Efficacy and Safety of Intravenous to Oral 6-Day Tedizolid Phosphate vs. Intravenous to Oral 10-Day Linezolid in Patients With Acute Bacterial Skin and Skin Structure Infection (ABSSSI)

Study Overview
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Brief Summary
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This study is aimed to evaluate the efficacy and safety between Tedizolid 200mg daily (intra venous) I.V. to oral for 6-day treatment compared with that of Linezolid 600mg twice daily I.V. to oral for 10-day treatment Acute Bacterial Skin and skin structure infection (ABSSSI).This is a double-blind, randomized, active control, 7-10days treatment for all subjects.

Detailed Description
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Number of participants with adverse evnets as a measure of safety and tolerability will be covered in Adverse Events section. ABSSSI Efficacy Safety Tedizolid Phosphate Linezolid

Official Title
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A Phase 3 Randomized, Double-Blind, Multicenter Study Comparing the Efficacy and Safety of Intravenous to Oral 6-Day Tedizolid Phosphate and Intravenous to Oral 10-Day Linezolid for the Treatment of Acute Bacterial Skin and Skin Structure Infections

Conditions
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Bacterial Infections

Intervention / Treatment
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* Drug: Tedizolid (BAY119-2631)
* Drug: Placebo Tedizolid (BAY119-2631)
* Drug: Linezolid
* Drug: Placebo Linezolid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females >/=18 years old Adequate venous access for a minimum of 2 I.V. doses of study drug Acute Bacterial Skin and skin structure infection (ABSSSI) meeting at least 1 of the clinical syndrome definitions listed below and requiring I.V. antibiotic therapy. Local symptoms must have started within 7 days before the Screening Visit Cellulitis/erysipelas Major cutaneous abscess Wound Infection Suspected or documented gram-positive infection from baseline Gram stain or culture. Exclusion Criteria: Uncomplicated skin and skin structure infections such as furuncles, minor abscesses Infections associated with, or in close proximity to, a prosthetic device Severe sepsis or septic shock Known bacteremia at time of screening ABSSSI due to or associated with any of the following: Suspected or documented gram-negative pathogens in patients with cellulitis/erysipelas or major cutaneous abscess that require an antibiotic with specific gram-negative coverage. Patients with wound infections where gram-negative adjunctive therapy is warranted may be enrolled if they meet the other eligibility criteria Diabetic foot infections, gangrene, or perianal abscess Concomitant infection at another site not including a secondary ABSSSI lesion (eg, septic arthritis, endocarditis, osteomyelitis) Infected burns Decubitus or chronic skin ulcer, or ischemic ulcer due to peripheral vascular disease (arterial or venous) Any evolving necrotizing process (ie, necrotizing fasciitis) Use of antibiotics as follows: Systemic antibiotic with gram-positive cocci activity for the treatment of any infection within 24 hours before the first infusion of study drug Patients who failed prior therapy for the primary infection site are also excluded from enrollment Topical antibiotic on the primary lesion within 24 hours before the first infusion of study drug except for antibiotic/antiseptic-coated dressing applied to the clean postsurgical wound Administration of Linezolid within 30 days before the first infusion of the study drug Recent history of opportunistic infections where the underlying cause of these infections is still active (eg, leukemia, transplant, acquired immunodeficiency syndrome [AIDS]) Previous exposure to Tedizolid Phosphate treatment

