Conditions: Skin Diseases, Bacterial Gram-Positive Bacterial Infections
Keywords: ABSSSI Acute bacterial skin and skin structure infection
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 196
Healthy volunteers: no

Brief summary:
The purpose of this study is to determine whether contezolid acefosamil is as safe and effective as linezolid in the treatment of adult patients with acute bacterial skin and skin structure infections

Detailed description:

Arms:
arm 1: contezolid acefosamil 1500 mg IV x 1 dose, followed by 1000 mg IV q12h for at least 3 total IV doses, followed by 1300 mg PO q12h for 10 to 14 days arm 2: linezolid 600 mg IV q12h for at least 3 total IV doses, followed by 600 mg PO q12h for 10 to 14 days

Interventions: intervention 1: contezolid acefosamil intervention 2: linezolid 600 mg
Intervention descriptions: intervention 1: IV and oral contezolid acefosamil given twice a day for 10 to 14 days intervention 2: IV and oral linezolid given twice a day for 10 to 14 days

Protocol document:
Prot_000.pdf: 
Clinical Protocol MRX4-201 
 
 
MicuRx Pharmaceuticals, Inc. 
Page 1 of 105 
CONFIDENTIAL 
Final, 19 Oct 2018 
CLINICAL PROTOCOL 
Protocol No. 
MRX4-201 
Title: 
A Phase 2, Multicenter, Randomized, Double-Blind Study to Evaluate 
the Safety and Efficacy of Contezolid Acefosamil Compared to 
Linezolid Administered Intravenously and Orally to Adults with 
Acute Bacterial Skin and Skin Structure Infection 
Study Phase: 
2 
Product Name: 
Contezolid acefosamil 
Indication: 
Treatment of patients with acute bacterial skin and skin structure 
infection (ABSSSI) 
Investigators:  
Multicenter Study 
Sponsor: 
MicuRx Pharmaceuticals, Inc. 
3916 Trust Way Hayward, CA 94545 
Phone: 1-510-782-2021 
Sponsor Contact: 
Edward Fang, MD 
SVP, Clinical Development 
MicuRx Pharmaceuticals, Inc 
Phone: 415-710-5481 
Email: efang@micurx.com 
Current Version 
Amendment 2 
Date 
Final, 19 October 2018 
Prior Versions: 
Original: 16 August 2018 
Amendment 1: 27 September 2018 
 
 
CONFIDENTIAL 
This document contains proprietary and confidential information of MicuRx Pharmaceuticals, Inc. Acceptance of 
this document constitutes agreement by the recipient that no previously unpublished information contained herein 
will be published or disclosed without the prior written approval of MicuRx Pharmaceuticals, Inc. with the 
exception that this document may be disclosed to study personnel under your supervision who need to know the 
contents for conducting the study and to appropriate Institutional Review Boards (IRBs) under the condition that 
the personnel have agreed to keep this information confidential. The foregoing shall not apply to disclosure required 
by governmental regulations or laws; however, MicuRx Pharmaceuticals, Inc. shall be promptly notified of any 
such disclosure. 
 
 


Clinical Protocol MRX4-201 
 
 
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PROTOCOL APPROVAL PAGE 
Protocol No. 
MRX4-201 
Title: 
A Phase 2, Multicenter, Randomized, Double-Blind Study to 
Evaluate the Safety and Efficacy of Contezolid Acefosamil 
Compared to Linezolid Administered Intravenously and Orally to 
Adult Subjects With Acute Bacterial Skin and Skin Structure 
Infection 
Version 
Amendment 2 
 
Date: 
Final, 19 October 2018 
 
 
Personnel Approving Protocol 
Signature 
Edward Fang, MD 
SVP, Clinical Development 
MicuRx Pharmaceuticals, Inc. 
 
Barry Hafkin, MD 
EVP, Chief Medical Officer 
MicuRx Pharmaceuticals, Inc. 
 
 


Clinical Protocol MRX4-201 
 
 
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Page 3 of 105 
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INVESTIGATOR AGREEMENT PAGE 
Protocol No. 
MRX4-201 
Title: 
A Phase 2, Multicenter, Randomized, Double-Blind Study to 
Evaluate the Safety and Efficacy of Contezolid Acefosamil 
Compared to Linezolid Administered Intravenously and Orally to 
Adult Subjects With Acute Bacterial Skin and Skin Structure 
Infection 
Version: 
Amendment 2 
Date: 
Final, 19 October 2018 
I have read and I understand protocol MRX4-201 and the Investigator’s Brochure. I agree to the 
following: 
1. 
To conduct the clinical study in compliance with Good Clinical Practice (GCP) and with 
all applicable regulatory requirement(s), according to the latest version of the protocol 
agreed to by the Sponsor and given approval/favorable opinion by the IRB 
2. 
To comply with procedures for data recording/reporting 
3. 
To permit monitoring, auditing, and inspection by the Sponsor, its designated 
representatives, and regulatory authorities 
4. 
To retain the essential documents in the Investigator/institution files until the Sponsor 
informs me or the institution that these documents are no longer needed 
5. 
To provide copies of the protocol, any subsequent protocol amendments, and all 
information provided by the Sponsor to the study personnel under my supervision. I will 
discuss these materials with them in the detail required to ensure that they are fully 
informed about the investigational drug and the study protocol as appropriate for their 
study-related responsibilities. 
 
 
 
Investigator Signature 
 
Date 
 
 
 


Clinical Protocol MRX4-201 
 
 
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Page 4 of 105 
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TABLE OF CONTENTS 
CLINICAL PROTOCOL ..................................................................................................1 
PROTOCOL APPROVAL PAGE ...................................................................................2 
INVESTIGATOR AGREEMENT PAGE .......................................................................3 
TABLE OF CONTENTS ..................................................................................................4 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................8 
List of Abbreviations .........................................................................................................8 
Definitions of Terms ........................................................................................................10 
1 
STUDY SYNOPSIS ..................................................................................................11 
2 
INTRODUCTION ....................................................................................................25 
2.1 
Background ..........................................................................................................25 
2.2 
Description of Contezolid and Contezolid Acefosamil .....................................26 
2.3 
Summary of Relevant Nonclinical Experience ..................................................27 
2.3.1 
Pharmacology, Microbiology, Toxicology, and Safety ...............................27 
2.4 
Summary of Relevant Clinical Experience ........................................................28 
2.5 
Safety and Tolerability of Contezolid Acefosamil.............................................29 
2.6 
Pharmacokinetics of Contezolid Acefosamil .....................................................30 
2.7 
Summary and Rationale for Study .....................................................................31 
2.8 
Rationale for Dose Regimens ..............................................................................33 
3 
STUDY DESIGN ......................................................................................................34 
3.1 
Study Objectives...................................................................................................34 
3.2 
Study Design Details ............................................................................................35 
3.3 
Number of Subjects..............................................................................................37 
3.4 
Randomization & Blinding .................................................................................37 
3.5 
Study Treatment ..................................................................................................38 
3.6 
Duration ................................................................................................................39 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS .........................................40 
4.1 
Inclusion Criteria .................................................................................................40 
4.2 
Exclusion Criteria ................................................................................................41 
4.3 
Subject Withdrawal from the Study ..................................................................44 
4.4 
Replacement of Subjects......................................................................................45 
4.5 
Study Termination by Sponsor and Termination Criteria ..............................45 
4.6 
Follow-up of Subjects Prematurely Discontinued from Study Drug or 
Withdrawn from Study .......................................................................................45 
5 
TREATMENT OF SUBJECTS ...............................................................................46 
5.1 
Study Drug ............................................................................................................46 
5.1.1 
Contezolid Acefosamil Study Drug ..............................................................46 
5.1.2 
Linezolid Study Drug .....................................................................................46 
5.1.3 
Adjunctive Therapy .......................................................................................47 
5.1.4 
Dose Adjustment ............................................................................................47 
5.1.5 
Study Drug Compliance ................................................................................47 
5.1.6 
Study Drug Storage........................................................................................48 
5.1.7 
Study Drug Accountability............................................................................49 
5.1.8 
Study Drug Handling and Disposal ..............................................................49 
5.2 
Prior & Concomitant Therapy ...........................................................................49 
6 
SUBJECT RESTRICTIONS ...................................................................................51 


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7 
STUDY PROCEDURES ..........................................................................................53 
7.1 
Screening/Baseline ...............................................................................................53 
7.2 
Day 1 ......................................................................................................................55 
7.3 
Day 2 ......................................................................................................................56 
7.4 
Early Assessment .................................................................................................56 
7.5 
Early Assessment to Day 6 ..................................................................................57 
7.6 
Day 7 ......................................................................................................................58 
7.7 
End of Therapy ....................................................................................................59 
7.8 
Post Therapy Evaluation .....................................................................................60 
7.9 
Late Follow-up .....................................................................................................61 
8 
ASSESSMENT OF THE ACUTE BACTERIAL SKIN AND SKIN 
STRUCTURE INFECTION ....................................................................................62 
8.1 
Clinical Assessments ............................................................................................62 
8.2 
Microbiological Assessments...............................................................................62 
8.3 
Digital Photography .............................................................................................64 
9 
ASSESSMENT OF EFFICACY ..............................................................................65 
9.1 
Clinical Response Definitions..............................................................................65 
9.1.1 
Early Clinical Response .................................................................................65 
9.1.2 
Investigator’s Assessment of Clinical Response ..........................................65 
9.2 
Microbiological Response Definitions ................................................................67 
9.2.1 
Per-Pathogen Microbiological Response .....................................................67 
9.2.2 
Per-Subject Microbiological Response ........................................................67 
9.2.3 
Emergent Infections .......................................................................................67 
10 ASSESSMENT OF SAFETY...................................................................................69 
10.1 
Adverse Events .....................................................................................................70 
10.1.1 
Definition ........................................................................................................70 
10.1.2 
Assessment of Severity ...................................................................................70 
10.1.3 
Relationship to Study Drug ...........................................................................71 
10.1.4 
Serious Adverse Events .................................................................................72 
10.1.5 
Treatment-emergent Adverse Event ............................................................74 
10.1.6 
Life-threatening Adverse Event....................................................................74 
10.1.7 
Unexpected Adverse Event............................................................................74 
10.2 
Reporting Laboratory and Electrocardiogram Abnormalities .......................75 
10.3 
Risks for Women of Childbearing Potential .....................................................75 
10.4 
Adverse Event Follow-up ....................................................................................76 
10.5 
Study Termination or Temporary Suspension..................................................76 
10.6 
Data Monitoring Committee ...............................................................................77 
11 ASSESSMENT OF PHARMACOKINETICS .......................................................78 
12 STATISTICAL METHODS ....................................................................................80 
12.1 
Determination of Study Sample Size ..................................................................80 
12.2 
Analysis Populations ............................................................................................80 
12.3 
Determination of Inclusion in Populations ........................................................82 
12.4 
Analysis of Study Populations and Subject Characteristics ............................83 
12.5 
Study Drug Exposure ..........................................................................................83 
12.6 
Efficacy Analyses .................................................................................................83 
12.6.1 
Primary Efficacy Evaluation ........................................................................84 


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12.6.2 
Secondary and Additional Efficacy Evaluations .........................................85 
12.7 
Safety Analyses .....................................................................................................87 
12.8 
Pharmacokinetic Analyses ..................................................................................87 
12.9 
Handling of Dropouts, Missing, Unused and Spurious Data ...........................87 
13 ADMINISTRATIVE CONSIDERATIONS ...........................................................88 
13.1 
Ethical Conduct of Study ....................................................................................88 
13.2 
Informed Consent ................................................................................................88 
13.3 
Institutional Review Board Approval ................................................................88 
13.4 
Investigator Requirements ..................................................................................88 
13.5 
Electronic Case Report Forms and Data Capture System ...............................89 
13.6 
Source Data & Document Maintenance ............................................................89 
13.7 
Study Monitoring Requirements ........................................................................90 
13.8 
Study Completion.................................................................................................90 
13.9 
Quality Control and Quality Assurance ............................................................90 
13.10 Retention of Records............................................................................................91 
13.11 Finance and Insurance ........................................................................................91 
13.12 Publication Policy.................................................................................................92 
14 REFERENCES .........................................................................................................93 
APPENDIX 1. 
ALLOWED PRIOR ANTIBIOTICS ...............................................96 
APPENDIX 2. 
AVOIDANCE OF HIGH-TYRAMINE FOODS AND DRINKS ..98 
APPENDIX 3. 
RESTRICTED MEDICATIONS .....................................................99 
APPENDIX 4. 
SAFETY LABORATORY TESTS .................................................100 
APPENDIX 5. 
INSTRUCTIONS FOR PRIMARY ABSSSI SITE 
MEASUREMENT ..................................................................................................101 
APPENDIX 6. 
LOCAL SIGNS AND SYMPTOMS OF ABSSSI .........................103 
APPENDIX 7. 
RECOMMENDED INSTRUCTIONS FOR PRIMARY ABSSSI 
SITE DIGITAL PHOTOGRAPHY ......................................................................104 
 
LIST OF TABLES 
Table 1: 
Schedule of Events ...................................................................................22 
Table 2: 
Clinical Response Definitions – Early Clinical Response .....................65 
Table 3: 
Clinical Response Definitions – Investigator’s Assessment .................66 
Table 4: 
Microbiological Outcome Categories .....................................................67 
Table 5: 
Emergent Infections .................................................................................68 
Table 6: 
Guidelines for Severity Assessments ......................................................71 
Table 7: 
Analysis Populations ................................................................................80 
Table 8: 
Summary of Primary and Secondary Efficacy Evaluations  by Analysis 
Population .................................................................................................84 
Table 9: 
Composite Assessment of Clinical Outcome ..........................................86 
Table 10: 
Allowed and Disallowed Prior Antibiotics in Study MRX4-201 .........96 
Table 11: 
Foods and Beverages to Avoida During Study Drug Administrationb 98 
 


Clinical Protocol MRX4-201 
 
 
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Page 7 of 105 
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LIST OF FIGURES 
Figure 1: 
Contezolid Acefosamil Metabolites ........................................................27 
Figure 2: 
Overview of Analysis Populations ..........................................................82 
Figure 3: 
Primary ABSSSI Site Measurement – Example .................................101 


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Page 8 of 105 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
List of Abbreviations 
Abbreviation 
Definition 
ABSSSI 
Acute bacterial skin and skin structure infection 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC0-t/0-12h/0-24h/0-∞ 
Area under the curve vs. time from time zero to last timepoint (e.g., 12 h, 24 h, infinity) 
BCS 
Biopharmaceutics classification system 
β-HCG 
Beta-human chorionic gonadotropin 
BID 
Twice daily 
CACO 
Composite assessment of clinical outcome 
CE 
Clinically evaluable  
CI 
Confidence interval 
Cmax 
Maximum concentration 
CNS 
Central nervous system 
CrCl 
Creatinine clearance 
CRO 
Clinical Research Organization 
CRP 
C-reactive protein 
CTCAE 
Common Terminology for Adverse Events 
D5W 
5% dextrose in water 
DEHP 
diethylhexyl phthalate 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
HIV 
Human immunodeficiency virus 
ICF 
Informed consent form 


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Abbreviation 
Definition 
ICH 
International Council for Harmonisation 
IM 
Intramuscular 
IRB 
Institutional Review Board 
ITT 
Intent-to-treat 
IV 
Intravenous 
IWRS 
Interactive web response system 
MAOI 
Monoamine oxidase inhibitor 
MDR 
Multidrug-resistant 
ME 
Microbiologically evaluable 
MITT 
Modified intent-to-treat 
micro-ITT 
Microbiological intent-to-treat 
MRSA 
Methicillin-resistant Staphylococcus aureus 
MSSA 
Methicillin-sensitive Staphylococcus aureus 
NCI 
National Cancer Institute 
NOAEL 
No observed adverse effect level 
NS 
Normal saline 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PO 
Oral  
PT 
Preferred term 
QC 
Quality control 
QD 
Once daily 
QTc 
Corrected QT interval  
QTcF 
Corrected QT interval using the Fridericia correction formula  
SAE 
Serious adverse event 
SAER 
Serious adverse event report 
SAP 
Statistical analysis plan 
SAR 
Suspected adverse reaction 


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Abbreviation 
Definition 
SOC 
System Organ Class 
SSRI 
Selective serotonin reuptake inhibitor 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to maximum concentration 
UA 
Urinalysis 
ULN 
Upper limit of normal 
US 
United States 
UV 
Ultraviolet  
VRE 
Vancomycin-resistant enterococci 
WBC 
White blood cell count 
 
Definitions of Terms 
Term 
Definition 
CACO 
Combined outcome of early response at EA and Investigator’s assessment of clinical 
outcome at PTE 
Contezolid 
The active metabolite of contezolid acefosamil moiety (formerly known as MRX-1) 
Contezolid acefosamil 
The investigational medicinal product in this study (formerly known as MRX-4); a 
prodrug that undergoes a 2-step conversion process to contezolid (active moiety) by 
means of MRX-1352 (an intermediate metabolite)  
EA 
Early assessment (48 to 72 hours after the start of the first dose of IV study drug) 
EOT 
End of therapy (last day of study drug) 
LFU 
Late follow-up (21-28 days after EOT) 
MRX-1320 
A primary metabolite of contezolid; MRX-1320 is also known as “M2” in other 
documents 
MRX-1352 
Intermediate metabolite in the 2-step process by which prodrug (contezolid acefosamil) 
is converted into contezolid (active moiety) 
PTE 
Post therapy evaluation (7 to 14 days after EOT) 
Subject 
An individual who participates in a clinical trial, either as a recipient of the 
investigational product(s) or as a control 
 


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1 STUDY SYNOPSIS 
Sponsor: MicuRx Pharmaceuticals, Inc. 
Protocol Number: MRX4-201 
Study Drug: Contezolid acefosamil for intravenous (IV) and oral (PO) administration 
Title: A Phase 2, Multicenter, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of 
Contezolid Acefosamil Compared to Linezolid Administered Intravenously and Orally to Adults with 
Acute Bacterial Skin and Skin Structure Infection 
Phase of Development: 2 
Study Site: Approximately 5 to 10 sites in the United States (US) 
Indication: Acute bacterial skin and skin structure infection (ABSSSI) 
Rationale: There is an unmet need for additional antibiotic choices to treat Gram-positive bacterial 
infections caused by organisms such as methicillin-resistant Staphylococcus aureus (MRSA) and 
vancomycin-resistant enterococci (VRE). 
Contezolid acefosamil (previously referred to as MRX-4), a sodium salt of a contezolid (previously 
referred to as MRX-1) prodrug, is a synthetic antibiotic in the oxazolidinone class of antimicrobials. 
Due to the low solubility of contezolid and inability to produce a practical IV formulation using 
contezolid, an orally bioavailable and water soluble new molecular entity (contezolid acefosamil) was 
developed, a full battery of preclinical studies was performed, and a successful Phase 1 program was 
completed. 
Contezolid is a novel oxazolidinone with potent in vitro activity against aerobic and anaerobic 
Gram-positive pathogens, with demonstration of clinical efficacy in ABSSSI in 2 previous Phase 2 
studies. Contezolid acefosamil, which rapidly converts to contezolid, is expected to offer similar or 
more consistent (i.e., improved) pharmacokinetic (PK) properties than other drugs in its class. 
Contezolid acefosamil will be available in both IV and PO formulations. Therefore, contezolid 
acefosamil may provide an attractive option to overcome the safety and tolerability challenges with 
current antibiotic choices in both the hospital and community settings. 
Both contezolid and contezolid acefosamil have proven to be highly efficacious in various models of 
animal infections caused by Gram-positive bacteria, including drug-resistant strains of S. aureus, 
Streptococcus pneumoniae, and enterococci. The animal models used for evaluation included murine 
sepsis and thigh infection. 
This study is designed to evaluate the safety and efficacy of IV and PO administered contezolid 
acefosamil compared to linezolid in adults with ABSSSI. The primary efficacy endpoint of clinical 
response at early assessment aligns with the current Food and Drug Administration Guidance for 
Industry, ABSSSI: Developing Drugs for Treatment (FDA, October 2013). 
Study Objectives: 
Primary: 
• 
Evaluate early clinical response of contezolid acefosamil compared to linezolid at early assessment 
(EA; 48 to 72 hours after the start of the first dose of IV study drug) in the intent-to-treat (ITT) 
population 
• 
Evaluate safety and tolerability of both contezolid acefosamil IV and PO formulations compared 
with linezolid 
Secondary: 
• 
Evaluate early clinical response at: 
- EA in the modified intent-to-treat (MITT) population 
- EA (overall and by baseline pathogen) in the microbiological intent-to-treat (micro-ITT) 
population 


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• 
Evaluate percent reduction in lesion size from baseline in ABSSSI lesions at Day 7 in the ITT and 
MITT populations 
• 
Evaluate the Investigator’s assessment of clinical response in the ITT, MITT, and clinically 
evaluable (CE) populations at each timepoint: 
- End of therapy (EOT; last day of study drug) in the ITT, MITT, and CE-EOT populations 
- Post therapy evaluation (PTE; 7 to 14 days after EOT) in the ITT, MITT, and CE-PTE 
populations 
- Late follow-up (LFU; 21-28 days after EOT) in the ITT, MITT, and CE-PTE populations 
• 
Evaluate per-subject microbiological response at: 
- PTE in the micro-ITT population 
- PTE in ME population 
• 
Evaluate per-pathogen microbiological response at: 
- PTE in the micro-ITT population 
- PTE in the ME population 
• 
Evaluate Investigator’s assessment of clinical response in the micro-ITT and ME populations at: 
- PTE (overall and by baseline pathogen) 
- LFU (overall and by baseline pathogen) 
• 
Characterize the PK of 3 contezolid acefosamil metabolites (MRX-1352, contezolid, and 
MRX-1320) using sparse PK sampling in adult subjects with ABSSSI 
• 
Evaluate composite assessment of clinical outcome (CACO) in the ITT, micro-ITT, and CE-PTE 
populations 
Study Design: 
This is a Phase 2, multicenter, randomized, double-blind safety and efficacy study of contezolid 
acefosamil 1500 IV x 1 dose, followed by 1000 mg IV every 12 hours (q12h) (± 2 hours), for at least 
3 total IV doses, followed by 1300 mg PO q12h (± 2 hours) compared with linezolid 600 mg IV q12h 
(± 2 hours), for at least 3 total IV doses, followed by 600 mg PO q12h (± 2 hours) in adult subjects with 
ABSSSI. Subjects will receive study drug for a total of 10 to 14 days. 
Up to 200 subjects will be enrolled to achieve approximately 150 clinically evaluable subjects in the 
CE-PTE population with ABSSSI from approximately 5 to 10 sites in the US. Randomization will have 
a 2:1 (contezolid acefosamil: linezolid) allocation ratio; therefore, up to 133 subjects will be randomized 
to receive contezolid acefosamil and up to 67 subjects will be randomized to receive linezolid. Efforts 
will be made to enroll a mixture of ABSSSI types (cellulitis/erysipelas, wound infection, and major 
cutaneous abscess); however, subjects with major cutaneous abscess should not comprise > 30% of 
randomized subjects. Subjects will be randomized to treatment provided they meet all inclusion and no 
exclusion criteria. Randomization will be stratified by ABSSSI type to better ensure proper balance 
between the treatment groups. 
Screening/baseline assessments for study eligibility will be performed within 24-hours prior to the start 
of the first dose of study drug. Subjects who provide informed consent, are willing and able to 
collaborate and cooperate with study protocol requirements and meet all study eligibility criteria will be 
enrolled and randomized in the study. 
Gram stain and culture specimens of the ABSSSI site must be collected from all subjects for 
microbiologic evaluation at screening/baseline. ABSSSI site specimens (purulent discharge, skin 
biopsy, or aspiration at the leading edge of the cellulitic area) in addition to blood cultures from 
2 separate venipuncture sites, will be obtained from all subjects prior to administration of antibacterial 
therapy whenever possible. All ABSSSI site specimens will be processed for Gram stain and culture at 
the local laboratory, and all blood cultures will be processed at the local laboratory. All bacterial isolates 
that are identified from an ABSSSI site specimen or blood culture at the local facilities collaborating 
laboratory will be sent to a designated central laboratory for confirmation of species identification and 
antimicrobial susceptibility testing. Microbiological methods will be detailed in the Laboratory Manual. 


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Subjects may receive adjunctive antimicrobial therapy with parenteral aztreonam (1 to 2 g IV/ 
intramuscular [IM] q8h, not to exceed 6 g/day) if the Investigator suspects or has confirmed the 
presence of aerobic Gram-negative pathogens, which, in addition to Gram-positive aerobic bacteria, are 
also associated with the pathogenic process. 
Subjects with only Gram-negative pathogens are not eligible for continued treatment under this protocol 
and will be discontinued from study drug as soon as Gram stain and culture confirms that the subject’s 
infection has no Gram-positive pathogen contributing to the subject’s disease. If no Gram-negative 
pathogens are isolated from the screening/baseline cultures by Day 3, aztreonam will be discontinued. 
Subjects with suspected infections primarily due to anaerobic organisms as the cause for ABSSSI or 
subjects requiring empiric adjunctive anaerobic antimicrobial coverage are excluded from treatment 
under this protocol. 
Prompt enrollment procedures are encouraged to allow for prompt administration of study drug. 
Subjects who received prior systemic antibacterial therapy with Gram-positive activity within 96 hours 
prior to randomization will be excluded from the study unless clear clinical evidence of prior treatment 
failure within the prior 96 hours is available. However, one exception to this criterion is the receipt of a 
single dose of a short-acting, non-oxazolidinone antibiotic (as provided in the study exclusion criteria 
and list of allowable antibiotics). Subjects who received a single dose of a short-acting non-
oxazolidinone Gram-positive active antibiotic within 96 hours prior to randomization will not comprise 
> 25% of randomized subjects. 
Randomized subjects will receive at least 3 doses of treatment with IV study drug followed by PO 
dosing, however subjects may receive the IV formulation for the entire treatment duration. Study 
treatment will be as follows: 
• 
Subjects randomized to contezolid acefosamil treatment will receive IV infusions of contezolid 
acefosamil q12h (± 2 hours) for a minimum of 3 infusions followed by 2 PO contezolid 
acefosamil capsules q12h (± 2 hours) for a total of 10 to 14 days of treatment. The IV dose of 
contezolid acefosamil will be 1500 mg infused over 60 minutes (± 5 minutes) for 1 dose 
followed by 1000 mg infused over 60 minutes (± 5 minutes); the PO dose of contezolid 
acefosamil will be 1300 mg (2 capsules each with 650 mg of contezolid acefosamil). 
• 
Subjects randomized to linezolid treatment will receive IV infusions of linezolid q12h 
(± 2 hours) for a minimum of 3 infusions followed by 2 PO linezolid capsules q12h (± 2 hours) 
for a total of 10 to 14 days of treatment. The IV dose of linezolid will be 600 mg infused over 
60 minutes (± 5 minutes); the PO dose of linezolid will be 600 mg (2 capsules each with 
300 mg of linezolid). 
It is expected that most subjects will remain in the hospital or clinic while receiving IV treatment with 
study drug for a minimum of 3 total IV doses; however, subjects who are clinically stable and have 
adequate home support with reliable transportation to/from the hospital or clinic may leave and return to 
the hospital or clinic for IV infusions. Study drug IV infusions are not to be administered at home. 
Subjects may receive the IV formulation for the entire treatment duration. If the primary ABSSSI lesion 
has not increased in area from the screening/baseline assessment and the Investigator determines that 
the subject has sufficient PO intake of food and drink to safely support the administration of PO doses 
of antibiotics, the subject may be switched to the PO formulation. Subjects who are switched from the 
IV to the PO formulation must remain in the hospital or clinic for observation for at least 90 minutes 
after the first PO dose and demonstrate good tolerability with the initial dose of PO treatment. Subjects 
will undergo follow-up visits as described in Table 1 in an outpatient setting to assess the safety, 
tolerability, and efficacy of the investigational products. 
Day 1 is the first day of study drug administration; subsequent study days are consecutive calendar days. 
For purposes of analysis, EA will be performed 48 to 72 hours after the start of the first dose of IV study 
drug, EOT will occur on the last calendar day of study drug (+ 1 day), PTE will occur 7 to 14 days after 
EOT, and LFU will occur 21 to 28 days after EOT.  


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The overall study design is as follows (see Table 1): 
Screening/ 
Baseline 
Study Treatment Period (Day 1 to EOT) 
PTE 
LFU 
Within 
24 hours 
prior to first 
dose 
Day 1 
EA  
(48-72 
hours) 
Day 7  
(± 1 day) 
EOT 
(+ 1 day) 
7-14 days 
after EOT 
21-28 days 
after EOT 
Confirm 
eligibility; 
Baseline 
clinical, 
laboratory, 
and safety 
assessments 
Randomize 
to treatment 
First dose of 
study drug 
Safety 
assessments 
PK samples 
(Days 1-2)a 
Clinical, 
laboratory, 
and safety 
assessments 
 
Clinical, 
laboratory, 
and safety 
assessments 
Last dose of 
study drug 
Clinical, 
laboratory, 
and safety 
assessments 
PK samplesa 
Clinical, 
laboratory, 
and safety 
assessments 
Investigator’s 
assessment of 
clinical 
relapse/failure 
and AE 
assessment 
EA = early assessment; EOT = end of therapy; IV = intravenous; LFU = late follow-up; 
PK = pharmacokinetic; PTE = post therapy evaluation 
a PK sampling will be sparse. Samples will be collected after the first IV dose and prior to and after the third 
IV dose (i.e. on Day 1 and Day 2) and at completion of therapy (IV or PO), as described in the 
Pharmacokinetic Assessments section (Section 11). 
 
Subjects must be evaluated directly by the Investigator (i.e., return to clinic for required assessments if 
being managed in the outpatient setting) from screening/baseline through PTE. If the subject has 
improved to the point that they have returned to their usual premorbid activity (work/school), and if the 
primary ABSSSI site has little or no pain, swelling, redness, or purulent/seropurulent drainage at the 
PTE visit, then the LFU visit, designed to provide an assessment of durability of response, may be 
performed over the telephone. 
In addition, documentation of the primary ABSSSI lesion by digital photography will occur at 
screening/baseline, EA, Day 7, and EOT. All subjects will have their primary ABSSSI site evaluated by 
the Investigator, including primary ABSSSI site measurements, as described below. 
When conducting a clinical examination of the primary ABSSSI site, the Investigator will perform and 
record the following: 
• 
Extent of the infection (area in cm2) as measured by the area of redness, edema, or induration using 
manual measurement of the longest length multiplied by the greatest perpendicular width, with a 
ruler provided by the Sponsor. Note that only measurement of the longest length and the greatest 
perpendicular width (and not calculation of area in cm2) will be collected and the area in cm2 will be 
calculated by the eCRF. Instructions for primary ABSSSI measurements are provided in  
Appendix 5. 
• 
Local signs and symptoms of erythema (and any distant extension of erythema), swelling/edema, 
localized warmth, tenderness on palpation, drainage, fluctuance, and induration, as described in 
Appendix 6. 
In addition, record the following information at screening/baseline only: 
• 
Primary anatomical site 
• 
Predisposing cause of infection, if any (e.g., trauma, arthropod bite, fungal dermatosis, surgery, 
spontaneous, etc.) 


