. The SIS consist of 7 items of exudate or pus, crusting, erythema or inflammation, tissue warmth, tissue edema, itching and pain. The items were rated on a 7-point scale ranging from 0 to 6, where 0 indicated absence of symptom and 6 indicated severe symptom. The total score ranged from 0 to 42, where 0 indicated absence of symptoms and higher score indicated more severe symptoms. Baseline was defined as the assessment value done on Day 1. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 1, Day 2, Day 3, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Mean Change From Baseline in Wound Area at Indicated Time Points [Day 1 (Baseline) up to Follow-up (28 Day Follow-up, Day 40)]
The area of the infected lesion size was calculated as the product between the length (L) and width (W) of the lesion size. The wound was measured by the investigator in centimeters (cm), using a standard metric ruler. Baseline was defined as the assessment value done on Day 1. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 1, Day 2, Day 3, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Percentage of Participants With Clinical Success at End of Therapy by Pathogen Isolated at Baseline [Up to Follow-up (28 Day Follow-up, Day 40)]
Clinical success was defined as total resolution of all signs and symptoms of infection recorded at Baseline, or improvement to such an extent that no further antimicrobial therapy was necessary, including a pus/exudates SIS of 0. The pathogens isolated at Baseline included staphylococcus aureus (methicillin-resistant staphylococcus aureus [MRSA] and methicillin-susceptible staphylococcus aureus [MSSA] as defined by susceptibility to cefoxitin or oxacilin), streptococcus pyogenes, other streptococcus species, other Gram-positive pathogens and Gram-negative pathogens. Data is categorized for the percentage of participants with clinical success for each of the pathogens, all pathogens and no pathogens.
Population Pharmacokinetic Parameters of Apparent Total Clearance of GSK1322322 From Plasma After Oral Administration (CL/F) [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)]
Blood samples were planned to be collected on Day 1, 0.25-1.5 hours post-initial dose (corresponding to the safety laboratory and ECG timepoint), and 1.5-3 hours post-initial dose (corresponding to the safety laboratory and ECG timepoint), and Day 4, 4-12 hours post-morning dose (corresponding to the safety laboratory and ECG timepoint), and Day 8, pre-morning dose (corresponding to safety laboratory and ECG timepoint) during the outpatient visit. The data for this outcome measure was not collected and assessed.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Anniston	Alabama	United States	36207
2	GSK Investigational Site	Chula Vista	California	United States	91911
3	GSK Investigational Site	La Mesa	California	United States	91942
4	GSK Investigational Site	Long Beach	California	United States	90813
5	GSK Investigational Site	Oceanside	California	United States	92056
6	GSK Investigational Site	Honolulu	Hawaii	United States	96813
7	GSK Investigational Site	West Reading	Pennsylvania	United States	19611

Sponsors and Collaborators

GlaxoSmithKline

Investigators

Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Publications

None provided.

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT01209078

Other Study ID Numbers:

113414

First Posted:

Sep 24, 2010

Last Update Posted:

Dec 4, 2017

Last Verified:

Sep 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Keywords provided by GlaxoSmithKline

methicillin-resistant Staphylococcus aureus

linezolid

repeat dose

GSK1322322

Additional relevant MeSH terms:

Infections

Communicable Diseases

Cellulitis

Skin Diseases, Infectious

Bacterial Infections

Linezolid

Study Results

Participant Flow

Recruitment Details	The study was planned on 75 male and female participants with Gram-positive acute bacterial skin and skin structure infection (ABSSSI) who were not receiving any antibacterial therapy, aged 18 years or older at eight study centers in the United States from 13 September 2010 to 20 December 2010.
Pre-assignment Detail	A total of 84 participants were enrolled in the study; of which, 57 participants were randomized in a ratio of 2:1 to receive GSK1322322 1500 milligram (mg) twice a day (BID) and 27 were randomized to receive linezolid 600 mg BID for 10 days.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 milliliter (mL) of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Period Title: Overall Study
STARTED	57	27
COMPLETED	41	24
NOT COMPLETED	16	3

Baseline Characteristics

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID	Total
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Total of all reporting groups
Overall Participants	57	27	84
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	44.4 (11.87)	41.5 (11.00)	43.5 (11.61)
Sex: Female, Male (Count of Participants)
Female	14 24.6%	4 14.8%	18 21.4%
Male	43 75.4%	23 85.2%	66 78.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	2 3.5%	0 0%	2 2.4%
Asian	1 1.8%	0 0%	1 1.2%
Native Hawaiian or Other Pacific Islander	1 1.8%	2 7.4%	3 3.6%
Black or African American	4 7%	2 7.4%	6 7.1%
White	47 82.5%	23 85.2%	70 83.3%
More than one race	2 3.5%	0 0%	2 2.4%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE)
Description	An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE is defined as any untoward medical occurrence that, at any dose, results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, or is a congenital anomaly/birth defect, may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes listed in this definition, associated with liver injury and impaired liver function defined as alanine aminotransferase (ALT) >=3 x upper limit of normal (ULN), and total bilirubin >=2 x ULN or international normalised ratio >1.5.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population was defined as all participants who received at least one dose of study medication.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Any AE	49 86%	20 74.1%
Any SAE	1 1.8%	1 3.7%

2. Primary Outcome

Title	Mean Clinical Chemistry Parameters of Albumin and Total Protein at Indicated Time Points
Description	Blood samples were obtained for analysis of albumin and total protein at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Albumin, Day 1	39.9 (3.41)	40.3 (3.47)
Albumin, Day 4	40.0 (3.70)	40.5 (2.66)
Albumin, Day 8	40.3 (4.04)	40.4 (3.35)
Albumin, Day 11	40.9 (3.59)	42.2 (2.83)
Albumin, 7 Day Follow-up	41.4 (4.03)	42.8 (3.02)
Albumin, 28 Day Follow-up	41.5 (4.03)	41.1 (3.04)
Total protein, Day 1	72.6 (5.86)	72.2 (6.86)
Total protein, Day 4	72.0 (5.98)	72.4 (6.80)
Total protein, Day 8	72.8 (5.94)	71.3 (4.46)
Total protein, Day 11	73.2 (6.19)	73.4 (4.58)
Total protein, 7 Day Follow-up	73.5 (5.79)	74.3 (6.44)
Total protein, 28 Day Follow-up	73.2 (6.35)	72.6 (4.42)

3. Primary Outcome

Title	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
Description	Blood samples were obtained for analysis of ALT, ALP, AST, FSH, GGT, LDH and creatine kinase at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
ALP, Day 1	102.5 (39.65)	97.7 (34.73)
ALP, Day 4	95.0 (21.99)	92.4 (26.32)
ALP, Day 8	94.8 (21.26)	88.2 (21.63)
ALP, Day 11	95.4 (23.88)	89.3 (19.06)
ALP, 7 Day Follow-up	95.6 (27.45)	90.9 (22.18)
ALP, 28 Day Follow-up	95.2 (27.79)	92.9 (29.85)
ALT, Day 1	26.5 (18.55)	27.3 (17.94)
ALT, Day 4	30.1 (29.46)	25.4 (12.11)
ALT, Day 8	34.3 (30.90)	34.0 (35.20)
ALT, Day 11	39.4 (51.29)	32.2 (30.22)
ALT, 7 Day Follow-up	37.5 (35.13)	32.6 (25.03)
ALT, 28 Day Follow-up	28.4 (19.03)	22.7 (10.66)
AST, Day 1	25.9 (14.49)	26.3 (14.66)
AST, Day 4	27.3 (15.01)	24.7 (7.69)
AST, Day 8	32.0 (25.19)	29.3 (18.97)
AST, Day 11	34.6 (30.89)	28.5 (15.97)
AST, 7 Day Follow-up	35.5 (25.72)	28.7 (11.37)
AST, 28 Day Follow-up	30.2 (21.83)	24.0 (10.11)
Creatine kinase, Day 1	118.1 (187.13)	191.1 (396.31)
Creatine kinase, Day 4	135.2 (98.96)	166.7 (209.06)
Creatine kinase, Day 8	117.3 (71.14)	120.3 (69.81)
Creatine kinase, Day 11	135.8 (113.14)	169.3 (200.90)
Creatine kinase, 7 Day Follow-up	204.7 (561.92)	189.1 (235.47)
Creatine kinase, 28 Day Follow-up	155.3 (168.84)	117.5 (64.86)
FSH, Day 1	21.47 (14.585)	16.05 (24.955)
GGT, Day 1	52.9 (51.70)	52.6 (52.17)
GGT, Day 4	55.3 (56.17)	53.4 (43.15)
GGT, Day 8	57.7 (52.08)	57.7 (45.20)
GGT, Day 11	55.7 (57.22)	53.5 (40.95)
GGT, 7 Day Follow-up	65.1 (70.73)	52.8 (39.12)
GGT, 28 Day Follow-up	50.1 (57.09)	42.1 (42.1)
LDH, Day 1	172.0 (NA)

