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Trial record 56 of 115 for:    centurion

TR-701 FA vs Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infections

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ClinicalTrials.gov Identifier: NCT01421511
Recruitment Status : Completed
First Posted : August 22, 2011
Results First Posted : September 8, 2014
Last Update Posted : August 29, 2018
Sponsor:
Information provided by (Responsible Party):
Trius Therapeutics LLC

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Skin and Subcutaneous Tissue Bacterial Infections
Interventions Drug: TR-701 FA
Drug: Linezolid
Enrollment 666
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Tedizolid Phosphate Linezolid
Hide Arm/Group Description IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo. IV to oral linezolid 600 mg twice daily for 10 days.
Period Title: Overall Study
Started 332 334
Completed 313 306
Not Completed 19 28
Reason Not Completed
Lost to Follow-up             11             14
Randomized but didn't receive study drug             1             7
Physician Decision             0             1
Withdrawal by Subject             6             5
Death             1             1
Arm/Group Title Tedizolid Phosphate Linezolid Total
Hide Arm/Group Description IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo. IV to oral linezolid 600 mg twice daily for 10 days. Total of all reporting groups
Overall Number of Baseline Participants 332 334 666
Hide Baseline Analysis Population Description
All randomized participants
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 332 participants 334 participants 666 participants
45.6  (15.79) 45.6  (15.57) 45.6  (15.67)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 332 participants 334 participants 666 participants
Female
107
  32.2%
120
  35.9%
227
  34.1%
Male
225
  67.8%
214
  64.1%
439
  65.9%
1.Primary Outcome
Title The Early Clinical Response Rate
Hide Description Responder: No increase in lesion surface area from baseline.
Time Frame 48-72 hours
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat analysis set includes data from all randomized participants.
Arm/Group Title Tedizolid Phosphate Linezolid
Hide Arm/Group Description:
IV to oral tedizolid phosphate 200 mg once daily for six days followed by four days of placebo.
IV to oral linezolid 600 mg twice daily for 10 days.
Overall Number of Participants Analyzed 332 334
Measure Type: Number
Unit of Measure: participants
283 276
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tedizolid Phosphate, Linezolid
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A two-sided 95% CI was calculated for the observed differences in the early clinical response rates at 48 to 72 Hours after the first infusion of study drug using the method of Miettinen and Nurminen without stratification. Noninferiority was concluded if the lower limit of the 95% CI was greater than -10%.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 2.6
Confidence Interval (2-Sided) 95%
-3.0 to 8.2
Estimation Comments Risk difference corresponds to the tedizolid responder rate minus the linezolid responder rate.
2.Secondary Outcome
Title Clinical Response at the End of Therapy Visit
Hide Description Responder: No increase in lesion surface area from baseline.
Time Frame Day 11
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat analysis set includes data from all randomized participants.
Arm/Group Title Tedizolid Phosphate Linezolid
Hide Arm/Group Description:
IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.
IV to oral linezolid 600 mg twice daily for 10 days.
Overall Number of Participants Analyzed 332 334
Measure Type: Number
Unit of Measure: participants
289 294
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tedizolid Phosphate, Linezolid
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A two-sided 95% CI was calculated for the observed differences in the programmatic clinical response at the EOT visit using the method of Miettinen and Nurminen without stratification. Noninferiority was concluded if the lower limit of the 95% CI was greater than -10% and the conditions of the hierarchical testing procedure were met.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -1.0
Confidence Interval (2-Sided) 95%
-6.1 to 4.1
Estimation Comments Risk difference corresponds to the tedizolid clinical response rate minus the linezolid clinical response rate.
3.Secondary Outcome
Title Clinical Response at the End of Therapy Visit in the Clinically Evaluable at End of Therapy Analysis Set
Hide Description Responder: No increase in lesion surface area from baseline.
Time Frame End of Therapy Day 11
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants receiving minimal study therapy, completed EOT assessment, no concomitant systemic antibiotic therapy and no confounding events or factors.
Arm/Group Title Tedizolid Phosphate Linezolid
Hide Arm/Group Description:
IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.
IV to oral linezolid 600 mg twice daily for 10 days.
Overall Number of Participants Analyzed 304 299
Measure Type: Number
Unit of Measure: participants
272 280
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tedizolid Phosphate, Linezolid
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A two-sided 95% CI was calculated for the observed differences in the clinical response rate based on the Investigator's assessment of clinical response at the EOT Visit using the method of Miettinen and Nurminen without stratification. Noninferiority was concluded if the lower limit of the 95% CI was greater than -10% and the conditions of the hierarchical testing procedure were met.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -4.1
Confidence Interval (2-Sided) 95%
-8.8 to 0.3
Estimation Comments Risk difference corresponds to the tedizolid clinical response rate minus the linezolid clinical response rate.
4.Secondary Outcome
Title Investigator’s Assessment of Clinical Success at the Post Treatment Evaluation Visit
Hide Description Clinical success defined as resolution/near resolution of disease specific signs and symptoms, absence/near resolution of baseline systemic signs of infection, and no further antibiotic therapy required for treatment of primary ABSSSI lesion.