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Efficacy assessments will include (see Section 9.1 for additional information): 
• Early clinical response assessment based on the eCRF data at EA where successful response (i.e., 
"responder") is defined as a reduction in primary ABSSSI lesion size ≥ 20% compared to baseline, 
and the subject did not receive a non-protocol specified systemic antibacterial agent with activity 
against Gram-positive organisms for the treatment of ABSSSI, and did not die of any cause up to 
EA. 
• Investigator’s assessment of clinical response at EOT and PTE: Clinical success at EOT and PTE is 
defined as resolution or near resolution of most baseline ABSSSI signs and symptoms, did not have 
any surgical procedure to treat the infection after 72 hours post-baseline that was not planned at 
baseline, no new signs, symptoms, or complications attributable to the ABSSSI, did not receive a 
non-protocol specified systemic antibacterial therapy with activity against Gram-positive organisms 
for the treatment of ABSSSI, and did not die of any cause up to EOT or PTE. 
• Investigator’s assessment of sustained clinical success and clinical relapse/failure at LFU. Sustained 
clinical success is defined as no new signs or symptoms of primary ABSSSI after PTE. Clinical 
relapse/failure is defined as new or worsened signs or symptoms of primary ABSSSI after PTE. 
Subjects who discontinue study drug or withdraw from the study itself will undergo all EOT 
assessments on the day of study drug discontinuation or study withdrawal (+ 1 day). Subjects who 
discontinue study drug will remain in the study and complete all assessments specified for the PTE and 
LFU visits. For subjects who withdraw from the study, efforts will be made to perform follow-up safety 
assessments per study schedule. The duration of treatment within the specified window will be 
determined by the Investigator based on the subject’s clinical status (e.g., therapy can be discontinued if 
the subject has improved, no more antibiotic treatment is medically necessary, and the risk of relapse is 
minimal). 
Estimated Study Duration: 
Subjects will receive study drug for 10 to 14 days. Subjects will then be followed for up to 28 days after 
the last calendar day of study drug. Therefore, the total duration of each subject’s participation in the 
study will be up to 42 days, excluding the screening/baseline visit that occurs within 24 hours prior to 
study drug administration on Day 1. 
Number of Subjects: 
Up to 200 (133 contezolid acefosamil : 67 linezolid) adult subjects with ABSSSI will be enrolled in this 
study. Randomization will have a 2:1 (contezolid acefosamil : linezolid) allocation ratio with 
stratification for ABSSSI type. 
Study Drug, Dosage, and Route of Administration: 
The active study drugs are contezolid acefosamil (IV and PO) and linezolid (IV and PO), which will be 
administered for a total of 10 to 14 days. 
All subjects will start with IV therapy, with either contezolid acefosamil 1500 mg IV x 1 dose followed 
by 1000 mg IV q12h (± 2 hours) or linezolid 600 mg IV q12h (± 2 hours), and all subjects will receive 
at least 3 total doses of IV study drug. 
Subjects may receive the IV formulations for the entire treatment duration or be switched to the PO 
formulations (after receiving at least 3 IV doses) to complete 10 to 14 days of treatment if the primary 
ABSSSI lesion has not increased in area from the screening/baseline assessment and the Investigator 
determines that the subject has sufficient PO intake of food and drink to safely support the 
administration of PO doses of antibiotics. 
For subjects who switch from IV to PO treatment, 2 contezolid acefosamil capsules (each capsule 
containing 650 mg of contezolid acefosamil for a total of 1300 mg) or 2 linezolid capsules (each capsule 
containing 300 mg of linezolid for a total of 600 mg) will be administered PO q12h [± 2 hours]) to 
complete a total of 10 to 14 days of treatment. The capsules containing contezolid acefosamil tablets 
and capsules containing linezolid powder will have approximately the same external appearance. 


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Final, 19 Oct 2018 
Eligibility Criteria: 
Inclusion Criteria: 
1. Males or females ≥ 18 years 
2. Willing and able to provide written informed consent 
3. ABSSSI that is confirmed or suspected to be caused by a Gram-positive pathogen, which meets the 
following criteria: 
a. Infection of the skin with a lesion size area of at least 75 cm2, or infection of the central face 
with a lesion size area of at least 50 cm2; lesion size measured by the area of redness, edema, or 
induration using manual measurement of the longest length multiplied by the greatest 
perpendicular width 
b. One of the following infection types: 
• Cellulitis/erysipelas: A 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, related to trauma or surgery that occurs 
within 30 days of trauma or surgery 
• 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 
4. Clinical findings from both of the following categories within 24 hours: 
a. At least 2 of the following local signs at the ABSSSI site: 
• Purulent or seropurulent drainage/discharge 
• Erythema 
• Fluctuance 
• Heat/localized warmth 
• Pain/tenderness to palpation 
• Swelling/induration 
b. At least 1 of the following signs of systemic inflammation: 
• Fever or hypothermia (PO or rectal temperature ≥ 38.0°C or ≤ 36.0°C) 
• White blood cell (WBC) count ≥ 10,000/mm3 or ≤ 4,000/mm3 
• Immature neutrophils (bands) ≥ 10%, irrespective of WBC count 
• Lymphadenopathy or lymphadenitis proximal to the ABSSSI site 
• C-reactive protein (CRP) > upper limit of normal 
5. Females must be either postmenopausal for ≥2 years or surgically sterile (having undergone tubal 
ligation, hysterectomy, or bilateral oophorectomy) or, if of childbearing potential, must have a 
negative pregnancy test at screening/baseline and be willing to use a highly effective method of 
contraception throughout the study such as 1 of the following: 
• 
Hormonal contraception (stable dose for 3 months) 
• 
Intrauterine device/intrauterine hormone-releasing system 
• 
Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, condom) 
6. Males if sexually active and nonsterile with female partners of childbearing potential must use 
2 methods of contraception (i.e., a barrier contraceptive such as condom with spermicidal 
foam), and be willing to continue to use such highly effective birth control measures while 
participating in the study and for 70 days following participation in the study. Males must also 
refrain from sperm donations during this time. 


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Final, 19 Oct 2018 
Exclusion Criteria: 
1. Prior receipt of any formulation of contezolid acefosamil or contezolid 
2. ABSSSI with any of the following characteristics: 
a. Known or suspected to involve anaerobic organisms (e.g., perineal wound infection, gluteal 
decubitus ulcer, perianal abscess, wound infection associated with surgery on gastrointestinal 
tract or female genital tract) 
b. Known or suspected invasive infection due primarily to fungal, mycobacterial, parasitic, or viral 
pathogens 
c. Involving an ischemic ulcer due to peripheral vascular disease 
d. Involving a decubitus ulcer or perirectal abscess 
e. Involving a diabetic foot ulcer 
f. Involving an infected burn 
g. Involving an underlying inflammatory skin disease that may obscure determination of response 
(e.g., chronic dermatitis) where inflammation may be prominent for an extended period of time, 
even after successful bacterial eradication has been achieved 
h. Involving pyoderma gangenosum 
i. Involving a bite from a human or animal other than an arthropod 
j. Involving a rapidly necrotizing process, such as necrotizing fasciitis 
k. Involving gangrene of any etiology 
l. Complicated by an immune deficiency in the subject (e.g., development of ecthyma 
gangrenosum, cellulitis, or wound in a neutropenic subject) 
m. Anatomically associated with prosthetic materials (e.g., venous catheters, permanent cardiac 
pacemaker battery packs, or joint replacement prostheses), even if the device is removed 
n. An infection complicating an area of the body that will require amputation 
o. Requiring significant surgical intervention (i.e. procedures that would not normally be 
performed at the bedside) that cannot be performed within 72 hours, unless previously planned, 
after initiating study drug therapy 
p. Estimated high cure rate after surgical incision alone or after aggressive local skin care (e.g., 
minor cutaneous abscess or furuncle) 
q. Associated with infection at other anatomic sites or spaces, such as endocarditis or other 
endovascular infection, thrombophlebitis, osteomyelitis, or septic arthritis 
r. Anticipated need for antibacterial therapy for > 14 days 
3. Pre-existing ABSSSI known or suspected to be caused by pathogens that are resistant to 
oxazolidinone antibiotics 
4. Inability to tolerate a PO study drug (e.g., nausea, vomiting, diarrhea, or any other condition that 
might impair ingestion or absorption of PO study drug) 
5. Poor venous access 
6. History of any intolerance, hypersensitivity or allergic reaction to any oxazolidinone antibiotic 
7. History of any intolerance, hypersensitivity or allergic reaction to aztreonam; note that while cross-
reactivity of aztreonam with other β-lactams is rare, this drug should be administered with caution 
to any subject with a history of hypersensitivity to β-lactams (e.g., penicillins, cephalosporins, 
and/or carbapenems) 
8. History of peripheral or optic neuropathy 
9. QTcF interval duration > 450 msec obtained as an average from the triplicate screening/baseline 
ECGs, history of QT prolongation, hypokalemia (serum potassium < 3.0 mEq/L) at 
screening/baseline, or other proarrhythmic conditions 
10. History of a known or suspected central nervous system (CNS) condition, such as hallucinations, 
depression, suicidal thoughts or suicidal acts, or of a CNS disorder that may predispose to seizures 
or lower the seizure threshold 


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Final, 19 Oct 2018 
11. History of known or suspected serotonin syndrome, neuroleptic malignant syndrome, or carcinoid 
syndrome 
12. Known or suspected pheochromocytoma or thyrotoxicosis or severe uncontrolled hypertension. 
13. History of known or suspected Clostridium difficile-associated diarrhea 
14. Evidence of significant hepatic, renal, hematologic, or immunologic disease as determined by the 
following: 
a. Total bilirubin > 2 times upper limit of normal ( x ULN) 
b. Alanine amino transferase (ALT) or aspartate amino transferase (AST) > 3 x ULN 
c. Estimated or documented creatinine clearance of < 30 mL/min 
d. Manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy 
e. Current or anticipated absolute neutrophils< 1500 neutrophils/mm3 
f. Platelet count < 75,000 cells/mm3 
g. Infection with human immunodeficiency virus (HIV) and a known CD4 count < 200 cells/mm3, 
or another acquired immune deficiency syndrome (AIDS)-defining illness 
h. Receipt of cancer chemotherapy, radiotherapy, or potent, non-corticosteroid immunosuppressant 
drugs (e.g., cyclosporine, azathioprine, tacrolimus, immune-modulating monoclonal antibody 
therapy) within the past 3 months, or the receipt of corticosteroids ≥ 10 mg of prednisone (or 
equivalent) per day for > 14 days in the prior 30 days 
15. Females who are pregnant or nursing 
16. Prior administration of systemic antibacterial therapy within 96 hours before randomization 
a. EXCEPTIONS: Subjects may be eligible if they meet the following conditions: 
EITHER: 
• Received a single dose of a non-oxazolidinone, short-acting, systemic antibiotic within 
96 hours prior to randomization. Note that such subjects will not comprise > 25% of 
randomized subjects. 
OR BOTH OF THE FOLLOWING: 
• Objective clinical evidence of treatment failure (persistent pain, erythema, induration, or 
purulent drainage) following at least 48 hours of prior, non-study, systemic antibacterial 
therapy  
AND 
• Microbiological evidence of failure (i.e. a Gram stain obtained from an appropriate ABSSSI 
specimen collected after the initiation of this prior therapy revealing WBC and Gram-
positive cocci, or isolation of a Gram-positive pathogen from an appropriate ABSSSI 
specimen that is resistant to the prior systemic antibacterial therapy) 
17. Prior (within the past 2 weeks) administration of, or expected or required concomitant (from the 
start of the study drug to EOT) administration of: 
a. Systemic adrenergic, dopaminergic, or serotonergic medications 
b. Monoamine oxidase inhibitors (MAOIs) (e.g., isocarboxazid, isoniazid, nialamide, phenelzine, 
procarbazine, and hydracarbazine) 
18. Life expectancy < 3 months or evidence of immediately life-threatening disease, including, but not 
limited to, current or impending respiratory failure, shock, acute coronary syndrome, unstable 
arrhythmias, hypertensive emergency, acute hepatic failure, active gastrointestinal bleeding, 
profound metabolic, or acute cerebrovascular events 
19. Unable to cooperate fully with the requirements of the study protocol, including the schedule of 
assessments, or likely to be non-compliant with any study requirements, or the Investigator 
determines that the subject should not participate in the study 


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Final, 19 Oct 2018 
Pharmacokinetic Assessments: 
This study will be conducted at multiple clinical sites, and some will have the appropriate equipment 
and facilities (including refrigerated centrifuges and -70ºC freezers) and experienced personnel to 
adequately collect, handle, store, and ship PK samples for bioanalysis. PK assessments will only be 
performed at selected clinical sites with this capability, and PK samples will be obtained from as many 
subjects as possible at these selected sites. Drug exposure will be predicted based on demographic data 
(e.g., body weight) for subjects from whom PK samples were not obtained. 
• 
One PK sample after the 1st IV dose (to characterize the loading dose): obtain 1 blood sample 
between 0.5 to 2 hours after the end of the 1st infusion 
• 
Three PK samples with the 3rd IV dose (to characterize drug exposure and approaching of steady 
state): 
• 
Obtain a 1st blood sample (trough level) within 2 hours before the 3rd IV dose 
• 
Obtain a 2nd blood sample between 0.5 and 3 hours after the end of the 3rd IV dose 
• 
Obtain a 3rd blood sample between 4 and 11 hours after the end of the 3rd IV dose but 
before the 4th dose (IV or PO) of study drug 
• 
Three PK samples at EOT (to evaluate potential drug accumulation): 
• 
Obtain 1 blood sample (trough level) within 2 hours before the last dose (IV or PO) 
• 
If the last dose is given PO: obtain 1 blood sample between 1.5 to 4 hours after the last 
dose, and obtain 1 additional sample between 5 to 12 hours after the last dose 
• 
If the last dose is given IV: obtain 1 blood sample between 0.5 and 3 hours after the end of 
the last infusion, and obtain 1 additional sample between 4 and 11 hours after the end of the 
last infusion 
The PK data acquisition and analysis strategy entail the use of a sparse PK sampling schedule for 
subjects randomized to contezolid acefosamil. This PK sampling strategy is designed to characterize the 
impact of the loading dose, and to obtain adequate estimates of drug exposure after the 3rd IV dose and 
the final IV or PO dose. Additionally, given the range of demographic data in the expected subject 
population, these PK data will be used to perform exploratory analyses on the impact of demographic 
characteristics (e.g., weight, body mass index, age, gender, race) upon the PK (including clearance) of 
the drug and its metabolites. Only those PK samples collected from subjects randomized to contezolid 
acefosamil will be analyzed. The bioanalytical laboratory will measure plasma concentrations of 
contezolid acefosamil metabolites (MRX-1352, contezolid, and MRX-1320) using validated and 
sensitive methods. 
Efficacy Endpoints: 
The Primary efficacy endpoint is early clinical response at EA for the ITT population as described in 
Efficacy Assessments above and in Section 9.1.1. 
Secondary efficacy endpoints will be determined at EA, Day 7, EOT, PTE, and LFU according to the 
table below. Early clinical response is defined in Table 2, Investigator’s assessment of clinical responses 
(including success and relapse) are defined in Table 3, per-subject microbiological responses are 
defined in Section 9.2.2, and microbiological responses per baseline pathogen are defined in 
Section 9.2.1. The CACO is a composite assessment of the early clinical response at EA and the 
Investigator’s assessment of clinical response at PTE (Section 12.6.2.2). 


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Final, 19 Oct 2018 
Efficacy Endpoints 
Efficacy Populations 
ITT 
MITT 
micro-
ITT 
CE-
EOT 
CE-
PTE 
ME 
Primary: 
 
 
 
 
 
 
Early clinical response at EA  
√ 
 
 
 
 
 
Secondary: 
 
 
 
 
 
 
Early clinical response at EA  
 
√ 
 
 
 
 
Early clinical response at EA (overall and 
by baseline pathogen) 
 
 
√ 
 
 
 
Percent reduction in lesion size at Day 7 
√ 
√ 
 
 
 
 
Investigator’s assessment of clinical 
response at EOT  
√ 
√ 
 
√ 
 
 
Investigator’s assessment of clinical 
response at PTE and LFU 
√ 
√ 
 
 
√ 
 
Per-subject microbiological response at 
PTE  
 
 
√ 
 
 
√ 
Per-pathogen microbiological response at 
PTE 
 
 
√ 
 
 
√ 
Investigators assessment of clinical 
response at PTE and LFU (overall and by 
baseline pathogen) 
 
 
√ 
 
 
√ 
CACO  
√ 
 
√ 
 
√ 
 
CACO = composite assessment of clinical outcome (combined outcome of early clinical response at EA and 
Investigator’s assessment of clinical response at PTE); CE = clinically evaluable; EA = early assessment; 
EOT = end of therapy; ITT = intent-to-treat; LFU = late follow-up; ME = microbiologically evaluable; MITT = 
modified intent-to-treat; micro-ITT = microbiological intent-to-treat; PTE = post therapy evaluation 
Safety and Tolerability Assessments: 
Safety will be assessed through the determination and recording of the occurrence of adverse events 
(AEs) and AEs of special interest, as well as by adverse changes in vital signs, ECG parameters, and 
laboratory data. Hematology evaluations, serum chemistries, and urinalysis will be performed at 
screening/baseline, EA, Day 7 (± 1 day), EOT (+ 1 day), and PTE. Additional safety events that occur 
after PTE will be assessed at LFU. Adverse events will be evaluated by relationship to study drug and 
severity. Serious adverse events (SAEs) will be identified. 
Statistical Methods: 
Sample Size Considerations: 
This study is not powered for inferential statistical analysis. Up to 133 subjects (100 evaluable subjects) 
in the contezolid acefosamil group and up to 67 subjects (50 evaluable subjects) in the linezolid group 
will allow for planning of future studies. If the responder rate is 0.8 at EA using early clinical response 
in the contezolid acefosamil group, then 133 evaluable subjects results in a 95% confidence interval 
(CI) of (0.72, 0.86) for the responder rate. 


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Final, 19 Oct 2018 
Analysis Populations: 
• ITT Population - All randomized subjects will be included in the ITT population, regardless of 
whether study drug is administered. 
• MITT Population- All randomized subjects in the ITT population, excluding subjects with only 
Gram-negative pathogen(s) at baseline. 
• Safety Population - All subjects who receive any amount of study drug will constitute the safety 
population. Subjects in the safety population will be analyzed according to study drug received. 
• Micro-ITT Population - All randomized subjects in the ITT population who have culture evidence of 
a baseline Gram-positive bacterial pathogen known to cause ABSSSI. 
• CE Populations (CE-EOT, CE-PTE) – All subjects in the ITT population who meet the minimal 
clinical disease criteria for ABSSSI; receive at least 80% of expected doses based on length of 
therapy; did not receive any potentially-effective systemic antibacterial therapies other than protocol 
specified study drug(s) between Day 1 and timepoint for assessment (except for adjunctive aztreonam 
or in cases of treatment failure). 
o To be included in the CE-EOT population, the following conditions must be met: 
 
Have an Investigator’s assessment of clinical response at EOT (i.e., response can’t be 
indeterminate) 
 
Had an EOT visit 
o To be included in the CE-PTE population, the following conditions must be met: 
 
Have an Investigator’s assessment of clinical response at PTE (i.e., response can’t be 
indeterminate unless the subject is deemed a clinical failure at the EOT visit) 
 
Had a PTE visit 
In addition to meeting the above criteria, subjects must meet the following specific conditions to be 
included in the CE populations: 
o Received at least 5 doses of study drug therapy to be considered an evaluable failure 
o Received at least 7 doses of study drug therapy to be considered an evaluable success 
o Did not have any major protocol violation 
• ME Population – All subjects in the micro-ITT population who also are in the CE-PTE population. 
• PK Population: All subjects who received at least 1 dose of contezolid acefosamil and had at least 
1 blood sample collected for analysis of MRX-1352, contezolid, or MRX-1320. 
Statistical Analysis: 
All baseline data will be summarized by treatment group. 
Pharmacokinetic data will be summarized using descriptive statistics and graphically displayed, and 
population PK modeling analyses will be performed. 
The primary efficacy analysis will be based on the early clinical response at EA in the ITT population. 
The number and percentage of subjects in each treatment group classified as responders will be 
tabulated and 95% CIs will be provided for each response rate. The 2-sided 95% CI for the difference in 
response rates between the 2 treatment groups will also be computed. All secondary endpoints will be 
summarized by treatment group as specified. For outcomes expressed as proportions (other than per-
pathogen outcomes), 95% CIs will be presented for descriptive purposes. Additional details will be 
provided in the Statistical Analysis Plan. 
Safety analyses include summaries of treatment-emergent AEs and SAEs, vital signs, laboratory 
evaluations (hematology, chemistry, and coagulation), and ECG parameters. 
Interim Analysis: 
An interim analysis is not planned. 
 


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Table 1: 
Schedule of Events 
Procedure or Assessment 
Screening/ 
Baseline1 
(≤ 24 hrs 
of first 
dose) 
Study Treatment Period 
PTE5 
LFU6 
Day 12 
Day 2 
EA3 
(48-72 
hours) 
Day 7 
(± 1 day) 
EOT4  
(+ 1 day) 
7-14 Days 
After EOT 
21-28 Days  
After EOT 
Informed consent7 
X 
 
 
 
 
 
 
 
Medical/surgical history  
X 
 
 
 
 
 
 
 
Prior and concomitant therapy8 
X 
X 
X 
X 
X 
X 
X 
X 
Examination, measurement, and signs 
and symptoms of ABSSSI9 
X10 
 
 
X 
X 
X 
X 
 
Document primary ABSSSI lesion by 
digital photography11 
X10 
 
 
X 
X 
X 
 
 
Investigator’s assessment of clinical 
response 
 
 
 
 
 
X 
X 
X 
Activity assessment12 
X 
 
 
 
 
X 
X 
X 
Complete physical examination13 
X10 
 
 
 
 
X 
 
 
Focused physical examination14 
 
 
 
X 
X 
 
X 
 
Vital signs15 
X10 
 
 
X 
X 
X 
X 
 
12-Lead ECG16 
X10 
X17 
 
X 
 
X 
X 
 
Height and weight 
X 
 
 
 
 
 
 
 
Adverse events18 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory tests19 
X10 
 
 
X 
X 
X 
X 
 
Serology tests 20 
X 
 
 
 
 
 
 
 
Pregnancy test21 
X10 
 
 
 
 
X 
 
 
Estimate CrCl22 
X 
 
 
 
 
 
 
 
PK samples23 
 
X 
X 
 
 
X 
 
 


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Procedure or Assessment 
Screening/ 
Baseline1 
(≤ 24 hrs 
of first 
dose) 
Study Treatment Period 
PTE5 
LFU6 
Day 12 
Day 2 
EA3 
(48-72 
hours) 
Day 7 
(± 1 day) 
EOT4  
(+ 1 day) 
7-14 Days 
After EOT 
21-28 Days  
After EOT 
ABSSSI specimen Gram stain and 
culture24 
X10 
 
 
X 
X 
X 
X 
 
Blood cultures25 
X10 
 
 
X 
X 
X 
X 
 
Randomization26 
 
X 
 
 
 
 
 
 
Administration of study drug  
(10 to 14 days)27 
 
X 
X 
X 
X 
X 
 
 
ABSSSI = acute bacterial skin and skin structure infection; β–HCG = beta-human chorionic gonadotropin; CrCl = creatinine clearance; CRP = c-reactive protein; EA = early 
assessment; ECG = electrocardiogram; EOT = end of therapy; eRT = eResearch Technologies; LFU = late follow-up; PK = pharmacokinetic; PTE = post therapy evaluation; 
UA = urinalysis. 
1. 
Screening/baseline assessments must occur within 24 hours prior to first administration of study drug. 
2. 
Day 1 is the first day of study drug administration; subsequent study days are consecutive calendar days. 
3. 
Perform EA assessments at 48 to 72 hours after the start of the first dose of IV study drug. 
4. 
Perform EOT assessments on the last calendar day of study drug (+ 1 day). Subjects who prematurely discontinue study drug or withdraw from the study should have all 
EOT assessments performed on the day of discontinuation of study drug or withdrawal from the study (+ 1 day). 
5. 
Perform PTE assessments 7 to 14 days after EOT. 
6. 
Perform LFU assessments 21 to 28 days after EOT. If the subject has improved to the point that they have returned to their usual premorbid activity (work/school), and if 
the primary site has little or no pain, swelling, redness, or purulent/seropurulent drainage at PTE, the LFU visit may be performed over the telephone. 
7. 
Written informed consent must be obtained prior to initiating any study assessment or procedure. 
8. 
Record all prior medications taken within 2 weeks prior to randomization; record all concomitant medications between Day 1 and EOT, and only concomitant 
antimicrobial agents and concomitant medications taken for an AE between EOT and LFU. 
9. 
Direct evaluation of signs and symptoms of ABSSSI by the Investigator at EA, Day 7, EOT, and PTE; assessments include manual measurement of the primary ABSSSI 
lesion size (longest length and perpendicular width) with a ruler provided by the Sponsor (Section 8.1). 
10. Procedures that must be repeated on Day 1 prior to dosing if they were collected > 24 hours prior to first administration of study drug. 
11. Document the primary ABSSSI lesion via digital photography at screening/baseline, EA, Day 7, and EOT using the digital camera provided by the Sponsor (Section 8.3). 
12. At screening/baseline, record if the subject’s premorbid activities (work/school) are compromised. At subsequent visits, record the date the subject returned to premorbid 
level of activity (work/school), as applicable. 
13. Perform a complete physical examination (i.e., general appearance, head, ears, eyes [including basic Snellen visual acuity and visual field testing], nose, throat, dentition, 
thyroid, chest [heart, lungs], abdomen, skin/soft tissues, neurological, extremities, back, neck, musculoskeletal, lymph nodes) at screening/baseline and EOT. 
14. Perform a limited, symptom directed physical examination as clinically indicated at EA, Day 7, and PTE. 


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15. Record vital signs (heart rate, blood pressure, respiratory rate, and temperature) at screening/baseline, EA, Day 7, EOT, and PTE. If > 1 temperature is measured within a 
calendar day, record the highest daily temperature measured. Vital signs will be collected prior to collection of blood laboratory samples. Oral or rectal temperatures are 
acceptable; the site of measurement will be collected in the eCRF. 
16. Obtain triplicate ECGs within a 15-minute period, each separated by at least 1 minute, at screening/baseline, Day 1 (predose and postdose), EA, EOT, and PTE. ECGs 
will be collected prior to collection of blood laboratory (including PK) samples. The time of prior dose of study drug and relationship of time of ECG to dose must be 
documented All ECGs will be performed on ECG machines provided by eRT and will be sent to eRT for central reading. 
17. Within 1 hour prior to start of IV infusion (unless screening/baseline ECG is performed in triplicate and is within 1 hour prior to start of IV infusion) and another within 
2 hours after completion of IV infusion. 
18. Adverse events are collected between written informed consent and LFU. During the LFU phone call, symptoms related to possible relapse of ABSSSI will be evaluated 
as part of the safety assessment. 
19. Perform safety laboratory tests, including hematology, chemistry, and coagulation tests, UA, and CRP, at screening/baseline, EA, Day 7, EOT, and PTE. Include urine 
microscopy if UA is positive for red blood cells, WBCs, or protein (Appendix 4). Samples for screening/baseline tests will be drawn and sent to local laboratory (to 
confirm eligibility) and central laboratory. All subsequent laboratory tests will be drawn and sent to the central laboratory. 
20. Serology tests include Anti-HBcAg anti-HBsAg, HBsAg, HCV Ab, HIV Ab (Appendix 4) 
21. Females of childbearing potential up to 2 years postmenopause must have a serum or urine β–HCG pregnancy test at baseline and EOT (otherwise, females must be 
surgically sterile, i.e., have had a tubal ligation, hysterectomy, or bilateral oophorectomy). Male and female subjects must agree to comply with using a highly effective 
form of birth control (see Section 10.3) from baseline through LFU. If the pregnancy test is positive at the EOT visit, or if a female partner of a male subject becomes 
pregnant, follow the reporting requirements in Section 10.3. 
22. Calculate estimated CrCl using screening/baseline height (m), actual weight (kg), and serum creatinine (Section 7.1). 
23. Obtain PK samples as follows (Section 11):   
• 
One sample after 1st IV dose, between 0.5 to 2 hrs after the end of the 1st infusion;  
• 
Three samples with the 3rd IV dose: obtain a 1st blood sample within 2 hours before the 3rd IV dose (trough level), a 2nd blood sample between 0.5 and 3 hours 
after the end of the 3rd IV dose,and a 3rd blood sample between 4 and 11 hours after the end of 3rd IV dose, but before the 4th dose (IV or PO);  
• 
Three samples at EOT: obtain 1 blood sample within 2 hours before the last dose (IV or PO). If the last dose is given PO: obtain 1 blood sample between 1.5 to 4 
hours after the last dose and obtain 1 additional sample between 5 to 12 hours after the last dose. If the last dose is given IV: obtain 1 blood sample between 
0.5 and 3 hours after the end of the last infusion and obtain 1 additional sample between 4 and 11 hours after the end of the last infusion. 
24. Obtain appropriate ABSSSI site specimen from all subjects at screening/baseline, and perform Gram stain and culture at the local laboratory (Section 8.2). The ABSSSI 
site specimen should be obtained before administration of antibacterial therapy whenever possible. Repeat post-screening/baseline ABSSSI specimen culture and Gram 
stain at subsequent visits only if clinically indicated (e.g., the subject is deemed a clinical failure or if purulence and discharge from the ABSSSI site continues after 
screening/baseline). 
25. Two sets of blood cultures (each set consists 1 aerobic and 1 anaerobic blood culture bottle from 2 separate venipuncture sites) will be collected from all subjects, 
regardless of location of management (inpatient or outpatient) (Section 8.2). The blood cultures should be obtained before administration of antibacterial therapy, 
whenever possible. Blood cultures must be repeated every 3 days (± 1 day) if the previous blood culture was positive, or at any time after screening/baseline if clinically 
indicated. 
26. Verify that the subject meets all study inclusion and exclusion criteria before randomization on Day 1. 
27. Subjects receive study drug q12h (± 2 hours) for 10-14 days. On Day 1, the first dose of study drug should be administered as quickly as possible after eligibility criteria 
are met. Subjects will receive the first 3 doses of study drug intravenously and then may switch to oral study drug if the primary ABSSSI lesion has not increased in area 
from the screening/baseline assessment and the Investigator determines that the subject has sufficient PO intake of food and drink to safely support the administration of 
PO doses of antibiotics. 
 


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2 INTRODUCTION 
2.1 
Background 
Acute bacterial skin and skin structure infections (ABSSSI) are common infectious diseases; 
approximately 6.3 million physician’s office visits per year are attributable to this infection 
(Pallin, 2008). The frequency and severity of ABSSSI, and the emergence of resistance to many 
of the antibacterial agents commonly used to treat this infection, have dramatically increased 
over the past 2 decades (Stevens, 2014). For example, there was a 29% increase in the total 
hospital admissions for ABSSSI between 2000 and 2004 (Edelsberg, 2009). In addition, annual 
emergency department visits for ABSSSI between 1993 and 2005 increased from 1.2 million to 
3.4 million patients (Pallin, 2009). Skin and soft tissue infection and ABSSSI in hospitalized 
patients contribute to prolonged length of stay and increase costs of medical care, as well as play 
an important role in driving antimicrobial resistance emergence (Rennie, 2003). 
The increases in incidence and severity of ABSSSI are in part attributed to the emergence of 
community-associated methicillin-resistant Staphylococcus aureus (MRSA) (Edelsberg, 2009). 
Community-associated MRSA has increased markedly to become the greatest problem facing 
therapy for ABSSSI in the outpatient setting (Deresinski, 2005; Diep, 2004; Eron, 2003). In a 
large global surveillance study to determine the bacteriology of ABSSSI between 1998 and 2004, 
S. aureus ranked first as the predominant ABSSSI pathogen in all regions studied (North 
America, Latin America, and Europe); among the North American S. aureus isolates, the 
prevalence of MRSA increased from approximately 42% in 1998 to 52% in 2004 (Moet, 2007). 
In the same global surveillance study, the second most frequently isolated Gram-positive 
pathogen of ABSSSI was Enterococcus spp., where the prevalence remained high in North 
America (approximately 10%) (Moet, 2007). Furthermore, the prevalence of 
vancomycin-resistant enterococci (VRE) was of greatest concern in North America compared 
with other regions, where rates of resistance increased from approximately 9% in 1998 to 15% in 
2004. In addition to S. aureus and enterococci, streptococci (e.g., group A, B, C, or G 
streptococci) and other staphylococci (e.g., coagulase-negative species) remain important causes 
of ABSSSI. 
It is important to note that ABSSSI may involve aerobic Gram-negative pathogens or may be 
polymicrobial (Gram-positive, Gram-negative bacteria, and possibly anaerobic bacteria), 
depending on host factors and risk factors (Stevens, 2014). Therefore, the goal of clinical 
evaluation of ABSSSI aims to establish the specific microbial cause to help determine optimal 
pathogen-directed therapy, which takes into account pathogen-specific and local antibiotic 
resistance patterns. As most cases of ABSSSI are caused by endogenous Gram-positive cocci 
(i.e., staphylococci and streptococci) ―many of which may be drug-resistant―empiric treatment 
algorithms are no longer simple; recent emerging resistance of S. aureus to methicillin, 
erythromycin, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole―and emerging 
resistance of streptococci to erythromycin and clindamycin―have dramatically altered options 
of empiric and definitive therapy. 