4. Primary Outcome

Title	Mean Clinical Chemistry Parameters of Creatinine, Uric Acid, Direct Bilirubin and Total Bilirubin at Indicated Time Points
Description	Blood samples were obtained for analysis of creatinine, uric acid, direct bilirubin and total bilirubin at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Creatinine, Day 1	68.73 (18.911)	66.99 (13.567)
Creatinine, Day 4	71.48 (14.307)	72.35 (13.123)
Creatinine, Day 8	74.85 (16.204)	73.42 (13.159)
Creatinine, Day 11	74.19 (16.223)	72.07 (12.370)
Creatinine, 7 Day Follow-up	70.84 (15.601)	75.06 (21.598)
Creatinine, 28 Day Follow-up	72.77 (20.980)	72.49 (13.537)
Uric acid, Day 1	322.5 (88.53)	293.3 (84.03)
Uric acid, Day 4	282.2 (78.77)	346.4 (74.21)
Uric acid, Day 8	323.2 (73.92)	360.4 (71.96)
Uric acid, Day 11	370.5 (88.00)	367.4 (84.86)
Uric acid, 7 Day Follow-up	386.0 (105.60)	363.8 (97.17)
Uric acid, 28 Day Follow-up	358.3 (89.30)	332.6 (79.96)
Direct bilirubin, Day 1	2.3 (1.36)	2.5 (1.05)
Direct bilirubin, Day 4	2.4 (1.39)	2.0 (1.00)
Direct bilirubin, Day 8	2.4 (1.24)	1.9 (0.93)
Direct bilirubin, Day 11	2.5 (1.32)	2.1 (0.95)
Direct bilirubin, 7 Day Follow-up	2.6 (2.16)	3.0 (1.18)
Direct bilirubin, 28 Day Follow-up	2.3 (1.16)	2.3 (0.92)
Total bilirubin, Day 1	8.7 (3.87)	8.4 (4.31)
Total bilirubin, Day 4	7.3 (2.66)	6.6 (1.87)
Total bilirubin, Day 8	7.6 (3.15)	6.6 (1.91)
Total bilirubin, Day 11	8.1 (3.07)	7.6 (2.17)
Total bilirubin, 7 Day Follow-up	8.1 (4.13)	8.9 (4.04)
Total bilirubin, 28 Day Follow-up	8.5 (3.81)	7.6 (3.01)

5. Primary Outcome

Title	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
Description	Blood samples were obtained for analysis of glucose, sodium, calcium, potassium, chloride, CO2 content /bicarbonate and urea/BUN at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Glucose, Day 1	6.21 (2.385)	6.63 (5.652)
Glucose, Day 4	6.13 (2.459)	6.77 (5.834)
Glucose, Day 8	5.94 (1.473)	5.77 (1.618)
Glucose, Day 11	6.27 (2.025)	6.65 (3.355)
Glucose, 7 Day Follow-up	5.96 (1.607)	6.40 (2.212)
Glucose, 28 Day Follow-up	6.10 (1.487)	6.76 (3.068)
Sodium, Day 1	138.3 (2.49)	138.3 (3.17)
Sodium, Day 4	137.3 (3.07)	138.3 (1.96)
Sodium, Day 8	137.8 (1.99)	138.4 (3.11)
Sodium, Day 11	138.6 (2.11)	138.2 (2.79)
Sodium, 7 Day Follow-up	139.2 (2.27)	138.5 (2.26)
Sodium, 28 Day Follow-up	138.8 (1.93)	138.8 (3.03)
Calcium, Day 1	2.264 (0.1523)	2.251 (0.1169)
Calcium, Day 4	2.217 (0.1094)	2.257 (0.0930)
Calcium, Day 8	2.267 (0.1055)	2.273 (0.0719)
Calcium, Day 11	2.301 (0.1070)	2.282 (0.0772)
Calcium, 7 Day Follow-up	2.315 (0.1082)	2.303 (0.0959)
Calcium, 28 Day Follow-up	2.306 (0.1268)	2.263 (0.0913)
Potassium, Day 1	4.18 (0.373)	4.08 (0.297)
Potassium, Day 4	4.19 (0.400)	4.11 (0.301)
Potassium, Day 8	4.18 (0.288)	4.13 (0.303)
Potassium, Day 11	4.12 (0.280)	4.04 (0.301)
Potassium, 7 Day Follow-up	4.16 (0.331)	4.06 (0.357)
Potassium, 28 Day Follow-up	4.04 (0.307)	4.13 (0.293)
Chloride, Day 1	102.3 (3.12)	102.4 (3.55)
Chloride, Day 4	101.9 (3.71)	103.0 (3.01)
Chloride, Day 8	102.9 (2.57)	103.8 (2.95)
Chloride, Day 11	104.2 (2.69)	102.7 (4.05)
Chloride, 7 Day Follow-up	104.7 (2.14)	102.6 (3.85)
Chloride, 28 Day Follow-up	103.7 (2.60)	103.7 (3.97)
CO2 content/bicarbonate, Day 1	21.7 (2.68)	21.1 (2.43)
CO2 content/bicarbonate, Day 4	22.3 (2.51)	23.0 (2.44)
CO2 content/bicarbonate, Day 8	22.2 (2.16)	22.5 (2.08)
CO2 content/bicarbonate, Day 11	21.6 (2.20)	22.8 (2.77)
CO2 content/bicarbonate, 7 Day Follow-up	21.9 (2.31)	22.0 (2.51)
CO2 content/bicarbonate, 28 Day Follow-up	22.3 (2.05)	21.5 (2.64)
Urea/BUN, Day 1	4.90 (1.695)	4.20 (1.137)
Urea/BUN, Day 4	4.81 (1.383)	4.48 (1.475)
Urea/BUN, Day 8	4.47 (1.188)	4.73 (1.452)
Urea/BUN, Day 11	4.69 (1.381)	4.87 (1.618)
Urea/BUN, 7 Day Follow-up	4.84 (1.665)	5.00 (1.836)
Urea/BUN, 28 Day Follow-up	4.88 (1.526)	4.85 (0.947)

6. Primary Outcome

Title	Mean Clinical Chemistry Parameter of Estradiol at Indicated Time Point
Description	Blood samples were obtained for analysis of estradiol at Day 1.
Time Frame	Day 1

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	6	3
Mean (Standard Deviation) [Picomole (pmol)/Liter]	261.8 (218.20)	61.3 (22.37)

7. Primary Outcome

Title	Mean Clinical Chemistry Parameter of High Sensitivity C-Reactive Protein at Indicated Time Points
Description	Blood samples were obtained for analysis of high sensitivity C-Reactive protein at Day 1, Day 2, Day 3, Day 4, Day 8, Day 11 and 7 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Time Frame	Up to Follow-up (7 Day Follow-up, Day 19)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 1	38.39 (35.968)	43.97 (42.829)
Day 2	33.76 (36.759)	40.72 (43.485)
Day 3	27.13 (32.425)	30.99 (42.930)
Day 4	15.71 (23.564)	21.82 (34.947)
Day 8	6.87 (7.561)	6.02 (5.280)
Day 11	7.56 (9.711)	4.74 (4.658)
7 Day Follow-up	10.25 (16.299)	7.29 (8.377)

8. Primary Outcome

Title	Mean Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC) and Platelet Count at Indicated Time Points
Description	Blood samples were obtained for analysis of basophils, eosinophils, lymphocytes, monocytes, total neutrophils, WBC and platelet count at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Basophils, Day 1	0.027 (0.0146)	0.035 (0.0272)
Basophils, Day 4	0.030 (0.0179)	0.035 (0.0247)
Basophils, Day 8	0.027 (0.0125)	0.035 (0.0343)
Basophils, Day 11	0.030 (0.0234)	0.020 (0.0088)
Basophils, 7 Day Follow-up	0.032 (0.0162)	0.027 (0.0199)
Basophils, 28 Day Follow-up	0.024 (0.0144)	0.031 (0.0187)
Eosinophils, Day 1	0.149 (0.1116)	0.140 (0.1022)
Eosinophils, Day 4	0.149 (0.1708)	0.145 (0.1018)
Eosinophils, Day 8	0.165 (0.1347)	0.155 (0.1016)
Eosinophils, Day 11	0.175 (0.1534)	0.168 (0.1155)
Eosinophils, 7 Day Follow-up	0.151 (0.0870)	0.128 (0.0947)
Eosinophils, 28 Day Follow-up	0.141 (0.1060)	0.150 (0.0959)
Monocytes, Day 1	0.432 (0.2097)	0.517 (0.2131)
Monocytes, Day 4	0.354 (0.1352)	0.408 (0.2819)
Monocytes, Day 8	0.370 (0.1265)	0.388 (0.1826)
Monocytes, Day 11	0.320 (0.1475)	0.420 (0.1800)
Monocytes, 7 Day Follow-up	0.345 (0.1544)	0.410 (0.1677)
Monocytes, 28 Day Follow-up	0.384 (0.1502)	0.471 (0.2175)
Total neutrophils, Day 1	6.533 (3.0198)	7.231 (2.4074)
Total neutrophils, Day 4	4.757 (2.1470)	4.984 (2.0237)
Total neutrophils, Day 8	4.371 (1.6688)	4.780 (2.6362)
Total neutrophils, Day 11	4.495 (2.0516)	4.524 (1.7753)
Total neutrophils, 7 Day Follow-up	4.111 (1.5873)	4.821 (2.0453)
Total neutrophils, 28 Day Follow-up	4.709 (1.9470)	5.496 (2.9618)
WBC count, Day 1	9.15 (3.420)	9.87 (2.673)
WBC count, Day 4	7.35 (2.551)	7.54 (2.462)
WBC count, Day 8	6.82 (1.997)	7.30 (2.895)
WBC count, Day 11	6.77 (2.209)	7.06 (2.172)
WBC count, 7 Day Follow-up	6.44 (2.077)	7.48 (2.432)
WBC count, 28 Day Follow-up	7.16 (2.415)	8.10 (3.268)
Platelet count, Day 1	285.5 (91.48)	255.0 (72.48)
Platelet count, Day 4	296.5 (93.96)	273.2 (74.68)
Platelet count, Day 8	293.0 (79.28)	268.3 (56.90)
Platelet count, Day 11	280.2 (78.24)	253.9 (62.44)
Platelet count, 7 Day Follow-up	264.0 (71.40)	249.8 (58.68)
Platelet count, 28 Day Follow-up	279.3 (74.61)	240.5 (69.81)
Lymphocytes, Day 1	2.012 (0.7487)	1.947 (0.6455)
Lymphocytes, Day 4	2.057 (0.8168)	1.968 (0.6718)
Lymphocytes, Day 8	1.890 (0.7039)	1.941 (0.7312)
Lymphocytes, Day 11	1.749 (0.6990)	1.925 (0.6202)
Lymphocytes, 7 Day Follow-up	1.806 (0.7018)	2.091 (0.8427)
Lymphocytes, 28 Day Follow-up	1.907 (0.7745)	1.955 (0.4947)

