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

NCT01209078 | Completed Phase 2 Results

• 1 other identifier: 113414
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 7

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).

Conditions

Skin Infections, Bacterial

Keywords

methicillin-resistant Staphylococcus aureus; linezolid; repeat dose; GSK1322322

Outcome Measures

Primary Outcomes (24)

• Number of Participants With Any Adverse Events (AE) and Serious Adverse Events (SAE)

  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.

  Up to Follow-up (28 Day Follow-up, Day 40)

• Mean Clinical Chemistry Parameters of Albumin and Total Protein at Indicated Time Points

  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.

  Up to Follow-up (28 Day Follow-up, Day 40)

• 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

  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.

  Up to Follow-up (28 Day Follow-up, Day 40)

• Mean Clinical Chemistry Parameters of Creatinine, Uric Acid, Direct Bilirubin and Total Bilirubin at Indicated Time Points

  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.

  Up to Follow-up (28 Day Follow-up, Day 40)

• 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

  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.

  Up to Follow-up (28 Day Follow-up, Day 40)

• Mean Clinical Chemistry Parameter of Estradiol at Indicated Time Point

  Blood samples were obtained for analysis of estradiol at Day 1.

  Day 1

• Mean Clinical Chemistry Parameter of High Sensitivity C-Reactive Protein at Indicated Time Points

  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.

  Up to Follow-up (7 Day Follow-up, Day 19)

• Mean Hematology Parameters of Basophils, Eosinophils, Lymphocytes, Monocytes, Total Neutrophils, White Blood Cells (WBC) and Platelet Count at Indicated Time Points

  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.

  Up to Follow-up (28 Day Follow-up, Day 40)

• Mean Hematology Parameter of Mean Corpuscle Volume (MCV) at Indicated Time Points

  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.

  Up to Follow-up (28 Day Follow-up, Day 40)

• Mean Hematology Parameter of Hemoglobin, Mean Corpuscle Hemoglobin Concentration (MCHC) at Indicated Time Points

  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.

  Up to Follow-up (28 Day Follow-up, Day 40)

• Mean Hematology Parameter of Mean Corpuscle Hemoglobin (MCH) at Indicated Time Points

  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.

  Up to Follow-up (28 Day Follow-up, Day 40)

• Mean Hematology Parameter of Red Blood Cell (RBC) Count and Reticulocyte Count at Indicated Time Points

  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.

  Up to Follow-up (28 Day Follow-up, Day 40)

• Mean Vital Sign Value of Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points

  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.

  Up to Day 11

• Mean Vital Sign Value of Heart Rate (HR) at Indicated Time Points

  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.

  Up to Day 11

• Mean Vital Sign Value of Respiratory Rate (RR) at Indicated Time Points

  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.

  Up to Day 11

• Mean Change From Baseline in SBP and DBP at Indicated Time Points

  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.

  Day 1 (Baseline) up to Day 11

• Mean Change From Baseline in HR at Indicated Time Points

  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.

  Day 1 (Baseline) up to Day 11

• Mean Change From Baseline in RR at Indicated Time Points

  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.

  Day 1 (Baseline) up to Day 11

• Mean Electrocardiogram (ECG) Values at Indicated Time Points

  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.

  Up to Day 11

• Mean Change From Baseline in ECG Values at Indicated Time Points

  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.

  Day 1 (pre-dose, Baseline) up to Day 11

• Mean ECG Rhythms at Indicated Time Points

  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).

  Up to Day 11

• Mean Change From Baseline in ECG Rhythms at Indicated Time Points

  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.

  Day 1 (pre-dose, Baseline) up to Day 11

• Number of Participants With Abnormal Transition From Baseline in Clinical Chemistry Values Relative to Normal Range

  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.

  Day 1 (pre-dose, Baseline) up Follow-up (28 Day Follow-up, Day 40)

• Number of Participants With Abnormal Transition From Baseline in Hematology Values Relative to Normal Range

  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.

  Day 1 (pre-dose, Baseline) up Follow-up (28 Day Follow-up, Day 40)

Secondary Outcomes (12)

• Number of Participants With Clinical Success of Clinical Response

  Up to Follow-up (28 Day Follow-up, Day 40)

• Percentage of Participants With Clinical Success of Clinical Outcome

  Day 11 (end of therapy) and Follow-up (7 Day Follow-up, Day 19)

• Percentage of Participants With Microbiological Success of Microbiological Outcome at End of Therapy

  Day 11 (end of therapy)

• Percentage of Participants With Microbiological Success of Microbiological Outcome at Follow-up

  Follow-up (7 Day Follow-up, Day 19)

• Percentage of Participants With Therapeutic Success of Therapeutic Outcome

  Follow-up (7 day Follow-up, Day 19)

Study Arms (2)

Regimen 1

EXPERIMENTAL

GSK1322322 1500mg and Placebo Linezolid given twice a day (BID) for 10 days

Drug: GSK1322322; Drug: Linezolid placebo

Regimen 2

ACTIVE COMPARATOR

Linezolid 600mg and placebo GSK1322322 given BID for 10 days

Drug: Linezolid; Drug: GSK1322322 placebo

Interventions

GSK1322322 DRUG

GSK1322322 1500mg BID

Regimen 1

Linezolid DRUG

Linezolid 600mg

Regimen 2

GSK1322322 placebo DRUG

Placebo

Regimen 2

Linezolid placebo DRUG

placebo

Regimen 1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (7)

GSK Investigational Site

Anniston, Alabama, 36207, United States

Location

GSK Investigational Site

Chula Vista, California, 91911, United States

Location

GSK Investigational Site

La Mesa, California, 91942, United States

Location

GSK Investigational Site

Long Beach, California, 90813, United States

Location

GSK Investigational Site

Oceanside, California, 92056, United States

Location

GSK Investigational Site

Honolulu, Hawaii, 96813, United States

Location

GSK Investigational Site

West Reading, Pennsylvania, 19611, United States

Location

Related Publications (1)

• Corey R, Naderer OJ, O'Riordan WD, Dumont E, Jones LS, Kurtinecz M, Zhu JZ. Safety, tolerability, and efficacy of GSK1322322 in the treatment of acute bacterial skin and skin structure infections. Antimicrob Agents Chemother. 2014 Nov;58(11):6518-27. doi: 10.1128/AAC.03360-14. Epub 2014 Aug 18.

  PMID: 25136015 DERIVED

Related Links

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

MeSH Terms

Conditions

Cellulitis

Interventions

GSK1322322; Linezolid

Condition Hierarchy (Ancestors)

Skin Diseases, Infectious; Infections; Suppuration; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Oxazolidinones; Oxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2010
• First Posted: September 24, 2010
• Study Start: August 17, 2010
• Primary Completion: January 18, 2011
• Study Completion: January 18, 2011
• Last Updated: December 4, 2017
• Results First Posted: December 4, 2017

Record last verified: 2017-09

Data Sharing

• IPD Sharing: Will share

Locations

US (7)