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The oxazolidinone class of antimicrobials have provided an important therapeutic option in the 
treatment of ABSSSI. Linezolid, the first oxazolidinone, was approved in 2000 and is highly 
efficacious for the treatment of both community-acquired and hospital acquired infections 
(Wilcox, 2005). In the US, linezolid is indicated for the treatment of VRE infections (including 
cases with concurrent bacteremia), nosocomial pneumonia (caused by methicillin-sensitive S. 
aureus [MSSA], MRSA, or S. pneumoniae, including multidrug-resistant [MDR] strains), 
uncomplicated and complicated skin and skin structure infections including diabetic foot 
infections without concomitant osteomyelitis (caused by MSSA, MRSA, Streptococcus 
pyogenes, or S. agalactiae), and community-acquired pneumonia caused by S. pneumoniae, 
including MDR strains and cases with concurrent bacteremia, or MSSA (Zyvox® Prescribing 
Information, 2018). There is an extremely low propensity toward developing bacterial resistance 
to linezolid in all target pathogens, even after over 14 years of clinical use. Despite these 
benefits, linezolid is subject to serious safety limitations, primarily due to myelosuppression and 
monoamine oxidase inhibition with associated drug-drug interactions, central nervous system 
(CNS) and blood pressure effects. While myelosuppression is reversible and uncommon with 
linezolid treatment regimens ≤ 14 days, extended treatment is also associated with mitochondrial 
toxicity resulting in optical neuropathy with rare but irreversible vision impairments (Zyvox® 
Prescribing Information, 2018). 
In June 2014, tedizolid (Sivextro®), a second oxazolidinone was approved by the Food and Drug 
Administration (FDA) for the treatment of ABSSSI caused by MSSA, MRSA, various 
Streptococcus species, and Enterococcus faecalis (FDA, 2014). The availability of both oral 
(PO) and intravenous (IV) formulations has added to their clinical utility, as have 
pharmacokinetic (PK)/pharmacodynamic (PD) characteristics that offer, among other things, a 
bioavailability of 90 to 100%, possibility of once daily (tedizolid) or twice daily (linezolid) 
dosing, and excellent and prolonged tissue penetration (Dryden, 2014; Flanagan, 2014). 
Introduction of new oxazolidinone compounds that are safe and effective, have a PO and IV 
formulation, and have important differentiating features over existing agents are needed to 
ensure continued effective treatment of ABSSSI and other serious Gram-positive infections 
caused by emerging resistant Gram-positive pathogens. 
2.2 
Description of Contezolid and Contezolid Acefosamil 
MicuRx Pharmaceuticals, Inc. pursued a research program to develop a novel oxazolidinone 
agent that maintains high antibacterial activity while potentially addressing the key toxicity 
issues associated with linezolid therapy. The initial drug candidate, contezolid (previously 
referred to as MRX-1), was well tolerated, safe, and shown to have efficacy comparable to 
linezolid (Gordeev, 2014). Contezolid is a Biopharmaceutics Classification System (BCS) 
class 2 molecule (poorly soluble in water), and absorption of oral contezolid was markedly 
improved when administered with food. In addition, the poor solubility made the production of 
an IV formulation impractical. To address these issues, contezolid acefosamil, a prodrug of 
contezolid, was developed to decrease the impact of food on oral absorption and to present the 
patient and physician the opportunity to utilize the same molecular entity for both IV and oral 
therapy. The main objective of the contezolid acefosamil and contezolid clinical program is to 
develop oxazolidinone antibiotics with improved tolerability and reduced toxicity compared to 


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the currently available oxazolidinones (linezolid and tedizolid) while maintaining efficacy in 
serious Gram-positive bacterial infections. 
Contezolid acefosamil, the sodium salt of a contezolid prodrug with high aqueous solubility, 
degrades into bioactive contezolid in aqueous environments in a 2-step process (Figure 1). In the 
first step, contezolid acefosamil quickly degrades into an intermediate metabolite, MRX-1352, 
when given either by the oral (PO) or intravenous (IV) route, and the second step results in the 
active moiety, contezolid. Additionally, the primary metabolite of contezolid is MRX-1320. The 
structure of contezolid has been previously published (Gordeev, 2014). Neither contezolid 
acefosamil nor MRX-1352 have direct antibacterial activity and must be converted to contezolid 
to become active. Neither contezolid acefosamil, nor MRX-1352, nor the side chain fragments 
cleaved during biotransformation are associated with unique toxicities in animal models. 
Figure 1: 
Contezolid Acefosamil Metabolites 
 
The complete nonclinical toxicology program with contezolid acefosamil demonstrated the 
following: 
 
• Whether given PO or IV, contezolid acefosamil has good tolerability and safety, and is 
comparable to contezolid in preclinical models of efficacy. 
• Contezolid acefosamil is well absorbed in animals as a PO agent when dosed with and 
without food. 
A further description of the physical and chemical characteristics of contezolid and contezolid 
acefosamil is found in the Investigator’s Brochure. Contezolid acefosamil is expected to offer 
similar or more consistent (i.e., improved) PK properties than contezolid and is expected to be 
available for both IV and PO administration in clinical practice. Therefore, contezolid acefosamil 
may provide an attractive option for ABSSSI and other significant Gram-positive infections in 
both hospital and community settings. 
2.3 
Summary of Relevant Nonclinical Experience 
2.3.1 
Pharmacology, Microbiology, Toxicology, and Safety 
The active pharmaceutical ingredient, contezolid has demonstrated excellent in vitro antibacterial 
activity against both nosocomial and community Gram-positive pathogens. Oral absorption of 
contezolid in the mouse, rat, and dog was rapid with maximum time to absorption (Tmax) of 0.5 
to 1 hour and a half-life (t1/2) of 1 to 2 hours. The mean effective protective dose (ED50) was 
similar to linezolid in in vivo mouse models of systemic and local infections caused by MRSA, 
penicillin-resistant S. pneumoniae, and VRE. Moreover, the minimum inhibitory concentration 
Contezolid 
Active moiety 


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for 90% of microbial strains (MIC90) is < 2 µg/mL against recent US surveillance isolates 
(Li, 2014). 
After IV administration in rats, contezolid acefosamil was rapidly metabolized into contezolid 
after 30 minutes; the prodrug, contezolid acefosamil, was not detectable in rat blood specimens 
(whole blood supernatant specimens). Peak concentrations of contezolid were demonstrated at 
0.7 hours. After multiple IV doses of 40 mg/kg contezolid acefosamil in rats, no accumulation of 
the active molecule or its metabolites were noted over a 7-day period of consecutive 
administrations. Studies with radiolabeled 14C-MRX-1 indicated primarily fecal excretion within 
the first 24 hours after PO administration. 
In toxicology studies, contezolid was generally well tolerated after 4-week PO dosing in rats and 
dogs. Results from contezolid acefosamil toxicology studies indicated that contezolid acefosamil 
was not genotoxic or phototoxic and did not cause sensitization. Contezolid acefosamil did not 
cause hemolysis or red blood cell coagulation and was generally well tolerated in a vascular 
irritation study. contezolid acefosamil had negative results on the bacterial reverse mutation test, 
did not induce any structural or numerical chromosome aberrations in CHO-WBL cells, and 
showed no evidence of rat bone marrow micronucleus damage or cytotoxicity. The no observed 
adverse effect level (NOAEL) of contezolid acefosamil for potential reproductive and/or 
developmental toxicity was 120 mg/kg/dose twice daily (BID) in male and female rats. The 
NOAEL of contezolid acefosamil for embryo-fetal development retardation was 40 mg/kg/dose 
BID (80 mg/kg/day: Cmax = 14,300 ng/mL, area under the curve [AUC]0-24h = 139,000 h ⃰ ng/mL 
on gestation day 17). Further details regarding the microbiology, and animal PK/PD of 
contezolid and contezolid acefosamil are available in the contezolid acefosamil IB. 
With its improved solubility, contezolid acefosamil is expected to offer similar or more 
consistent (i.e., improved) PK properties than contezolid, and can be administered by both IV 
and PO routes of administration in clinical practice. The available in vitro microbiology and in 
vivo animal efficacy data support continued clinical development of contezolid acefosamil as a 
potential human therapeutic agent for the treatment of moderate to severe bacterial infections 
caused by Gram-positive pathogens, most notably MRSA and other drug-resistant Gram-positive 
pathogens. 
2.4 
Summary of Relevant Clinical Experience 
Contezolid is the active moiety of contezolid acefosamil. Several clinical studies were conducted 
with contezolid, including 2 Phase 1 clinical studies (MRX-I-01, MRX-I-02) and one proof-of-
concept Phase 2 clinical study (MRX-I-03). From the Phase 1 and 2 studies, contezolid 
administered PO in single or multiple doses up to 800 mg every 12 hours for up to 28 days was 
well tolerated in healthy adult subjects. 
However, the physical and chemical characteristics of the active pharmaceutical ingredient 
ensured that no commercially practical IV formulation was likely to be developed for contezolid. 
Thus, research was directed toward finding a related compound with antimicrobial characteristics 
similar to contezolid but with greater solubility. Contezolid acefosamil, the prodrug of 
contezolid, fits the required characteristics. 


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Two clinical studies have been completed with contezolid acefosamil. MRX4-001 was the first-
in-human study of PO contezolid acefosamil conducted in healthy volunteers in the US 
(Section 6.2 of the Investigator’s Brochure). MRX4-002 was the first-in-human study of IV 
contezolid acefosamil in healthy volunteers, and evaluated IV contezolid acefosamil 
administration and compared both the PO and IV administrations (Section 6.3 of the 
Investigator’s Brochure). An overview of the safety, tolerability, and PK from these studies is 
presented below, with additional details provided in the Investigator’s Brochure. 
2.5 
Safety and Tolerability of Contezolid Acefosamil 
In the Phase 1 contezolid acefosamil studies, safety and tolerability were assessed through 
adverse event reporting, collection of medical histories and concomitant medications, urine drug 
screens, urine and serum pregnancy tests, laboratory evaluations including hematology and 
coagulation tests, urinalyses, physical examinations, vital signs, and electrocardiograms (ECG). 
In Study MRX4-001, a total of 122 subjects were exposed to contezolid acefosamil or placebo 
administered orally in single doses of up to 3000 mg and multiple doses of up to 1500 mg every 
12 hours for 10 days. In Study MRX4-002, a total of 98 subjects were enrolled, and 96 subjects 
were exposed to contezolid acefosamil or placebo administered via IV in single doses of up to 
2400 mg and multiple doses of up to 2100 mg QD for 10 days; 12 of 98 subjects also received 2 
doses of orally administered contezolid acefosamil 1500 mg q12h in the crossover portion of the 
study. 
In general, in both studies, contezolid acefosamil was well tolerated at these doses, and the safety 
profile of contezolid acefosamil was consistent with oxazolidinone class effects. Findings 
included: 
• The majority of treatment-emergent adverse events (TEAEs) in both studies were mild in 
severity. 
• There were no severe or serious adverse events (SAEs) or deaths. 
• There were no unusual or unexpected TEAEs judged related to study drug. 
• Overall, the nature and extent of TEAEs, and treatment-related TEAEs, were similar between 
all treatment groups for both PO and IV administration, including placebo. 
• In Study MRX4-001 (PO administration), discontinuations due to TEAEs were observed in 
2 subjects (pyrexia in the 500 mg cohort, judged by the Investigator to be unrelated to study 
drug and vomiting in the 1500 mg cohort, judged possibly related to study drug). In Study 
MRX4-002 (IV administration), there were no discontinuations due to TEAEs; however, 
1 subject voluntarily withdrew consent from the study due to AEs of nausea, somnolence, 
asthenia, and headache which occurred within the first 12 hours after receiving a single 
1500 mg oral dose and were judged possibly related to study drug. 
• During PO administration (Study MRX4-001), the most frequently reported treatment-related 
TEAEs in study Part 1 (single ascending doses of contezolid acefosamil or placebo) were 


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headache and nausea. The most frequently reported treatment-related TEAE in Part 2 
(multiple ascending doses of contezolid acefosamil or placebo) was nausea. The most 
frequently reported treatment-related TEAEs during Part 3 (contezolid acefosamil or placebo 
and omeprazole) were headache, nausea, and vomiting. 
• During IV administration (Study MRX-002), the most frequently reported TEAEs for IV 
contezolid acefosamil and IV placebo involved the infusion site. In Part 1, only 1 AE, 
dysgeusia, was considered related to IV contezolid acefosamil. In Part 2, the most frequently 
reported AEs related to IV contezolid acefosamil were infusion site irritation and infusion 
site pain. In Part 3 (crossover portion investigating IV and oral formulations), the most 
frequently reported AE related to contezolid acefosamil was headache. 
• Two AEs of neutropenia were reported in Study MRX4-001 (all in subjects treated with PO 
contezolid acefosamil), and 3 in Study MRX4-002 (2 in subjects treated with IV contezolid 
acefosamil and 1 in subject treated with placebo); all 5 events were National Cancer Institute 
(NCI) Common Terminology for Adverse Event (CTCAE) Grade 2 (moderate) and none 
were judged related to study drug. 
• No impact of contezolid acefosamil administration (PO or IV) on laboratory values or ECGs 
interpretations was observed; no clinically significant laboratory values were attributed to the 
study treatment, and there were no significant results on any ECG interpretation. 
• In general, contezolid acefosamil was well tolerated when given orally as a single 1500 mg 
dose in combination with omeprazole. 
For more details on the PK of contezolid acefosamil in the MRX-001 and MRX-002 studies, see 
Sections 6.2 and 6.3 of the Investigator’s Brochure. 
2.6 
Pharmacokinetics of Contezolid Acefosamil 
In Study MRX04-001, the PK of orally administered contezolid acefosamil was evaluated after 
single ascending doses of 250, 500, 750, 1000, 1500, 2000, 2500, and 3000 mg (including an 
evaluation of food effect at the 1500 mg dose), multiple ascending doses of 500 mg q12h, 7500 
mg q12h, 1000 mg q12h, and 1500 mg q12h for 10 days, and in a crossover study alone at 
1500 mg and when co-administered with omeprazole. 
In Study MRX4-002, the PK of IV contezolid acefosamil was evaluated after single ascending 
doses of 150, 300, 600, 1200, 1800, 2100, and 2400 mg, multiple ascending doses of 600 mg 
q12h, 900 mg q12h, and 2100 mg QD for 10 days, and a crossover study comparing IV 
(2100 mg) and oral (2 doses of 1500 mg tablets q12h) formulations of contezolid acefosamil. 
The general findings are described below. 
• Contezolid acefosamil was rapidly metabolized after both single and multiple oral doses of 
contezolid acefosamil. When contezolid acefosamil was administered orally, no quantifiable 
contezolid acefosamil concentrations were observed at any of the sampled timepoints, and 
therefore PK parameters for contezolid acefosamil could not be estimated. When 


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administered via IV, blood concentrations of contezolid acefosamil increased with dose and 
declined rapidly after the infusion, with an estimated T1/2 of 8 to 11 minutes. 
• Contezolid acefosamil concentrations were transient and very low after IV administration 
and undetectable after oral administration compared with those observed for the contezolid 
acefosamil metabolites. 
• Exposure to the active moiety, contezolid, in blood increased approximately dose-
proportionally with increasing oral and IV doses of contezolid acefosamil, particularly after 
multiple doses. During multiple dosing, there was no apparent accumulation for the 2100 mg 
QD IV regimen or for oral regimens of up to 1000 mg q12h; however, contezolid 
concentrations do gradually increase in systemic circulation over time as time to steady state 
may require up to 7 days when oral or IV contezolid acefosamil is dosed above 1000 mg 
q12h. Exposure after 10 days may increase up to 2 fold when dosed q12h given IV and up to 
1.7 fold when 1500 mg is given orally q12h. 
• Exposure to contezolid in blood after orally administered contezolid acefosamil 1500 mg 
q12h (2 doses separated by 12 hours) was similar to that observed after contezolid acefosamil 
IV 2100 mg (single dose); the bioavailability of contezolid after orally administered 
contezolid acefosamil was approximately 66% of that after IV contezolid acefosamil. Based 
on relative amounts of MRX-1352, contezolid in blood and plasma, and MRX-1320 in 
plasma, there was no appreciable binding to blood components. 
• Although oral administration of contezolid acefosamil 1500 mg under fed conditions resulted 
in a delay in contezolid Tmax by approximately 0.8 hours, from 2.42 hours to 3.25 hours, the 
maximum contezolid exposure (Cmax) was similar after administration of 1500 mg contezolid 
acefosamil under fed and fasted conditions; the geometric mean ratio was 91.83%. An 
increase in total contezolid exposure (AUC0-t, AUC0-∞) of approximately 24% was observed 
in the presence of food; geometric mean ratios were 123.77% and 123.74%, respectively. 
Intrasubject variability ranged from 14.78% (AUC0-∞) to 19.20% (Cmax). Therefore, the drug 
product can be taken with or without food. 
• After co-administration of contezolid acefosamil plus omeprazole, maximum contezolid 
exposure (Cmax) was approximately 20% higher compared to that after administration of 
contezolid acefosamil alone. Total contezolid exposure (AUC0-t and AUC0-∞) was similar 
across treatments. Intrasubject variability ranged from 16.49% (AUC0-t) to 16.57% (AUC0-∞). 
Therefore, no significant drug interaction is noted with concomitant omeprazole treatment. 
• No clear gender-related trends were observed. 
For more details on the PK of contezolid acefosamil in the MRX-001 and MRX-002 studies, see 
Sections 6.2 and 6.3 of the Investigator’s Brochure. 
2.7 
Summary and Rationale for Study 
There is an unmet need for additional antibiotic choices to treat Gram-positive bacterial 
infections caused by organisms such as MRSA and VRE. 


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Contezolid acefosamil, a sodium salt of a contezolid prodrug, is a synthetic antibiotic in the 
oxazolidinone class of antimicrobials. Due to the low solubility of contezolid and inability to 
produce a practical IV formulation using contezolid, an orally bioavailable and water soluble 
new molecular entity (contezolid acefosamil) was developed, a full battery of preclinical studies 
was performed, and a successful Phase 1 program evaluating both the oral and IV formulations 
of contezolid acefosamil was completed under a US IND. 
Contezolid is a novel oxazolidinone with potent in vitro activity against aerobic and anaerobic 
Gram-positive pathogens, with demonstration of clinical efficacy in ABSSSI in 2 previous 
Phase 2 studies. Contezolid acefosamil, which rapidly converts to contezolid, is expected to offer 
patients and physicians an effective and better tolerated option for the treatment of serious 
Gram-positive bacterial infections. Contezolid acefosamil will be available in both IV and PO 
formulations. 
Both contezolid and contezolid acefosamil have proven to be highly efficacious in various 
models of animal infections caused by Gram-positive bacteria, including drug-resistant strains of 
S. aureus, Streptococcus pneumoniae, and enterococci. The animal models used for evaluation 
included murine sepsis and thigh infection. 
The therapeutic benefit of linezolid (comparator) for the treatment of ABSSSI has been 
established (Zyvox® Prescribing Information, 2018). Based on linezolid prescribing information, 
contezolid acefosamil, an oxazolidinone, is contraindicated in patients with known 
hypersensitivity to oxazolidinones and in patients taking any monoamine oxidase inhibitors 
(MAOIs) or within 2 weeks of taking an MAOI. Warnings and precautions in the label include 
the risks for myelosuppression, peripheral and optic neuropathy, serotonin syndrome, 
Clostridium difficile-associated diarrhea, potential drug interactions producing hypertension, and 
hypoglycemia. Further information is provided in the contezolid acefosamil IB and can also be 
obtained from the prescribing information for linezolid (Zyvox® Prescribing Information, 2018). 
Refer to the IB for additional information. 
The current study is a Phase 2, multicenter, randomized, double-blind study designed to evaluate 
the safety and efficacy of IV and PO administered contezolid acefosamil compared to linezolid 
(Zyvox®) in adult subjects with ABSSSI. The study design incorporates recommendations from 
the US Food and Drug Administration 2013 Guidance for Industry (ABSSSI: Developing Drugs 
for Treatment) (FDA, 2013). The primary efficacy endpoint of early clinical response at early 
assessment aligns with the current FDA guidance. The secondary efficacy endpoint of the 
Investigator’s assessment of clinical response at PTE is based on current EU guidance (EMA, 
2013). The safety parameters monitored during the study are well-accepted measures of safety in 
clinical study subjects. Contezolid acefosamil PK concentrations will not be assessed in this 
study based on Phase 1 study results indicating rapid conversion (within 0.25 hours) of 
contezolid acefosamil to MRX-1352, an intermediate metabolite of the prodrug, and subsequent 
conversion to active contezolid. Blood specimens will be collected to understand the PK 
performance of contezolid acefosamil tablets used in this study population. The levels of the 
following contezolid acefosamil metabolites will be assessed: MRX-1352, contezolid, and 
MRX-1320. 


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2.8 
Rationale for Dose Regimens 
The contezolid acefosamil dose regimen chosen for evaluation in this study is derived from 
3 lines of evidence: 
• From clinical PK/PD studies in the mouse thigh infection model. 
• From the Phase 1 studies in which administration of contezolid acefosamil was generally safe 
and well tolerated when administered to healthy volunteers at doses up to 2100 mg IV QD 
over 60 minutes for 10 days (MRX4-002), and when contezolid acefosamil was administered 
at doses up to 1500 mg PO BID for 10 days (MRX4-001). 
• Exposure of contezolid in blood after these respective doses was similar, the bioavailability 
of contezolid after contezolid acefosamil administered PO was approximately 66% of that 
after contezolid acefosamil administered via IV. And the exposure of 1000 mg of contezolid 
acefosamil IV q12h and 1300 mg contezolid acefosamil q12h by the PO route only slightly 
exceed the (contezolid) drug exposure when contezolid is given under optimal conditions. 
• From 2 Phase 2 studies which showed that contezolid dosed at 800 mg twice daily was 
non-inferior to linezolid 600 mg given twice daily. 
The linezolid dose regimen is based on the current prescribing information (Zyvox® Prescribing 
Information, 2018). 


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3 STUDY DESIGN 
3.1 
Study Objectives 
The objectives of this study are to compare contezolid acefosamil to linezolid in treating ABSSSI 
that is confirmed or suspected to be caused by Gram-positive pathogens. 
Primary: 
• Evaluate early clinical response of contezolid acefosamil compared to linezolid at early 
assessment (EA; 48 to 72 hours after the start of the first dose of IV study drug) in the intent-
to-treat (ITT) population 
• Evaluate safety and tolerability of both contezolid acefosamil IV and PO formulations 
compared with linezolid 
Secondary: 
• Evaluate early clinical response at: 
- EA in the MITT population 
- EA (overall and by baseline pathogen) in the microbiological intent-to-treat (micro-ITT) 
population 
• Evaluate percent reduction in lesion size from baseline in ABSSSI lesions at Day 7 in the 
ITT and modified intent-to-treat (MITT) populations 
• Evaluate the Investigator’s assessment of clinical response in the ITT, MITT, and clinically 
evaluable (CE) populations at each timepoint: 
- End of therapy (EOT; last day of study drug) in the ITT, MITT, and CE-EOT populations 
- Post therapy evaluation (PTE; 7 to 14 days after the EOT) in the ITT, MITT, and CE-
PTE populations 
- Late follow-up (LFU; 21-28 days after EOT) in the ITT, MITT, and CE-PTE populations 
• Evaluate per-subject microbiological response at: 
- PTE in the micro-ITT population 
- PTE in ME population 
• Evaluate per-pathogen microbiological response at: 
- PTE in the micro-ITT population 


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- PTE in the ME population 
• Evaluate Investigator’s assessment of clinical response in the micro-ITT and ME populations 
at: 
- PTE (overall and by baseline pathogen) 
- LFU (overall and by baseline pathogen) 
• Characterize the PK of 3 contezolid acefosamil metabolites (MRX-1352, contezolid, and 
MRX-1320) using sparse PK sampling in adult subjects with ABSSSI 
• Evaluate composite assessment of clinical outcome (CACO) in the ITT, micro-ITT, and CE-
PTE populations 
3.2 
Study Design Details 
This is a Phase 2, multicenter, randomized, double-blind safety and efficacy study of contezolid 
acefosamil 1500 mg IV x 1 dose, followed by 1000 mg IV every 12 hours (q12h) (± 2 hours) for 
at least 3 total IV doses, followed by 1300 mg PO q12h (± 2 hours) compared with linezolid 
600 mg IV q12h (± 2 hours) for at least 3 total IV doses followed by 600 mg PO q12h 
(± 2 hours) in adult subjects with ABSSSI. Subjects will receive study drug for a total of 10 to 
14 days. 
Up to 200 subjects (133 contezolid acefosamil : 67 linezolid) will be enrolled to achieve 
approximately 150 (100 contezolid acefosamil : 50 linezolid) clinically evaluable subjects at 
approximately 5 to 10 sites within the US and randomized 2:1 (contezolid acefosamil : linezolid) 
for treatment of ABSSSI that is confirmed or suspected to be due to a Gram-positive bacterial 
pathogen. Randomization will be stratified by ABSSSI types to better ensure proper balance 
between the treatment groups. Subjects will receive at least 3 doses of the IV formulation of 
study drug before switching to the PO formulation. Subjects will receive study drug 10 to 
14 days as described in Section 3.5. 
Screening/baseline assessments for study eligibility will be performed within 24 hours prior to 
the start of the first dose of study drug. Subjects who provide informed consent, are willing and 
able to collaborate and cooperate with study protocol requirements, and meet all study eligibility 
criteria will be randomized in the study. 
Gram stain and culture specimens of the ABSSSI site must be collected from all subjects for 
microbiologic evaluation at screening/baseline. ABSSSI site specimens (purulent discharge, skin 
biopsy, or aspiration at the leading edge of the cellulitic area) in addition to blood cultures from 
2 separate venipuncture sites, will be obtained from all subjects prior to administration of 
antibacterial therapy whenever possible. All ABSSSI site specimens will be processed for Gram 
stain and culture at the local laboratory, and all blood cultures will be processed at the local 
laboratory. All bacterial isolates that are identified from an ABSSSI site specimen or blood 
culture at the local laboratory will be sent to the central laboratory for confirmation of species 


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identification and antimicrobial susceptibility testing (Section 8.2). Microbiological methods will 
be detailed in the Laboratory Manual. 
If Gram-positive and Gram-negative pathogens are suspected (Gram stain suggests both a 
Gram-positive and Gram-negative pathogen) or proven from screening/baseline microbiologic 
laboratory results or history, the subject will be eligible for treatment under this protocol. 
Subjects with both Gram-positive and Gram-negative pathogens will receive adjunctive 
antimicrobial therapy with parenteral aztreonam (Section 5.1.3). Subjects with only 
Gram-negative pathogens are not eligible for continued treatment under this protocol and will be 
discontinued from the study as soon as Gram stain or culture confirms that the subject’s infection 
has no Gram-positive pathogen contributing to the subject’s disease. If no Gram-negative 
pathogens are isolated from the screening/baseline cultures by Day 3, aztreonam will be 
discontinued. Subjects with suspected infections primarily due to anaerobic organisms as the 
cause for ABSSSI or subjects requiring empiric adjunctive anaerobic antimicrobial coverage are 
excluded from treatment under this protocol. 
Prompt enrollment procedures are encouraged to allow for prompt administration of study drug. 
Subjects who received prior systemic antibacterial therapy with Gram-positive activity within 
96 hours prior to randomization are excluded from the study unless clear clinical evidence of 
prior treatment failure within the prior 96 hours is available (Section 4.2). However, one 
exception to this criterion is the receipt of a single dose of a short-acting, non-oxazolidinone 
antibiotic (Section 5.2). Subjects who received a single dose of a short-acting non-oxazolidinone 
Gram-positive antibiotic within 96 hours prior to randomization will not comprise > 25% of 
randomized subjects. 
It is expected that most subjects will remain in the hospital or clinic while receiving IV treatment 
with study drug for a minimum of 3 total IV doses; however, subjects who are clinically stable 
and have adequate home support with reliable transportation to/from the hospital or clinic may 
leave and return to the hospital or clinic for IV infusions. Study drug IV infusions are not to be 
administered at home. Subjects may receive the IV formulation for the entire treatment duration. 
If the primary ABSSSI lesion has not increased in area from the screening/baseline assessment 
and the Investigator determines that the subject has sufficient PO intake of food and drink to 
safely support the administration of PO doses of antibiotics, subjects may be switched to the PO 
formulation. Subjects who are switched from the IV to the PO formulation of study drug must 
remain in the hospital or clinic for observation for at least 90 minutes after the first PO dose. The 
subject may be discharged on PO medication only after good tolerability has been demonstrated 
with the initial dose of PO treatment (Section 3.5). 
Subjects will undergo follow-up visits as described in Table 1 and Section 7. Subjects must be 
evaluated directly by an Investigator (i.e., return to clinic for required assessments if being 
managed in the outpatient setting) from screening/baseline through PTE. If the subject has 
improved to the point that they have returned to their usual premorbid activity (work/school), 
and if the primary ABSSSI site has little or no pain, swelling, redness or purulent/seropurulent 
drainage at the PTE visit, the LFU visit may be performed over the telephone (Section 8.1). 
Additionally, documentation of the primary ABSSSI lesion by digital photography will occur at 
screening/baseline and at various timepoints during and after study treatment (Section 8.3). 