9. Primary Outcome

Title	Mean Hematology Parameter of Mean Corpuscle Volume (MCV) at Indicated Time Points
Description	Blood samples were obtained for analysis of MCV at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg	Linezolid 600 mg
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 1	90.5 (5.24)	91.1 (8.53)
Day 4	89.8 (5.52)	91.6 (7.13)
Day 8	89.4 (5.88)	91.2 (7.01)
Day 11	89.7 (5.38)	90.7 (6.96)
7 Day Follow-up	89.1 (4.91)	91.5 (7.00)
28 Day Follow-up	90.1 (5.60)	91.3 (7.63)

10. Primary Outcome

Title	Mean Hematology Parameter of Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) at Indicated Time Points
Description	Blood samples were obtained for analysis of MCHC at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Hemoglobin, Day 1	136.7 (15.67)	134.2 (19.49)
Hemoglobin, Day 4	132.9 (15.49)	133.5 (18.44)
Hemoglobin, Day 8	135.8 (16.47)	134.0 (19.03)
Hemoglobin, Day 11	135.9 (16.83)	136.4 (19.04)
Hemoglobin, 7 Day Follow-up	137.7 (19.71)	135.8 (19.08)
Hemoglobin, 28 Day Follow-up	139.6 (17.82)	136.1 (18.35)
MCHC, Day 1	334.0 (8.73)	331.9 (12.38)
MCHC, Day 4	335.1 (9.42)	333.5 (15.25)
MCHC, Day 8	336.6 (8.73)	335.7 (12.60)
MCHC, Day 11	335.5 (7.73)	336.4 (14.24)
MCHC, 7 Day Follow-up	337.8 (7.39)	335.4 (10.67)
MCHC, 28 Day Follow-up	336.1 (8.53)	334.3 (11.80)

11. Primary Outcome

Title	Mean Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) at Indicated Time Points
Description	Blood samples were obtained for analysis of MCH at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 1	30.22 (1.970)	30.24 (3.284)
Day 4	30.08 (2.169)	30.58 (2.957)
Day 8	30.10 (2.165)	30.63 (2.970)
Day 11	30.06 (2.107)	30.59 (3.014)
7 Day Follow-up	30.14 (2.021)	30.71 (2.845)
28 Day Follow-up	30.26 (2.070)	30.56 (3.002)

12. Primary Outcome

Title	Mean Hematology Parameter of Red Blood Cell (RBC) Count and Reticulocyte Count at Indicated Time Points
Description	Blood samples were obtained for analysis of RBC count and reticulocyte at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline value was defined as the assessment done on Day 1.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
RBC count, Day 1	4.53 (0.413)	4.43 (0.397)
RBC count, Day 4	4.43 (0.370)	4.36 (0.454)
RBC count, Day 8	4.52 (0.430)	4.37 (0.389)
RBC count, Day 11	4.52 (0.410)	4.46 (0.436)
RBC count, 7 Day Follow-up	4.56 (0.489)	4.42 (0.457)
RBC count, 28 Day Follow-up	4.61 (0.430)	4.44 (0.376)
Reticulocytes, Day 1	0.07 (0.032)	0.06 (0.021)
Reticulocytes, Day 4	0.06 (0.024)	0.05 (0.020)
Reticulocytes, Day 8	0.07 (0.026)	0.05 (0.023)
Reticulocytes, Day 11	0.07 (0.031)	0.07 (0.025)
Reticulocytes, 7 Day Follow-up	0.06 (0.029)	0.08 (0.027)
Reticulocytes, 28 Day Follow-up	0.07 (0.031)	0.06 (0.023)

13. Primary Outcome

Title	Mean Vital Sign Value of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points
Description	Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three BP measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single BP was obtained at all other time points during the study.
Time Frame	Up to Day 11

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
DBP, Day 1	78.1 (10.39)	74.5 (10.46)
DBP, Day 2	76.0 (10.81)	76.7 (9.70)
DBP, Day 3	73.6 (10.92)	77.3 (11.01)
DBP, Day 4	69.7 (9.63)	76.8 (12.02)
DBP, Day 8	73.5 (10.77)	72.1 (11.23)
DBP, Day 11	73.6 (9.75)	72.8 (10.97)
SBP, Day 1	125.6 (14.21)	123.1 (12.72)
SBP, Day 2	119.2 (13.78)	125.1 (12.74)
SBP, Day 3	120.0 (14.52)	126.9 (15.96)
SBP, Day 4	119.3 (13.56)	126.1 (14.83)
SBP, Day 8	122.7 (14.78)	121.2 (16.02)
SBP, Day 11	122.0 (14.53)	120.4 (13.25)

14. Primary Outcome

Title	Mean Vital Sign Value of Heart Rate (HR) at Indicated Time Points
Description	Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three HR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single HR was obtained at all other time points during the study.
Time Frame	Up to Day 11

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 1	74.9 (13.75)	73.9 (14.11)
Day 2	81.2 (14.54)	76.2 (12.80)
Day 3	77.6 (12.81)	76.1 (11.70)
Day 4	71.9 (11.21)	74.6 (17.08)
Day 8	69.9 (10.52)	69.2 (12.07)
Day 11	70.9 (12.86)	74.0 (12.22)

15. Primary Outcome

Title	Mean Vital Sign Value of Respiratory Rate (RR) at Indicated Time Points
Description	Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three RR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single RR was obtained at all other time points during the study.
Time Frame	Up to Day 11

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 1	17.1 (1.95)	17.9 (1.70)
Day 2	17.3 (1.78)	17.4 (1.98)
Day 3	17.4 (2.08)	17.3 (1.85)
Day 4	17.3 (1.92)	17.4 (1.85)
Day 8	17.1 (1.66)	17.2 (1.76)
Day 11	17.6 (2.20)	16.8 (1.96)

16. Primary Outcome

Title	Mean Change From Baseline in SBP and DBP at Indicated Time Points
Description	Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three BP measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single BP was obtained at all other time points during the study. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 2, Day 3, Day 4, Day 8 and Day 11) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Time Frame	Day 1 (Baseline) up to Day 11

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
SBP, Day 2	-6.5 (12.23)	1.6 (15.35)
SBP, Day 3	-5.2 (11.24)	3.7 (18.64)
SBP, Day 4	-6.5 (11.31)	3.1 (15.21)
SBP, Day 8	-2.5 (12.23)	-2.7 (13.95)
SBP, Day 11	-2.7 (12.70)	-2.6 (15.44)
DBP, Day 2	-2.6 (8.64)	1.8 (6.46)
DBP, Day 3	-4.8 (8.64)	2.7 (13.59)
DBP, Day 4	-8.7 (9.02)	2.5 (12.10)
DBP, Day 8	-4.7 (9.92)	-2.8 (11.00)
DBP, Day 11	-4.4 (7.61)	-1.7 (9.53)

17. Primary Outcome

Title	Mean Change From Baseline in HR at Indicated Time Points
Description	Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three HR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single HR was obtained at all other time points during the study. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 2, Day 3, Day 4, Day 8 and Day 11) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Time Frame	Day 1 (Baseline) up to Day 11

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 2	6.5 (13.74)	3.7 (11.93)
Day 3	2.2 (11.47)	4.0 (11.48)
Day 4	-1.4 (10.28)	2.5 (19.57)
Day 8	-3.0 (10.98)	-2.7 (12.05)
Day 11	-2.5 (12.07)	1.7 (12.28)

18. Primary Outcome

Title	Mean Change From Baseline in RR at Indicated Time Points
Description	Vital sign assessments were conducted at Day 1 (pre-dose), Day 2 (pre-dose), Day 3 (pre-dose), Day 4 (4-12 hours post-dose), Day 8 (pre-dose) and Day 11. The assessments were made with the participant in a semi-supine position, having rested in that position for at least 10 minutes beforehand. Three RR measurements were taken at pre-dose on Day 1. The mean value recorded at pre-dose was classified as Baseline. Single RR was obtained at all other time points during the study. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 2, Day 3, Day 4, Day 8 and Day 11) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Time Frame	Day 1 (Baseline) up to Day 11

