Comparative Study of Levonadifloxacin (IV and Oral) With Linezolid (IV and Oral) in Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Study Overview
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Brief Summary
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This is a phase III, multi-center, randomized, active-comparator, study in subjects with ABSSSI. The study has two subgroups for assessment of efficacy and safety - oral subgroup 1 and IV subgroup 2. Each subgroup will comprise of two treatment arms.

Detailed Description
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Subjects willing to participate in the study and fulfilling all eligibility criteria will receive either oral therapy (subgroup 1) or IV therapy (subgroup 2). The investigator can initiate treatment with either oral or IV therapy based on clinical judgement i.e subjects who require IV therapy (like subjects with severe ABSSSI or where oral administration is not feasible).

Official Title
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A Phase III, Multi-centre, Randomized Study to Compare the Efficacy and Safety of Levonadifloxacin (IV and Oral) With Linezolid (IV and Oral) in Acute Bacterial Skin and Skin Structure Infections (ABSSSI)

Conditions
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Acute Bacterial Skin and Skin Structure Infections

Intervention / Treatment
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* Drug: Oral Levonadifloxacin/Linezolid Tablet
* Drug: Intravenous Levonadifloxacin/Linezolid Infusion


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must be willing to participate in the study and provide a written informed consent Subjects with ABSSSI characterized by any of the following infection types: Cellulitis/erysipelas: diffuse skin infection characterized by spreading areas of redness, edema, and/or induration Wound infection: An infection characterized by purulent drainage from a wound with surrounding redness, edema, and/or induration Major cutaneous abscess: An infection characterized by a collection of pus within the dermis or deeper that is accompanied by redness, edema, and/or induration Subjects with lesion size area of at-least 75 cm2. Lesion size will be measured by the area of redness, edema, or induration Subjects with suspected and/or documented evidence of Gram-positive infection Exclusion Criteria: 1. ABSSSI meeting any of the following criteria: Severely impaired arterial blood supply (such that the likelihood of amputation of the infected anatomical site is likely) ABSSSI expected to require more than 10 days of antimicrobial therapy as per the discretion of the Investigator Subject with suspected or confirmed osteomyelitis or septic arthritis or gangrene ABSSSI requiring surgical intervention (except surgical incision and drainage for abscess) 2. Subjects who have received prior antibiotic therapy within past 24 hours for the treatment of current episode of ABSSSI. Following are the exceptions to this criteria: Subjects who received a single dose of a short-acting antibacterial drug within 24 hours of enrolment Subjects with evidence of clinical progression of ABSSSI while on antibacterial drug therapy after at-least 48 hours Subjects who received an antibacterial drug for surgical prophylaxis and subsequently develop ABSSSI 3. Subjects with current history or diagnosis of HIV, positive test result for hepatitis B surface antigen (HBsAg) or Hepatitis C virus (HCV) 4. Subjects with any clinically significant abnormalities in pulmonary, gastrointestinal, endocrine, hepatic or renal systems

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: levonadifloxacin<br>oral levonadifloxacin (1000 mg BID) or IV levonadifloxacin (800 mg BID) | Drug: Oral Levonadifloxacin/Linezolid Tablet<br>* oral levonadifloxacin (1000 mg BID) or oral linezolid (600 mg BID)<br>Drug: Intravenous Levonadifloxacin/Linezolid Infusion<br>* IV levonadifloxacin (800 mg BID) or IV linezolid (600 mg BID)<br>|
| Active Comparator: linezolid<br>oral linezolid (600 mg BID) or IV linezolid (600 mg BID) | Drug: Oral Levonadifloxacin/Linezolid Tablet<br>* oral levonadifloxacin (1000 mg BID) or oral linezolid (600 mg BID)<br>Drug: Intravenous Levonadifloxacin/Linezolid Infusion<br>* IV levonadifloxacin (800 mg BID) or IV linezolid (600 mg BID)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The non-inferiority of oral levonadifloxacin with oral linezolid in ABSSSI by measuring the Overall Clinical Response at Test of Cure (TOC) visit in modified Intentto-treat (mITT) population in oral treatment subgroups |  | 0-14 days | 
| To establish the non-inferiority of IV levonadifloxacin with IV linezolid in ABSSSI measuring the Overall Clinical Response at Test of Cure (TOC) visit in modified Intentto-treat (mITT) population in IV treatment subgroups |  | 0-14 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety of oral and IV levonadifloxacin based on adverse events reported, vital signs and physical examination findings, clinical laboratory evaluation, and ECG collected during the study. |  | 0-14 days |