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ABSSSI specimen Gram stain and cultures will be collected from the primary site of infection at 
each visit from EA through LFU only if clinically indicated (e.g., the subject is deemed a clinical 
failure or relapse or purulence and discharge from the ABSSSI site continues after 
screening/baseline). 
Subjects will be monitored for the occurrence of AEs throughout the study, including AEs that 
are associated with the oxazolidinone class of antibiotics. Physical examinations, vital signs, 
ECGs, and clinical laboratory tests (hematology, chemistry, coagulation, and UA) will be 
performed at screening/baseline and at various timepoints during and after study treatment 
(Table 1). 
3.3 
Number of Subjects 
Up to 200 (133 contezolid acefosamil : 67 linezolid) adult subjects with ABSSSI will be enrolled 
in this study. Randomization will have a 2:1 (contezolid acefosamil: linezolid) allocation ratio 
with stratification for ABSSSI type. 
3.4 
Randomization & Blinding 
Efforts will be made to enroll a mixture of ABSSSI types (cellulitis/erysipelas, wound infection, 
and major cutaneous abscess); however, subjects with major cutaneous abscess should not 
comprise > 30% of randomized subjects. Additionally, subjects who received a single dose of a 
short-acting non-oxazolidinone Gram-positive antibiotic within 96 hours prior to randomization 
will not comprise > 25% of randomized subjects. 
Subjects will be randomized to treatment provided they meet all inclusion and no exclusion 
criteria (see Section 4.1 and Section 4.2, respectively). Subjects will be randomized using an 
interactive web response system (IWRS) to contezolid acefosamil or linezolid with a 2:1 ratio. 
Randomization will be stratified by ABSSSI type (cellulitis/erysipelas, wound infection, or 
major cutaneous abscess) to better ensure proper balance between the treatment groups. After 
informed consent has been obtained and study eligibility established, the study site’s Pharmacist 
or Pharmacist’s designee will obtain the study drug assignment from the IWRS. A subject is 
considered randomized when the Pharmacist or Pharmacist’s designee receives the 
randomization number or study drug assignment. 
This is a double-blind study. Those blinded to study drug assignment include the Sponsor, 
Investigator, study statistician, clinical study personnel participating in direct subject care, or 
those involved in clinical evaluations. Those unblinded to study drug assignment include the 
pharmacy personnel, the unblinded study monitor, and the bioanalytical laboratory. Blinded 
personnel must not make any effort to determine which study drug therapy is being administered. 
Blinded personnel will remain blinded to study drug assignment until all subjects have 
completed the study and the database is locked. Procedures to ensure that the blind is maintained 
are detailed in the Study Procedures Manual. 
If study drug is determined not to be safe and/or not tolerated, the study drug assignment for 
those subjects with a significant safety concern may be unblinded. The Investigator and Medical 


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Monitor will review the data, discuss the findings, and jointly decide to unblind the treatment 
assignment, continue enrollment, or terminate enrollment in the study. 
The blind may also be broken in the case of a medical emergency requiring the Investigator to 
know the identity of the study drug to appropriately guide the subject’s medical management. 
Emergency unblinding should take place through the IWRS system for both IV and oral doses, 
and both the Clinical Research Organization (CRO) and the Sponsor should be notified. Prior to 
any unblinding, the Investigator is strongly advised to discuss options with the Medical Monitor 
or appropriate Sponsor study personnel. If the blind is broken for any reason and the Investigator 
is unable to contact the Sponsor before unblinding, the Investigator must notify the Sponsor as 
soon as possible, without revealing the subject’s study drug treatment assignment (unless 
important to the safety of subjects remaining in the study). All instances of unblinding will be 
thoroughly investigated and documented by the unblinded study monitor. 
3.5 
Study Treatment 
Study treatments include contezolid acefosamil and linezolid administered as IV infusions 
followed by PO dosing as follows: 
• Contezolid acefosamil 1500 mg IV will be infused over 60 minutes (± 5 minutes) for 1 dose 
followed by at least 2 IV doses of 1000 mg IV infused over 60 minutes (± 5 minutes) q12h 
(± 2 hours) for at least 3 total IV doses, followed by contezolid acefosamil 1300 mg 
(2 capsules each with 650 mg of contezolid acefosamil) PO q12h (± 2 hours), for a total of 
10 to 14 days of treatment. 
• Linezolid 600 mg IV will be infused over 60 minutes (± 5 minutes) q12h (± 2 hours) for at 
least 3 total IV doses, followed by linezolid 600 mg (2 capsules each of 300 mg linezolid) PO 
q12h (± 2 hours), for a total of 10 to 14 days of treatment. 
Treatment with study drug will commence with the IV formulation as soon as possible after 
eligibility criteria are met. Treatment with the IV formulation will continue for at least 3 total IV 
doses, after which subjects may be switched to the PO formulation if the primary ABSSSI lesion 
has not increased in area from the baseline/screening assessment and the Investigator determines 
that the subject has sufficient PO intake of food and drink to safely support the administration of 
PO doses of antibiotics; however, subjects may receive the IV formulation for the entire 
treatment duration. It is expected that most subjects will remain in the hospital or clinic while 
receiving IV treatment with study drug for a minimum of 3 total IV doses; however, subjects 
who are clinically stable and have adequate home support with reliable transportation to/from the 
hospital or clinic may leave and return to the hospital or clinic for IV infusions. Study drug IV 
infusions are not to be administered at home. Subjects who are switched from the IV to the PO 
formulation of study drug must remain in the hospital or clinic for observation for at least 90 
minutes after the first PO dose, and until the initial dose of the PO formulation is clearly 
tolerated in the judgment of the Investigator. During outpatient management, subjects will record 
study drug dosing details on subject-specific drug accountability logs. 
To maintain the study blind, both contezolid acefosamil and linezolid PO study drug will be 
encapsulated to approximate the same external appearance. Either study drug product may be 


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taken with or without food. Subjects randomized to contezolid acefosamil will receive 2 capsules 
(650 mg each) q12h (± 2 hours), and subjects randomized to linezolid will receive 2 capsules 
(300 mg each) q12h (± 2 hours). Additional treatment information is provided in Section 5. 
Subjects are to receive 10 to 14 calendar days of study drug. The duration of treatment within the 
specified window will be determined by the Investigator based on the subject’s clinical status 
(e.g., therapy can be discontinued if the subject has improved, no more antibiotic treatment is 
medically necessary, and the risk of relapse is minimal). 
Prior to any premature discontinuation of study drug, the study site personnel should notify the 
Medical Monitor if the subject’s medical condition allows (see Section 4.6 for follow-up of 
subjects who prematurely discontinue study drug or study). 
3.6 
Duration 
Subjects will receive study drug for 10 to 14 days. Subjects will then be followed for up to 
28 days after the last calendar day of study drug. Therefore, the total duration of each subject’s 
participation in the study will be up to 42 days, excluding the screening/baseline visit that occurs 
within 24 hours prior to the start of study drug administration on Day 1. 


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4 SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Inclusion Criteria 
Subjects must meet the following inclusion criteria: 
1. Males or females ≥ 18 years 
2. Willing and able to provide written informed consent 
3. ABSSSI that is confirmed or suspected to be caused by a Gram-positive pathogen, which 
meets the following criteria: 
a. Infection of the skin with a lesion size area of at least 75 cm2, or infection of the central 
face with a lesion size area of at least 50 cm2; lesion size measured by the area of redness, 
edema, or induration using manual measurement of the longest length multiplied by the 
greatest perpendicular width 
b. One of the following infection types: 
▪ 
Cellulitis/erysipelas: A 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, related to trauma or surgery that 
occurs within 30 days of trauma or surgery 
▪ 
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 
4. Clinical findings from both of the following categories within 24 hours: 
a. At least 2 of the following local signs at the ABSSSI site: 
▪ 
Purulent or seropurulent drainage/discharge 
▪ 
Erythema 
▪ 
Fluctuance 
▪ 
Heat/localized warmth 
▪ 
Pain/tenderness to palpation 
▪ 
Swelling/induration 
b. At least 1 of the following signs of systemic inflammation: 


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▪ 
Fever or hypothermia (PO or rectal temperature ≥ 38.0°C or ≤ 36.0°C) 
▪ 
White blood cell (WBC) count ≥ 10,000/mm3 or ≤ 4,000/mm3 
▪ 
Immature neutrophils (bands) ≥ 10%, irrespective of WBC count 
▪ 
Lymphadenopathy or lymphadenitis proximal to the ABSSSI site 
▪ 
C-reactive protein (CRP) > upper limit of normal 
5. Females must be either postmenopausal for ≥2 years or surgically sterile (having undergone 
tubal ligation, hysterectomy, or bilateral oophorectomy) or, if of childbearing potential, must 
have a negative pregnancy test result at screening/baseline and be willing to use a highly 
effective method of contraception throughout the study such as 1 of the following: 
▪ 
Hormonal contraception (stable dose for 3 months) 
▪ 
Intrauterine device/intrauterine hormone-releasing system 
▪ 
Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, 
condom) 
6. Males if sexually active and nonsterile with female partners of childbearing potential must 
use 2 methods of contraception (i.e., a barrier contraceptive such as condom with spermicidal 
foam), and be willing to continue to use such highly effective birth control measures while 
participating in the study and for 70 days following participation in the study. Males must 
also refrain from sperm donations during this time. 
4.2 
Exclusion Criteria 
Subjects must NOT meet any of the following exclusion criteria: 
1. Prior receipt of any formulation of contezolid acefosamil or contezolid. 
2. ABSSSI with any of the following characteristics: 
a. Known or suspected to involve anaerobic organisms (e.g., perineal wound infection, 
gluteal decubitus ulcer, perianal abscess, wound infection associated with surgery on 
gastrointestinal tract or female genital tract) 
b. Known or suspected invasive infection due primarily to fungal, mycobacterial, parasitic, 
or viral pathogens 
c. Involving an ischemic ulcer due to peripheral vascular disease 
d. Involving a decubitus ulcer or perirectal abscess 
e. Involving a diabetic foot ulcer 


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f. Involving an infected burn 
g. Involving an underlying inflammatory skin disease that may obscure determination of 
response (e.g., chronic dermatitis) where inflammation may be prominent for an extended 
period of time, even after successful bacterial eradication has been achieved 
h. Involving pyoderma gangenosum 
i. Involving a bite from a human or animal other than an arthropod 
j. Involving a rapidly necrotizing process, such as necrotizing fasciitis 
k. Involving gangrene of any etiology 
l. Complicated by an immune deficiency in the subject (e.g., development of ecthyma 
gangrenosum, cellulitis, or wound in a neutropenic subject) 
m. Anatomically associated with prosthetic materials (e.g., venous catheters, permanent 
cardiac pacemaker battery packs, or joint replacement prostheses), even if the device is 
removed 
n. An infection complicating an area of the body that will require amputation 
o. Requiring significant surgical intervention (i.e., procedures that would not normally be 
performed at the bedside) that cannot be performed within 72 hours, unless previously 
planned, after initiating study drug therapy. 
p. Estimated high cure rate after surgical incision alone or after aggressive local skin care 
(e.g., minor cutaneous abscess or furuncle) 
q. Associated with infection at other anatomic sites or spaces, such as endocarditis or other 
endovascular infection, thrombophlebitis, osteomyelitis, or septic arthritis 
r. Anticipated need for antibacterial therapy for > 14 days 
3. Pre-existing ABSSSI known or suspected to be caused by pathogens that are resistant to 
oxazolidinone antibiotics 
4. Inability to tolerate a PO study drug (e.g., nausea, vomiting, diarrhea, or any other condition 
that might impair ingestion or absorption of PO study drug) 
5. Poor venous access 
6. History of any intolerance, hypersensitivity or allergic reaction to any oxazolidinone 
antibiotic 
7. History of any intolerance, hypersensitivity or allergic reaction to aztreonam; note that while 
cross-reactivity of aztreonam with other β-lactams is rare, this drug should be administered 


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with caution to any subject with a history of hypersensitivity to β-lactams (e.g., penicillins, 
cephalosporins, and/or carbapenems) 
8. History of peripheral or optic neuropathy 
9. QTcF interval duration > 450 msec obtained as an average from the triplicate 
screening/baseline ECGs, history of QT prolongation, hypokalemia (serum potassium 
< 3.0 mEq/L) at screening/baseline, or other proarrhythmic conditions 
10. History of a known or suspected CNS condition, such as hallucinations, depression, suicidal 
thoughts or suicidal acts, or of a CNS disorder that may predispose to seizures or lower the 
seizure threshold 
11. History of known or suspected serotonin syndrome, neuroleptic malignant syndrome, or 
carcinoid syndrome 
12. Known or suspected pheochromocytoma or thyrotoxicosis or severe uncontrolled 
hypertension 
13. History of known or suspected Clostridium difficile-associated diarrhea 
14. Evidence of significant hepatic, renal, hematologic, or immunologic disease as determined by 
the following: 
a. Total bilirubin > 2 times upper limit of normal (x ULN) 
b. Alanine amino transferase (ALT) or aspartate amino transferase (AST) > 3 x ULN 
c. Estimated or documented creatinine clearance (CrCl) of < 30 mL/min 
d. Manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy 
e. Current or anticipated as absolute neutrophils < 1500 neutrophils/mm3 
f. Platelet count < 75,000 cells/mm3 
g. Infection with human immunodeficiency virus (HIV) and a known CD4 count 
< 200 cells/mm3, or another acquired immune deficiency syndrome (AIDS)-defining 
illness 
h. Receipt of cancer chemotherapy, radiotherapy, or potent, non-corticosteroid 
immunosuppressant drugs (e.g., cyclosporine, azathioprine, tacrolimus, 
immune-modulating monoclonal antibody therapy) within the past 3 months, or the 
receipt of corticosteroids ≥ 10 mg of prednisone (or equivalent) per day for > 14 days in 
the prior 30 days 
15. Females who are pregnant or nursing 


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16. Prior administration of systemic antibacterial therapy within 96 hours before randomization 
a. EXCEPTIONS: Subjects may be eligible if they meet the following conditions: 
EITHER: 
▪ 
Received a single dose of a non-oxazolidinone, short-acting, systemic antibiotic 
within 96 hours prior to randomization (Appendix 1). Note that such subjects will not 
comprise > 25% of randomized subjects 
OR BOTH OF THE FOLLOWING: 
▪ 
Objective clinical evidence of treatment failure (persistent pain, erythema, induration, 
purulent drainage) following at least 48 hours of prior, non-study, systemic 
antibacterial therapy 
AND 
▪ 
Microbiological evidence of failure (i.e., a Gram stain obtained from an appropriate 
ABSSSI specimen collected after the initiation of this prior therapy revealing WBC 
and Gram-positive cocci, or isolation of a Gram-positive pathogen from an 
appropriate ABSSSI specimen that is resistant to the prior systemic antibacterial 
therapy) 
17. Prior (within the past 2 weeks) administration of, or expected or required concomitant (from 
the start of the study drug to EOT) administration of: 
a. Systemic adrenergic, dopaminergic, or serotonergic medications (Appendix 3) 
b. Monoamine oxidase inhibitors (MAOIs) (e.g., isocarboxazid, isoniazid, nialamide, 
phenelzine, procarbazine, and hydracarbazine) 
18. Life expectancy < 3 months or evidence of immediately life-threatening disease, including, 
but not limited to, current or impending respiratory failure, shock, acute coronary syndrome, 
unstable arrhythmias, hypertensive emergency, acute hepatic failure, active gastrointestinal 
bleeding, profound metabolic, or acute cerebrovascular events 
19. Unable to cooperate fully with the requirements of the study protocol, including the schedule 
of assessments, or likely to be non-compliant with any study requirements, or the 
Investigator determines that the subject should not participate in the study 
4.3 
Subject Withdrawal from the Study 
Subjects should be encouraged to complete all study assessments. All subjects have the right to 
withdraw at any time during the study without prejudice. 


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4.4 
Replacement of Subjects 
None of the subjects will be replaced once they have been randomized. 
4.5 
Study Termination by Sponsor and Termination Criteria 
The Sponsor reserves the right to terminate any investigational site or the clinical study at any 
time. Reasons for termination may include, but are not limited to, the following: 
• Unacceptable safety and tolerability 
• The incidence or severity of AEs or SAEs in this study indicates a potential health hazard to 
subjects 
• Serious or persistent noncompliance by the Investigator with the protocol, clinical research 
agreement, Good Clinical Practice (GCP), or applicable regulatory guidelines in conducting 
the study 
• Institutional Review Board (IRB) decision to terminate or suspend approval for the 
Investigator 
• Investigator request to withdraw from participation 
• Subject enrollment is unsatisfactory 
4.6 
Follow-up of Subjects Prematurely Discontinued from Study Drug or Withdrawn 
from Study 
Subjects who prematurely discontinue study drug will remain in the study. Efforts will be made 
to complete all protocol-specified assessments listed for the EOT visit at the time of study drug 
discontinuation (+ 1 day) (Section 7.7), and to perform follow-up safety and outcome 
assessments specified for the PTE visit (Section 7.8) and the LFU visit (Section 7.9) as 
scheduled. Complete safety assessments at the EOT visit before beginning rescue therapy, as 
appropriate. Any ongoing AEs should be followed to resolution or to a satisfactory outcome, as 
determined by the Investigator. 
For subjects who withdraw or are withdrawn from the study itself, efforts will be made to 
complete all protocol-specified assessments listed for the EOT visit at the time of withdrawal 
(+ 1 day) (Section 7.7), as appropriate, and to perform follow-up safety assessments as specified 
for the PTE visit (Section 7.8) and the LFU visit (Section 7.9) as scheduled. Complete the safety 
assessments at the EOT visit before beginning rescue therapy, as appropriate. Any ongoing AEs 
should be followed to resolution or to a satisfactory outcome, as determined by the Investigator. 
Subjects who withdraw will not be replaced. 


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5 TREATMENT OF SUBJECTS 
5.1 
Study Drug 
5.1.1 
Contezolid Acefosamil Study Drug 
Contezolid acefosamil study drug will be supplied as lyophilized powder for reconstitution as an 
IV formulation and an immediate release oral formulation. The clinical label will identify the 
product by name, lot number, Sponsor, storage conditions, and expiry date. Administration of the 
study drug is limited for investigational use only. Refer to the Pharmacy Manual for additional 
information. 
5.1.1.1 
Contezolid Acefosamil for Intravenous Administration 
Contezolid acefosamil drug product will be supplied in 20 ml vials containing 1000 mg, of 
contezolid acefosamil, 24.53 mg of sodium citrate dihydrate, and 9.60 mg of citrate is produced 
by filter sterilization and lyophilization. The drug product was produced for the Sponsor by 
Lyophilization Services of New England. 
The drug product powder is to be reconstituted in 300 mL of 5% dextrose in water (D5W) or 
normal saline (NS) for intravenous administration. The first IV dose of contezolid acefosamil 
will be 1500 mg, and all subsequent IV doses will be 1000 mg each. The contezolid acefosamil 
solution in either a diethylhexyl phthalate (DEHP) containing or non-DEHP containing IV bag is 
stable for up to 16 hours at 25ºC (77ºF), and stable for up to 48 hours at 4ºC (39.2ºF). To ensure 
long term stability of the drug product, the lyophilized vials will be maintained at -20ºC at the 
investigative site until it is to be reconstituted for use in the clinic. 
An unblinded pharmacist will prepare and blind the contezolid acefosamil IV infusion and will 
be unblinded to the subject’s assigned treatment; however, all other staff will be blinded to the 
subject’s treatment. Please refer to the Pharmacy Manual for details on dose preparation and 
administration. 
5.1.1.2 
Contezolid Acefosamil for Oral Administration 
Contezolid acefosamil for PO administration is an immediate-release tablet containing 650 mg 
contezolid acefosamil. To maintain the study blind, contezolid acefosamil tablets will be 
over-encapsulated to approximate the same external appearance as linezolid study drug. All PO 
doses of contezolid acefosamil will be 1300 mg (2 capsules). Contezolid acefosamil capsules 
will be included as part of a blinded kit to ensure all study staff will be blinded to the subject’s 
treatment. 
5.1.2 
Linezolid Study Drug 
Linezolid (Zyvox®) is an FDA-approved commercially available product and will be supplied as 
IV and PO formulations. The clinical label will identify the product by name, lot number, 
Sponsor, storage conditions, and expiry date. Refer to the Pharmacy Manual for additional 
information. 


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5.1.2.1 
Linezolid for Intravenous Administration 
Linezolid for IV administration will be provided as 300 mL (600 mg linezolid) single-use, ready 
to use flexible plastic infusion bags in a foil laminate overwrap. All IV doses of linezolid will be 
600 mg. Please refer to the Pharmacy Manual for details on dose preparation and administration. 
The unblinded pharmacist will prepare and blind the linezolid IV infusion and will be unblinded 
to the subject’s assigned treatment; however, all other staff will be blinded to the subject’s 
treatment. 
5.1.2.2 
Linezolid for Oral Administration 
Linezolid for PO administration will be provided as 300 mg capsules. To maintain the study 
blind, linezolid capsules will approximate the same external appearance as contezolid acefosamil 
study drug. All PO doses of linezolid will be 600 mg (2 capsules). Capsules containing linezolid 
will be included as part of a blinded kit to ensure all study staff will be blinded to the subject’s 
treatment. 
5.1.3 
Adjunctive Therapy 
Linezolid has no useful antimicrobial activity against Gram-negative pathogens and is not 
indicated for the treatment of Gram-negative infections; it is critical that specific Gram-negative 
therapy with aztreonam be initiated immediately if a concomitant Gram-negative pathogen is 
documented or suspected. The PK of linezolid and aztreonam are not altered when co-
administered (Zyvox® Prescribing Information, 2018). 
According to standard of care treatment guidelines, subjects will receive adjunctive antimicrobial 
therapy with parenteral aztreonam (1 to 2 g IV/ intramuscular (IM) q8h, not to exceed 6 g/day) 
for confirmed or suspected aerobic Gram-negative pathogens as causes of the ABSSSI in 
addition to Gram-positive pathogens. Outpatients may receive either IM or IV aztreonam at the 
Investigator's discretion (e.g., IV aztreonam may be administered as outpatient parenteral 
antibiotic therapy in an infusion center). If no Gram-negative pathogen is isolated from the 
screening/baseline cultures by Day 3, aztreonam is to be discontinued. 
Parenteral aztreonam will be provided by the study sites and should be prepared and 
administered in accordance with current FDA label information (Azactam® Package Insert, 
2013). 
5.1.4 
Dose Adjustment 
No adjustments to study drug doses or frequencies are allowed. 
5.1.5 
Study Drug Compliance 
Each dose of IV study drug will be administered by study staff, who are oriented to the details of 
the clinical protocol and under direct supervision by the Investigator. 


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The following study drug compliance information will be documented as study information and 
reported in the electronic case report form (eCRF): 
• The dates and times of administration of each IV study drug infusion. 
• For IV infusion, the infusion start and stop times will be recorded, and specify if the total 
volume of study drug solution was administered (if infusion is halted or interrupted for any 
reason, record the time of premature discontinuation and re-initiation of infusion). An 
unblinded member of the study staff will inspect the infusion line and bag at the end of 
infusion to confirm that the full dose has been infused, followed by a rapid IV push to clear 
any residual study drug in the line. Infusion bags will be retained by the pharmacy for drug 
accountability purposes until after the study close-out monitoring visit by the unblinded 
monitor. 
• The total volume infused for IV infusion, and number of capsules administered for PO 
administration. 
For any infusion that is incomplete or otherwise not administered over 60 minutes (± 5 minutes), 
the actual volume infused, infusion duration, and conditions or complications that prevented 
complete and/or timely administration must be documented. In any case, study site personnel 
should strive to administer the entire dose regardless of the inter-current problems of drug 
administration. 
Recording of the date and whether each dose of study drug was administered will be used to 
document compliance with the assigned dosing regimen for oral drug. Subjects managed as 
outpatients will be given diaries to log times and dates of study drug administration; this 
information will be entered in the eCRF. The determination of blood concentrations of 
contezolid acefosamil (and metabolites) during the analytical phase will serve as a further check 
of compliance. 
5.1.6 
Study Drug Storage 
Unused study drug supplies should be stored according to the directions on the study drug labels. 
• Contezolid acefosamil: Lyophilized contezolid acefosamil (for IV formulation) must be 
stored in a secure area (e.g., a locked freezer), protected from moisture, and kept at or below 
-20°C until the time of preparation for study drug administration. Once reconstituted with 
D5W or NS, the solution is stable in either a DEHP containing or non-DEHP containing IV 
bag for up to 16 hours at 25ºC (77ºF), and stable for up to 48 hours at 4ºC (39.2ºF). 
Contezolid acefosamil capsules (over-encapsulated tablets) must be stored at 2 to 8ºC 
(35.6 to 46.4ºF) at the study site but can be stored at 20 to 25ºC (68 to 77ºF) after dispensing 
to the study subject for up to 7 days. 
• Linezolid: Store infusion bags at 20 to 25ºC (68 to 77ºF) and protect from light. It is 
recommended that the infusion bags be kept in the overwrap until ready to use. Each 
overwrap contains a peel-off label. Apply the peel-off label to the infusion bag for barcode 
scanning before use. Protect infusion bags from freezing (Zyvox® Prescribing Information, 


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2018). For linezolid capsules, please refer to storage instructions for contezolid acefosamil 
capsules. Keep bottles tightly closed to protect from moisture. 
Refer to the Pharmacy Manual for any additional storage, handling, or updated stability data of 
the study drug supplies. 
5.1.7 
Study Drug Accountability 
All supplies of contezolid acefosamil and linezolid required for completion of this study will be 
provided by the Sponsor. Adjunctive therapy with aztreonam will be supplied by the study sites. 
The unblinded pharmacy personnel are responsible for ensuring that a current record of 
inventory and drug accountability is maintained during study conduct. A specifically designated 
unblinded study monitor or designee will be responsible for drug accountability at the site. The 
Investigator is ultimately responsible for ensuring that a current record of inventory/drug 
accountability is maintained. Inventory and accountability records must be readily available for 
inspection by the Sponsor or designee, or applicable regulatory authorities at any time. 
Each shipment of study drug will contain a packing slip or equivalent to assist in maintaining 
current and accurate inventory records. Upon receipt of the study drug, the unblinded pharmacy 
personnel will visually inspect the shipment and verify the number and condition of study drug 
(vials, infusion bags, capsules) received. Refer to the Pharmacy Manual for additional 
information. 
Sites will be provided with subject-specific drug accountability logs and subjects will be 
instructed to maintain a diary of their drug dosing during outpatient management throughout the 
treatment period. 
5.1.8 
Study Drug Handling and Disposal 
Only upon written authorization from MicuRx or its representative, all partially used study drug 
must be destroyed at the investigative site or at another site designated by the Sponsor. 
Unopened drug kits will be destroyed at a site designated by the Sponsor. The Investigator is 
responsible for ensuring that MicuRx, or its representative, has provided written authorization 
that procedures for proper disposal of the study drug have been established, and that appropriate 
records of the disposal are documented and maintained. 
5.2 
Prior & Concomitant Therapy 
All prescription medications and over-the-counter medications, including herbal, nutritional, and 
dietary supplements (e.g., any antacid, iron supplement, or multivitamin) administered within 
2 weeks (14 days) prior to randomization and during the study between Day 1 and EOT will be 
documented in the eCRF. Only concomitant antimicrobial agents and concomitant medications 
taken for an AE between EOT and LFU will be documented. Any changes in prior or 
concomitant medications will also be recorded. 


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Subjects who have received prior systemic antibacterial therapy within 96 hours prior to 
randomization are generally excluded from the study; however, exceptions to this criterion 
include: 
• Receipt of a short-acting, systemic, non-oxazolidinone antibiotic and 
• Clear failure of an alternative course of prior antibiotic therapy (Section 4.2, Appendix 1). 
In addition, the following medications are not allowed from 2 weeks prior to administration of 
study drug through EOT (Section 4.2): 
• Systemic adrenergic, dopaminergic, or serotonergic medications (Appendix 3) 
• Any MAOI (e.g., isocarboxazid, isoniazid, nialamide, phenelzine, procarbazine, and 
hydracarbazine) 
Concomitant topical or systemic antibacterial therapy, other than study drug and adjunctive 
parenteral aztreonam, is not allowed between screening/baseline and PTE (unless the subject is a 
clinical failure). 
The following additional adjunctive therapy is allowed, as clinically indicated: 
• Daily dressing changes 
• Topical solutions including nonspecific antimicrobial solutions (e.g., povidone-iodine); 
however, topical therapy with specific antibacterial activity is not allowed (e.g., mupirocin, 
retapamulin, fusidic acid) 
• Surgical debridement 
• Hyperbaric oxygen treatments 
• Surgical interventions (i.e., incision and drainage, aspiration puncture, or excision with or 
without grafting) planned at the initiation of treatment through 72 hours after the start of 
dosing 


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6 SUBJECT RESTRICTIONS 
Subjects are required to: 
• Avoid taking any of the following concomitant medications between Day 1 (first 
administration of study drug) and EOT (last calendar day of study drug). 
○ Any adrenergic, dopaminergic, or serotonergic medication, including selective serotonin 
reuptake inhibitors (SSRIs) or tricyclic antidepressants (Appendix 3). 
○ Any MAOI (e.g., isocarboxazid, isoniazid, nialamide, phenelzine, procarbazine, and 
hydracarbazine). 
○ Any non-study systemic antibiotic or topical antimicrobial therapy with specific 
antibacterial activity (e.g., topical mupirocin, retapamulin, or fusidic acid); note that the 
use of topical solutions including nonspecific antimicrobial solutions (e.g., povidone-
iodine) are allowed. 
○ Note: While hypoglycemic medications are not contraindicated, such agents (e.g., insulin 
or PO hypoglycemic) should be used with caution. Postmarketing cases of symptomatic 
hypoglycemia have been reported in subjects with diabetes mellitus receiving 
hypoglycemic agents when treated with linezolid. While a causal relationship between 
linezolid (or other oxazolidinones) and hypoglycemia has not been established, diabetic 
subjects should be cautioned of potential hypoglycemic reactions when treated with study 
drug. If hypoglycemia occurs, a decrease in the dose the hypoglycemic agent, or 
discontinuation of the hypoglycemic agent and/or study drug may be required. 
• Avoid consumption of large amounts of foods or beverages with high-tyramine content, 
including those foods that have been processed by aging, fermentation, pickling, or smoking 
to improve flavor (e.g., aged cheeses, fermented or air-dried meats, sauerkraut, soy sauce, tap 
beers) from Day 1 to EOT; see Appendix 2 for a detailed list. 
• Females must be either postmenopausal for ≥2 years or surgically sterile (having undergone 
tubal ligation, hysterectomy, or bilateral oophorectomy) or, if of childbearing potential, must 
have a negative serum or urine pregnancy test (β-HCG) at screening/baseline and be willing 
to use a highly effective method of contraception throughout the study such as 1 of the 
following: 
○ Hormonal contraception (stable dose for 3 months) 
○ Intrauterine device/intrauterine hormone-releasing system 
○ Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, condom) 
• Males (if sexually active and nonsterile) with female partners of childbearing potential must 
use 2 methods of contraception (i.e., a barrier contraceptive such as condom with spermicidal 
foam) and be willing to continue to use these same birth control measures while participating 


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in the study (and for 70 days following participation in the study). Males must also refrain 
from sperm donations during this time. 


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7 STUDY PROCEDURES 
The schedule of events is provided in Table 1. 
• Written informed consent must be obtained prior to initiating any study assessment or 
procedure. 
• It is expected that most subjects will remain in the hospital or clinic while receiving IV study 
drug for a minimum 3 infusions; however, subjects who are clinically stable and have 
adequate home support with reliable transportation to/from the hospital or clinic may leave 
and return to the hospital or clinic for IV infusions. Study drug IV infusions are not to be 
administered at home. Subjects who are switched to the PO formulation of study drug must 
remain in the hospital or clinic for observation for at least 90 minutes after the first PO dose, 
and until the initial dose(s) of the PO formulation are clearly tolerated in the judgment of the 
Investigator (Section 3.5). 
• All assessments and procedures on dosing days are obtained predose, unless otherwise 
specified. 
• After screening/baseline, microbiological assessments (ABSSSI site and/or blood cultures) 
should be repeated only if clinically indicated (e.g., if a subject is deemed a clinical failure or 
if purulence and discharge from the ABSSSI site continues after screening/baseline). 
• Refer to Section 4.6 for follow-up of subjects who prematurely discontinue study drug or the 
study. 
7.1 
Screening/Baseline 
Study eligibility must be confirmed within 24 hours prior to the first administration of study 
drug. The following screening/baseline assessments and procedures will be performed ≤24 hours 
of first dose (see Table 1 for those assessments that need to be repeated predose on Day 1 if the 
first dose of study drug is administered > 24 hours after the screening/baseline assessments): 
• Obtain written informed consent prior to initiating any study-related assessment or procedure 
• Obtain complete medical and surgical history 
• Obtain prior and concomitant medication history. Record all prior medications taken within 2 
weeks prior to randomization (Section 5.2). 
• Perform ABSSSI clinical assessments: 
○ Perform primary ABSSSI site measurement and a direct evaluation of signs and 
symptoms of ABSSSI (Section 8.1, Appendix 5, Appendix 6). 
○ Perform digital photography of the primary ABSSSI lesion with a digital camera 
provided by the Sponsor (Section 8.3, Appendix 7). 