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 2	0.4 (1.80)	-0.7 (2.07)
Day 3	0.5 (2.41)	-0.7 (1.43)
Day 4	0.4 (2.35)	-0.6 (2.14)
Day 8	0.2 (1.98)	-0.8 (1.75)
Day 11	0.6 (2.11)	-1.2 (1.89)

19. Primary Outcome

Title	Mean Electrocardiogram (ECG) Values at Indicated Time Points
Description	12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart. The mean PR interval, RR interval, QRS duration, uncorrected QT interval (UncQT) and QTcB (QT corrected by Bazett's formula) and QTcF (corrected by Friedericia's formula) was calculated from automated ECG readings. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour). The mean value recorded pre-dose on Day 1 was classified as Baseline.
Time Frame	Up to Day 11

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
PR interval, Day 1, mean pre-dose	158.0 (15.88)	155.0 (20.17)
PR interval, Day 1, 0.25-1.5 h post-dose	157.0 (15.80)	159.2 (22.72)
PR interval, Day 1,1.5-3 h post-dose	158.5 (17.07)	157.2 (23.87)
PR interval, Day 4, 4-12 h post-dose	165.8 (18.35)	159.2 (21.39)
PR interval, Day 8, pre morning dose	167.4 (16.52)	158.1 (23.98)
PR interval, Day 11, 0 h	158.6 (19.72)	159.3 (19.37)
QRS duration, Day 1, mean pre-dose	94.0 (8.94)	95.9 (6.67)
QRS duration, Day 1, 0.25-1.5 h post-dose	93.9 (9.19)	97.1 (6.70)
QRS duration, Day 1,1.5-3 h post-dose	95.7 (8.76)	96.1 (8.40)
QRS duration, Day 4, 4-12 h post-dose	95.7 (8.91)	93.7 (6.76)
QRS duration, Day 8, pre morning dose	95.5 (10.07)	95.3 (8.81)
QRS duration, Day 11, 0 h	95.2 (8.41)	96.2 (8.22)
UncQT interval, Day 1, mean pre-dose	376.7 (36.76)	378.2 (39.50)
UncQT interval, Day 1, 0.25-1.5 h post-dose	370.8 (35.79)	375.1 (28.51)
UncQT interval, Day 1,1.5-3 h post-dose	370.3 (36.01)	374.0 (25.42)
UncQT interval, Day 4, 4-12 h post-dose	392.6 (32.26)	378.4 (37.77)
UncQT interval, Day 8, pre morning dose	397.1 (31.64)	390.3 (27.18)
UncQT interval, Day 11, 0 h	385.3 (32.05)	382.2 (41.47)
QTcB interval, Day 1, mean pre-dose	416.0 (26.09)	411.6 (28.57)
QTcB interval, Day 1, 0.25-1.5 h post-dose	421.1 (22.91)	407.9 (28.74)
QTcB interval, Day 1,1.5-3 h post-dose	424.1 (24.89)	412.7 (25.40)
QTcB interval, Day 4, 4-12 h post-dose	422.9 (23.65)	413.2 (22.61)
QTcB interval, Day 8, pre morning dose	420.1 (22.82)	411.0 (26.94)
QTcB interval, Day 11, 0 h	414.5 (17.76)	413.1 (22.21)
QTcF interval, Day 1, mean pre-dose	402.0 (24.04)	399.7 (28.20)
QTcF interval, Day 1, 0.25-1.5 h post-dose	403.1 (22.51)	396.3 (24.78)
QTcF interval, Day 1,1.5-3 h post-dose	405.0 (24.14)	399.2 (22.47)
QTcF interval, Day 4, 4-12 h post-dose	412.3 (22.76)	400.9 (21.28)
QTcF interval, Day 8, pre morning dose	412.0 (21.87)	403.7 (21.54)
QTcF interval, Day 11, 0 h	404.1 (16.95)	402.0 (24.27)
RR interval, Day 1, mean pre-dose	832.9 (173.04)	854.6 (150.70)
RR interval, Day 1, 0.25-1.5 h post-dose	783.8 (148.25)	855.0 (126.77)
RR interval, Day 1,1.5-3 h post-dose	770.7 (149.27)	825.8 (101.01)
RR interval, Day 4, 4-12 h post-dose	868.7 (133.65)	860.7 (185.66)
RR interval, Day 8, pre morning dose	900.4 (134.96)	918.6 (150.00)
RR interval, Day 11, 0 h	873.4 (155.04)	865.0 (170.76)

20. Primary Outcome

Title	Mean Change From Baseline in ECG Values at Indicated Time Points
Description	12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rate and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart. The mean PR interval, RR interval, QRS duration, uncorrected QT interval (UncQT) and QTcB (QT corrected by Bazett's formula) and QTcF (corrected by Friedericia's formula) was calculated from automated ECG readings. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour). Mean value recorded pre-dose on Day 1 was classified as Baseline. Change from Baseline was calculated by subtracting the Baseline value from individual post-Baseline (Day 1 post-dose, Day 4, Day 8 and Day 11) values.
Time Frame	Day 1 (pre-dose, Baseline) up to Day 11

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
PR interval, Day 1, 0.25-1.5 h post dose	-1.0 (9.64)	4.2 (12.88)
PR interval, Day 1, 1.5-3 h post dose	0.4 (12.09)	1.3 (11.79)
PR interval, Day 4, 4-12 h post dose	6.3 (11.03)	2.2 (11.75)
PR interval, Day 8, pre morning dose	7.1 (12.08)	-0.0 (13.79)
PR interval, Day 11, 0 h	-1.2 (13.86)	1.5 (14.27)
QRS duration, Day 1, 0.25-1.5 h post dose	-0.2 (6.32)	1.2 (5.52)
QRS duration, Day 1, 1.5-3 h post dose	1.6 (5.85)	0.3 (6.84)
QRS duration, Day 4, 4-12 h post dose	1.6 (5.25)	-2.2 (7.28)
QRS duration, Day 8, pre morning dose	1.0 (6.54)	-0.2 (8.18)
QRS duration, Day 11, 0 h	1.2 (7.19)	-0.2 (7.50)
UncQT interval, Day 1, 0.25-1.5 h post dose	-6.0 (18.66)	-3.1 (15.70)
UncQT interval, Day 1, 1.5-3 h post dose	-7.1 (19.33)	-7.2 (20.09)
UncQT interval, Day 4, 4-12 h post dose	14.1 (24.16)	0.5 (36.55)
UncQT interval, Day 8, pre morning dose	17.6 (29.12)	10.5 (26.68)
UncQT interval, Day 11, 0 h	8.2 (30.04)	1.5 (29.88)
QTcB interval, Day 1, 0.25-1.5 h post dose	5.1 (18.67)	-3.8 (13.50)
QTcB interval, Day 1, 1.5-3 h post dose	8.5 (16.86)	1.9 (17.59)
QTcB interval, Day 4, 4-12 h post dose	8.4 (21.55)	7.3 (16.70)
QTcB interval, Day 8, pre morning dose	5.4 (23.19)	3.3 (21.13)
QTcB interval, Day 11, 0 h	0.0 (19.45)	3.0 (20.16)
QTcF interval, Day 1, 0.25-1.5 h post dose	1.1 (14.99)	-3.4 (10.86)
QTcF interval, Day 1, 1.5-3 h post dose	3.0 (13.39)	-1.2 (14.74)
QTcF interval, Day 4, 4-12 h post dose	10.6 (16.68)	4.9 (16.57)
QTcF interval, Day 8, pre morning dose	9.8 (19.31)	5.9 (17.99)
QTcF interval, Day 11, 0 h	2.9 (18.09)	2.3 (18.28)
RR interval, Day 1, 0.25-1.5 h post dose	-49.2 (108.01)	0.4 (88.51)
RR interval, Day 1, 1.5-3 h post dose	-66.4 (104.58)	-43.0 (102.48)
RR interval, Day 4, 4-12 h post dose	23.7 (143.89)	-12.2 (194.88)
RR interval, Day 8, pre morning dose	51.6 (160.59)	44.6 (146.43)
RR interval, Day 11, 0 h	33.9 (142.01)	-5.1 (153.97)

21. Primary Outcome

Title	Mean ECG Rhythms at Indicated Time Points
Description	12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rhythm and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart and the mean of the three measurements was calculated. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour).
Time Frame	Up to Day 11

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 1, mean pre-dose	75.0 (14.33)	72.8 (15.01)
Day 1, 0.25-1.5 h post-dose	79.2 (14.34)	72.0 (13.04)
Day 1,1.5-3 h post-dose	80.4 (14.22)	73.7 (9.19)
Day 4, 4-12 h post-dose	70.6 (10.67)	73.0 (16.39)
Day 8, pre-morning dose	68.2 (10.37)	67.2 (12.28)
Day 11, 0 h	70.9 (13.15)	72.0 (13.94)

