Safety and Efficacy Study of Contezolid Acefosamil and Contezolid Compared to Linezolid Administered Intravenously and Orally to Adults With Moderate or Severe Diabetic Foot Infections (DFI)

Study Overview
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Brief Summary
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This is a Phase 3, multicenter, randomized, double-blind, safety and efficacy study of contezolid acefosamil (IV)/contezolid (PO) compared with linezolid (IV and PO) administered for a total of 14 to 28 days in adult subjects with moderate or severe DFI.

Detailed Description
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Approximately 865 subjects (519 contezolid acefosamil/contezolid: 346 linezolid) will be enrolled with moderate or severe DFI that are confirmed or suspected to be due to a Gram-positive bacterial pathogen (MITT analysis set).

Official Title
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A Phase 3, Multicenter, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of Contezolid Acefosamil and Contezolid Compared to Linezolid Administered Intravenously and Orally to Adults With Moderate or Severe Diabetic Foot Infections (DFI)

Conditions
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Diabetic Foot Infection

Intervention / Treatment
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* Drug: contezolid acefosamil (IV)/contezolid (PO)
* Drug: Linezolid (IV and PO)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have diabetes mellitus (type 1 or 2) per the American Diabetes Association criteria Have a foot infection that started at or below the malleolus and does not extend above the knee Foot infection that meets the IWGDF DFI criteria for classification 3 (moderate infection) or 4 (severe infection) Foot infection had acute onset or worsening of signs and symptoms within the past 14 days Exclusion Criteria: Previous DFI known or suspected to be caused by Gram-positive pathogens that are resistant to oxazolidinone antibiotics DFI with presumptive evidence or suspicion of osteomyelitis Necrotizing fasciitis, crepitant cellulitis, wet gangrene, gas gangrene, ecthyma gangrenosum, septic arthritis, or severely impaired arterial supply to any portion of the affected foot which may need revascularization before the end of the study Evidence of significant hepatic, renal, hematologic, or immunologic disease Females who are pregnant or breastfeeding Prior receipt of any formulation of contezolid acefosamil or contezolid Inability to cooperate fully with the requirements of the study protocol, including the schedule of events, or likely to be noncompliant with any study requirements, or the Investigator determines that the subject should not participate in the study

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: contezolid acefosamil/contezolid<br> | Drug: contezolid acefosamil (IV)/contezolid (PO)<br>* Contezolid acefosamil (IV)/contezolid (PO) administered for a total of 14 to 28 days (28 to 56 doses)<br>|
| Active Comparator: linezolid<br> | Drug: Linezolid (IV and PO)<br>* Linezolid (IV and PO) administered for a total of 14 to 28 days (28 to 56 doses)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical laboratory assessment - complete blood count | Will be evaluated under safety of contezolid acefosamil (IV)/contezolid (PO) compared with linezolid (IV and PO) | 28-35 days after End-of-Therapy (EOT) | 
| Vital signs - heart rate | Will be evaluated under safety of contezolid acefosamil (IV)/contezolid (PO) compared with linezolid (IV and PO) | 28-35 days after End-of-Therapy (EOT) | 
| Adverse events - symptoms reported by subjects | Evaluate safety of contezolid acefosamil (IV)/contezolid (PO) compared with linezolid (IV and PO) | 28-35 days after End-of-Therapy (EOT) | 
| Clinical response calculated with percentage of subjects with resolution of DFI signs and symptoms and requiring no further therapy as assessed by Investigators | The primary objective is to evaluate the Investigator's assessment of clinical response at the D35 visit in subjects receiving contezolid acefosamil/contezolid compared to subjects receiving linezolid in the MITT analysis | Day 35 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response calculated with percentage of subjects with resolution of DFI signs and symptoms and requiring no further therapy as assessed by Investigators | Evaluate the Investigator's assessment of clinical response at EOT visit in the MITT analysis set | 14-28 days | 
| Clinical response calculated with percentage of subjects with resolution of DFI signs and symptoms and requiring no further therapy as assessed by Investigators | Evaluate the Investigator's assessment of clinical response at Day 10 (D10) and Late Follow-Up visits (LFU; 28-35 days after EOT) in the MITT analysis set | Day 10, 28-35 days after EOT |