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• Perform a complete physical examination (i.e., general appearance, head, ears, eyes 
[including basic Snellen visual acuity and visual field testing], nose, throat, dentition, 
thyroid, chest [heart, lungs], abdomen, skin/soft tissues, neurological, extremities, back, 
neck, musculoskeletal, lymph nodes). 
• Record vital signs (heart rate, blood pressure, respiratory rate, and temperature). If 
> 1 temperature is measured within a calendar day, record the highest daily temperature 
measured. Vital signs will be collected prior to collection of blood laboratory samples. Oral 
or rectal temperatures are acceptable; the site of measurement will be collected in the eCRF. 
• Record height and weight. 
• Obtain triplicate 12-lead ECG recordings within a 15-minute period, each separated by at 
least one minute. The ECG recordings will be obtained prior to collection of blood laboratory 
samples. All ECGs will be performed using the ECG machines provided by eResearch 
Technologies (eRT) and will be sent to eRT for central reading. 
• Assess, identify, and record any AEs or SAEs from the time the informed consent is signed. 
• Perform microbiological assessments (see Section 8.2); additional microbiological specimen 
collection and processing details are available in the Laboratory Manual: 
○ Obtain appropriate ABSSSI site specimen for bacterial culture and Gram stain from all 
subjects and refer the specimens for Gram stain and culture to the local laboratory for 
processing. The ABSSSI site specimen should be obtained before administration of 
antibacterial therapy whenever possible. Repeat ABSSSI specimen cultures and Gram 
stain at subsequent visits only if clinically indicated (e.g., if subject is deemed a clinical 
failure or purulence and discharge at the ABSSSI site continues after screening/baseline). 
○ Obtain 2 sets of blood cultures (each consisting of 1 aerobic and 1 anaerobic blood 
culture bottle from 2 separate venipuncture sites) from all subjects. The blood cultures 
should be obtained before administration of antibacterial therapy, whenever possible. 
Blood cultures must be repeated every 3 days (± 1 day) if the previous blood culture was 
positive, or at any time after screening/baseline if clinically indicated. If the repeat blood 
culture remains positive with the bacterial pathogen initially isolated, the Investigator 
must consider modifying the subject’s antibiotic therapy and discuss the case with the 
Medical Monitor. 
• Record if the subject’s premorbid activities (work/school) are compromised 
• Obtain samples for laboratory assessments (see Appendix 4 for specific tests). Laboratory 
samples for screening/baseline will be drawn and sent to both the local laboratory (for 
eligibility) and to the central laboratory. 
○ Obtain blood samples for hematology, chemistry, CRP, serology, and coagulation tests. 


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○ Obtain urine sample for UA (includes urine microscopy if UA is positive for RBCs, 
WBCs, or protein). 
○ Perform serum or urine β-HCG pregnancy test for females of childbearing potential up to 
2 years postmenopause. (Alternatively, females must be surgically sterile, i.e., have had a 
tubal ligation, hysterectomy, or bilateral oophorectomy.) 
○ Obtain the subject’s estimated CrCl. The subject’s estimated CrCl will be calculated by 
the local laboratory (for eligibility purposes) using screening/baseline height (m), actual 
weight (kg), and serum creatinine: 
Males: 
CrCl =  
(140 – age in years) × weight (kg) 
 
72 × serum creatinine (mg/dL) 
 
Females: 
CrCl =  (140 – age in years) × weight (kg) × 0.85 
 
72 × serum creatinine (mg/dL) 
• Verify that the subject meets all inclusion criteria (Section  4.1) and none of the exclusion 
criteria (Section 4.2). 
7.2 
Day 1 
Day 1 is the first day of study drug administration; subsequent study days are consecutive 
calendar days. Select screening/baseline assessments need to be repeated on Day 1 (predose) if 
the screening/baseline assessments occurred > 24 hours before the first dose of study drug is 
administered (see Table 1). Eligible subjects are randomized on Day 1. It is expected that most 
subjects will remain in the hospital or clinic while receiving the IV formulation of study drug for 
a minimum of 3 IV doses; however, subjects who are clinically stable and have adequate home 
support may leave and return to the hospital or clinic for IV infusions. Study drug IV infusions 
are not to be administered at home (Section 3.5). 
The following will be performed on Day 1: 
• Verify the subject meets all inclusion criteria and exclusion criteria before randomization 
(Section 4.1 and Section 4.2, respectively). 
• Randomize the subject to treatment. 
• IV study drug will be administered q12h (± 2 hour) as described in Section 3.5. 
• A PK sample will be collected from those who elect to participate in the PK portion of the 
study between 0.5 and 2 hours after the 1st IV dose, as outlined in Section 11.  


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• Obtain triplicate 12-lead ECG recordings within a 15-minute period, each separated by at 
least one minute, within 1 hour prior to the start of IV infusion and 2 hours after the 
completion of the IV infusion. The ECG recordings will be obtained prior to collection of 
any blood laboratory samples. 
• Assess, identify, and record any AEs or SAEs. 
Refer to Section 4.6 for follow-up of subjects who prematurely discontinue study drug or the 
study. 
7.3 
Day 2 
On Day 2, subjects continue to receive the IV formulation of study drug to complete at least a 
total of 3 infusions. Subjects who are switched from the IV to the PO formulation of study drug 
must remain in the hospital or clinic for observation for at least 90 minutes after the first PO 
dose, and until the initial dose of the PO formulation is clearly tolerated in the judgment of the 
Investigator (Section 3.5). 
No specific assessments or procedures are scheduled on Day 2 except PK samples at select sites: 
• Obtain specimen for PK assessments at specified sites for selected subjects: 
○ Obtain a 1st blood sample (trough level) within 2 hours before the 3rd IV dose, a 2nd 
blood sample between 0.5 and 3 hours after the end of the 3rd IV dose, and a 3rd blood 
sample between 4 and 11 hours after the end of the 3rd IV dose but before the 4th dose of 
study drug (IV or PO). 
In-person evaluation by the Investigator is not required unless clinically indicated (e.g., perform 
microbiological assessments, including ABSSSI site specimen and blood cultures, only if 
clinically indicated [e.g., if study drug is prematurely withdrawn for insufficient therapeutic 
effect]). Subjects continue to receive blinded study drug q12h (± 2 hours) and any new 
concomitant medications and AEs or SAEs are recorded. 
Refer to Section 4.6 for follow-up of subjects who prematurely discontinue study drug or the 
study. 
7.4 
Early Assessment 
Perform EA assessments 48 to 72 hours after the start of the first dose of IV study drug. Clinical 
assessments of ABSSSI from this visit will be used to programmatically determine the clinical 
response based on data recorded on the eCRF (Section 9.1.1). If the subject is receiving 
adjunctive antimicrobial therapy with aztreonam and no Gram-negative pathogen is isolated 
from the screening/baseline cultures by Day 3, aztreonam should be discontinued (Section 5.1.3). 
The following will be performed: 


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• Record any new concomitant medications; verify the subject is not taking any restricted 
medications (Section 6). 
• Perform ABSSSI clinical assessments: 
○ Perform primary ABSSSI site measurement and a direct evaluation of signs and 
symptoms of ABSSSI (Section 8.1, Appendix 5, Appendix 6). 
○ Perform digital photography of the primary ABSSSI lesion with a digital camera 
provided by the Sponsor (Section 8.3, Appendix 7). 
• Perform a limited, symptom directed physical examination as clinically indicated. 
• Record vital signs (heart rate, blood pressure, respiratory rate, and temperature) as described 
in Section 7.1. 
• Obtain triplicate 12-lead ECG recordings within a 15-minute period, each separated by at 
least one minute, prior to collection of laboratory (including PK) blood samples. Time of 
prior dose of study drug and relationship of time of ECG to dose must be documented. 
• Assess, identify, and record any AEs or SAEs. 
• Perform microbiological assessments as described in Section 7.1 and Section 8.2, including 
ABSSSI site specimen (if clinically indicated) and blood cultures (if previous blood culture 
was positive or if clinically indicated). 
• Obtain samples for laboratory assessments after a minimum 8-hour fast (Appendix 4): 
○ Obtain blood samples for hematology, chemistry, CRP, and coagulation tests. 
○ Obtain urine sample for UA (includes urine microscopy if UA is positive for RBCs, 
WBCs, or protein). 
• Continue study drug administration q12h (± 2 hours). If the subject received optional 
adjunctive parenteral aztreonam and no Gram-negative pathogen was isolated from ABSSSI 
site specimen culture or blood culture by Day 3, aztreonam must be discontinued 
(Section 5.1.3). 
Refer to Section 4.6 for follow-up of subjects who prematurely discontinue study drug or the 
study. 
7.5 
Early Assessment to Day 6 
No specific assessments or procedures are scheduled between EA and Day 6. In-person 
evaluation by the Investigator need not occur unless clinically indicated. Examples include: 


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• Clinically indicated microbiological assessments as described in Section 7.1 and Section 8.2, 
including ABSSSI site specimen (if clinically indicated) and blood cultures (if previous 
blood culture was positive or if clinically indicated). 
• Investigator has determined that the subject may be switched from the IV formulation of 
study drug to the PO formulation. 
Record any new concomitant medications and record any AEs or SAEs if the subject is seen 
during an unscheduled visit. 
Refer to Section 4.6 for follow-up of subjects who prematurely discontinue study drug or the 
study. 
7.6 
Day 7 
The subject will be seen on Day 7 (± 1 day) primarily for safety assessments and to evaluate for 
signs and symptoms of ABSSSI. The following will be performed: 
• Record any new concomitant medications; verify the subject is not taking any restricted 
medications (Section 6). 
• Perform ABSSSI clinical assessments: 
○ Perform primary ABSSSI site measurement and a direct evaluation of signs and 
symptoms of ABSSSI (Section 8.1, Appendix 5, Appendix 6). 
○ Perform digital photography of the primary ABSSSI lesion with a digital camera 
provided by the Sponsor (Section 8.3, Appendix 7). 
• Perform a limited, symptom directed physical examination as clinically indicated. 
• Record vital signs (heart rate, blood pressure, respiratory rate, and temperature) as described 
in Section 7.1. 
• Assess, identify, and record any AEs or SAEs. 
• Perform microbiological assessments as described in Section 7.1 and Section 8.2, including 
ABSSSI site specimen (if clinically indicated) and blood cultures (if previous blood culture 
was positive or if clinically indicated). 
• Obtain samples for laboratory assessments after a minimum 8-hour fast (Appendix 4): 
○ Obtain blood samples for hematology, chemistry, CRP, and coagulation tests. 
○ Obtain urine sample for UA (includes urine microscopy if UA is positive for RBCs, 
WBCs, or protein). 


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• Continue study drug administration q12h (± 2 hours) 
Refer to Section 4.6 for follow-up of subjects who prematurely discontinue study drug or the 
study. 
7.7 
End of Therapy 
Perform EOT assessments on the last calendar day of study drug administration (or the next day). 
The EOT visit will alternatively be performed for subjects who withdraw from study drug 
treatment (Section 4.6). 
Subjects will receive study drug for 10 to 14 days as described in Section 3.5. If a subject 
requires a longer course of therapy for any reason (e.g., unresolved ABSSSI, S. aureus 
bacteremia, deep-seated abscesses [e.g., psoas abscess, epidural abscess], osteomyelitis, 
endocarditis), the subject will be deemed a clinical failure and open-label antimicrobial(s) should 
be started, at the discretion of the Investigator. Such cases must be discussed with the Medical 
Monitor. 
The following will be performed: 
• Record any new concomitant medications; verify the subject is not taking any restricted 
medications (Section 6). 
• Perform ABSSSI clinical assessments: 
○ Perform ABSSSI site measurement and a direct evaluation of signs and symptoms of 
ABSSSI (Section 8.1, Appendix 5, Appendix 6). 
○ Perform digital photography of the primary ABSSSI lesion with a digital camera 
provided by the Sponsor (Section 8.3, Appendix 7). 
○ Perform Investigator’s assessment of clinical response (Section 9.1.2). 
• Perform a complete physical examination, including eye examination [i.e., Snellen visual 
acuity and visual field testing] as described in Section 7.1. 
• Record vital signs (heart rate, blood pressure, respiratory rate, and temperature) as described 
in Section 7.1. 
• Obtain triplicate 12-lead ECG recordings within a 15-minute period, each separated by at 
least one minute. The ECG recordings will be obtained prior to collection of blood laboratory 
(including PK) samples. Time of prior dose of study drug and relationship of time of ECG to 
dose must be documented. 
• Assess, identify, and record any AEs or SAEs. 


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• Record the date the subject returned to premorbid level of activity (work/school), as 
applicable. 
• Perform microbiological assessments as described in Section 7.1 and Section 8.2, including 
ABSSSI site specimen (if clinically indicated) and blood cultures (if previous blood culture 
was positive or clinically indicated). 
• Obtain samples for laboratory assessments after a minimum 8-hour fast (Appendix 4): 
○ Obtain blood samples for hematology, chemistry, CRP, and coagulation tests. 
○ Obtain urine sample for UA (includes urine microscopy if UA is positive for RBCs, 
WBCs, or protein). 
○ Obtain blood or urine sample for β-HCG pregnancy test (females of childbearing 
potential up to 2 years postmenopause). (Alternatively, females must be surgically sterile; 
i.e., have had a tubal ligation, hysterectomy, or bilateral oophorectomy.) 
• Obtain specimen for PK assessments at specified sites for selected subjects: 
○ Obtain one blood sample (trough level) within 2 hours before the last dose (IV or PO).  If 
the last dose is given PO: obtain 1 blood sample between 1.5 to 4 hours after the last 
dose, and obtain 1 additional sample between 5 to 12 hours after the last dose.  If the last 
dose is given IV: obtain 1 blood sample between 0.5 and 3 hours after the end of the last 
infusion, and obtain 1 additional sample between 4 and 11 hours after the end of the last 
infusion (Section 11). 
Refer to Section 4.6 for follow-up of subjects who prematurely discontinue study drug or the 
study. 
7.8 
Post Therapy Evaluation 
Perform PTE assessments 7 to 14 days after EOT. The following will be performed: 
• Record any new concomitant medications (antimicrobial agents only). 
• Perform clinical assessments: 
○ Perform a direct evaluation of signs and symptoms of ABSSSI (Section 8.1, Appendix 5, 
Appendix 6). 
○ Perform Investigator’s assessment of clinical response (Section 9.1.2). 
• Perform a limited, symptom directed physical examination as clinically indicated. 
• Record vital signs (heart rate, blood pressure, respiratory rate, and temperature) as described 
in Section 7.1. 


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• Obtain triplicate 12-lead ECG recordings within a 15-minute period, each separated by at 
least one minute. The ECG recordings will be obtained prior to collection of blood laboratory 
samples. 
• Assess, identify, and record any AEs or SAEs. 
• Record the date the subject returned to premorbid level of activity (work/school), as 
applicable. 
• Perform microbiological assessments as described in Section 7.1 and Section 8.2 including 
ABSSSI site specimen (if clinically indicated) and blood cultures (if previous blood culture 
was positive, or if clinically indicated). 
• Obtain samples for laboratory assessments after a minimum 8-hour fast (Appendix 4): 
○ Obtain blood samples for hematology, chemistry, CRP, and coagulation tests. 
○ Obtain urine sample for UA (urine microscopy if UA is positive for RBCs, WBCs, or 
protein). 
Refer to Section 4.6 for follow-up of subjects who prematurely discontinue from the study. 
7.9 
Late Follow-up 
The LFU assessment, designed to provide an assessment of durability of response, is performed 
21 to 28 days after EOT. If the subject has improved to the point that they have returned to their 
usual premorbid activity (work/school), and if the primary ABSSSI site had little or no pain, 
swelling, redness, or purulent/seropurulent drainage at the PTE visit, then the LFU visit may be 
performed over the telephone. Symptoms related to possible relapse of ABSSSI (primary site) 
will be evaluated as part of the safety assessment. If conducted by telephone and clinical 
relapse/failure is suspected, the subject should be examined and evaluated in-person. 
The following will be performed: 
• Record any new concomitant medications (antimicrobial agents only). 
• Perform Investigator’s assessment of clinical response (Section 9.1.2). 
• Record the date the subject returned to premorbid level of activity (work/school), as 
applicable. 
• Assess, identify, and record any AEs or SAEs. 


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8 ASSESSMENT OF THE ACUTE BACTERIAL SKIN AND SKIN 
STRUCTURE INFECTION 
8.1 
Clinical Assessments 
All subjects must have their primary ABSSSI site evaluated by the Investigator, including 
ABSSSI site measurements described below. Digital photographs of the ABSSSI site will also be 
taken as described in Section 8.3. When conducting a clinical examination of the primary 
ABSSSI site, the Investigator will perform and record the following: 
• Extent of the infection (area in cm2), as measured by the area of redness, edema, or 
induration using manual measurement of the longest length multiplied by the greatest 
perpendicular width, with a ruler provided by the Sponsor. Note that only measurement of 
the longest length and the greatest perpendicular width (and not calculation of area in cm2) 
will be collected and the area in cm2 will be calculated by the eCRF. Instructions for primary 
ABSSSI measurements are provided in Appendix 5. 
• Local signs and symptoms of erythema (and any distant extension of erythema), 
swelling/edema, localized warmth, tenderness on palpation, drainage, fluctuance, and 
induration as described in Appendix 6. 
In addition, record the following information at screening/baseline only: 
• Primary anatomical site 
• Predisposing cause of infection, if any (e.g., trauma, arthropod bite, fungal dermatosis, 
surgery, spontaneous, etc.) 
8.2 
Microbiological Assessments 
As detailed in Section 7.1, all subjects enrolled with ABSSSI in this study must undergo 
microbiological assessments (i.e., ABSSSI site specimens and blood cultures) at 
screening/baseline and these samples should be obtained from all subjects prior to administration 
of antibacterial therapy whenever possible. 
The screening/baseline microbiological assessments are critical, in that microbiological response 
is an important secondary outcome of the study (Section 3.1). Also, the antibacterial spectrum of 
study drug (contezolid acefosamil or linezolid) is limited to Gram-positive pathogens (e.g., 
staphylococci and streptococci); therefore, it is important to determine whether non-Gram-
positive pathogens are involved in the ABSSSI, in addition to Gram-positive pathogens. 
Adjunctive parenteral aztreonam should be administered for confirmed or suspected aztreonam-
susceptible aerobic Gram-negative pathogens as causes of the ABSSSI in addition to Gram-
positive pathogens (Section 5.1.3); however, subjects with suspected Gram-negative pathogens 
only (e.g., infection caused by Pseudomonas aeruginosa in a subject with severe burns) must be 
excluded. Similarly, polymicrobial ABSSSI involving anaerobic organisms must be excluded 
from the study, as empiric antibiotics with anti-anaerobic activity are not allowed, and subjects 


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with suspected or known mycobacterial or fungal ABSSSI are not eligible for study entry 
(Section 4.2). 
The method used for obtaining a microbiological ABSSSI site specimen for Gram stain and 
culture depends on the ABSSSI type: 
• For cellulitis, obtain a specimen by needle aspiration or skin biopsy at the proximal leading 
edge of erythema, edema, or induration for Gram stain and aerobic bacterial culture. 
• For wound infection, obtain a deep-site tissue specimen (e.g., tissue biopsy) or needle 
aspiration from an area that is physically contiguous with the wound for Gram stain and 
aerobic bacterial culture. 
• For major cutaneous abscess, obtain purulent material during the drainage procedure for 
Gram stain and aerobic bacterial culture. 
Superficial swabs of infected areas are not acceptable, due to the high probability that such 
specimens could be contaminated with clinically insignificant, and therefore misleading, isolates. 
However, deep swabs taken during significant surgical interventions are acceptable. 
In addition, 2 sets of blood cultures (each consisting of 1 aerobic and 1 anaerobic blood culture 
bottle from 2 separate venipuncture sites) will be collected from all subjects, regardless of 
location of management (inpatient or outpatient). The blood cultures should be obtained before 
administration of antibacterial therapy, whenever possible. Blood cultures must be repeated 
every 3 (± 1) days if the previous blood culture was positive, or at any time after 
screening/baseline if clinically indicated. If the repeat blood culture remains positive with the 
bacterial pathogen initially isolated, the Investigator must consider modifying the subject’s 
antibiotic therapy and discuss the case with the Medical Monitor. 
After screening/baseline, microbiological assessments (ABSSSI site and/or blood cultures) 
should be repeated only when clinically indicated (e.g., at EOT if study drug is prematurely 
withdrawn for insufficient clinical effect [clinical failure] at the time of relapse or recurrence 
after EOT, or if purulence and discharge from the ABSSSI site continues after 
screening/baseline). 
For all microbiological specimens (ABSSSI site and blood), Gram stain, and culture should be 
performed at the local laboratory according to local standards of care. If bacterial growth occurs 
from culture, the isolate(s) must be sent to the central laboratory for confirmation of organism 
identity (to genus and species level) and susceptibility. Refer to the Laboratory Manual for 
specific procedures pertaining to the collection, processing, storage, and shipment of bacterial 
isolates. 
Antimicrobial susceptibility testing should be performed at the local laboratory according to 
local standards of care; all clinically significant Gram-positive pathogens should be tested locally 
for linezolid susceptibility, as appropriate. Note that susceptibility testing for contezolid 
acefosamil will not be available at the local laboratory. After the cultured isolates are sent to the 
central laboratory, the central laboratory will test all Gram-positive isolates for both linezolid and 


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contezolid acefosamil susceptibilities. Staphylococcus aureus will also be tested for oxacillin 
susceptibility as a marker for methicillin resistance by both the central and local laboratories. All 
clinically significant non-anaerobic Gram-negative isolates will be tested for aztreonam 
susceptibility by both the central and local laboratories. 
The local laboratory should retain all isolates until confirmation of a viable organism is received 
from the central laboratory. Backup cultures will be requested when the central laboratory does 
not receive a viable culture, or recovers an organism different from the one recorded by the local 
laboratory. Refer to the Laboratory Manual for additional details. 
8.3 
Digital Photography 
Documentation of the primary ABSSSI lesion by digital photography will occur at 
screening/baseline, EA, Day 7, and EOT using the digital camera provided by the Sponsor. 
Investigators must follow the specific digital photograph procedures that are detailed in the 
Infection Site Assessment and Measurement Manual and Appendix 7. 


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9 ASSESSMENT OF EFFICACY 
9.1 
Clinical Response Definitions 
9.1.1 
Early Clinical Response 
Objective determinations of early clinical response will be made at EA (responder, 
nonresponder, or indeterminate) as defined in Table 2. Clinical responses will be classified 
programmatically based on data recorded on the eCRF. 
Table 2: 
Clinical Response Definitions – Early Clinical Response 
Timepoint 
Classification  
Definition 
Early Assessment: 
 
Responder 
Percent reduction in primary ABSSSI lesion size is ≥ 20% compared to baseline 
Did not receive a non-protocol specified systemic antibacterial agent with activity 
against Gram-positive organisms for the treatment of ABSSSI 
Did not die of any cause up to EA 
Nonresponder 
Percent reduction in primary ABSSSI lesion size is < 20% compared to baseline, or 
Received a non-protocol specified systemic antibacterial agent with activity against 
Gram-positive organisms for the treatment of ABSSSI, or 
Died of any cause up to EA 
Indeterminate 
Study data are unavailable for evaluation of efficacy for any reason (e.g., missing 
data, lost to follow-up, did not attend the EA clinic appointment) 
ABSSSI = acute bacterial skin and skin structure infection; EOT = end of therapy; I & D = incision and drainage; 
PTE = post therapy evaluation 
9.1.2 
Investigator’s Assessment of Clinical Response 
The Investigator’s assessment of clinical response at EOT, PTE, and LFU will be classified as 
defined in Table 3. Investigator assessed clinical failures at EOT will be carried forward as the 
clinical response at PTE. 


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Table 3: 
Clinical Response Definitions – Investigator’s Assessment 
Timepoint 
Classification  
Definition 
EOT and PTE: 
 
Success 
Resolution or near resolution of most baseline ABSSSI signs and symptoms 
No surgical procedure to treat the infection after 72 hours post-baseline that was not 
planned at baseline 
No new signs, symptoms or complications attributable to the ABSSSI 
No inter-current non-protocol specified systemic antibacterial therapy with activity 
against Gram-positive organisms for the treatment of ABSSSI 
Did not die of any cause up to EOT or PTE 
Failure 
Lack of resolution or near resolution of most baseline ABSSSI signs and symptoms 
Any surgical procedure to treat the infection > 72 hours post-baseline that was 
unplanned at baseline 
New signs, symptoms, or complications attributable to the ABSSSI 
Inter-current non-protocol specified antibacterial therapy administered for the treatment 
of the primary ABSSSI lesion or might have potential antibiotic activity directed toward 
the Gram-positive pathogens implicated in the ABSSSI 
Died of any cause up to EOT and PTE 
Indeterminate 
Study data are unavailable for evaluation of efficacy for any reason (e.g., missing data, 
lost to follow-up). No baseline Gram-positive organisms for the treatment of ABSSSI. 
LFU: 
 
Sustained clinical 
success 
No new signs or symptoms of primary ABSSSI after PTE 
Clinical 
relapse/failure 
New or worsened signs or symptoms of primary ABSSSI after PTE 
Indeterminate 
Study data are unavailable for evaluation of efficacy for any reason (e.g., missing data, 
lost to follow-up). No baseline Gram-positive organisms for the treatment of ABSSSI. 
 
ABSSSI = acute bacterial skin and skin structure infection; EA = early assessment; EOT = end of therapy; I & D = incision and 
drainage; LFU = late follow-up; PTE = post therapy evaluation 
Prior to any premature discontinuation of study drug, the study site personnel should notify the 
Medical Monitor if the subject’s medical condition allows. 
Data for all subjects will be reviewed to ensure the Investigators are following the protocol 
defined criteria for clinical response and queries will be issued as needed to clarify any response 
that does not meet the protocol definition. 


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9.2 
Microbiological Response Definitions 
9.2.1 
Per-Pathogen Microbiological Response 
A microbiological outcome at the PTE visit will be determined in the micro-ITT and ME 
populations for each pathogen isolated from the ABSSSI site or blood at screening/baseline. 
Microbiological outcome categories include eradication, presumed eradication, persistence, 
presumed persistence, and indeterminate, as defined in Table 4. Favorable microbiological 
outcomes include eradication or presumed eradication. Unfavorable microbiological outcomes 
include persistence or presumed persistence. 
Table 4: 
Microbiological Outcome Categories 
Outcome Category 
Definition 
Eradication 
An adequate source specimen demonstrates absence of the original 
screening/baseline pathogen 
Presumed eradication 
An adequate source specimen was not available to culture and the subject was 
assessed as a clinical success by the Investigator at PTE 
Persistence 
An adequate source specimen demonstrates continued presence of the original 
screening/baseline pathogen 
Presumed persistence 
An adequate source specimen was not available to culture and the subject was 
assessed as a clinical failure by the Investigator at PTE 
Indeterminate 
An adequate source specimen was not available to culture and the subject’s 
clinical response was assessed as indeterminate 
9.2.2 
Per-Subject Microbiological Response 
An overall microbiological response at the PTE visit will be determined in the micro-ITT and 
ME populations for each subject based on individual outcomes for each screening/baseline 
pathogen. For a subject to have a favorable per-subject microbiological response, the outcome 
for each screening/baseline pathogen must be favorable (eradicated or presumed eradicated, as 
defined in Table 4). For a subject to have an unfavorable per-subject microbiological response, 
the outcome for a screening/baseline pathogen must be unfavorable (persistence, presumed 
persistence, as defined in Table 4). If the same pathogen is isolated from multiple sites (e.g., 
blood and ABSSSI site culture), the worst response will be used to determine the per-subject 
microbiological response. 
9.2.3 
Emergent Infections 
ABSSSI caused by pathogens first appearing after screening/baseline will be categorized as 
either superinfections or new infections as defined in Table 5. 


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Table 5: 
Emergent Infections 
Category 
Definition 
Superinfection 
Isolation of a new pathogen(s) (other than the original screening/baseline 
pathogen[s]) from the primary ABSSSI site and from an appropriate ABSSSI 
specimen which is accompanied by signs and symptoms of infection requiring 
alternative systemic antimicrobial therapy during the period up to and including 
EOT, based on the Investigator’s assessment of clinical response.  
New infection 
Isolation of a new pathogen(s) (other than the original screening/baseline 
pathogen[s]) from the primary ABSSSI site and from an appropriate ABSSSI 
specimen which is accompanied by signs and symptoms of infection requiring 
alternative systemic antimicrobial therapy after EOT, based on the Investigator’s 
assessment of clinical response. 
ABSSSI = acute bacterial skin and skin structure infection; EOT = end-of-therapy 


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10 ASSESSMENT OF SAFETY 
All subjects will be monitored for the occurrence of AEs throughout the study, including AEs of 
special interest that are associated with the oxazolidinone class of antibiotics. 
Electrocardiograms, hematology evaluations, chemistry, coagulation, and UA will be performed 
at screening/baseline and at various timepoints during and after the dosing period (Table 1). Each 
recorded AE will be described by its duration (i.e., start and end dates), severity, seriousness, and 
suspected relationship to the study drug. Adverse events will be graded as mild, moderate, or 
severe, as detailed in Section 10.1.2_Assessment_of_Severity. Relationship of the AE to study 
drug will be characterized as related (including possibly related or definitely related) and 
unrelated, as detailed in Section 10.1.3. 
As detailed in Section 3.4, if study drug is determined not to be safe and tolerated, the study drug 
assignment for those subjects with a significant safety concern may be unblinded after discussion 
between the Investigator and Sponsor. The blind may also be broken in the case of a medical 
emergency requiring the Investigator to know the identity of the study drug to appropriately 
guide the subject’s medical management. Prior to any unblinding, the Investigator is strongly 
advised to discuss options with the Medical Monitor or appropriate Sponsor study personnel. If 
the blind is broken for any reason and the Investigator is unable to contact the Sponsor before 
unblinding, the Investigator must notify the Sponsor as soon as possible, without revealing the 
subject’s study drug treatment assignment (unless important to the safety of subjects remaining 
in the study). All instances of unblinding will be thoroughly investigated and documented by the 
unblinded study monitor. 
Reports of AEs will be collected for all subjects from the time informed consent is signed. The 
Investigator will assess all AEs and SAEs and record the following information on the 
appropriate eCRF page: 
• Date and time of onset 
• Date of resolution or stabilization 
• Severity 
• Relationship to study drug 
• Action taken with study medication 
The Investigator should distinguish between local and systemic AEs. An example of a possible 
systemic AE includes generalized rash or pruritus related to an allergic reaction. An example of a 
possible local AE includes a focal rash or irritation that is localized to a cutaneous area 
surrounding a venous blood draw. 
Clinically indicated laboratory tests (emergency or unscheduled tests) should be conducted at the 
local laboratory. For example, laboratory workup of an AE of anemia could include iron tests, 
reticulocyte count, and blood smear, among other local laboratory tests. The Investigator should 


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employ best medical judgment in determining how to manage AEs and SAEs. Any questions 
regarding AE or SAE management should be directed to the Medical Monitor. 
Prior to any premature discontinuation of study drug or unblinding of study drug assignment, the 
study site personnel should notify the Medical Monitor if the subject’s medical condition allows. 
10.1 
Adverse Events 
10.1.1 
Definition 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug related. An AE can be any unfavorable or unintended sign, symptom, or 
disease temporally associated with the use of a drug, without any judgment about causality. 
Adverse events are collected from the time the informed consent is signed. 
An AE does not include the following: 
• Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, transfusion); the 
condition that necessitates the procedure is an AE. 
• Any pre-existing disease or condition, or laboratory or ECG abnormality, present or detected 
prior to administration of study drug that does not worsen. 
• Laboratory or ECG abnormalities without clinical manifestations, which do not require 
medical intervention, or that do not result in termination or delay of study medication (see 
Section 10.2_Reporting_Laboratory_and for further detail). 
• Situations where an untoward medical occurrence has not occurred (e.g., hospitalization for 
elective surgery, social, or convenience admissions). 
• Overdose of any study drug or concomitant medication without any signs or symptoms, 
unless the subject is hospitalized for observation. 
• Worsening of the primary ABSSSI for which the subject was enrolled. 
10.1.2 
Assessment of Severity 
Severity of AEs will be assessed by the Investigator was mild, moderate, or severe (Table 6). 
This assessment is subjective and the Investigator should use medical judgment to compare the 
reported AE to similar types of events observed in clinical practice. It is important to recognize 
that severity is not equivalent to event seriousness (see Section 10.1.4.2). 