22. Primary Outcome

Title	Mean Change From Baseline in ECG Rhythms at Indicated Time Points
Description	12-lead ECGs were obtained during the study using an ECG machine that automatically calculated the heart rhythm and measured PR, QRS, RR, QT, and QTc intervals. It was performed with the participant in a semi-supine position having rested in that position for at least 10 minutes beforehand. Three measurements were taken at pre-dose on Day 1 at least 5 minutes apart and the mean of the three measurements was calculated. The assessments were done at Day 1 (pre-dose, 0.25-1.5 hours post-initial dose and 1.5-3 hours post-initial dose), Day 4 (4-12 hours post-morning dose), Day 8 (pre-morning dose) and Day 11 (0 hour). The value recorded pre-dose on Day 1 was the Baseline. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 1 post-dose, Day 4, Day 8 and Day 11) values.
Time Frame	Day 1 (pre-dose, Baseline) up to Day 11

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 1, 0.25-1.5 h post-dose	4.2 (8.69)	-0.9 (6.29)
Day 1, 1.5-3 h post-dose	5.9 (9.23)	2.9 (8.35)
Day 4, 4-12 h post-dose	-3.1 (11.37)	2.4 (16.48)
Day 8, pre morning dose	-5.2 (12.40)	-3.5 (10.12)
Day 11, 0 h	-3.2 (11.94)	1.1 (11.39)

23. Primary Outcome

Title	Number of Participants With Abnormal Transition From Baseline in Clinical Chemistry Values Relative to Normal Range
Description	The parameters of clinical chemistry included albumin, total protein, ALT, ALP, AST, GGT, LDH and creatine kinase, creatinine, uric acid, direct bilirubin, total bilirubin, glucose, sodium, calcium, potassium, chloride, CO2 content /bicarbonate and urea/BUN and high sensitivity C-Reactive protein. The assessments were done at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline was defined as the assessment done on Day 1 (pre-dose). Data is reported for number of participants with abnormal transition from Baseline 'to high' or 'to low' relative to normal range. Only those parameters for which at least one value of abnormal transition was reported are summarized.
Time Frame	Day 1 (pre-dose, Baseline) up Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 2, C-Reactive protein, to high	1 1.8%	0 0%
Day 3, C-Reactive protein, to high	1 1.8%	0 0%
Day 4, ALT, to high	1 1.8%	0 0%
Day 4, ALP, to high	1 1.8%	0 0%
Day 4, AST, to high	2 3.5%	1 3.7%
Day 4, Calcium, to low	6 10.5%	0 0%
Day 4, CO2/bicarbonate, to low	4 7%	3 11.1%
Day 4, Chloride, to low	1 1.8%	0 0%
Day 4, Creatine kinase, to high	5 8.8%	3 11.1%
Day 4, Creatinine, to low	2 3.5%	2 7.4%
Day 4, GGT, to high	3 5.3%	1 3.7%
Day 4, Glucose, to low	2 3.5%	0 0%
Day 4, Glucose, to high	7 12.3%	2 7.4%
Day 4, Potassium, to low	1 1.8%	0 0%
Day 4, Sodium, to low	6 10.5%	0 0%
Day 4, Total protein, to low	1 1.8%	1 3.7%
Day 4, Urea/BUN, to low	2 3.5%	0 0%
Day 4, Urea/BUN, to high	0 0%	1 3.7%
Day 4, Uric acid, to low	5 8.8%	0 0%
Day 8, ALT, to high	1 1.8%	2 7.4%
Day 8, Albumin, to low	1 1.8%	0 0%
Day 8, AST, to high	4 7%	2 7.4%
Day 8, Calcium, to low	3 5.3%	0 0%
Day 8, Chloride, to high	1 1.8%	0 0%
Day 8, Creatine kinase, to high	4 7%	1 3.7%
Day 8, Creatinine, to low	4 7%	1 3.7%
Day 8, GGT, to high	4 7%	1 3.7%
Day 8, Glucose, to low	1 1.8%	1 3.7%
Day 8, Glucose, to high	7 12.3%	5 18.5%
Day 8, Sodium, to low	1 1.8%	1 3.7%
Day 8, Urea/BUN, to low	2 3.5%	0 0%
Day 8, Uric acid, to low	2 3.5%	0 0%
Day 11, ALT, to high	3 5.3%	2 7.4%
Day 11, AST, to high	5 8.8%	2 7.4%
Day 11, Calcium, to low	1 1.8%	0 0%
Day 11, CO2/bicarbonate, to low	5 8.8%	2 7.4%
Day 11, Chloride, to low	0 0%	1 3.7%
Day 11, Chloride, to high	1 1.8%	1 3.7%
Day 11, Creatine kinase, to high	2 3.5%	0 0%
Day 11, Creatinine, to low	2 3.5%	2 7.4%
Day 11, GGT, to high	3 5.3%	0 0%
Day 11, Glucose, to low	3 5.3%	0 0%
Day 11, Glucose, to high	8 14%	2 7.4%
Day 11, C-Reactive protein, to high	1 1.8%	1 3.7%
Day 11, Potassium, to low	0 0%	1 3.7%
Day 11, Sodium, to low	0 0%	1 3.7%
Day 11, Total protein, to high	1 1.8%	0 0%
Day 11, Urea/BUN, to low	2 3.5%	0 0%
Day 11, Urea/BUN, to high	0 0%	1 3.7%
Day 11, Uric acid, to low	0 0%	1 3.7%
Day 11, Uric acid, to high	2 3.5%	0 0%
7 Day Follow-up, ALT, to high	6 10.5%	3 11.1%
7 Day Follow-up, AST, to high	6 10.5%	0 0%
7 Day Follow-up, Calcium, to low	1 1.8%	0 0%
7 Day Follow-up, Calcium, to high	1 1.8%	0 0%
7 Day Follow-up, CO2/bicarbonate, to low	4 7%	2 7.4%
7 Day Follow-up, Chloride, to low	0 0%	1 3.7%
7 Day Follow-up, Chloride, to high	1 1.8%	1 3.7%
7 Day Follow-up, Creatine kinase, to high	4 7%	3 11.1%
7 Day Follow-up, Creatinine, to low	4 7%	3 11.1%
7 Day Follow-up, Creatinine, to high	0 0%	1 3.7%
7 Day Follow-up, Direct bilirubin, to high	1 1.8%	0 0%
7 Day Follow-up, GGT, to high	3 5.3%	0 0%
7 Day Follow-up, Glucose, to high	4 7%	2 7.4%
7 Day Follow-up, C-Reactive protein, to high	0 0%	1 3.7%
7 Day Follow-up, Potassium, to low	1 1.8%	1 3.7%
7 Day Follow-up, Sodium, to low	1 1.8%	0 0%
7 Day Follow-up, Total bilirubin, to high	1 1.8%	0 0%
7 Day Follow-up, Total protein, to high	1 1.8%	1 3.7%
7 Day Follow-up, Urea/BUN, to low	1 1.8%	1 3.7%
7 Day Follow-up, Urea/BUN, to high	1 1.8%	1 3.7%
7 Day Follow-up, Uric acid, to low	1 1.8%	1 3.7%
7 Day Follow-up, Uric acid, to high	5 8.8%	0 0%
28 Day Follow-up, ALT, to high	2 3.5%	0 0%
28 Day Follow-up, ALP, to high	0 0%	1 3.7%
28 Day Follow-up, AST, to high	1 1.8%	1 3.7%
28 Day Follow-up, Calcium, to low	3 5.3%	0 0%
28 Day Follow-up, Calcium, to high	1 1.8%	0 0%
28 Day Follow-up, CO2/bicarbonate, to low	1 1.8%	6 22.2%
28 Day Follow-up, Chloride, to low	0 0%	1 3.7%
28 Day Follow-up, Chloride, to high	2 3.5%	3 11.1%
28 Day Follow-up, Creatine kinase, to high	5 8.8%	2 7.4%
28 Day Follow-up, Creatinine, to low	2 3.5%	3 11.1%
28 Day Follow-up, Creatinine, to high	1 1.8%	0 0%
28 Day Follow-up, GGT, to high	1 1.8%	1 3.7%
28 Day Follow-up, Glucose, to high	7 12.3%	3 11.1%
28 Day Follow-up, Potassium, to low	2 3.5%	1 3.7%
28 Day Follow-up, Sodium, to low	0 0%	2 7.4%
28 Day Follow-up, Total protein, to low	2 3.5%	0 0%
28 Day Follow-up, Total protein, to high	1 1.8%	0 0%
28 Day Follow-up, Urea/BUN, to low	1 1.8%	0 0%
28 Day Follow-up, Uric acid, to low	0 0%	2 7.4%
28 Day Follow-up, Uric acid, to high	1 1.8%	0 0%