Time Frame Post-Treatment Evaluation (7-14 days after the End of Therapy)
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat analysis set includes data from all randomized participants.
Arm/Group Title Tedizolid Phosphate Linezolid
Hide Arm/Group Description:
IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.
IV to oral linezolid 600 mg twice daily for 10 days.
Overall Number of Participants Analyzed 332 334
Measure Type: Number
Unit of Measure: participants
292 293
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tedizolid Phosphate, Linezolid
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A two-sided 95% CI was calculated for the observed differences in the clinical success rate based on the Investigator's assessment of clinical response at the PTE Visit using the method of Miettinen and Nurminen without stratification. Noninferiority was concluded if the lower limit of the 95% CI was greater than -10% and the conditions of the hierarchical testing procedure were met.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.3
Confidence Interval (2-Sided) 95%
-4.8 to 5.3
Estimation Comments Risk difference corresponds to the tedizolid clinical success rate minus the linezolid clinical success rate.
5.Secondary Outcome
Title Investigator's Assessment of Clinical Success of the Post Therapy Evaluation Visit in Clinically Evaluable-Post Treatment Evaluation Analysis Set.
Hide Description Clinical success defined as resolution/near resolution of disease specific signs and symptoms, absence/near resolution of baseline systemic signs of infection, no new signs, symptoms or complications attributable to the ABSSSI and no further antibiotic therapy required for treatment of primary ABSSSI lesion.
Time Frame Post-Treatment Evaluation (7-14 days after the End of Therapy)
Hide Outcome Measure Data
Hide Analysis Population Description
All randomized participants receiving minimal study therapy, completed EOT and PTE Investigator's assessments, no concomitant systemic antibiotic therapy through PTE, and no confounding events or factors.
Arm/Group Title Tedizolid Phosphate Linezolid
Hide Arm/Group Description:
IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.
IV to oral linezolid 600 mg twice daily for 10 days.
Overall Number of Participants Analyzed 290 280
Measure Type: Number
Unit of Measure: participants
268 269
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tedizolid Phosphate, Linezolid
Comments [Not Specified]
Type of Statistical Test Non-Inferiority or Equivalence
Comments A two-sided 95% CI was calculated for the observed differences in the clinical success rate based on the Investigator's assessment of clinical response at the PTE Visit using the method of Miettinen and Nurminen without stratification. Noninferiority was concluded if the lower limit of the 95% CI was greater than -10% and the conditions of the hierarchical testing procedure were met.
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value -3.7
Confidence Interval (2-Sided) 95%
-7.7 to 0.2
Estimation Comments Risk difference corresponds to the tedizolid clinical success rate minus the linezolid clinical success rate.
6.Secondary Outcome
Title Investigator's Assessment of Clinical Response at the 48-72 Hour Visit
Hide Description Clinical improvement defined as improvement in overall clinical status.
Time Frame 48-72 Hours
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat analysis set includes data from all randomized participants.
Arm/Group Title Tedizolid Phosphate Linezolid
Hide Arm/Group Description:
IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.
IV to oral linezolid 600 mg twice daily for 10 days.
Overall Number of Participants Analyzed 332 334
Measure Type: Number
Unit of Measure: participants
304 302
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tedizolid Phosphate, Linezolid
Comments A two-sided 95% CI was calculated for the observed differences in the clinical response rate based on the Investigator's assessment of clinical response at the 48-72 Hour Visit using the method of Miettinen and Nurminen without stratification.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 1.2
Confidence Interval (2-Sided) 95%
-3.3 to 5.6
Estimation Comments Risk difference corresponds to the tedizolid clinical response rate minus the linezolid clinical response rate.
7.Secondary Outcome
Title Investigator's Assessment of Clinical Response at the Day-7 Visit
Hide Description Clinical improvement defined as improvement in overall clinical status.
Time Frame Day 7
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat analysis set includes data from all randomized participants.
Arm/Group Title Tedizolid Phosphate Linezolid
Hide Arm/Group Description:
IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.
IV to oral linezolid 600 mg twice daily for 10 days.
Overall Number of Participants Analyzed 332 334
Measure Type: Number
Unit of Measure: participants
309 308
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Tedizolid Phosphate, Linezolid
Comments A two-sided 95% CI was calculated for the observed differences in the clinical response rate based on the Investigator's assessment of clinical response at the Day 7 Visit using the method of Miettinen and Nurminen without stratification.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Risk Difference (RD)
Estimated Value 0.9
Confidence Interval (2-Sided) 95%
-3.2 to 4.9
Estimation Comments Risk difference corresponds to the tedizolid clinical response rate minus the linezolid clinical response rate.
8.Secondary Outcome
Title Change From Baseline in Patient-reported Pain, by Study Visit
Hide Description 0=no pain, 10=worst pain Only 1 visit per participant for Day 4-6, only 1 visit for Day 7-9, and only 1 visit for Day 10-13.