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Table 6: 
Guidelines for Severity Assessments 
Severity 
Definition 
Mild 
Symptom(s) barely noticeable to the subject, transient, or does (do) not make the 
subject uncomfortable. The AE does not influence regular, daily performance or 
functioning (e.g., functioning at work or school). Special treatment (e.g., with a 
prescription drug) is not ordinarily required for relief of symptom(s). 
Moderate 
Symptom(s) of a sufficient severity introduce a low level of inconvenience or concern 
to the subject. The AE may alter regular, daily performance or functioning (e.g., 
functioning at work or school), but is ameliorated with simple therapeutic measures.  
Severe 
Symptom(s) of a sufficient severity to cause the subject severe discomfort, interrupt 
daily activities, or lead to cessation of administration of study drug. Treatment for 
symptom(s) is needed. A severe AE does not necessarily qualify as an SAE 
(Section 10.1.4.2). 
 
10.1.3 
Relationship to Study Drug 
For each reported AE, the Investigator must make an assessment of the relationship of the event 
to the study drug using the following scale: 
• Unrelated: The event is definitely not associated with administration of study drug, and is 
judged clearly due to causes other than the study drug. 
• Possibly related (Suspected Adverse Reaction [SAR]): A causal relationship between the 
study drug and the AE is at least a reasonable possibility, i.e. the relationship cannot be ruled 
out. This implies a lesser degree of certainty about causality than a definitely related AE. 
Additional evidence to suggest a SAR includes: 
○ Individual occurrences of uncommon AEs that are known to be strongly associated with 
drug exposure (e.g., angioedema, blood dyscrasias, rhabdomyolysis, hepatic injury, 
anaphylaxis, Stevens-Johnson Syndrome). 
○ One or more occurrences of an AE that is uncommon in the study population, but not 
commonly associated with drug exposure (e.g., heart valve lesions in young adults, 
intussusception in healthy infants). 
• Definitely Related (Adverse Reaction): A causal relationship between the study drug and the 
AE is definite. 
These criteria, in addition to good clinical judgment, should be used as a guide for determining 
the causal assessment. If the event is believed to be unrelated to administration of study drug, 
then an alternative explanation should be provided. 


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10.1.4 
Serious Adverse Events 
An SAE is defined as any adverse experience occurring at any dose of study medication that 
occurs between the time informed consent is signed and within 30 days after the final 
administration of study drug that results in any of the following outcomes: 
• Death 
• Life-threatening situation (subject is at immediate risk of death) 
• Inpatient hospitalization (excluding hospitalization prior to randomization due to initial 
management of ABSSSI at baseline and new hospitalizations due to progression of the 
underlying primary ABSSSI lesion) or prolongation of existing hospitalization 
• Persistent or significant disability/incapacity 
• Congenital anomaly/birth defect in the offspring of a subject who received study drug 
• Events that jeopardize the subject sufficiently that medical or surgical intervention may be 
required to prevent one of the above outcomes (e.g., bronchospasm requiring urgent 
management in an emergency room, blood dyscrasias that do not result in hospitalization, 
seizures that do not result in hospitalization) 
10.1.4.1 
Serious Adverse Event Reporting 
The Sponsor has requirements for expedited reporting of SAEs meeting specific criteria to 
worldwide regulatory authorities. Therefore, the Sponsor must be notified immediately regarding 
any SAE that occurs after administration of study drug. All SAEs must be reported to the 
Medical Monitor within 24 hours of the investigational site’s knowledge of the event. 
The study site will transmit a SAE Report (SAER) by email (preferred) or facsimile (backup) to 
InClin Drug Safety. An initial report can be made via telephone in the case of an urgent event or 
question, but a completed SAER must still be emailed or faxed within 24 hours of the site’s 
knowledge of the event. The investigational site will be provided with SAER forms wherein the 
following information is requested. In addition, relevant eCRF pages should be appended to 
communicate relevant study drug and subject outcome information. The information needed for 
completing an SAER is as follows: 
• Subject identification, Investigator name, and site number. 
• SAE information: event term, onset date, severity, and causal relationship. 
• The outcomes attributable to the event (e.g., death, a life-threatening AE, inpatient 
hospitalization, prolongation of existing hospitalization, a persistent or significant disability 
or incapacity, or other important medical event[s]). 


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• A summary of relevant test results, pertinent laboratory data, and any other relevant medical 
history. 
• The first and last dates of administration of study drug. NOTE: As this is a double-blind 
study, SAERs should not indicate specific study drug assignments. 
• Indicate if the study drug was discontinued or if the administration of study drug schedule 
modified. 
• Supplemental information may include the following hospital records: laboratory results, 
radiology reports, progress notes, admission and emergency room notes, holding and 
observation notes, discharge summaries, autopsy reports, and death certificates. 
The SAER should be faxed within 24 hours with as much of the above information as available 
at the time. The following minimum information is required for reporting an SAE: subject 
identification, reporting source, and an event or outcome. Supplemental information may be 
transmitted using a follow-up report and should not delay the initial report. The Sponsor may 
contact the investigational site to solicit additional information or to follow-up on the event. 
The Investigator must take all therapeutic measures necessary for resolution of the SAE. Any 
medications or procedures necessary for treatment of the SAE must be recorded on the 
appropriate pages of the eCRF. 
10.1.4.2 
 “Serious” Versus “Severe” Adverse Events 
To avoid confusion or misunderstanding over the difference between the terms "serious" and 
"severe," which are not synonymous, the following note of clarification is provided (excerpted 
from International Council for Harmonisation [ICH] E2A): 
The term "severe" is used to describe the intensity (severity) of a specific event (as in mild, 
moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor 
medical significance (such as severe headache). This is not the same as "serious," which is based 
on subject/event outcome or action criteria usually associated with events that pose a threat to a 
subject's life or functioning. Seriousness (not severity) serves as a guide for defining regulatory 
reporting obligations. 
10.1.4.3 
SAE Definition Clarifications 
• Death is an outcome of an AE, and not an AE in itself. 
• All deaths during administration of study drug or occurring within 30 days of the last 
administration of study drug, regardless of cause or relationship, must be reported using the 
SAER. 
• “Occurring at any dose” does not imply that the subject is actively receiving study drug at the 
time of the event. 


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• “Life-threatening” means that the subject was at immediate risk of death from the event as it 
occurred. This does not include an event that might have led to death, had it occurred with 
greater severity. 
• Complications that occur during hospitalizations are AEs. If an AE prolongs hospitalization, 
it is an SAE. 
• “Inpatient hospitalization” means the subject has been formally admitted to a hospital for 
medical reasons, for any length of time. This may or may not be overnight. It does not 
include presentation and care within an emergency department (although an emergency 
department visit may define a medically important event, which is also considered an SAE). 
• The Investigator should attempt to establish a diagnosis of the event based on signs, 
symptoms, and other clinical information. In such cases, the diagnosis should be documented 
as the AE or SAE, rather than as the individual signs or symptoms. 
10.1.5 
Treatment-emergent Adverse Event 
A treatment-emergent adverse event (TEAE) is defined as an AE that occurs during or after the 
first administration of study drug and up through the last study visit or evaluation, or an SAE that 
occurs during or after the first administration of study drug up through 30 days after the final 
administration of study drug. 
10.1.6 
Life-threatening Adverse Event 
A life-threatening AE is an AE that, in the view of either the Investigator or Sponsor, places the 
subject at immediate risk of death. It does not include an AE that, had it occurred in a more 
severe form, might have caused death. 
10.1.7 
Unexpected Adverse Event 
An AE is considered “unexpected” if it is not listed in the IB or is not listed at the specificity or 
severity that has been observed; or, if an IB is not required or available, is not consistent with the 
risk information described in the general investigational plan. For example, under this definition, 
hepatic necrosis would be unexpected (by virtue of greater severity) if the IB referred only to 
elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and cerebral 
vasculitis would be unexpected (by virtue of greater specificity) if the IB listed only cerebral 
vascular accidents. "Unexpected," as used in this definition, also refers to AEs that are mentioned 
in the IB as occurring with a class of drugs or as anticipated from the pharmacological properties 
of the drug, but are not specifically mentioned as occurring with the particular drug under 
investigation. 
Some AEs are listed in the IB as occurring with the same class of drugs, or as anticipated from 
the pharmacological properties of the drug, even though they have not been observed with the 
drug under investigation. Such events would be considered unexpected until they have been 
observed with the drug under investigation. 


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10.2 
Reporting Laboratory and Electrocardiogram Abnormalities 
Laboratory and ECG abnormalities should not be recorded as AEs unless they are associated 
with clinical signs or symptoms, or require medical intervention. However, laboratory and ECG 
abnormalities (e.g., clinically significant changes detected on clinical chemistry, hematology, 
UA, etc.) independent from the underlying medical condition that require medical or surgical 
intervention, or lead to study drug interruption or discontinuation, must be recorded as an AE if 
applicable. If the laboratory abnormality is part of a clinical condition or syndrome, it should be 
recorded as the syndrome or diagnosis rather than an isolated laboratory or ECG abnormality. In 
addition, laboratory and ECG abnormalities or other abnormal test assessments that are 
associated with signs or symptoms must be recorded as AEs if they meet the definition of an AE 
(or SAE). 
10.3 
Risks for Women of Childbearing Potential 
The risks of treatment with contezolid acefosamil during pregnancy have not been fully 
evaluated. Therefore, females must be either postmenopausal for ≥2 years or surgically sterile 
(having undergone tubal ligation, hysterectomy, or bilateral oophorectomy) or, if of childbearing 
potential, must have a negative serum or urine pregnancy test (β–HCG) at screening/baseline and 
be willing to use a highly effective method of contraception throughout the study such as 1 of the 
following: 
• Hormonal contraception (stable dose for 3 months) 
• Intrauterine device/intrauterine hormone-releasing system 
• Barrier contraceptive method (diaphragm, cervical cap, contraceptive sponge, condom) 
Additionally, males (if sexually active and nonsterile) with female partners of childbearing 
potential must use 2 methods of contraception (i.e., a barrier contraceptive such as condom with 
spermicidal foam), and be willing to continue to use these same birth control measures while 
participating in the study (and for 70 days following participation in the study). Males must also 
refrain from sperm donations during this time. 
Female subjects must be instructed to inform the Investigator immediately if they become 
pregnant during the study. Male subjects must also be instructed to inform the Investigator 
immediately if a female partner becomes pregnant through at least 70 days (10 weeks) after 
dosing. In the event of a confirmed pregnancy, the following actions should be taken: 
• Study drug should be stopped immediately. 
• The pregnancy should be reported to the Medical Monitor within 24 hours of notification 
using the Pregnancy Report Form. 
• The Investigator should counsel the subject regarding the possible effects of prior study drug 
exposure on the fetus and the need to inform the study site of the outcome of the pregnancy. 


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• The subject must be monitored until the immediate post-natal period or until termination of 
the pregnancy. The outcome should be reported to the Medical Monitor using the Pregnancy 
Outcome Form. 
Pregnancy is not an AE, in and of itself. However, any pregnancy complication or elective 
termination of a pregnancy for medical reasons will be recorded as an AE or SAE. A 
spontaneous abortion is always considered an SAE and will be reported as described in the AE 
and SAE sections. Furthermore, any SAE occurring as an adverse pregnancy outcome post-study 
must be reported to the Medical Monitor. 
10.4 
Adverse Event Follow-up 
All AEs and SAEs will be followed to resolution or stabilization. Adverse events that have not 
resolved by a study visit, but have stabilized, will be categorized as such in the database. 
Non-serious AEs that are ongoing at the end of the study will be identified as ‘Ongoing’. 
10.5 
Study Termination or Temporary Suspension 
The study may be terminated if significant violations of GCP that compromise the ability to 
achieve the study objectives or compromise subject safety are observed at any time during the 
study (Section 4.5). The study may be temporarily suspended or terminated should the 
Investigator, Sponsor, or IRB determine that the safety of study subjects is significantly 
jeopardized. The decision for a temporary or permanent study hold will depend on the nature, 
frequency, and severity of AEs that were observed in all enrolled subjects to date. In a temporary 
study hold, no additional subjects will be enrolled into the study or dosed with study drug until 
the study team (including the Investigator and the Medical Monitor) decides it is safe to proceed 
with the study. The study will be terminated or temporarily suspended if any of the following 
events occur in a single subject who is receiving active contezolid acefosamil (as determined 
after unblinding) during the study period: 
• Hy’s law criteria met; these are defined as elevations of ALT or AST to > 3 times ULN and 
elevation of serum total bilirubin to ≥ 2 times ULN with serum alkaline phosphatase < 2 
times ULN, and no other disease or condition can be found to explain the liver test 
abnormalities (FDA, 2009) 
• Clinically significant cardiac arrhythmia (e.g., Torsade de Pointes) 
• Symptomatic anemia with a hemoglobin level < 8.0 g/dL, as confirmed on repeat testing, or 
requirement for blood transfusion 
• Platelet count < 50 x 103/mm3, as confirmed on repeat testing 
• WBC count < 2.0 x 103/mm3 or absolute neutrophil count <1,000/mm3, as confirmed on 
repeat testing 
• Rash defined as an SAE (Section 10.1.4) 


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• Peripheral or optic neuropathy 
• Serotonin syndrome 
• Seizure 
• Anaphylaxis or allergy-related angioedema 
As noted above, safety assessments will be monitored and evaluated on a regular basis by the 
study team, and any abnormal clinical or laboratory findings or trends will be closely monitored 
and followed regardless of severity or causality (e.g., before an event reaches a severe grading 
level or reaches a termination criterion cutoff). 
10.6 
Data Monitoring Committee 
A DMC will not be utilized in this study. 


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11 ASSESSMENT OF PHARMACOKINETICS 
This study will be conducted at multiple clinical sites, and some will have the appropriate 
equipment and facilities (including refrigerated centrifuges and -70ºC freezers) and experienced 
personnel to adequately collect, handle, store, and ship PK samples for bioanalysis. PK 
assessments will only be performed at selected clinical sites with this capability, and PK samples 
will be obtained from as many subjects as possible at these selected sites. Drug exposure will be 
predicted based on demographic data (e.g., body weight) for subjects from whom PK samples 
were not obtained. 
• One PK sample after the 1st IV dose (to characterize the loading dose): obtain 1 blood 
sample between 0.5 to 2 hours after the end of the 1st infusion 
• Three PK samples with the 3rd IV dose (to characterize drug exposure and approaching of 
steady state):  
○ Obtain a 1st blood sample (trough level) within 2 hours before the 3rd IV dose 
○ Obtain a 2nd blood sample between 0.5 and 3 hours after the end of the 3rd IV dose 
○ Obtain a 3rd blood sample between 4 and 11 hours after the end of the 3rd IV dose but 
before the 4th dose (IV or PO) of study drug. 
• Three PK samples at EOT (to evaluate potential drug accumulation):  
○ Obtain 1 blood sample (trough level) within 2 hours before the last dose (IV or PO)  
○ If the last dose is given PO: obtain 1 blood sample between 1.5 to 4 hours after the last 
dose, and obtain 1 additional sample between 5 to 12 hours after the last dose 
○ If the last dose is given IV: obtain 1 blood sample between 0.5 and 3 hours after the end 
of the last infusion, and obtain 1 additional sample between 4 and 11 hours after the end 
of the last infusion 
The PK data acquisition and analysis strategy entail the use of a sparse PK sampling schedule for 
subjects randomized to contezolid acefosamil. This PK sampling strategy is designed to 
characterize the impact of the loading dose, and to obtain adequate estimates of drug exposure 
after the 3rd IV dose and the final dose (IV or PO). Additionally, given the range of demographic 
data in the expected subject population, these PK data will be used to perform exploratory 
analyses on the impact of demographic characteristics (e.g., weight, body mass index, age, 
gender, race) upon the PK (including clearance) of the drug and its metabolites. Only those PK 
samples collected from subjects randomized to contezolid acefosamil will be analyzed. 
The bioanalytical laboratory will measure plasma concentrations of contezolid acefosamil 
metabolites (MRX-1352, contezolid, and MRX-1320) using validated and sensitive bioanalytical 
methods. Specific instructions for the collection of plasma drug concentration specimens will be 
provided in the Laboratory Manual and should be reviewed prior to collection. 


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When more than one assessment is scheduled at any given timepoint, clinical assessments should 
precede all blood draws, including ECGs. For subjects managed as outpatients, schedule the 
clinic visits appropriately to collect PK samples at the end of IV therapy and the EOT visit as 
described above. 
The PK population is defined in Section 12.2. Selected PK samples may be used in the 
identification of contezolid acefosamil metabolites. Additional details will be provided in the 
PK Analysis Plan. 


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12 STATISTICAL METHODS 
All data will be summarized separately by study drug (contezolid acefosamil or linezolid). 
Descriptive statistics (number, mean, standard deviation, median, minimum, and maximum) will 
be presented for continuous variables for each study drug. Frequency distributions (counts and 
percentages) will be presented for categorical variables. Listings will be provided for individual 
subject study data. 
A comprehensive Statistical Analysis Plan (SAP) will be prepared and finalized prior to database 
lock. 
12.1 
Determination of Study Sample Size 
This study is not powered for inferential statistical analysis. Approximately 133 subjects 
(100 evaluable subjects) in the contezolid acefosamil group and 67 subjects (50 evaluable 
subjects) in the linezolid group will allow for planning of future studies. If the responder rate is 
0.8 at EA using early clinical response in the contezolid acefosamil group, then 133 evaluable 
subjects results in a 95% confidence interval (CI) of (0.72, 0.86) for the responder rate. 
12.2 
Analysis Populations 
The analysis populations are defined in Table 7, and the relationship between the analysis 
populations are displayed in Figure 2. 
Table 7: 
Analysis Populations 
Analysis 
Populations 
Definitions 
ITT Population 
All randomized subjects will be included in the ITT population, regardless of whether 
study drug is administered. 
MITT Population 
All randomized subjects in the ITT population, excluding subjects with only a Gram-
negative pathogen(s) at baseline. 
Safety Population 
All subjects who receive any amount of study drug will constitute the safety population. 
Subjects in the safety population will be analyzed according to study drug received. 
Micro-ITT 
Population 
All randomized subjects in the ITT population who have culture evidence of a baseline 
Gram-positive bacterial pathogen known to cause ABSSSI. 
CE Populations 
(CE-EOT, CE-PTE) 
All subjects in the ITT population who meet the minimal clinical disease criteria for 
ABSSSI; receive at least 80% of expected doses based on length of therapy; did not 
receive any potentially-effective systemic antibacterial therapies other than protocol 
specified study drug(s) between Day 1 and timepoint for assessment (except for 
adjunctive aztreonam or in cases of treatment failure). 
To be included in the CE-EOT population, the following conditions must be met: 
• 
Have an Investigator’s assessment of clinical response at EOT (i.e., response 
can’t be indeterminate) 
• 
Had an EOT visit 
To be included in the CE-PTE population, the following conditions must be met: 


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Analysis 
Populations 
Definitions 
• 
Have an Investigator’s assessment of clinical response at PTE (i.e., response 
can’t be indeterminate unless the subject is deemed a clinical failure at the EOT 
visit) 
• 
Had a PTE visit 
In addition to meeting the above criteria, subjects must meet the following specific 
conditions to be included in the CE population: 
• 
Received at least 5 doses of study drug therapy to be considered an evaluable 
failure 
• 
Received at least 7 doses of study drug therapy to be considered an evaluable 
success 
• 
Did not have any major protocol violation 
ME Population 
All subjects in the micro-ITT population who also are in the CE-PTE population. 
PK Population 
All subjects who receive at least 1 dose of contezolid acefosamil and had at least 1 blood 
sample collected for analysis of MRX-1352, contezolid, or MRX-1320. 
ABSSSI = acute bacterial skin and skin structure infection; CE = clinically evaluable; EOT = end of therapy; 
ITT = intent-to-treat; ME = microbiologically evaluable; ME = microbiologically evaluable; micro-
ITT = microbiological intent-to-treat; PK = pharmacokinetic; PTE = post therapy evaluation 


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Figure 2: 
Overview of Analysis Populations 
 
ABSSSI = acute bacterial skin and skin structure infection; CE = clinically evaluable; EOT = end of therapy; 
ITT = intent-to-treat; ME = microbiologically evaluable; ME = microbiologically evaluable; micro-
ITT = microbiological intent-to-treat; MITT= modified intent-to-treat; PK = pharmacokinetic; PTE = post therapy 
evaluation 
12.3 
Determination of Inclusion in Populations 
Inclusion in the ITT, safety, and PK populations will be determined programmatically from 
eCRF data. Inclusion in the MITT and micro-ITT population will be determined by the Medical 


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Monitor. The Medical Monitor will decide whether each isolate is considered a pathogen. 
Inclusion in the CE populations will be determined based on a combination of programmatic and 
manual review by the Medical Monitor. Inclusion in the ME population will be determined 
programmatically. All manual reviews and determinations of population inclusion/exclusion will 
be done prior to study unblinding. 
12.4 
Analysis of Study Populations and Subject Characteristics 
Enrollment, study drug administered, premature discontinuations from study medication, 
withdrawals from the study, and protocol deviations will be summarized by treatment group. A 
protocol deviation is defined as any variation from the protocol (e.g., enrollment of a subject who 
did not meet all inclusion and exclusion criteria, failure to perform the assessments and 
procedures within the required time frame). 
Demographics (age, race, sex), description of the baseline ABSSSI type, medical history, and 
baseline clinical signs and symptoms of ABSSSI will be summarized by treatment group. 
Baseline pathogens identified at the primary ABSSSI site will also be summarized by treatment 
group. 
The number and percentage of subjects in each population and reasons for exclusion from 
populations will be listed and summarized by treatment group. 
12.5 
Study Drug Exposure 
By treatment group summaries will be provided for the total number of doses, the number of IV 
doses, and the number of PO doses. Compliance to study drug will be calculated based on the 
total number of doses taken, divided by the total number of expected doses. 
12.6 
Efficacy Analyses 
Primary and secondary efficacy evaluations will be summarized by analysis population, as 
indicated in Table 8. 


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Table 8: 
Summary of Primary and Secondary Efficacy Evaluations  
by Analysis Population 
Efficacy Endpoints 
Efficacy Populations 
ITT 
MITT 
micro-
ITT 
CE-EOT 
CE-PTE 
ME 
Primary: 
 
 
 
 
 
 
Early clinical response at EA  
√ 
 
 
 
 
 
Secondary: 
 
 
 
 
 
 
Early clinical response at EA  
 
√ 
 
 
 
 
Early clinical response at EA (overall 
and by baseline pathogen) 
 
 
√ 
 
 
 
Percent reduction in lesion size at 
Day 7 
√ 
√ 
 
 
 
 
Investigator’s assessment of clinical 
response at EOT  
√ 
√ 
 
√ 
 
 
Investigator’s assessment of clinical 
response at PTE and LFU 
√ 
√ 
 
 
√ 
 
Per-subject microbiological response 
at PTE  
 
 
√ 
 
 
√ 
Per-pathogen microbiological 
response at PTE 
 
 
√ 
 
 
√ 
Investigators assessment of clinical 
response at PTE and LFU (overall 
and by baseline pathogen) 
 
 
√ 
 
 
√ 
CACO  
√ 
 
√ 
 
√ 
 
CACO = composite assessment of clinical outcome (combined outcome of early clinical response at EA and 
Investigator’s assessment of clinical response at PTE); CE = clinically evaluable; EA = early assessment; EOT = end 
of therapy; ITT = intent-to-treat; LFU = late follow-up; ME = microbiologically evaluable; MITT = modified intent-
to-treat; micro-ITT = microbiological intent-to-treat; PTE = post therapy evaluation 
12.6.1 
Primary Efficacy Evaluation 
The primary efficacy analysis is an examination of the number of responders in the contezolid 
acefosamil treated group vs the number of responders in the linezolid group at EA in the ITT 
population. This aligns with the FDA’s primary efficacy endpoint of interest in ABSSSI studies 
(FDA, 2013). Subjects will be programmatically categorized into responders, non-responders or 
indeterminate based on the eCRF data as previously discussed in Section 9.1.1. Subjects who are 
lost to follow-up or who have missing data will be classified as indeterminate. The number of 
responders, non-responders, and indeterminate responses will be summarized by treatment group 
and an exact 95% CI will be provided for the responder rates in each treatment group. The 
difference between the responder rates will be calculated and 95% CI for the difference between 
response rates will be calculated using a Wald continuity correction. 


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12.6.2 
Secondary and Additional Efficacy Evaluations 
12.6.2.1 
Percent Reduction in Lesion Size 
Changes from baseline in the percent reduction in lesion area at Day 7 will be summarized by 
treatment group in the ITT and MITT populations and also by treatment group excluding patients 
who took non-study antibiotics with the potential to have activity against ABSSSI through the 
study visit. 
12.6.2.2 
Clinical Outcomes 
Early clinical response at EA will be classified programmatically based on eCRF data as 
previously discussed in Section 9.1.1. The number and percentage of subjects classified 
programmatically as a responder, nonresponder, and indeterminate at EA will be tabulated for 
the populations specified in Table 8 for both treatment groups, and the difference in response 
rates will be summarized along with the 95% CI for the rate of response. 
The Investigator’s assessment of clinical response will be classified as previously discussed in 
Section 9.1.2. The number of subjects with an Investigator’s assessment of clinical success, 
clinical failure, and indeterminate at EOT and PTE will be tabulated for both treatment groups 
for the populations specified in Table 8 (by definition, subjects with an indeterminate response 
will be excluded from summaries in the CE-EOT and CE-PTE populations). The 95% CI will be 
provided for the rate of clinical success for each treatment group. The difference in clinical 
success rates will also be summarized. The 95% CI will be provided for the difference in rates of 
success at PTE in the ITT and CE-PTE populations only, which are the primary analyses of 
interest in the EU (EMA, 2013). The durability of clinical response (rate of sustained clinical 
response and clinical relapse/failure) at LFU will be summarized by treatment group in the 
micro-ITT and ME populations. 
The rates of success as assessed by the CACO (Table 9) will be summarized in the ITT, micro-
ITT, and CE-PTE populations. The CACO will be programmatically determined from the 
programmatic assessment of early clinical response at the EA visit and the Investigator’s 
assessment of clinical response at PTE. 


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Table 9: 
Composite Assessment of Clinical Outcome 
Early Clinical Response at  
EA Visit 
Investigator’s Assessment of 
Clinical Response at PTE Visit 
Composite Assessment of  
Clinical Outcome (CACO) 
Responder 
Success 
Success 
Responder 
Failure 
Failure 
Responder 
Indeterminate 
Indeterminate 
Nonresponder 
Success 
Failure 
Nonresponder 
Failure 
Failure 
Nonresponder 
Indeterminate 
Failure 
Indeterminate 
Success 
Indeterminate 
Indeterminate 
Failure 
Failure 
Indeterminate 
Indeterminate 
Indeterminate 
EA = early assessment; PTE = post therapy evaluation 
12.6.2.3 
Microbiological Outcomes 
The number and percentage of subjects with favorable microbiological responses will be 
summarized at PTE in the ME and micro-ITT populations. Responses include eradication, 
presumed eradication, persistence, presumed persistence, and indeterminate (Table 4). To have 
an overall favorable microbiological response, the outcome for each baseline pathogen must be 
favorable. Of these responses, eradication and presumed eradication will be regarded as a 
favorable outcome. Persistence and presumed persistence will be regarded as an unfavorable 
outcome. If a subject has > 1 baseline pathogen, all pathogens must have a favorable response to 
have overall favorable response. A 2-sided exact 95% CI will be constructed for the percentage 
of subjects with favorable and non-favorable response and a 95% CI will be calculated for the 
difference in the per-subject favorable microbiological response using a Wald continuity 
correction. 
Microbiologic response by baseline pathogen will be determined as the proportion of patients 
with a favorable microbiological response (eradication or presumed eradication) at the PTE visit 
for each pathogen isolated at baseline from the ABSSSI site. The number and percentage of 
patients in each treatment group with a microbiologically favorable outcome will be tabulated for 
the micro-ITT and ME analysis sets. 
The number and percentage of subjects in each treatment group with an Investigator’s 
assessment of clinical response of success at the PTE and LFU visit will be tabulated by baseline 
pathogen in the micro-ITT and ME populations. The number and percentage of subjects in each 
treatment group who are responders at the EA visit using early clinical response will also be 
tabulated by baseline pathogen in the micro-ITT population. 
Emergent infections (e.g., superinfection, new infection) will not be considered in the 
microbiological response and will be listed separately (Section 9.2.3). 


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12.7 
Safety Analyses 
Evaluation of the safety and tolerability of contezolid acefosamil (IV and PO) q12h (± 2 hours) 
for 10 to 14 days in the treatment of ABSSSI is an important objective for this Phase 2 study. 
Safety will be evaluated by presenting summaries of AEs, vital signs, laboratory evaluations 
(hematology, chemistry, and coagulation), and ECG parameters. For each safety parameter, the 
last assessment made prior to the first administration of study drug will be used as the baseline 
for all analyses. 
The incidence of TEAEs (defined in Section 10.1.5) will be presented by SOC and PT according 
to Medical Dictionary of Regulatory Activities (MedDRA®); by SOC, PT, and relationship to 
study drug; and by SOC, PT, and severity. In addition, the incidence of SAEs and TEAEs 
leading to discontinuation of study drug will be presented by SOC, PT, and relationship to study 
drug. If the incidence of SAEs and TEAEs leading to discontinuation of study drug is low, only a 
listing will be provided. 
Descriptive statistics of vital signs at each timepoint measured, as well as the change from 
baseline and potentially clinically significant changes, will be presented by treatment group. 
Potentially clinically significant changes will be defined in the SAP. Descriptive statistics for 
ECGs will also be presented for each timepoint measured. Descriptive statistics for clinical 
laboratory tests and for the change from baseline will be presented by study visit and treatment 
group. 
12.8 
Pharmacokinetic Analyses 
Characterization of the population PK of contezolid acefosamil metabolites (IV and PO) q12h 
(± 2 hours) in the treatment of ABSSSI is an important secondary objective for this study. 
Plasma samples from subjects in the PK population (Section 12.2) will be analyzed for 
contezolid acefosamil metabolite concentration (MRX-1352, contezolid, and MRX-1320) using 
validated and sensitive bioanalytical methods. Key basic PK parameters will be assessed at the 
end of the first dose of IV therapy, prior to and at 2 timepoints after the end of the third dose of 
IV therapy, and prior to and after 2 timepoints after the end of the last dose or infusion (IV or 
PO) at the EOT visit (refer to Section 11 for the timing of the analysis). Only those PK samples 
collected from subjects randomized to contezolid will be analyzed.  
Pharmacokinetic data will be summarized using descriptive statistics and graphically displayed, 
and population PK modeling analyses will be performed. Further details of the PK sample 
collection and analyses are provided the PK Analysis Plan and Laboratory Manual. 
12.9 
Handling of Dropouts, Missing, Unused and Spurious Data 
Every effort will be made to collect all data at specified times. For the primary efficacy outcome 
measure, per-subject clinical response rate at EA in the ITT population, subjects with a missing 
EA visit will be classified as indeterminate. Missing data for secondary efficacy outcomes will 
be handled similarly. A detailed description of the handling of drop outs and missing, unused, 
and spurious data will be provided in the SAP. 