24. Primary Outcome

Title	Number of Participants With Abnormal Transition From Baseline in Hematology Values Relative to Normal Range
Description	The parameters of clinical chemistry included basophils, eosinophils, lymphocytes, monocytes, total neutrophils, WBC count, platelet count, MCV, hemoglobin, MCHC, MCH, RBC count and reticulocyte count. The assessments were done at Day 1, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up. Baseline was defined as the assessment done on Day 1 (pre-dose). Data is reported for number of participants with abnormal transition from Baseline 'to high' or 'to low' relative to normal range. Only those parameters for which at least one value of abnormal transition was reported are summarized.
Time Frame	Day 1 (pre-dose, Baseline) up Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Safety Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 4, Eosinophils, to low	6 10.5%	1 3.7%
Day 4, Eosinophils, to high	1 1.8%	0 0%
Day 4, Hemoglobin, to low	3 5.3%	3 11.1%
Day 4, Lymphocytes, to low	1 1.8%	0 0%
Day 4, MCHC, to low	2 3.5%	0 0%
Day 4, Monocytes, to low	3 5.3%	1 3.7%
Day 4, Monocytes, to high	0 0%	1 3.7%
Day 4, Platelet count, to high	2 3.5%	1 3.7%
Day 4, RBC count, to low	2 3.5%	4 14.8%
Day 4, Reticulocytes, to low	1 1.8%	1 3.7%
Day 4, Reticulocytes, to high	2 3.5%	1 3.7%
Day 4, Total neutrophils, to low	1 1.8%	0 0%
Day 4, Total neutrophils, to high	1 1.8%	0 0%
Day 4, WBC count, to low	2 3.5%	1 3.7%
Day 4, WBC count, to high	1 1.8%	0 0%
Day 8, Eosinophils, to low	3 5.3%	2 7.4%
Day 8, Hemoglobin, to low	1 1.8%	2 7.4%
Day 8, Lymphocytes, to low	1 1.8%	0 0%
Day 8, MCHC, to low	1 1.8%	0 0%
Day 8, MCV, to high	1 1.8%	0 0%
Day 8, Monocytes, to low	3 5.3%	0 0%
Day 8, Platelet count, to high	2 3.5%	0 0%
Day 8, RBC count, to low	1 1.8%	2 7.4%
Day 8, Reticulocytes, to low	0 0%	4 14.8%
Day 8, Reticulocytes, to high	5 8.8%	2 7.4%
Day 8, Total neutrophils, to low	3 5.3%	0 0%
Day 8, Total neutrophils, to high	0 0%	1 3.7%
Day 8, WBC count, to low	2 3.5%	0 0%
Day 11, Eosinophils, to low	2 3.5%	1 3.7%
Day 11, Hemoglobin, to low	2 3.5%	2 7.4%
Day 11, Hemoglobin, to high	1 1.8%	0 0%
Day 11, Lymphocytes, to low	3 5.3%	0 0%
Day 11, Monocytes, to low	5 8.8%	1 3.7%
Day 11, Platelet count, to high	1 1.8%	0 0%
Day 11, RBC count, to low	2 3.5%	1 3.7%
Day 11, Reticulocytes, to low	3 5.3%	1 3.7%
Day 11, Reticulocytes, to high	3 5.3%	4 14.8%
Day 11, Total neutrophils, to low	1 1.8%	1 3.7%
Day 11, Total neutrophils, to high	1 1.8%	0 0%
Day 11, WBC count, to low	2 3.5%	0 0%
Day 11, WBC count, to high	1 1.8%	0 0%
7 Day Follow-up, Eosinophils, to low	0 0%	3 11.1%
7 Day Follow-up, Hemoglobin, to low	1 1.8%	1 3.7%
7 Day Follow-up, Lymphocytes, to low	1 1.8%	1 3.7%
7 Day Follow-up, Monocytes, to low	5 8.8%	1 3.7%
7 Day Follow-up, Platelet count, to low	1 1.8%	0 0%
7 Day Follow-up, RBC count, to low	2 3.5%	1 3.7%
7 Day Follow-up, Reticulocytes, to low	4 7%	0 0%
7 Day Follow-up, Reticulocytes, to high	1 1.8%	10 37%
7 Day Follow-up, Total neutrophils, to low	1 1.8%	0 0%
7 Day Follow-up, Total neutrophils, to high	1 1.8%	1 3.7%
7 Day Follow-up, WBC count, to low	1 1.8%	0 0%
7 Day Follow-up, WBC count, to high	1 1.8%	1 3.7%
28 Day Follow-up, Eosinophils, to low	1 1.8%	1 3.7%
28 Day Follow-up, Hemoglobin, to low	1 1.8%	3 11.1%
28 Day Follow-up, Hemoglobin, to high	1 1.8%	0 0%
28 Day Follow-up, Lymphocytes, to low	1 1.8%	0 0%
28 Day Follow-up, Lymphocytes, to high	1 1.8%	0 0%
28 Day Follow-up, MCHC, to low	1 1.8%	0 0%
28 Day Follow-up, Monocytes, to low	1 1.8%	0 0%
28 Day Follow-up, Platelet count, to low	0 0%	1 3.7%
28 Day Follow-up, Platelet count, to high	2 3.5%	0 0%
28 Day Follow-up, RBC count, to low	0 0%	4 14.8%
28 Day Follow-up, Reticulocytes, to low	0 0%	1 3.7%
28 Day Follow-up, Reticulocytes, to high	3 5.3%	4 14.8%
28 Day Follow-up, Total neutrophils, to low	1 1.8%	0 0%
28 Day Follow-up, Total neutrophils, to high	1 1.8%	1 3.7%
28 Day Follow-up, WBC count, to low	1 1.8%	0 0%
28 Day Follow-up, WBC count, to high	2 3.5%	1 3.7%

25. Secondary Outcome

Title	Number of Participants With Clinical Success of Clinical Response
Description	The clinical response was evaluated by the investigator at end of therapy (within 3 days post therapy; Day 12-14) and Follow-up (7 day Follow-up; Day 16 to 19 and 28 day Follow-up; Day 37 to 40). Clinical response was determined after clinical evaluation of reviewing clinical signs and symptoms. Clinical success was defined as total resolution of all signs and symptoms of infection recorded at Baseline, or improvement to such an extent that no further antimicrobial therapy was necessary, including a pus/exudate skin infection score (SIS) of 0.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
Intent-to-Treat Clinical (ITTC) Population was defined as all randomized participants who received at least one dose of study medication. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 11	38 66.7%	24 88.9%
7 Day Follow-up	38 66.7%	25 92.6%
28 Day Follow-up	37 64.9%	23 85.2%

26. Secondary Outcome

Title	Percentage of Participants With Clinical Success of Clinical Outcome
Description	The clinical response was determined by the investigator after clinical evaluation of reviewing clinical signs and symptoms at end of therapy (within 3 days post therapy; visit window of Day 12-14) and 7 day Follow-up ( visit window of Day 16 to 19), and the resulting clinical outcome was assigned, for each participant. Clinical success was defined as total resolution of all signs and symptoms of infection recorded at Baseline, or improvement to such an extent that no further antimicrobial therapy was necessary, including a pus/exudates SIS of 0.
Time Frame	Day 11 (end of therapy) and Follow-up (7 Day Follow-up, Day 19)

Outcome Measure Data

Analysis Population Description
ITTC Population.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
End of therapy	66.7 117%	88.9 329.3%
Follow-up	64.9 113.9%	88.9 329.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for end of therapy Clinical Success.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-22.2
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Follow-up Clinical Success.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-24.0
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

27. Secondary Outcome

Title	Percentage of Participants With Microbiological Success of Microbiological Outcome at End of Therapy
Description	The 'by pathogen' microbiological response was determined by comparing the Baseline (Day 1) culture results to the culture results at the end of therapy (visit window of Day 12-14), and the corresponding microbiological outcome (success or failure) by participant was then assigned. Microbiological success was defined as: elimination of Baseline pathogens (defined as microbiological eradication in microbiological response); clinical outcome was success such that no culture was obtained due to lack of culturable material, secondary to adequate clinical response, and was documented in the electronic case report form (eCRF) (defined as presumed microbiological eradication in microbiological response); new pathogen not previously identified, was identified at end of therapy in a participant who was a 'clinical success' (defined as colonization in microbiological response).
Time Frame	Day 11 (end of therapy)

Outcome Measure Data

Analysis Population Description
Intent-to-Treat Bacteriology (ITTB) Population was defined as all randomized participants who received at least one dose of study medication and who had a pathogen isolated at Baseline.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	37	18
Number [Percentage of participants]	59.5 104.4%	94.4 349.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-35.0
	Confidence Interval	(2-Sided) 95% -60.6 to -9.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

28. Secondary Outcome

Title	Percentage of Participants With Microbiological Success of Microbiological Outcome at Follow-up
Description	The 'by pathogen' microbiological response was determined by comparing the Baseline (Day 1) culture results to culture results at Follow-up (Day 16-19), and corresponding microbiological outcome (success or failure) by participant was then assigned. Microbiological success was defined as: Baseline pathogen was eradicated or presumed eradicated at end of therapy, or Baseline pathogens were present at end of therapy and is absent at Follow-up (microbiological eradication in microbiological response); Baseline pathogen was eradicated or presumed eradicated at end of therapy, or the Baseline pathogens were present at end of therapy and, participant was a 'clinical success', such that no culture was obtained due to lack of culturable material, secondary to adequate clinical response, and was documented in the eCRF (microbiological eradication); a new pathogen, not previously identified at Baseline, was identified at Follow-up in a participant who was a 'clinical success' (colonization)
Time Frame	Follow-up (7 Day Follow-up, Day 19)

Outcome Measure Data

Analysis Population Description
ITTB Population.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	37	18
Number [Percentage of participants]	59.5 104.4%	94.4 349.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-35.0
	Confidence Interval	(2-Sided) 95% -60.6 to -9.4
	Parameter Dispersion	Type: Value:
	Estimation Comments