Time Frame Multiple
Hide Outcome Measure Data
Hide Analysis Population Description
The Intent to Treat analysis set includes data from all randomized participants.
Arm/Group Title Tedizolid Phosphate Linezolid
Hide Arm/Group Description:
IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo.
IV to oral linezolid 600 mg twice daily for 10 days.
Overall Number of Participants Analyzed 332 334
Mean (Standard Deviation)
Unit of Measure: units on a scale
Day 2 -1.7  (2.05) -2.1  (2.29)
Day 4-6 -3.1  (2.67) -3.3  (2.56)
Day 7-9 -4.9  (2.89) -4.9  (2.96)
Day 10-13 -5.4  (2.80) -5.6  (2.84)
Time Frame Collected from signing of the ICF through the late follow-up visit (up to 38 days).
Adverse Event Reporting Description Numbers for at risk include all treated participants.
 
Arm/Group Title Tedizolid Phosphate Linezolid
Hide Arm/Group Description IV to oral tedizolid phosphate 200 mg once daily for 6 days followed by 4 days of placebo. IV to oral linezolid 600 mg twice daily for 10 days.
All-Cause Mortality
Tedizolid Phosphate Linezolid
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Tedizolid Phosphate Linezolid
Affected / at Risk (%) Affected / at Risk (%)
Total   7/331 (2.11%)   9/327 (2.75%) 
Cardiac disorders     
Acute coronary syndrome  1  0/331 (0.00%)  1/327 (0.31%) 
Acute myocardial infarction  1  0/331 (0.00%)  1/327 (0.31%) 
Myocardial infarction  1  1/331 (0.30%)  0/327 (0.00%) 
Immune system disorders     
Anaphylactic reaction  1  0/331 (0.00%)  1/327 (0.31%) 
Infections and infestations     
Cellutitis  1  0/331 (0.00%)  2/327 (0.61%) 
Escherichia urinary tract infection  1  1/331 (0.30%)  0/327 (0.00%) 
Meningitis tuberculous  1  0/331 (0.00%)  1/327 (0.31%) 
Pneumonia  1  1/331 (0.30%)  0/327 (0.00%) 
Septic shock  1  1/331 (0.30%)  0/327 (0.00%) 
Staphyloccal bacteraemia  1  1/331 (0.30%)  0/327 (0.00%) 
Urinary tract infection bacterial  1  0/331 (0.00%)  1/327 (0.31%) 
Investigations     
Blood glucose increased  1  0/331 (0.00%)  1/327 (0.31%) 
Metabolism and nutrition disorders     
Diabetes mellitus  1  1/331 (0.30%)  0/327 (0.00%) 
Renal and urinary disorders     
Nephrolithiasis  1  1/331 (0.30%)  0/327 (0.00%) 
Vascular disorders     
Hypertension  1  1/331 (0.30%)  0/327 (0.00%) 
Thrombophlebitis superficial  1  0/331 (0.00%)  1/327 (0.31%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.1)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Tedizolid Phosphate Linezolid
Affected / at Risk (%) Affected / at Risk (%)
Total   84/331 (25.38%)   90/327 (27.52%) 
Gastrointestinal disorders     
Diarrhoea  1  11/331 (3.32%)  17/327 (5.20%) 
Nausea  1  26/331 (7.85%)  36/327 (11.01%) 
Vomiting  1  10/331 (3.02%)  17/327 (5.20%) 
General disorders     
Fatigue  1  8/331 (2.42%)  7/327 (2.14%) 
Infections and infestations     
Abscess  1  14/331 (4.23%)  10/327 (3.06%) 
Cellulitis  1  9/331 (2.72%)  6/327 (1.83%) 
Vulvovaginal mycotic infection  1  2/331 (0.60%)  7/327 (2.14%) 
Nervous system disorders     
Dizziness  1  4/331 (1.21%)  7/327 (2.14%) 
Headache  1  20/331 (6.04%)  22/327 (6.73%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (13.1)
Analyses for this study were conducted using 2 statistical plans, 1 for the US FDA and 1 for the EMA, to address differing guidance on the development of antibacterials. These differences are reflected in the EudraCT and clinicaltrials.gov records.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Sponsor intends to pursue publication of the results of the study in cooperation with a lead Investigator, subject to the terms and conditions of the clinical study agreement between the Sponsor and Investigators. Sponsor approval in writing is required for publication of any data subsets. Final authorship will be determined in accordance with the International Committee of Medical Journal Editors definition of authorship.
Results Point of Contact
Name/Title: Philippe Prokocimer, MD
Organization: Cubist Pharmaceuticals, Inc.
Phone: 858-452-0370 ext 241
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Trius Therapeutics LLC
ClinicalTrials.gov Identifier: NCT01421511     History of Changes
Other Study ID Numbers: 1986-010
TR701-113 ( Other Identifier: TriusRX Unique ID )
First Submitted: August 19, 2011
First Posted: August 22, 2011
Results First Submitted: July 15, 2014
Results First Posted: September 8, 2014
Last Update Posted: August 29, 2018