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13 ADMINISTRATIVE CONSIDERATIONS 
13.1 
Ethical Conduct of Study 
This study will be conducted in accordance with applicable United States (US) FDA clinical trial 
regulations and guidelines, the ICH (E6) GCP guidelines, the European Union Directive 
2001/20/EC for clinical trials conducted in the European Union, and the IRB/EC/REB and local 
legal requirements. 
13.2 
Informed Consent 
This study will be conducted in compliance with ICH E6 GCP: Consolidated Guidelines 
pertaining to informed consent. Subjects will give written consent to participate in the study at 
the first visit, prior to initiation of any study-related procedure, after having been informed about 
the nature and purpose of the study, participation and termination conditions, risks, and benefits. 
A copy of the informed consent document must be provided to the subject. If applicable, it will 
be provided in certified translation for non-English-speaking subjects. Signed consent forms 
must remain in the subject’s study file and be available for verification by the Sponsor or 
representatives of a competent regulatory agency at any time. 
13.3 
Institutional Review Board Approval 
This study will be conducted in compliance with the protocol approved by the IRB and 
according to ICH and GCP consolidated guidelines and the ethical principles of the Declaration 
of Helsinki. 
No major deviation from the protocol will be implemented without the prior review and approval 
of the IRB except when it may be necessary to eliminate an immediate hazard to a research 
subject. In such case, the deviation will be reported to the IRB as soon as possible. 
This protocol, the informed consent document, and all relevant supporting data must be 
submitted to the IRB for approval. Approval by the IRB of the protocol, informed consent 
document, and any advertisement used to recruit study subjects must be obtained before the 
study may be initiated. 
The Investigator is responsible for informing the IRB of any changes made to the protocol, and 
to advise them, at least once a year, about the progress of the study. The Investigator is also 
responsible for notifying the IRB of any SAEs and significant AEs that occur during the study. 
13.4 
Investigator Requirements 
Each Investigator must adhere to the protocol as detailed in this document and agree that the 
Sponsor or Sponsor representative must approve any change to the protocol before seeking 
approval from the IRB. Each Investigator will be responsible for enrolling only those subjects 
who have met the protocol inclusion and exclusion criteria. 


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13.5 
Electronic Case Report Forms and Data Capture System 
This study will be performed using an eCRF. All eCRF data are to be completed by designated 
site personnel. All data entry, modification, or deletion will be recorded automatically in the 
electronic audit trail. All electronic data entered by the site (including the electronic audit trail) 
will be maintained or made available at the site in compliance with 21 CFR Part 11 and other 
applicable retention regulations. 
Before the first subject is dosed at an investigational site, the Sponsor or Sponsor representative 
will meet with the Investigator and the study center’s personnel to train them on recording the 
data on the eCRFs using an electronic data capture system. The Investigator or designee will be 
responsible for reviewing eCRFs, resolving data queries generated by the Sponsor or Sponsor 
representative via the system, providing missing or corrected data, and approving all changes 
performed on the subject data. This approval method will include applying an electronic 
signature, a uniquely assigned user name, and a password that together will represent a 
traditional handwritten signature. This electronic signature will be certified as outlined in 21 
CFR Part 11. The Sponsor will retain the original eCRF data and audit trail. An electronic or 
certified paper copy of all completed eCRF data, including query resolution correspondence, will 
be provided to the Investigator at the end of the study. 
Queries may be issued electronically to the clinical study center and answered electronically by 
that study center’s personnel. The identifying information (assigned user name, date, and time) 
for both the originator of the query and the originator of the data change (if applicable) will be 
collected. 
All data collected in the context of this study will be stored and evaluated per regulatory 
requirements and applicable guidance for electronic records. 
13.6 
Source Data & Document Maintenance 
All data collected on the eCRFs must have a source record. 
The Investigator agrees by his/her participation that the results of this study may be used for 
submission to national or international registration. The Sponsor or Sponsor’s representative has 
ethical, legal, and scientific obligations to monitor this study in a detailed and orderly manner in 
accordance with established research principles and applicable local regulations. As part of a 
concerted effort to fulfill these obligations, the Sponsor’s monitors or representatives will visit 
the center during the study on a regular basis, in addition to maintaining telephone and written 
communication. 
The Investigator is required to provide the Sponsor with all study data, complete reports, and 
access to all study records. The Investigator must retain a comprehensive and centralized filing 
system of all clinical study-related documentation that is suitable for inspection by the Sponsor 
and representatives of regulatory authorities. The Investigator will allow the Sponsor or its 
representative, or an appropriate representative of the competent authorities, to inspect all 
clinical study-related documentation for confirmation of data throughout the study period. 


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Data generated by this study must be available for inspection by any regulatory authorities, by 
the Sponsor and by the IRB as appropriate. At a subject’s request, medical information may be 
given to his or her personal physician or other appropriate medical personnel responsible for his 
or her welfare. Medical information obtained from subjects during the course of this study is 
confidential and disclosure to third parties other than those noted above is prohibited. 
13.7 
Study Monitoring Requirements 
The Sponsor or Sponsor representative will conduct center visits to inspect study data, subjects’ 
medical records, and eCRFs in accordance with current ICH E6 GCP guideline, and the 
respective US or foreign regulations and guidelines, as applicable. The Sponsor or Sponsor 
representative will also be able to review query status remotely, which may warrant additional 
communication with the Investigator and the study center’s personnel. The Investigator will 
make available to the Sponsor, or Sponsor representative, source documents, signed informed 
consent forms (ICFs), and all other study-related documents. 
The Investigator will allow the Sponsor or Sponsor representative and applicable regulatory 
authorities to inspect facilities and records relevant to this study. 
13.8 
Study Completion 
The Sponsor requires the availability of the following data and materials before a study can be 
considered complete or terminated: 
• Laboratory findings, clinical data, and all special test results from baseline through LFU for 
subjects enrolled. 
• eCRFs (including queries) properly completed by appropriate study personnel and 
electronically signed and dated by the Investigator. 
• Complete drug accountability records (drug inventory log and an inventory of returned or 
destroyed clinical material). 
• Copies of protocol amendments and IRB approval and notification, if appropriate. 
• A summary of the study prepared by the Investigator (an IRB summary letter is acceptable) 
Trial Conduct & Ethical Considerations. 
This study will be conducted in compliance with the ICH of Technical Requirements for 
Registration of Pharmaceuticals for Human Use E6 GCP: Consolidated Guidelines, the ethical 
principles of the Declaration of Helsinki, FDA GCP guidelines, and any additional IRB-required 
procedures. 
13.9 
Quality Control and Quality Assurance 
Written standard operating procedures (SOPs) will be followed to ensure that the study is 
conducted and data are generated, documented (recorded), and reported in compliance with the 


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protocol, GCP, and the applicable regulatory requirements. Quality control (QC) will be applied 
to each stage of data handling. Regular monitoring, as defined in ICH GCP, Section 1.8, “The act 
of overseeing the progress of a clinical trial, and of ensuring that it is conducted, recorded, and 
reported in accordance with the protocol, SOPs, GCP, and the applicable regulatory 
requirement(s)”, will be conducted throughout the conduct of the study. 
The purpose of monitoring is to verify that: 
• Rights and well-being of the human subjects are protected; 
• The reported study data are accurate, complete, and verifiable from source documents; 
• The conduct of the study is in compliance with the currently approved protocol and 
amendment(s), with GCP, and with the applicable regulatory requirements; 
• Monitoring is an integral role in the QC of a clinical trial and is designed to verify the quality 
of the study. 
To fulfill the quality assurance requirements of GCP, audits will be conducted to assess and 
assure the reliability and integrity of a study’s QC systems and recognized standards. 
The purpose of an audit is to: 
• Ensure subject safety; 
• Assure compliance to study protocol procedures, regulatory requirements, and SOPs; 
• Assure data quality. 
13.10 Retention of Records 
Essential documents pertaining to the conduct of this study and the distribution of investigational 
drugs including eCRFs, ICFs, laboratory test results, and medication inventory records should be 
retained until at least 2 years after the last approval of a marketing application in an ICH region 
and until there are no pending or contemplated marketing applications in an ICH region or at 
least 2 years have elapsed since the formal discontinuation of clinical development of an 
investigational product. These documents should be retained for a longer period however if 
required by the applicable regulatory requirements or by an agreement with the Sponsor. It is the 
responsibility of the Sponsor to notify the Investigator/institution as to when these documents no 
longer need to be retained. 
13.11 Finance and Insurance 
The financing and insurance for this study are outlined in the Clinical Trial Agreement. 


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13.12 Publication Policy 
The data generated in this clinical study are the exclusive property of the Sponsor and are 
confidential. The Sponsor will make all reasonable efforts to publish the results of the study in an 
appropriate peer-reviewed journal. Authorship on the primary publication of the results from this 
study will be based on contributions to study design, enrollment, data analysis, and interpretation 
of results. 
 
 


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Azactam® (aztreonam) [Package Insert]. Princeton, NJ. Bristol-Myers Squibb, 2013. 
Bressler AM, Zimmer SM, Gilmore JL, Somani J. Peripheral neuropathy associated with 
prolonged use of linezolid. Lancet Infect Dis. 2004;4:528-31. 
Committee for Medicinal Products for Human Use (CHMP). Addendum to the Guideline on the 
Evaluation of Medicinal Products Indicated for Treatment of Bacterial Infections. European 
Medicines Agency. 2013;EMA/CPMP/351889/2013. Available at: 
http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/general_content_00112
0.jsp&mid=WC0b01ac0580034cf2 
Deresinski S. Methicillin-resistant Staphylococcus aureus: an evolutionary, epidemiologic, and 
therapeutic odyssey. Clin Infect Dis. 2005;40:562-573. 
Diep BA, Sensabaugh GF, Somboona NS, Carleton HA, Perdreau-Remington F. Widespread 
skin and soft-tissue infections due to two methicillin-resistant Staphylococcus aureus strains 
harboring the genes for Panton–Valentine leucocidin. J Clin Microbiol. 2004;42: 2080-2084. 
Dryden MS. Linezolid pharmacokinetics and pharmacodynamics in clinical treatment. J 
Antimicrob Chemother. 2011; 66 Suppl 4: iv7–iv15. 
Edelsberg J, Taneja C, Zervos M, et al. Trends in US hospital admissions for skin and soft tissue 
infections. Emerg Infect Dis. 2009; 15:1516–8. 
Flanagan S, Fang E, Munoz KA, Minassian SL, Prokocimer PG. Single- and multiple-dose 
pharmacokinetics and absolute bioavailability of tedizolid. Pharmacother. 2014;34(9):891-900. 
French G. Safety and tolerability of linezolid. J Antimicrob Chemother 2003;51, Suppl. S2: 
ii45-ii53. 
Eron LJ, Lipsky BA, Low DE, Nathwani D, Tice AD, Volturo GA. Managing skin and soft 
tissue infections: expert panel recommendations on key decision points. J Antimicrob 
Chemother. 2003;52 Suppl 1:i3-i17. 
Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for 
Industry—Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for Treatment. 
Oct 2013. Available at: http://www.fda.gov/downloads/Drugs/.../Guidances/ucm071185.pdf 
Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for 
Industry—Drug-Induced Liver Injury: Premarketing Clinical Evaluation. Jul 2009.  Available at:  
https://www.fda.gov/downloads/guidances/UCM174090.pdf.  
Food and Drug Administration. FDA approves Sivextro to treat skin infections. FDA News 
Release 2014. Available at: 
https://www.fda.gov/downloads/aboutfda/centersoffices/oc/officeofscientificandmedicalprogram
s/ucm569664.pdf 
Gerson SL, Kaplan SL, Bruss JB, Le V, Arellano FM, Hafkin B, Kuter DJ. Hematologic effects 
of linezolid: Summary of clinical experience. Antimicrob Agents Chemother. 
2002;46:2723-2726. 


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Gordeev MF, Yuan ZY. New potent antibacterial oxazolidinone (MRX-I) with an improved class 
safety profile. J Med Chem. 2014;57:4487-4497. 
Holden K. Meal Ideas and Menus: Avoiding High-tyramine Foods Made Easy. Teva 
Neuroscience, Inc., 2006. Kansas City. PDF accessed at 
http://www.mc.vanderbilt.edu/documents/neurology/files/Tyramine%20Menu%20Book%20062
27101.pdf 
Kopterides P, Papadomichelakis E, Armaganidis A. Linezolid use associated with lactic acidosis. 
Scand J Infect Dis. 2005;37(2):153-4. 
Li CR, Zhai QQ,Wang XK,et al. In vivo antibacterial activity of MRX-I, a new oxazolidinone, 
Antimicrob Agents Chemother. 2014;58(4):2418-2421. 
Miettinen O and Nurminen M. Comparative analysis of two rates. Statistics in Medicine. 
1985;4(2):213-26. 
Moet GJ, Jonesa RN, Biedenbach DJ, Stilwell MG, Fritsche TR. Contemporary causes of skin 
and soft tissue infections in North America, Latin America, and Europe: Report from the 
SENTRY Antimicrobial Surveillance Program (1998–2004). Diagn Microbiol Infect Dis. 
2007;57:7-13. 
Pallin DJ, Egan DJ, Pelletier AJ, Espinola JA, Hooper DC, Camargo CA Jr. Increased US 
emergency department visits for skin and soft tissue infections, and changes in antibiotic choices, 
during the emergence of community-associated methicillin-resistant Staphylococcus aureus. Ann 
Emerg Med. 2008;51:291–8. 
Pallin DJ, Espinola JA, Leung DY, Hooper DC, Camargo CA Jr. Epidemiology of dermatitis and 
skin infections in United States physicians’ offices, 1993–2005. Clin Infect Dis. 2009;49:901–7. 
Ramsey TD, Lau TTY, Ensom MHH. Serotonergic and adrenergic drug interactions associated 
with linezolid: a critical review and practical management approach. Annals Pharmacother. 
2013;47:543-560. 
Rayner CR, Baddour LM, Brimingham MC, Norden C, Meagher AK, Schentag JJ. Linezolid in 
the treatment of osteomyelitis: results of compassionate use experience. Infection. 2004;32:8-14. 
Rennie RP, Jones RN, Mutnick AH. Occurrence and antimicrobial susceptibility patterns of 
pathogens isolated from skin and soft tissue infections: report from the SENTRY Antimicrobial 
Surveillance Program (United States and Canada, 2000). Diagn Microbiol Infect Dis. 
2003;45:287-293. 
Rubenstein E, Isturiz R, Standiford HC, Smith LG, Oliphant TH, Cammarata S, Hafkin B, Le V, 
Remington J. Worldwide assessment of linezolid’s clinical safety and tolerability: 
comparator-controlled phase III studies. Antimicrob Agents Chemother. 2003;47(6):1824-1831. 
Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJC, Gorbach SL. Practice 
guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by 
the Infectious Diseases Society of America. Clin Infect Dis. 2014;59(2):e10–52. 
Versalovic J, Carroll KC, Funke G, et al. Manual of Clinical Microbiology, 10th Edition. ASM 
Press, Inc. 2011. Washington, D.C. 


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Wilcox MH. Update on linezolid: the first oxazolidinone antibiotic. Expert Opin Pharmacother. 
2005;6(13):2315-2326. 
Zyvox® (Linezolid) [Prescribing Information]. New York, NY. Pfizer, 2018. 


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Appendix 1. Allowed Prior Antibiotics 
Prior (within 96 hours prior to randomization) administration of systemic antibacterial therapy is 
an exclusion criterion (Section 4.2); however, subjects may be eligible for the study despite prior 
antimicrobial therapy if they received a single dose of a non-oxazolidinone, short-acting 
systemic antibiotic within 96 hours prior to randomization. Alternatively, subjects may be 
eligible despite prior antimicrobial therapy if there is 1) objective clinical evidence of treatment 
failure such as persistent pain, erythema, induration, and/or purulent drainage (if present) 
following at least 48 hours of prior, non-study, systemic antibacterial therapy; and 2) 
microbiological evidence of failure (i.e., a Gram stain obtained from an appropriate ABSSSI 
specimen collected after the initiation of this prior therapy revealing WBC and Gram-positive 
cocci, or isolation of a Gram-positive pathogen from an appropriate ABSSSI specimen that is 
resistant to the prior systemic antibacterial therapy). 
For the purposes of this protocol, short-acting is defined as having a dosage frequency of more 
than QD. The allowed and disallowed antibacterials listed in Table 10 are based in part from the 
antimicrobial agents listed in the 2014 Infectious Diseases Society of America (IDSA) 
Guidelines for the management of skin and soft tissue infections (Stevens, 2014). If a subject 
received a prior short-acting systemic antibiotic that is not listed here, the Investigator must 
contact the Medical Monitor to ensure subject eligibility. 
Table 10: 
Allowed and Disallowed Prior Antibiotics in Study MRX4-201 
Allowed Antibiotics 
(One dose within 96 hours prior to randomization) 
Disallowed Antibiotics 
Penicillins: 
Amoxicillin 
Nafcillin 
NONE 
Amoxicillin-Clavulanate 
Oxacillin 
 
Amoxicillin-Sulbactam 
Penicillin-G 
 
Ampicillin 
Penicillin-V 
 
Ampicillin-Sulbactam 
Piperacillin 
 
Dicloxacillin 
Piperacillin-Tazobactam 
 
Cephalosporins: 
Cefaclor 
Cefpodoxime  
Ceftriaxone 
Cefadroxil 
Cefprozil  
 
Cefazolin 
Ceftaroline  
 
Cefdinir 
Ceftazidime 
 
Cefepime 
Ceftibuten 
 
Cefixime  
Cefuroxime 
 
Cefditoren  
Cephalexin 
 
Cefotaxime  
Loracarbef 
 


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Allowed Antibiotics 
(One dose within 96 hours prior to randomization) 
Disallowed Antibiotics 
Carbapenems: 
Doripenem 
Ertapenem 
Imipenem 
 
Meropenem 
 
Glycopeptides: 
Televancin 
Dalbavancin 
Vancomycin 
Oritavancin 
Fluoroquinolones: 
Ciprofloxacin 
Levofloxacin 
 
Moxifloxacin 
Macrolides: 
Clarithromycin 
Erythromycin 
Azithromycin 
Clarithromycin XL  
Tetracyclines: 
Doxycycline 
Minocycline 
Minocycline Extended Release 
Miscellaneous: 
Clindamycin 
Metronidazole 
Trimethoprim-sulfamethoxazole/Co-trimoxazole 
Daptomycin 
Oxazolidinones: 
NONE 
Linezolid 
Tedizolid 


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Appendix 2. Avoidance of High-Tyramine Foods and Drinks 
As linezolid and other oxazolidinones are MAOIs, a significant pressor response has been 
observed in normal adult subjects receiving linezolid and concomitant tyramine doses of 
> 100 mg (Zyvox® Prescribing Information, 2018); therefore, subjects receiving linezolid or 
contezolid acefosamil need to avoid consuming large amounts of foods or beverages with 
high-tyramine content. Foods high in tyramine content include those that may have undergone 
protein changes by aging, fermentation, pickling, or smoking to improve flavor, such as aged 
cheeses, fermented or air-dried meats, sauerkraut, soy sauce, and tap beers (Table 11). The 
tyramine content of any protein-rich food may be increased if stored for long periods or 
improperly refrigerated. 
The following table of high-tyramine foods and drinks to avoid in large amounts during study 
drug administration in this study has been modified from "Meal Ideas and Menus: Avoiding 
High-tyramine Foods Made Easy" (Holden, 2006), and serves as a general guidance. Questions 
as to whether additional foods or beverages must be avoided should be directed to the Medical 
Monitor. 
Table 11: 
Foods and Beverages to Avoida During Study Drug Administrationb 
Cheeses 
Beverages 
Meat, Poultry & Fish 
Produce 
Condiments 
Canadian or New 
York Cheddar 
Stilton 
Camembert 
Swiss 
Blue/Gorgonzola 
Vermouth 
Tap beer 
Korean beer 
Dry sausages (e.g., 
mortadella, salami) 
Chinese dried duck 
Aged chicken livers 
Smoked or pickled fish 
(e.g., lox) 
Pickled herring 
Caviar 
Soups, gravies, or sauces 
containing meat extracts 
(e.g., bouillon, beef broth) 
Sauerkraut 
Fava beans and 
broad beans 
(Italian green 
beans) 
Banana peel 
Kimchi 
Miso soup, 
fermented soy 
bean/bean curd, 
tofu 
Soy sauce 
Concentrated yeast 
extract (Marmite®, 
Vegemite®) 
Thai or Vietnamese 
fish sauce 
a Similar aged, fermented, pickled, or smoked foods or beverages not shown in this table (e.g., unlisted cheeses or 
alcoholic beverages) should be generally avoided or consumed rarely with caution. 
b Foods that need to be avoided from Day 1 until EOT  
 


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Appendix 3. Restricted Medications 
Oxazolidinones are reversible, nonselective MAOIs; therefore, they have the potential for 
interaction with adrenergic and serotonergic agents (Zyvox® Prescribing Information, 2018). 
Exclusion Criterion 17 states that prior (within the past 2 weeks) or expected/required 
concomitant (from the start of the study drug to EOT) administration of systemic adrenergic or 
serotonergic medications are excluded (Section 4.2). Such agents include the following: 
Adrenergic Agents 
Adrenergic agents, including indirect-acting sympathomimetic agents, vasopressors, and 
dopaminergic agents, should be used with caution when administered concomitantly with 
oxazolidinones― patients receiving concomitant linezolid may experience a reversible 
enhancement of the pressor response to such adrenergic agents (Zyvox® Prescribing Information, 
2018). Examples of such agents include: 
• Adrenergic receptor agonists; examples include dobutamine, dopamine, epinephrine 
(adrenaline), norepinephrine, phenylpropanolamine, pseudoephedrine 
• Norepinephrine reuptake inhibitors; examples include bupropion and methylphenidate 
• Azapirones; examples include buspirone and gepirone 
Serotonergic Agents 
Spontaneous reports of serotonin syndrome, including fatal cases, have been reported with the 
co-administration of linezolid and serotonergic agents (e.g., antidepressants such as SSRIs). 
Symptoms and signs of serotonin syndrome include hyperthermia, rigidity, myoclonus, 
autonomic instability, and mental status changes that include extreme agitation progressing to 
delirium and coma. In this study, study drug (contezolid acefosamil or linezolid) should not be 
administered to patients taking any of the following medications: 
• Serotonin reuptake inhibitors (SSRIs); examples include paroxetine, sertraline, fluoxetine, 
fluvoxamine, and citalopram 
• Tricyclic antidepressants; examples include clomipramine and imipramine 
• Serotonin 5-HT1 receptor agonists (triptans); examples include almotriptan, eletriptan, 
frovatriptan, naratriptan, rizatriptan, sumatriptan, and zolmitriptan 


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Appendix 4. Safety Laboratory Tests 
Hematology: 
• 
Hemoglobin 
• 
Hematocrit 
• 
Erythrocyte count 
• 
Leukocyte count (WBCs) 
• 
Neutrophils 
• 
Lymphocytes 
• 
Monocytes 
o Eosinophils 
o Basophils 
o Platelets 
 
Coagulation: 
• 
Prothrombin time/International normalized 
ratio (PT/INR) 
• 
Partial thromboplastin time 
• 
Activated partial thromboplastin time (aPTT) 
 
Urinalysis: 
• 
Specific gravity 
• 
pH 
• 
Protein 
• 
Glucose 
• 
Ketones 
• 
Bilirubin 
• 
Occult blood 
• 
Nitrites 
• 
Urobilinogen 
• 
Leukocyte esterase 
 
Urine Microscopy:a 
• 
WBCs 
• 
Red blood cells 
• 
Casts 
• 
Bacteria 
• 
Crystals 
Chemistry (Serum Concentrations): 
• 
Glucose 
• 
Calcium 
• 
Albumin 
• 
Total protein 
• 
Sodium 
• 
Potassium 
• 
Bicarbonate 
• 
Chloride 
• 
Urea nitrogen 
• 
Creatinine 
• 
Alkaline phosphatase 
• 
Alanine aminotransferase 
• 
Aspartate aminotransferase 
• 
Total and direct bilirubin 
• 
Magnesium 
• 
Lactate dehydrogenase 
• 
Phosphorus 
• 
Uric Acid 
• 
Creatine kinase 
• 
Gamma-glutamyl transferase 
• 
Indirect bilirubin 
• 
Cholesterol 
• 
Triglycerides 
• 
β-Human chorionic gonadotropin for females 
• 
C-reactive protein (CRP) 
 
SCREENING/BASELINE ONLY: 
• 
Creatinine clearance 
• 
Anti-HBcAg (anti-hepatitis B core antigen) 
• 
Anti-HBsAg (anti-hepatitis B surface antigen) 
• 
HBsAg (hepatitis B surface antigen) 
• 
HCV Ab (hepatitis C antibody) 
• 
HIV Ab (human immunodeficiency virus 
antibody) 
a 
Performed if UA is positive for red blood cells, WBCs, or protein. 


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Appendix 5. Instructions for Primary ABSSSI Site Measurement 
1. Measurements of erythema, edema, or induration, whichever is largest, should be done with a 
head-to-toe orientation by measuring the longest length head-to-toe and then the widest width 
perpendicular to that length. Note: the furthest edges of head-to-toe erythema, edema, and/or 
induration, whichever is largest should be the focus of the measurement. Note: in subjects 
with darker skin, the perimeter of erythema, edema, and/or induration may be difficult to 
delineate. Palpation may help delineate the perimeter of the inflammatory lesion. 
2. Measure in this manner and document the measurement in the source document and eCRF. 
3. A surface area (cm2) will be calculated by the eCRF. 
Figure 3: 
Primary ABSSSI Site Measurement – Example 
Longest length: 
 


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Widest width perpendicular: 
 


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Appendix 6. Local Signs and Symptoms of ABSSSI 
Local signs and symptoms will be assessed for the primary ABSSSI site. 
The Investigator is to provide a categorical assessment and comparison to baseline of the 
following parameters using the scale below: 
Parameter 
Absent 
Mild 
Moderate 
Severe 
Erythema 
None 
Pink 
Red 
Fiery red 
Swelling/edema 
None 
Swelling just apparent  
on casual inspection  
(up to 2 mm of pitting) 
Marked swelling  
(≤ 4 mm of pitting) 
Maximal swelling  
(> 4 mm of pitting) 
Localized warmth 
None 
Slightly warm 
Warm 
Hot 
Tenderness on 
palpation 
None 
Slight or mild tolerable 
discomfort on palpitation 
Uncomfortable with  
light palpitation or 
pressure 
Intolerable by even a  
mild stimulus such as  
sheet touching 
Drainage 
None 
Serous 
Seropurulent  
Purulent 
Fluctuance 
None 
Present 
Not applicable 
Not applicable 
Induration 
None 
Present 
Not applicable 
Not applicable 
 


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Appendix 7. Recommended Instructions for Primary ABSSSI Site Digital Photography 
Digital photographs of the primary ABSSSI site will be taken with digital cameras provided by 
the Sponsor as described below.  (IMPORTANT NOTE: Depending upon the location of the 
infection site on a subject’s face or body, a digital image may include certain unique features that 
could reveal the subject’s identity. In order to protect and preserve patient privacy, please 
obscure or cover any unique features of the subject (such as eyes, nose or tattoos) prior to 
capturing the digital image.) 
1. Drape area behind subject with a white sheet. 
2. Place disposable ruler on the skin adjacent to the lesion. Define outer edge of erythema, 
edema, or induration, whichever is largest, with a marker at each visit. 
3. Using the ruler or another piece of paper, place identifying information (date, subject 
number, body part) adjacent to the lesion. 
4. Position camera approximately 2 feet (60 cm) from the lesion. 
5. Take a picture at a 90-degree perpendicular angle from the lesion. 
6. Do not use any zoom settings. 
7. Turn the flash setting to “Off” if enough light is available from other sources. Otherwise, use 
the flash on auto exposure setting. 
8. Use rest of camera’s automatic settings for focus and lighting. 
9. Place a light source on each side of the subject to help prevent shadows. 
10. Capture at least a 4 to 6-inch border around the lesion to assess the status of skin surrounding 
the lesion. If the lesion wraps around a limb and cannot be fully seen in 1 photograph, take 
multiple perpendicular photographs to allow documentation of the entire lesion. If multiple 
photographs are required, mark the top and bottom of the lesion on the subject to indicate the 
border of the viewing field of each photograph. 
11. After the digital photograph is taken, confirm on the camera screen that the picture is clear, in 
focus, and that all information on the ruler, including the ruler scale, is visible and legible 
(repeat if necessary).   
a. Please ensure the final image at each visit is saved to the camera’s storage card and the 
storage card is maintained in the study files.   
b. Print the picture and include in the subject’s source documents.   
c. In order to protect and preserve patient privacy, please obscure or cover any unique 
features of the subject (such as eyes, nose or tattoos) that were not able to be covered 
prior to capturing the digital image.     


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d. After photographs are taken, discard the paper ruler per institutional guidelines. 
The Sponsor may request that digital images be sent to the Sponsor for review.  All images from 
all patients will also be collected on a memory drive or card for storage.  Photographic data will 
be archived and may be analyzed at a later timepoint.   

SAP_001.pdf: 
 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
A Phase 2, Multicenter, Randomized, Double-Blind Study to Evaluate the Safety and 
Efficacy of Contezolid Acefosamil Compared to Linezolid Administered Intravenously and 
Orally to Adults with Acute Bacterial Skin and Skin Structure Infection 
Study: MRX4-201 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CONFIDENTIAL 
 
May 28, 2019  
 
 


 
 
 
 
STATISTICAL ANALYSIS PLAN APPROVAL 
Study: MRX4-201 
Version 1.0 
 
 
 
 
 
 
_________________________ 
 
 
 
 
_____________ 
Denis Boisvert, MS 
 
 
 
 
 
 
Date 
Study Statistician 
InClin, Inc. 
 
 
 
 
_________________________ 
 
 
 
 
_____________ 
Edward Fang, MD 
 
 
 
 
 
 
Date 
SVP, Clinical Development 
MicuRX Pharmaceuticals, Inc. 
 
 
 
 
_________________________ 
 
 
 
 
_____________ 
Amy Bassett, MPH 
 
 
 
 
 
 
Date 
Study Director 
MicuRX Pharmaceuticals, Inc. 
 