29. Secondary Outcome

Title	Percentage of Participants With Therapeutic Success of Therapeutic Outcome
Description	Therapeutic outcome was combined clinical and microbiological outcome. Therapeutic outcome was a measure of the overall efficacy response, and a therapeutic success referred to participants who had been deemed both a 'clinical success' and a 'microbiological success'. All other combinations (other than 'clinical success' + 'microbiological success') were deemed failures for therapeutic outcome. Therapeutic outcome was determined programmatically, obtained at 7 day Follow-up.
Time Frame	Follow-up (7 day Follow-up, Day 19)

Outcome Measure Data

Analysis Population Description
Per Protocol Bacteriology (PPB) Population was defined as ITTB participants who adhered to protocol-specific criteria (i.e., no protocol violation ): taking 80% of medications and/or not missing more than 48 h in a row of study drug, and have both end of therapy and 7 day Follow-up to be evaluable and a documented pathogen cultured at Baseline.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	22	17
Number (95% Confidence Interval) [Percentage of participants]	0.8636 1.5%	1.0000 3.7%

30. Secondary Outcome

Title	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
Description	SF-MPQ-2 is composed of 22 items that describes different quantities of pain and related symptoms. Sub-score of continuous pain represents mean of throbbing pain, cramping pain, gnawing pain, aching pain, heavy pain and tender (mean of items 1, 5, 6, 8, 9 and 10). Sub-score of intermittent pain represents mean of shooting pain, stabbing pain, sharp pain, splitting pain, electric-shock pain and piercing (mean of items 2, 3, 4, 11, 16 and 18). Sub-score of neuropathic pain represents mean of hot-burning pain, cold-freezing pain, pain caused by light touch, itching, tingling or pins and needles, numbness (mean of items 7, 17, 19, 20, 21 and 22). Sub-score of affective descriptors represents mean of tiring-exhaustive, sickening, fearful, punishing-cruel (mean of items 12, 13, 14 and 15). Scores ranged from 0 to 10, where 0 indicated absence of symptom and higher score indicated more severe symptoms. Assessments were done at Day 1, Day 2, Day 3, Day 4, Day 8, Day 11 and 7 Day Follow-up.
Time Frame	Up to Follow-up (7 Day Follow up, Day 19)

Outcome Measure Data

Analysis Population Description
ITTC Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Continuous Pain, Day 1	4.459 (2.8567)	4.889 (2.2773)
Continuous Pain, Day 2	3.407 (2.4454)	3.533 (2.6745)
Continuous Pain, Day 3	2.826 (2.5509)	2.744 (2.8477)
Continuous Pain, Day 4	2.645 (2.7701)	2.067 (2.4462)
Continuous Pain, Day 8	1.420 (1.9653)	1.389 (2.0534)
Continuous Pain, Day 11	0.882 (1.3387)	0.806 (1.3976)
Continuous Pain, 7 Day Follow-up	0.733 (1.3018)	0.533 (1.2342)
Intermittent Pain, Day 1	3.836 (3.1349)	3.802 (2.9067)
Intermittent Pain, Day 2	2.337 (2.4214)	2.693 (2.9867)
Intermittent Pain, Day 3	2.078 (2.4989)	2.244 (2.7913)
Intermittent Pain, Day 4	1.906 (2.6239)	1.620 (2.4188)
Intermittent Pain, Day 8	0.871 (1.8040)	1.236 (1.9640)
Intermittent Pain, Day 11	0.504 (0.9927)	0.688 (1.4902)
Intermittent Pain, 7 Day Follow-up	0.581 (1.3429)	0.440 (1.1656)
Neuropathic Pain, Day 1	3.520 (2.5554)	3.846 (2.3705)
Neuropathic Pain, Day 2	2.705 (2.0982)	2.193 (2.2632)
Neuropathic Pain, Day 3	2.327 (2.0089)	2.026 (2.3526)
Neuropathic Pain, Day 4	2.391 (2.3476)	1.613 (2.0473)
Neuropathic Pain, Day 8	1.508 (1.7878)	1.410 (2.0042)
Neuropathic Pain, Day 11	0.813 (1.1113)	0.778 (1.2450)
Neuropathic Pain, 7 Day Follow-up	0.690 (1.1515)	0.593 (1.1707)
Affective Descriptors, Day 1	3.360 (3.0063)	2.806 (2.9000)
Affective Descriptors, Day 2	2.226 (2.5925)	2.500 (2.9244)
Affective Descriptors, Day 3	1.929 (2.4088)	1.692 (2.6517)
Affective Descriptors, Day 4	1.641 (2.4736)	1.330 (2.2287)
Affective Descriptors, Day 8	0.852 (1.5970)	1.021 (2.0811)
Affective Descriptors, Day 11	0.640 (1.1320)	0.490 (1.2079)
Affective Descriptors, 7 Day Follow-up	0.483 (1.0400)	0.430 (1.1099)

31. Secondary Outcome

Title	Mean Exudate or Pus Sub-score of SIS at Indicated Time Points
Description	The SIS consist of 7 items of exudate or pus, crusting, erythema or inflammation, tissue warmth, tissue edema, itching and pain. The exudate or pus sub-score of SIS was rated on a 7-point scale ranging from 0 to 6, where 0 indicated absence of symptom and 6 indicated severe symptom. Assessments were done at Day 1, Day 2, Day 3, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
ITTC Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 1	3.2 (2.23)	3.2 (2.39)
Day 2	3.0 (1.81)	2.8 (1.97)
Day 3	2.1 (1.56)	2.2 (1.86)
Day 4	1.5 (1.60)	1.7 (1.51)
Day 8	0.8 (1.29)	0.4 (0.71)
Day 11	0.2 (0.70)	0.0 (0.00)
7 Day Follow-up	0.1 (0.37)	0.0 (0.00)
28 Day Follow-up	0.0 (0.00)	0.0 (0.00)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 2 exudate or pus score.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.17
	Confidence Interval	(2-Sided) 95% -0.41 to 0.74
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 3 exudate or pus score.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.12
	Confidence Interval	(2-Sided) 95% -0.70 to 0.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 4 exudate or pus score.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.16
	Confidence Interval	(2-Sided) 95% -0.74 to 0.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 8 exudate or pus score.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.35
	Confidence Interval	(2-Sided) 95% -0.25 to 0.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 11 exudate or pus score.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95% -0.49 to 0.72
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for 7 Day Follow- up exudate or pus score.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.06
	Confidence Interval	(2-Sided) 95% -0.53 to 0.66
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for 28 Day Follow- up exudate or pus score.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.03
	Confidence Interval	(2-Sided) 95% -0.65 to 0.58
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

32. Secondary Outcome

Title	Mean Total SIS at Indicated Time Points
Description	The investigator evaluated the infection by grading the infected lesion according to SIS. The SIS consist of 7 items of exudate or pus, crusting, erythema or inflammation, tissue warmth, tissue edema, itching and pain. The items were rated on a 7-point scale ranging from 0 to 6, where 0 indicated absence of symptom and 6 indicated severe symptom. The total score ranged from 0 to 42, where 0 indicated absence of symptoms and higher score indicated more severe symptoms. Assessments were done at Day 1, Day 2, Day 3, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
ITTC Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 1	25.7 (5.44)	26.0 (4.39)
Day 2	22.2 (5.24)	23.3 (5.01)
Day 3	17.2 (6.09)	18.1 (6.59)
Day 4	14.6 (6.47)	14.1 (6.19)
Day 8	8.8 (5.52)	6.9 (4.17)
Day 11	3.7 (3.53)	2.3 (2.11)
7 Day Follow-up	2.4 (2.55)	1.8 (2.07)
28 Day Follow-up	0.3 (1.29)	0.1 (0.34)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 2 total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.86
	Confidence Interval	(2-Sided) 95% -3.04 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 3 total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95% -2.94 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 4 total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95% -1.68 to 2.75
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 8 total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.79
	Confidence Interval	(2-Sided) 95% -0.46 to 4.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 11 total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95% -1.09 to 3.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for 7 Day Follow-up total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95% -1.49 to 2.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for 28 Day Follow-up total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95% -2.09 to 2.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (final values) of GSK1322322 1500 mg and Linezolid 600 mg.