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: Tedizolid Phosphate (Sivextro, BAY119-2631)<br>Participants received 200 mg Tedizolid Phosphate once daily intravenous (I.V.) infusion to oral for 6 days, followed by 4 days of placebo. | Drug: Tedizolid (BAY119-2631)<br>* 50 % of the participants will be randomized to this arm and will receive 200 mg Tedizolid once daily i.v to oral from 1-6 days<br>Drug: Placebo Tedizolid (BAY119-2631)<br>* 50 % of the participants will be randomized to this arm and will receive 200 mg Placebo Tedizolid once daily i.v to oral from 7-10 days<br>Drug: Placebo Linezolid<br>* 50 % of the participants will be randomized to this arm and will receive 600 mg Placebo Linezolid twice daily i.v. to oral from 1-10 days<br>|
| Active Comparator: Linezolid<br>Participants received 600 mg Linezolid twice daily I.V. infusion to oral for 10 days. | Drug: Placebo Tedizolid (BAY119-2631)<br>* 50 % of the participants will be randomized to this arm and will receive 200 mg Placebo Tedizolid once daily i.v to oral from 7-10 days<br>Drug: Linezolid<br>* 50 % of the participants will be randomized to this arm and will receive 600 mg Linezolid twice daily i.v. to oral from 1-10 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Early Clinical Response at 48-72 Hours After the First Infusion of Study Drug in the ITT Analysis Set. | Early clinical response is defined as responder if there is >=20% reduction in the area of erythema, edema, and/or induration (length × width) of the primary acute bacterial skin and skin structure infections (ABSSSI) lesion, compared with baseline at the 48-72 Hour visit. | Baseline and 48-72 hours visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Programmatically Defined Clinical Response at End of Therapy (EOT) Visit in the ITT Analysis Set | Clinical Failure: Presence of fever; No lesion size decrease from baseline; Clinician assessment of tenderness worse than mild; Persistent same or great intensity purulent drainage of wound infection; Confounding use of systemic concomitant antibiotic; TEAE lead to study drug discontinuation; Require additional antibiotic treatment for primary lesion; Unplanned major surgical intervention. Clinical Success: Afebrile or fever due to other cause; Lesion size decrease from baseline; Clinician assessment of mild/absent tenderness; None/lesser intensity purulent drainage of wound infection; None confounding use of systemic concomitant antibiotic; None TEAE leading to study drug discontinuation; No additional antibiotic therapy for primary lesion; No unplanned major surgical intervention; No osteomyelitis after baseline; For wound/abscess: no incision/drainage of the ABSSSI site after Day1 unless planned. For cellulitis/ersipelas: no incision/drainage of the ABSSSI site after 48-72 H Visit. | Baseline and EOT visit (Day 11) | 
| Programmatically Defined Clinical Response at End of Therapy (EOT) Visit in the Clinically Evaluable at EOT (CE-EOT) Analysis Set | Clinical response will be defined as percentage of participants with clinical success, clinical failure or indeterminate. | Baseline and EOT visit (Day 11) | 
| Overall Investigator's Assessment of Clinical Success at Post Therapy Evaluation (PTE) Visit (7-14 Days After EOT Visit) in the ITT Analysis Set | The Investigator made an assessment of clinical response at the PTE Visit (7-14 days after the EOT Visit +2 days). Participants assessed as a clinical failure at the EOT Visit are considered a clinical failure at the PTE Visit. Percentage of participants with clinical success, clinical failure or indeterminate were reported. | Baseline and post-therapy evaluation visit (7-14 days after Day 11) | 
| Overall Investigator's Assessment of Clinical Success at Post Therapy Evaluation (PTE) Visit (7-14 Days After EOT Visit) in the Clinically Evaluable at Post Therapy Evaluation (CE-PTE) Analysis Set | The Investigator made an assessment of clinical response at the PTE Visit (7-14 days after the EOT Visit +2 days). Participants assessed as a clinical failure at the EOT Visit are considered a clinical failure at the PTE Visit. Percentage of participants with clinical success, clinical failure or indeterminate were reported. | Baseline and post-therapy evaluation visit (7-14 days after Day 11) | 
| Investigator's Assessment of Clinical Response at 48-72 Hours | The Investigator made an assessment of clinical response at the 48-72 Hour Visit based on following definition: Improving (Improvement in overall clinical status of ABSSSI compatible with continuation of study drug therapy); Stable (Signs and symptoms stable, no apparent change in overall clinical status but compatible with continuation of study drug therapy); Other. | Baseline and at 48-72 hours | 
| Investigator's Assessment of Clinical Response at Day 7 Visit | The Investigator made an assessment of clinical response at Day 7 Visit based on following definition: Improving (Improvement in overall clinical status of ABSSSI compatible with continuation of study drug therapy); Other. | Baseline and Day 7 visit | 
| Value of the Visual Analog Scale (VAS) Pain Scores at Each Time Point | The patient-reported level of pain were assessed by the visual analog scale (VAS) pain score. VAS pain score ranged from 0 mm (no pain) to 100 mm (worst pain ever). It used a 100 mm VAS to instruct the patient to indicate the point along the line that represents the pain they are feeling. Once the patient indicates how much pain they are feeling, measure the distance from no pain and enter the value. | Up to EOT visit (Day 11) | 
| Change From Baseline in the Visual Analog Scale (VAS) Pain Scores at Each Time Point | The patient-reported level of pain were assessed by the visual analog scale (VAS) pain score. VAS pain score ranged from 0 mm (no pain) to 100 mm (worst pain ever). It used a 100 mm VAS to instruct the patient to indicate the point along the line that represents the pain they are feeling. Once the patient indicates how much pain they are feeling, measure the distance from no pain and enter the value. | Up to EOT visit (Day 11) | 
| Value of the Faces Rating Scale (FRS) Pain Scores at Each Time Point | The patient-reported level of pain were assessed by the faces rating scale (FRS) pain score. Ask the patient to rate their pain from 0 to 10 with 0 being no pain at all and 10 being the worst pain then enter the numerical value. | Up to EOT visit (Day 11) | 
| Change From Baseline in the Faces Rating Scale (FRS) Pain Scores at Each Time Point | The patient-reported level of pain were assessed by the faces rating scale (FRS) pain score. The patient-reported level of pain were assessed by the faces rating scale (FRS) pain score. Ask the patient to rate their pain from 0 to 10 with 0 being no pain at all and 10 being the worst pain then enter the numerical value. | Up to EOT visit (Day 11) |