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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01209078
First Posted: September 24, 2010
Last Update Posted: December 4, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose
This study will determine the safety, tolerability and efficacy of GSK1322322 verses Linezolid in subjects with Acute Bacterial Skin and Skin Structure Infection (ABSSSI).

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

Study Type: Interventional
Study Design: Allocation: Randomized
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

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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) [ 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) ]
    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.


Enrollment: 84
Actual Study Start Date: August 17, 2010
Study Completion Date: January 18, 2011
Primary Completion Date: January 18, 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Regimen 1
GSK1322322 1500mg and Placebo Linezolid given twice a day (BID) for 10 days
Drug: GSK1322322
GSK1322322 1500mg BID
Drug: Linezolid placebo
placebo
Active Comparator: Regimen 2
Linezolid 600mg and placebo GSK1322322 given BID for 10 days
Drug: Linezolid
Linezolid 600mg
Drug: GSK1322322 placebo
Placebo

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

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01209078


Locations
United States, Alabama
GSK Investigational Site
Anniston, Alabama, United States, 36207
United States, California
GSK Investigational Site
Chula Vista, California, United States, 91911
GSK Investigational Site
La Mesa, California, United States, 91942
GSK Investigational Site
Long Beach, California, United States, 90813
GSK Investigational Site
Oceanside, California, United States, 92056
United States, Hawaii
GSK Investigational Site
Honolulu, Hawaii, United States, 96813
United States, Pennsylvania
GSK Investigational Site
West Reading, Pennsylvania, United States, 19611
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Clinical Study Report  This link exits the ClinicalTrials.gov site
Identifier: 113414
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Identifier: 113414
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the ClinicalTrials.gov site
Identifier: 113414
For additional information about this study please refer to the GSK Clinical Study Register
Dataset Specification  This link exits the ClinicalTrials.gov site
Identifier: 113414
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the ClinicalTrials.gov site
Identifier: 113414
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the ClinicalTrials.gov site
Identifier: 113414
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Identifier: 113414
For additional information about this study please refer to the GSK Clinical Study Register

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01209078     History of Changes
Other Study ID Numbers: 113414
First Submitted: September 14, 2010
First Posted: September 24, 2010
Results First Submitted: September 22, 2017
Results First Posted: December 4, 2017
Last Update Posted: December 4, 2017
Last Verified: September 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
URL: http://

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

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