33. Secondary Outcome

Title	Mean Change From Baseline in Total SIS at Indicated Time Points
Description	The investigator evaluated the infection by grading the infected lesion according to SIS. The SIS consist of 7 items of exudate or pus, crusting, erythema or inflammation, tissue warmth, tissue edema, itching and pain. The items were rated on a 7-point scale ranging from 0 to 6, where 0 indicated absence of symptom and 6 indicated severe symptom. The total score ranged from 0 to 42, where 0 indicated absence of symptoms and higher score indicated more severe symptoms. Baseline was defined as the assessment value done on Day 1. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 1, Day 2, Day 3, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Time Frame	Day 1 (Baseline ) up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
ITTC Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 2	-3.4 (4.83)	-3.1 (4.98)
Day 3	-8.4 (6.39)	-8.0 (6.79)
Day 4	-10.9 (6.98)	-11.9 (6.84)
Day 8	-16.8 (7.22)	-19.0 (6.38)
Day 11	-22.0 (6.06)	-23.6 (4.82)
7 Day Follow-up	-23.0 (5.91)	-24.2 (4.75)
28 Day Follow-up	-25.1 (5.54)	-26.1 (3.98)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 2 total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.86
	Confidence Interval	(2-Sided) 95% -3.04 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 3 total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-0.77
	Confidence Interval	(2-Sided) 95% -2.94 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 4 total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.54
	Confidence Interval	(2-Sided) 95% -1.68 to 2.75
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 8 total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.79
	Confidence Interval	(2-Sided) 95% -0.46 to 4.05
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 11 total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.19
	Confidence Interval	(2-Sided) 95% -1.09 to 3.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for 7 Day Follow-up total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.74
	Confidence Interval	(2-Sided) 95% -1.49 to 2.98
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for 28 Day Follow-up total SIS.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	0.21
	Confidence Interval	(2-Sided) 95% -2.09 to 2.52
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

34. Secondary Outcome

Title	Mean Change From Baseline in Wound Area at Indicated Time Points
Description	The area of the infected lesion size was calculated as the product between the length (L) and width (W) of the lesion size. The wound was measured by the investigator in centimeters (cm), using a standard metric ruler. Baseline was defined as the assessment value done on Day 1. The change from Baseline was calculated by subtracting the Baseline value from the individual post-Baseline (Day 1, Day 2, Day 3, Day 4, Day 8, Day 11, 7 Day Follow-up and 28 Day Follow-up) values. If either the Baseline or post-Baseline value was missing, the change from Baseline was set to missing as well.
Time Frame	Day 1 (Baseline) up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
ITTC Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Day 2	-23.22 (52.486)	-20.71 (88.184)
Day 3	-67.69 (93.511)	-124.27 (188.568)
Day 4	-119.96 (86.544)	-209.79 (224.125)
Day 8	-192.92 (175.606)	-291.86 (338.675)
Day 11	-234.99 (276.801)	-329.93 (362.831)
7 Day Follow-up	-231.32 (273.285)	-335.20 (363.233)
28 Day Follow-up	-242.92 (277.312)	-344.99 (383.444)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 2 wound area.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-68.85
	Confidence Interval	(2-Sided) 95% -132.8 to -4.95
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 3 wound area.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	-3.06
	Confidence Interval	(2-Sided) 95% -66.54 to 60.43
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 4 wound area.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Median Difference (Net)
	Estimated Value	31.47
	Confidence Interval	(2-Sided) 95% -33.53 to 96.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 8 wound area.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	43.94
	Confidence Interval	(2-Sided) 95% -22.43 to 110.31
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Day 11 wound area.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	34.21
	Confidence Interval	(2-Sided) 95% -33.03 to 101.45
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for 7 Day Follow-up wound area.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	37.57
	Confidence Interval	(2-Sided) 95% -28.25 to 103.40
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for 28 Day Follow-up wound area.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	37.40
	Confidence Interval	(2-Sided) 95% -30.77 to 105.56
	Parameter Dispersion	Type: Value:
	Estimation Comments	The point estimate was calculated as least square mean difference (net values) of GSK1322322 1500 mg and Linezolid 600 mg.

35. Secondary Outcome

Title	Percentage of Participants With Clinical Success at End of Therapy by Pathogen Isolated at Baseline
Description	Clinical success was defined as total resolution of all signs and symptoms of infection recorded at Baseline, or improvement to such an extent that no further antimicrobial therapy was necessary, including a pus/exudates SIS of 0. The pathogens isolated at Baseline included staphylococcus aureus (methicillin-resistant staphylococcus aureus [MRSA] and methicillin-susceptible staphylococcus aureus [MSSA] as defined by susceptibility to cefoxitin or oxacilin), streptococcus pyogenes, other streptococcus species, other Gram-positive pathogens and Gram-negative pathogens. Data is categorized for the percentage of participants with clinical success for each of the pathogens, all pathogens and no pathogens.
Time Frame	Up to Follow-up (28 Day Follow-up, Day 40)

Outcome Measure Data

Analysis Population Description
ITTC Population. Only those participants available at the specified time points were analyzed.

Arm/Group Title	GSK1322322 1500 mg BID	Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.	Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	57	27
Staphylococcus aureus (all)	58.3 102.3%	93.8 347.4%
MRSA	50.0 87.7%	87.5 324.1%
MSSA	71.4 125.3%	100.0 370.4%
Streptococcus pyogenes	33.3 58.4%	100.0 370.4%
Other Streptococcus species	100.0 175.4%
Other Gram-positive pathogens	100.0 175.4%
Gram-negative pathogens	75.0 131.6%	100.0 370.4%
All pathogens	58.1 101.9%	95.7 354.4%
No pathogens	80.0 140.4%	77.8 288.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Staphylococcus aureus (all).
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-35.4
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for MRSA.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-37.5
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for MSSA.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-28.6
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Streptococcus pyogenes.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-66.7
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for Gram-negative pathogens.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-25.0
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for All pathogens.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	-37.5
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	GSK1322322 1500 mg BID, Linezolid 600 mg BID
	Comments	GSK1322322 1500 mg versus Linezolid 600 mg for No pathogens.
	Type of Statistical Test	Superiority or Other
	Comments

Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments

Method of Estimation	Estimation Parameter	Difference
	Estimated Value	2.2
	Confidence Interval	() % to
	Parameter Dispersion	Type: Value:
	Estimation Comments

36. Secondary Outcome

Title	Population Pharmacokinetic Parameters of Apparent Total Clearance of GSK1322322 From Plasma After Oral Administration (CL/F)
Description	Blood samples were planned to be collected on Day 1, 0.25-1.5 hours post-initial dose (corresponding to the safety laboratory and ECG timepoint), and 1.5-3 hours post-initial dose (corresponding to the safety laboratory and ECG timepoint), and Day 4, 4-12 hours post-morning dose (corresponding to the safety laboratory and ECG timepoint), and Day 8, pre-morning dose (corresponding to safety laboratory and ECG timepoint) during the outpatient visit. The data for this outcome measure was not collected and assessed.
Time Frame	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)

Outcome Measure Data

Analysis Population Description
Pharmacokinetic (PK) Concentration Population defined all Participants in the "Safety Population" who underwent plasma PK sampling during the study and from whom a measurable plasma concentration above the assay's limit of quantification were obtained for one of the treatment regimens. No participants were analyzed for this outcome measure.

Arm/Group Title	GSK1322322 1500 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.
Measure Participants	0

Adverse Events

	GSK1322322 1500 mg BID		Linezolid 600 mg BID
Time Frame	AEs were collected up to Follow-up (28 Day Follow-up, Day 40)
Adverse Event Reporting Description	Safety Population was used.

Arm/Group Title	GSK1322322 1500 mg BID		Linezolid 600 mg BID
Arm/Group Description	Participants received oral dose of GSK1322322 1500 mg as 3 tablets of 500 mg each, BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo capsules to linezoid in the morning and evening. The study medication was taken with 240 mL of water or liquid.		Participants received oral dose of linezolid 600 mg tablet BID in the morning and evening for 10 days. Blinding was maintained by administration of matching placebo tablets to GSK1322322 in the morning and evening. The study medication was taken with 240 mL of water or liquid.
All Cause Mortality
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/27 (0%)
Serious Adverse Events
	GSK1322322 1500 mg BID		Linezolid 600 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/57 (1.8%)		1/27 (3.7%)
Infections and infestations
Abscess limb	0/57 (0%)		1/27 (3.7%)
Cellulitis	0/57 (0%)		1/27 (3.7%)
Injury, poisoning and procedural complications
Multiple drug overdose	1/57 (1.8%)		0/27 (0%)
Other (Not Including Serious) Adverse Events
	GSK1322322 1500 mg BID		Linezolid 600 mg BID
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	38/57 (66.7%)		16/27 (59.3%)
Gastrointestinal disorders
Nausea	14/57 (24.6%)		4/27 (14.8%)
Diarrhoea	8/57 (14%)		2/27 (7.4%)
Vomiting	9/57 (15.8%)		1/27 (3.7%)
Flatulence	0/57 (0%)		2/27 (7.4%)
General disorders
Fatigue	3/57 (5.3%)		0/27 (0%)
Pain	3/57 (5.3%)		0/27 (0%)
Pyrexia	1/57 (1.8%)		2/27 (7.4%)
Infections and infestations
Skin infection	1/57 (1.8%)		2/27 (7.4%)
Upper respiratory tract infection	3/57 (5.3%)		0/27 (0%)
Investigations
Blood glucose increased	6/57 (10.5%)		3/27 (11.1%)
Alanine aminotransferase increased	4/57 (7%)		2/27 (7.4%)
Blood creatine phosphokinase increased	1/57 (1.8%)		2/27 (7.4%)
Haemoglobin decreased	3/57 (5.3%)		0/27 (0%)
Nervous system disorders
Headache	7/57 (12.3%)		2/27 (7.4%)
Dizziness	5/57 (8.8%)		1/27 (3.7%)
Skin and subcutaneous tissue disorders
Pruritus	3/57 (5.3%)		1/27 (3.7%)
Rash maculo-papular	3/57 (5.3%)		0/27 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.

Results Point of Contact

Name/Title	GSK Response Center
Organization	GlaxoSmithKline
Phone	866-435-7343
Email

Responsible Party:

GlaxoSmithKline

ClinicalTrials.gov Identifier:

NCT01209078

Other Study ID Numbers:

113414

First Posted:

Sep 24, 2010

Last Update Posted:

Dec 4, 2017

Last Verified:

Sep 1, 2017