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

Study Overview
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Brief Summary
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This is a randomized, double-blind, double-dummy, multicenter, global Phase 3 study of IV to oral TR-701 FA 200 mg once daily for 6 days versus IV to oral Zyvox® (linezolid) 600 mg every 12 hours for 10 days for the treatment of ABSSSI in adults. Patients are to start treatment with at least 2 IV doses and may receive IV therapy for the entire treatment duration. Approximately 100 to 140 sites globally will participate in this study. Patients with an ABSSSI caused by suspected or documented gram positive pathogen(s) at baseline will be randomized 1:1 to study treatment.

Detailed Description
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The primary objective is to determine the noninferiority (NI) in the early clinical response rate of intravenous (IV) to oral 6 day TR-701 free acid (FA) compared with that of IV to oral 10-day linezolid treatment at 48-72 hours after the first infusion of study drug in the intent-to-treat (ITT) analysis set in patients with acute bacterial skin and skin structure infections (ABSSSI).

Official Title
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A Phase 3 Randomized, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of IV to Oral 6-Day TR-701 Free Acid and IV to Oral 10-Day Linezolid for the Treatment of ABSSSI

Conditions
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Skin and Subcutaneous Tissue Bacterial Infections

Intervention / Treatment
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* Drug: TR-701 FA
* Drug: Linezolid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients requiring IV antibiotic therapy and with systemic signs of infection diagnosed with ABSSSI. Diagnosed with Cellulitis/ erysipelas, major cutaneous abscess, or wound infections Exclusion Criteria: Uncomplicated skin infections Severe sepsis or septic shock ABSSSI solely due to gram-negative pathogens

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TR-701 FA<br>• TR-701 FA IV followed by TR-701 FA tablets | Drug: TR-701 FA<br>* TR-701 FA 200 mg once daily in 250 mL sterile saline for injection as a 60 minute IV infusion TR-701 FA Tablets, 200 mg, orally once daily<br>|
| Active Comparator: Linezolid<br>• Linezolid IV followed by Linezolid Tablets | Drug: Linezolid<br>* Linezolid 600 mg IV Injection twice daily in 300 mL sterile saline for injection as a 60 minute IV infusion Linezolid Tablets, 600 mg, orally every 12 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Early Clinical Response Rate | Responder: No increase in lesion surface area from baseline. | 48-72 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Response at the End of Therapy Visit | Responder: No increase in lesion surface area from baseline. | Day 11 | 
| Clinical Response at the End of Therapy Visit in the Clinically Evaluable at End of Therapy Analysis Set | Responder: No increase in lesion surface area from baseline. | End of Therapy Day 11 | 
| Investigator's Assessment of Clinical Success at the Post Treatment Evaluation Visit | 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. | Post-Treatment Evaluation (7-14 days after the End of Therapy) | 
| Investigator's Assessment of Clinical Success of the Post Therapy Evaluation Visit in Clinically Evaluable-Post Treatment Evaluation Analysis Set. | 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. | Post-Treatment Evaluation (7-14 days after the End of Therapy) | 
| Investigator's Assessment of Clinical Response at the 48-72 Hour Visit | Clinical improvement defined as improvement in overall clinical status. | 48-72 Hours | 
| Investigator's Assessment of Clinical Response at the Day-7 Visit | Clinical improvement defined as improvement in overall clinical status. | Day 7 | 
| Change From Baseline in Patient-reported Pain, by Study Visit | 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. | Multiple | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ABSSSI, Tedizolid Phosphate, TR-701, Acute Bacterial Skin and Skin Structure Infections