	
	


MicuRX Pharmaceuticals (Protocol MRX4-201)  
1 
Statistical Analysis Plan – Version 1.0 
Confidential 
 
May 28, 2019 
 
TABLE OF CONTENTS 
 
1 
ABBREVIATIONS AND DEFINITIONS ........................................................................ 3 
1.1 
Abbreviations: ........................................................................................................... 3 
1.2 
Definitions of Terms: ................................................................................................. 5 
2 
INTRODUCTION .......................................................................................................... 5 
3 
STUDY DESIGN........................................................................................................... 6 
4 
STUDY OBJECTIVES .................................................................................................. 9 
4.1 
Primary Objectives .................................................................................................... 9 
4.2 
Secondary Objectives ............................................................................................... 9 
5 
DATA MANAGEMENT ................................................................................................10 
6 
PATHOGEN DETERMINATION ..................................................................................10 
7 
DEFINITION OF ANALYSIS POPULATIONS .............................................................13 
7.1 
Intent-to-Treat (ITT) Population ................................................................................14 
7.2 
Modified Intent-to-Treat (MITT) Population ..............................................................14 
7.3 
Safety Population ....................................................................................................14 
7.4 
Microbiological Intent-to-Treat (Micro-ITT) Population .............................................14 
7.5 
Clinically Evaluable Population at End-of-Therapy (CE-EOT) and the Post-Therapy 
Evaluation (CE-PTE) ...........................................................................................................14 
7.6 
Microbiologically Evaluable Population (ME) ............................................................16 
7.7 
Pharmacokinetic Population (PK) ............................................................................16 
7.8 
Evaluability Determination .......................................................................................16 
8 
DEFINITION OF OUTCOME MEASURES ..................................................................17 
8.1 
Clinical Outcome Definitions ....................................................................................17 
8.1.1 
Programmatic Clinical Response at Early Assessment (Day 3 or Day 4) (EA) .....17 
8.1.2 
Investigator Assessment of Clinical Response at End-of-Therapy (EOT) .............17 
8.1.3 
Investigator-Assessment of Clinical Response at Post-therapy Evaluation (PTE) 18 
8.1.4 
Investigator Assessment of Clinical Response at Late Follow-up (LFU) ...............20 
8.1.5 
Composite Assessment of Clinical Outcome (CACO) ..........................................20 
8.2 
Microbiologic Response ...........................................................................................21 
8.2.1 
Per-Pathogen Microbiological Response at EOT and PTE Visits .........................21 
8.2.2 
Per-Subject Microbiological Response at PTE and Overall Assessment at PTE ..22 
8.3 
Emergent Infections .................................................................................................23 
8.4 
Safety Outcomes .....................................................................................................23 
8.5 
Pharmacokinetic Outcomes .....................................................................................23 
9 
STATISTICAL METHODS AND GENERAL CONSIDERATIONS ...............................24 
9.1 
Sample Size ............................................................................................................24 


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9.2 
Randomization and Masking ....................................................................................24 
9.3 
Interim Analysis .......................................................................................................25 
9.4 
Standard Calculations ..............................................................................................25 
9.5 
Handling of Missing Data .........................................................................................26 
9.6 
Comments on Statistical Analysis ............................................................................27 
10 
STATISTICAL ANALYSES .........................................................................................28 
10.1 
Subject Disposition ..................................................................................................28 
10.2 
Demographics and Baseline Characteristics ............................................................29 
10.3 
Medical and Surgical History ...................................................................................29 
10.4 
Baseline Disease Characteristics .............................................................................30 
10.5 
Baseline Microbiology ..............................................................................................30 
10.6 
Prior and Concomitant Medications .........................................................................31 
10.7 
Study Drug Exposure and Compliance ....................................................................32 
10.8 
Efficacy Analyses.....................................................................................................33 
10.8.1 Primary Efficacy Analysis .....................................................................................34 
10.8.2 Secondary Efficacy Analysis ................................................................................35 
10.8.3 Additional Efficacy Analysis .................................................................................36 
10.8.4 Microbiological Outcomes ....................................................................................36 
10.9 
Safety Analyses .......................................................................................................37 
10.9.1 Adverse Events ....................................................................................................37 
10.9.2 Laboratory Values ................................................................................................38 
10.9.3 Vital Signs ............................................................................................................40 
10.9.4 Electrocardiogram ................................................................................................40 
10.9.5 Physical Examinations .........................................................................................41 
10.9.6 Basic Ophthalmoscopy Exams and Visual Fields .................................................41 
10.9.7 Pharmacokinetic Analyses ...................................................................................42 
10.9.8 Protocol Deviations ..............................................................................................42 
11 
DEVIATIONS FROM THE PROTOCOL ......................................................................43 
12 
REFERENCE LIST ......................................................................................................43 
APPENDIX A) SCHEDULE OF EVENTS ............................................................................44 
APPENDIX B) DIVISION OF MICROBIOLOGY AND INFECTIOUS DISEASES ADULT 
TOXICITY TABLE ...............................................................................................................48 
APPENDIX C) SAFETY LABORATORY TESTS ................................................................50 
APPENDIX D) ALLOWED PRIOR ANTIBIOTICS ..............................................................51 
APPENDIX E) LOCAL SIGNS AND SYMPTOMS OF ABSSSI ..........................................52 


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1 
Abbreviations and Definitions 
1.1 
Abbreviations: 
Abbreviation 
Definition 
ABSSSI 
Acute bacterial skin and skin structure infection 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANC 
Absolute Neutrophil Count 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical class 
BMI 
Body Mass Index 
CACO 
Composite assessment of clinical outcome 
CE 
Clinically evaluable  
CI 
Confidence interval 
CN 
Clinically Notable 
CSR 
Clinical Study Report 
CRO 
Contract Research Organization 
CTCAE 
Common Terminology for Adverse Events 
CV 
Coefficient of Variation 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
GGT 
Gamma-glutamyl transferase 
GM 
Geometric Mean 
H 
High 
ITT 
Intent-to-treat 
IV 
Intravenous 
IWRS 
Interactive web response system 
L 
Low 


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Abbreviation 
Definition 
LDH 
Lactate dehydrogenase 
LLN 
Lower Limit of Normal 
MAOI 
Monoamine oxidase inhibitor 
MAX 
Maximum 
ME 
Microbiologically evaluable 
MIC 
Minimum Inhibitory Concentration 
MIC50 
Minimum Inhibitory Concentration to inhibit the growth of 50% 
MIC90 
Minimum Inhibitory Concentration to inhibit the growth of 90% 
MIN 
Minimum 
MITT 
Modified intent-to-treat 
micro-ITT 
Microbiological intent-to-treat 
MRSA 
Methicillin-resistant Staphylococcus aureus 
MSSA 
Methicillin-sensitive Staphylococcus aureus 
NRL 
Normalized Range Low 
NRH 
Normalized Range High 
PK 
Pharmacokinetic 
PO 
Oral  
PT 
Preferred term 
QD 
Once daily 
QTcF 
Corrected QT interval using the Fridericia correction formula  
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard Deviation 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 


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Abbreviation 
Definition 
WBC 
White blood cell count 
WHO 
World Health Organization 
 
1.2 
Definitions of Terms: 
Term 
Definition 
CACO 
Combined outcome of early response at EA and Investigator’s assessment of clinical 
outcome at PTE 
Contezolid 
The active metabolite of contezolid acefosamil moiety (formerly known as MRX-1) 
Contezolid acefosamil 
The investigational medicinal product in this study (formerly known as MRX-4); a 
prodrug that undergoes a 2-step conversion process to contezolid (active moiety) by 
means of MRX-1352 (an intermediate metabolite)  
Dose 
Any amount of drug (IV or PO) taken at the time of dosing. 
EA 
Early assessment (48 to 72 hours after the start of the first dose of IV study drug) 
EOT 
End of therapy (last day of study drug) 
LFU 
Late follow-up (21-28 days after EOT) 
MRX-1320 
A primary metabolite of contezolid; MRX-1320 is also known as “M2” in other 
documents 
MRX-1352 
Intermediate metabolite in the 2-step process by which prodrug (contezolid 
acefosamil) is converted into contezolid (active moiety) 
PTE 
Post therapy evaluation (7 to 14 days after EOT) 
Subject 
An individual who participates in a clinical trial, either as a recipient of the 
investigational product(s) or as a control 
 
 
2 
Introduction 
This document presents the Statistical Analysis Plan (SAP) for the protocol MRX4-201, “A 
Phase 2, Multicenter, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy 
of Contezolid Acefosamil Compared to Linezolid Administered Intravenously and Orally to 
Adults with Acute Bacterial Skin and Skin Structure Infection”. The statistical plan described 
is an a priori plan and no analyses have been conducted prior to the preparation of this plan. 
This SAP summarizes the study design and objectives and provides details of the outcome 


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definitions and statistical methods that will be used to analyze the data from protocol MRX4-
201. Changes made to the SAP after it has been signed but prior to study unblinding will be 
documented in an amendment. Any important changes made to the analyses will be 
described in the clinical study report (CSR). This SAP is based on the original protocol 
version dated August 16, 2018, protocol amendment 1 dated September 27, 2018, and 
protocol amendment 2 dated October 19, 2018. 
3 
Study Design  
This is a Phase 2, multicenter, randomized, double-blind safety and efficacy study of 
contezolid acefosamil 1500 IV x 1 dose, followed by 1000 mg IV every 12 hours (q12h) 
(± 2 hours), for at least 3 total IV doses, followed by 1300 mg PO q12h (± 2 hours) 
compared with linezolid 600 mg IV q12h (± 2 hours), for at least 3 total IV doses, followed by 
600 mg PO q12h (± 2 hours) in adult subjects with ABSSSI. Subjects will receive study drug 
for a total of 10 to 14 days. 
Up to 200 subjects will be enrolled to achieve approximately 150 clinically evaluable 
subjects in the CE-PTE population with ABSSSI from approximately 5 to 10 sites in the US. 
Randomization will have a 2:1 (contezolid acefosamil: linezolid) allocation ratio; therefore, 
up to 133 subjects will be randomized to receive contezolid acefosamil and up to 67 
subjects will be randomized to receive linezolid. Efforts will be made to enroll a mixture of 
ABSSSI types (cellulitis/erysipelas, wound infection, and major cutaneous abscess); 
however, subjects with major cutaneous abscess should not comprise > 30% of randomized 
subjects. Subjects will be randomized to treatment provided they meet all inclusion and no 
exclusion criteria. Randomization will be stratified by ABSSSI type to better ensure proper 
balance between the treatment groups. 
Subjects may receive adjunctive antimicrobial therapy with parenteral aztreonam (1 to 2 g 
IV/ intramuscular [IM] q8h, not to exceed 6 g/day) if the Investigator suspects or has 
confirmed the presence of aerobic Gram-negative pathogens, which, in addition to Gram-
positive aerobic bacteria, are also associated with the pathogenic process. Subjects with 
only Gram-negative pathogens are not eligible for continued treatment under this protocol 
and will be discontinued from study drug as soon as Gram stain and culture confirms that 
the subject’s infection has no Gram-positive pathogen contributing to the subject’s disease. 


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Subjects who received prior systemic antibacterial therapy with Gram-positive activity within 
96 hours prior to randomization will be excluded from the study unless clear clinical 
evidence of prior treatment failure within the prior 96 hours is available. However, one 
exception to this criterion is the receipt of a single dose of a short-acting, non-oxazolidinone 
antibiotic (as provided in the study exclusion criteria and list of allowable antibiotics). 
Subjects who received a single dose of a short-acting non-oxazolidinone Gram-positive 
active antibiotic within 96 hours prior to randomization will not comprise > 25% of 
randomized subjects. 
Randomized subjects will receive at least 3 doses of treatment with IV study drug followed 
by PO dosing, however subjects may receive the IV formulation for the entire treatment 
duration. Study treatment will be as follows: 
x 
Subjects randomized to contezolid acefosamil treatment will receive IV infusions of 
contezolid acefosamil q12h (± 2 hours) for a minimum of 3 infusions followed by 2 
PO contezolid acefosamil capsules q12h (± 2 hours) for a total of 10 to 14 days of 
treatment. The IV dose of contezolid acefosamil will be 1500 mg infused over 
60 minutes (± 5 minutes) for 1 dose followed by 1000 mg infused over 60 minutes 
(± 5 minutes); the PO dose of contezolid acefosamil will be 1300 mg (2 capsules 
each with 650 mg of contezolid acefosamil). 
x 
Subjects randomized to linezolid treatment will receive IV infusions of linezolid q12h 
(± 2 hours) for a minimum of 3 infusions followed by 2 PO linezolid capsules q12h 
(± 2 hours) for a total of 10 to 14 days of treatment. The IV dose of linezolid will be 
600 mg infused over 60 minutes (± 5 minutes); the PO dose of linezolid will be 
600 mg (2 capsules each with 300 mg of linezolid). 
Subjects may receive the IV formulation for the entire treatment duration. The primary 
ABSSSI lesion will be recorded in the eCRF at the screening/baseline visit.  If the primary 
ABSSSI lesion has not increased in area from the screening/baseline assessment and the 
Investigator determines that the subject has sufficient PO intake of food and drink to safely 
support the administration of PO doses of antibiotics, the subject may be switched to the PO 
formulation. Subjects will undergo follow-up visits as described in Table 1 in an outpatient 
setting to assess the safety, tolerability, and efficacy of the investigational products. 
Day 1 is the first day of study drug administration; subsequent study days are consecutive 
calendar days. For purposes of analysis, Early Assessment (EA) will be performed 48 to 


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72 hours after the start of the first dose of IV study drug, End of Therapy (EOT) will occur on 
the last calendar day of study drug (+ 1 day), Post Therapy Evaluation (PTE) will occur 
7 to 14 days after EOT, and Late Follow-up (LFU) will occur 21 to 28 days after EOT. 
Subjects will receive study drug for 10 to 14 days. Subjects will then be followed for up to 
28 days after the last calendar day of study drug. Therefore, the total duration of each 
subject’s participation in the study will be up to 42 days, excluding the screening/baseline 
visit that occurs within 24 hours prior to study drug administration on Day 1. The study 
design is shown schematically in Table 1 and a detailed “Schedule of Study Procedures” is 
provided in Appendix A 
Table 1: Schedule of Study Procedures 
Screening/ 
Baseline 
Study Treatment Period (Day 1 to EOT) 
PTE 
LFU 
Within 
24 hours 
prior to first 
dose 
Day 1 
EA  
(48-72 
hours) 
Day 7  
(± 1 day) 
EOT 
(+ 1 day) 
7-14 days 
after EOT 
21-28 days 
after EOT 
Confirm 
eligibility; 
Baseline 
clinical, 
laboratory, 
and safety 
assess-
ments 
Randomize 
to treatment 
First dose of 
study drug 
Safety 
assessments 
PK samples 
(Days 1-2)a 
Clinical, 
laboratory, 
and safety 
assessments 
 
Clinical, 
laboratory, 
and safety 
assessments 
Last dose of 
study drug 
Clinical, 
laboratory, 
and safety 
assessments 
PK samples a 
Clinical, 
laboratory, 
and safety 
assessments 
Investigator’s 
assessment of 
clinical 
relapse/failure 
and AE 
assessment 
EA = early assessment; EOT = end of therapy; IV = intravenous; LFU = late follow-up; PK = pharmacokinetic; 
PTE = post therapy evaluation 
a PK sampling will be sparse. Samples will be collected after the first IV dose and prior to and after the third IV 
dose (i.e. on Day 1 and Day 2) and at completion of therapy (IV or PO), as described in the Pharmacokinetic 
Assessments section. 
 
Subjects who discontinue study drug or withdraw from the study itself will undergo all EOT 
assessments on the day of study drug discontinuation or study withdrawal (+ 1 day). 
Subjects who discontinue study drug will remain in the study and complete all assessments 
specified for the PTE and LFU visits. For subjects who withdraw from the study, efforts will 
be made to perform follow-up safety assessments per study schedule. None of the subjects 
will be replaced once they have been randomized. The duration of treatment within the 
specified window will be determined by the Investigator based on the subject’s clinical status 
(e.g., therapy can be discontinued if the subject has improved, no more antibiotic treatment 
is medically necessary, and the risk of relapse is minimal). 


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Gram stain and culture specimens of the ABSSSI site will be collected from all subjects for 
microbiologic evaluation at screening/baseline. ABSSSI site specimens (purulent discharge, 
skin biopsy, or aspiration at the leading edge of the cellulitis area) in addition to blood 
cultures from 2 separate venipuncture sites will be obtained from all subjects prior to 
administration of antibacterial therapy whenever possible. ABSSSI specimen culture and 
Gram stains will be repeated at subsequent visits only if clinically indicated (e.g., subject is 
deemed a clinical failure or if purulence and discharge from the ABSSSI site continues after 
screening/baseline). Blood cultures must be repeated every 3 days (+/- 1 day) if the 
previous blood culture was positive or at any time after screening/baseline if clinically 
indicated. 
4 
Study Objectives 
4.1 
Primary Objectives 
The primary objectives are as follows: 
x 
Evaluate early clinical response of contezolid acefosamil compared to linezolid at 
early assessment (EA; 48 to 72 hours after the start of the first dose of IV study drug) 
in the intent-to-treat (ITT) population 
x 
Evaluate safety and tolerability of both contezolid acefosamil IV and PO formulations 
compared with linezolid 
4.2 
Secondary Objectives 
The secondary objectives are as follows: 
x 
Evaluate early clinical response at: 
- EA in the modified intent-to-treat (MITT) population 
- EA (overall and by baseline pathogen) in the microbiological intent-to-treat 
(micro-ITT) population 
x 
Evaluate percent reduction in lesion size from baseline in ABSSSI lesions at Day 7 in 
the ITT and MITT populations 
x 
Evaluate the Investigator’s assessment of clinical response in the ITT, MITT, and 
clinically evaluable (CE) populations at each timepoint: 
- End of therapy (EOT; last day of study drug) in the ITT, MITT, and CE-EOT 
populations 


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- Post therapy evaluation (PTE; 7 to 14 days after EOT) in the ITT, MITT, and CE-
PTE populations 
- Late follow-up (LFU; 21-28 days after EOT) in the ITT, MITT, and CE-PTE 
populations 
x 
Evaluate per-subject microbiological response at: 
- PTE in the micro-ITT population 
- PTE in ME population 
x 
Evaluate per-pathogen microbiological response at: 
- PTE in the micro-ITT population 
- PTE in the ME population 
x 
Evaluate Investigator’s assessment of clinical response in the micro-ITT and ME 
populations at: 
- PTE (overall and by baseline pathogen) 
- LFU (overall and by baseline pathogen) 
x 
Characterize the PK of 3 contezolid acefosamil metabolites (MRX-1352, contezolid, 
and MRX-1320) using sparse PK sampling in adult subjects with ABSSSI 
x 
Evaluate composite assessment of clinical outcome (CACO) in the ITT, micro-ITT, 
and CE-PTE populations 
5 
Data Management 
Data management procedures, including database design, development of the data 
dictionary, and coding of medical history, adverse events and medications, will be performed 
at a Contract Research Organization (CRO). Data will be entered into an electronic case 
report form (e-CRF) at the study sites. A series of logic and consistency checks will be 
conducted to ensure accuracy and completeness of the clinical database. Safety laboratory 
results, microbiology data, electrocardiogram data, and pharmacokinetic data will be 
electronically transmitted from external vendors. After database lock, randomization data will 
be provided electronically from the IWRS vendor. Refer to the Data Management Plan for 
further Data Management details. 
6 
Pathogen Determination 
Pathogens will be identified based on the genus and species identification from the central 
laboratory. If the local laboratory grows an acceptable pathogen but the central laboratory is 
not able to grow the isolate, if isolates are lost during transportation or storage, or there are 


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major discrepancies between the local and central laboratory in the identification of species, 
the central laboratory or other Sponsor designee will request that the local laboratory resend 
the isolate. If the central laboratory cannot determine the genus and species of the isolate 
for any reason, the local laboratory determination of genus and species will be used for 
pathogen identification.  
Screening/baseline samples are collected within 24 hours of the first dose of study drug on 
either Day 1 or Day -1.  If more than one baseline ABSSSI site sample was obtained using a 
an acceptable ABSSSI specimen (purulent discharge, skin biopsy, or aspiration at the 
leading edge of the cellulitis area) or more than one baseline blood sample was obtained, 
isolates from all samples will be reviewed for pathogen determination. For subjects with 
cellulitis/erysipelas, if no acceptable baseline infectious material has been obtained, or if no 
pathogens have been identified from the baseline sample, then a Day 2 or 3 ABSSSI site 
sample can be used as baseline if the sample is considered acceptable.   
The organisms identified in Table 2 will always be considered a pathogen when isolated 
from an acceptable ABSSSI specimen.  Additional pathogens will be identified during 
pathogen review prior to unblinding of the study. 


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Table 2:  ABSSSI Pathogens  
x 
Enterococcus faecalis 
x 
Enterococcus faecium 
x 
Escherichia coli 
x 
Group C beta-hemolytic streptococci 
x 
Klebsiella pneumoniae 
x 
Methicillin-resistant Staphylococcus 
aureus (MRSA) 
x 
Methicillin-susceptible Staphylococcus 
aureus (MSSA) 
x 
Proteus mirabilis 
x 
Pseudomonas aeruginosa 
x 
Staphylococcus haemolyticus 
x 
Staphylococcus lugdunensis 
x 
Streptococcus agalactiae 
x 
Streptococcus anginosus 
x 
Streptococcus constellatus 
x 
Streptococcus dysglactiae 
x 
Streptococcus intermedius 
x 
Streptococcus pyogenes (Group A 
streptococci) 
x 
Streptococcus viridans group 
 
The following organisms will never be considered a pathogen when isolated from an 
ABSSSI specimen:  
Table 3: Not ABSSSI Pathogens 
x 
Bacillus spp. 
x 
Candida spp. or other fungi 
x 
Corynebacterium spp. 
x 
Micrococcus spp. 
x 
Staphylococcus epidermidis 
x 
Staphylococcus hominis 
x 
Staphylococcus saprophyticus  
x 
Staphylococcus warneri 
 
All other organisms not listed above will be assessed on a case-by-case basis via manual 
review by the Sponsor (e.g., Gram-negative organisms, anaerobes). If needed, subject 
clinical (e.g., type of infection, type of specimen, subject underlying conditions, etc.) and 
microbiological information (e.g., Gram stain, etc.) will be used to assist in determining if the 
isolate is a pathogen. In addition, all polymicrobial infections (i.e., ABSSSI caused by more 
than 1 pathogen) and all cases of bacteremia will be reviewed manually. 
 


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7 
Definition of Analysis Populations 
The relationship between the analysis sets is shown in Figure 1 below. 
 
 
Figure 1:  Overview of Analysis Populations 
 
 
ABSSSI = acute bacterial skin and skin structure infection; CE = clinically evaluable; EOT = end of therapy; 
ITT = intent-to-treat; ME = microbiologically evaluable; micro-ITT = microbiological intent-to-treat; MITT= 
modified intent-to-treat; PK = pharmacokinetic; PTE = post therapy evaluation 
 


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7.1 
Intent-to-Treat (ITT) Population 
The ITT population will consist of all randomized subjects regardless of whether or not the 
subject received study drug. A subject is considered randomized when the Investigator or 
Investigator’s designee receives the IWRS-generated randomization number. 
7.2 
Modified Intent-to-Treat (MITT) Population 
All randomized subjects in the ITT population, excluding subjects with only a Gram-negative 
pathogen(s) at baseline. 
7.3 
Safety Population 
The Safety population will consist of all randomized subjects who receive any amount of 
study drug. All safety analyses will be conducted in this population and will be presented in 
the summary tables by the treatment the subject actually received. In the event that a 
subject received both contezolid acefosamil and linezolid then that subject will be included in 
the contezolid acefosamil arm. 
7.4 
Microbiological Intent-to-Treat (Micro-ITT) Population 
The Micro-ITT population will consist of all subjects in the ITT population who have culture 
evidence of a baseline Gram-positive bacterial pathogen known to cause ABSSSI. Analyses 
in this population will be presented in summary tables by the treatment arm to which the 
subject was randomized. 
7.5 
Clinically Evaluable Population at End-of-Therapy (CE-EOT) and the Post-
Therapy Evaluation (CE-PTE) 
The CE-EOT and CE-PTE populations will consist of all subjects in the ITT population who: 
x 
meet the minimal clinical disease criteria for ABSSSI described in the study 
Inclusion Criteria (Protocol Section 4.1), 
x 
receive at least 80% of expected doses based on length of therapy,  
x 
did not receive any potentially-effective systemic or topical antibacterial therapies 
other than protocol specified study drug(s) for an indication other than ABSSSI 
between Day 1 and timepoint for assessment (except for adjunctive aztreonam or in 
cases of treatment failure), where the timepoint for assessment is EOT for the CE-
EOT population and PTE for the CE-PTE population.   
x 
Did not have major protocol violations including but not limited to:  


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o Prior administration of systemic antibacterial therapy within 96 hours before 
randomization Exceptions: Subjects may be eligible if they meet the following 
conditions, either:  
▪ Received a single dose of a non-oxazolidinone, short-acting, systemic 
antibiotic within 96 hours prior to randomization (Appendix 1). Note that such 
subjects will not comprise > 25% of randomized subjects  
or both of the following:  
▪ Objective clinical evidence of treatment failure (persistent pain, erythema, 
induration, purulent drainage) following at least 48 hours of prior, non-study, 
systemic antibacterial therapy  
and  
▪ Microbiological evidence of failure (i.e., a Gram stain obtained from an 
appropriate ABSSSI specimen collected after the initiation of this prior 
therapy revealing WBC and Gram-positive cocci, or isolation of a Gram-
positive pathogen from an appropriate ABSSSI specimen that is resistant to 
the prior systemic antibacterial therapy) 
o Received the wrong study drug or unblinded before the timepoint of assessment 
for reasons other than safety 
In addition, to be included in the CE-EOT population, the following conditions must be met: 
x 
Have an Investigator’s assessment of clinical response at EOT (i.e., response can’t 
be indeterminate) 
x 
Had an EOT visit within 1 calendar day of last dose of study drug (+1 day) [i.e., 
within 48 hours of the last dose of study drug] 
To be included in the CE-PTE population, the following conditions must be met: 
x 
Have an Investigator’s assessment of clinical response at PTE (i.e., response can’t 
be missing or indeterminate unless the subject is deemed a clinical failure at the 
EOT visit) 
x 
Had a PTE visit within 7-14 days after the EOT visit unless the patient was 
considered a failure at either EOT or PTE based on the Investigator’s assessment of 


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clinical response.  If the EOT visit is out of the study window, then the PTE visit must 
still be within 7-14 days of the EOT visit.  If the EOT visit is missed, then the PTE 
visit must be within 7-14 days of the last dose of study drug. 
Additional minimal dose requirements for clinical failure or success at EOT or PTE: 
x 
Subjects who are defined as clinical failures at EOT or PTE with fewer than 5 doses 
of study drug are not included in the CE-EOT or CE-PTE populations, respectively. 
x 
Subjects who are defined as clinical successes at EOT or PTE with fewer than 7 
doses of study drug are not included in the CE-EOT or CE-PTE populations, 
respectively. 
7.6 
Microbiologically Evaluable Population (ME) 
The ME Population includes all subjects in the CE-PTE Population with culture evidence of 
a baseline Gram-positive bacterial pathogen known to cause ABSSSI (i.e., meets both CE-
PTE and Micro-ITT Population definitions). 
7.7 
Pharmacokinetic Population (PK) 
All subjects who receive at least 1 dose of contezolid acefosamil and had at least 1 blood 
sample collected for analysis of MRX-1352, contezolid, or MRX-1320. 
7.8 
Evaluability Determination  
The Medical Monitor will review both clinical and microbiological data for determination of 
criteria used to assess inclusion in the analysis populations and for determination of 
baseline and post-baseline pathogens. The Medical Monitor will be blinded to treatment 
assignment and will review the data concurrent with the conduct of the study. 
Inclusion into the ITT and Safety Populations will be determined programmatically from the 
eCRF data. Inclusion into the CE-EOT and CE- PTE Populations will be determined 
programmatically from the eCRF data and manual review conducted by the Medical Monitor. 
The Medical Monitor may review subject data to confirm that population criteria are satisfied.   
Inclusion into the MITT and ME Populations will be determined programmatically by 
incorporating the outcome of the review of the isolates by the Medical Monitor. The Medical 
Monitor will determine whether each isolate (baseline and post-baseline) is considered a 
pathogen based on a review of information from samples including infection type, type of 
specimen, Gram stain results, and local and central laboratory genus and species 


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identification. In the event that a local culture is completed, but a central lab culture not 
available, then the local lab result will be used. 
8 
Definition of Outcome Measures 
8.1 
Clinical Outcome Definitions 
 
8.1.1 Programmatic Clinical Response at Early Assessment (Day 3 or Day 4) (EA) 
Clinical response at EA will be determined programmatically based on data recorded on the 
e-CRF.   Note that the protocol EA visit window is 48-72 hours after the first dose of study 
drug, but the window is extended to the lower bound of 46 hours for analysis purposes. 
A subject will be classified programmatically as a ‘responder at EA’ if the percent reduction 
in the primary ABSSSI lesion area is greater than or equal to 20% compared to baseline, 
and the subject did not receive a systemic antibacterial agent with activity against Gram-
positive organisms for the treatment of ABSSSI through 72 hours, and did not die of any 
cause within 72 hours of the first dose of study drug. 
A subject will be classified programmatically as a ‘non-responder at EA’ if the percent 
reduction in the primary ABSSSI lesion size is less than 20% compared to baseline, or the 
subject received a systemic antibacterial agent with activity against gram-positive organisms 
for the treatment of ABSSSI through 72 hours, or died of any cause within 72 hours of the 
first dose of study drug. 
A subject will be classified programmatically as ‘indeterminate at EA’ if study data are 
unavailable for evaluation of efficacy for any reason (e.g., missing data, lost to follow-up, or 
if the EA visit is out of the 46-72 hour window).  If there is more than one ABSSSI 
measurement within the 46-72 hour window, the last measurement will be used to assess 
the clinical response at EA. 
If the baseline lesion measurement is missing and there is one within 6 hours of the first 
dose of study drug, this measurement may be considered the baseline measurement. 
8.1.2 Investigator Assessment of Clinical Response at End-of-Therapy (EOT) 
Investigator-determined ‘clinical success at EOT’ is defined by all of the following: 
x 
Resolution or near resolution of most baseline ABSSSI symptoms and signs,  


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x 
No new signs, symptoms, or complications attributable to the ABSSSI, 
x 
No post-baseline surgical procedure through EOT, to treat the infection that was not 
already planned at baseline, 
x 
No inter-current non-protocol specified systemic antibacterial therapy with activity 
against Gram-positive organisms for the treatment of ABSSSI, and 
x 
Did not die of any cause up to EOT. 
Investigator-determined ‘clinical failure at EOT’ is defined by any of the following: 
x 
Lack of resolution or near resolution of most baseline ABSSSI symptoms and signs, 
x 
New signs, symptoms, or complications attributable to the ABSSSI, 
x 
No post-baseline surgical procedure through EOT, to treat the infection that was not 
already planned at baseline, 
x 
Inter-current non-protocol specified antibacterial therapy administered for the 
treatment of the primary ABSSSI lesion or might have potential antibiotic activity 
directed toward the Gram-positive pathogens implicated in the ABSSSI, or 
x 
Died of any cause up to EOT. 
Investigator-determined ‘Indeterminate at EOT’ is defined as: 
x 
Study data are unavailable for evaluation of efficacy for any reason (e.g., missing 
data, lost to follow-up).  
8.1.3 Investigator-Assessment of Clinical Response at Post-therapy Evaluation 
(PTE) 
Investigator-determined ‘clinical success at PTE’ is defined by all of the following: 
x 
Resolution or near resolution of most baseline ABSSSI symptoms and signs,  
x 
No new signs, symptoms or complications attributable to the ABSSSI, 
x 
No post-baseline surgical procedure through PTE, to treat the infection that was not 
already planned at baseline, 
x 
No inter-current non-protocol specified systemic antibacterial therapy with activity 
against Gram-positive organisms for the treatment of ABSSSI, and 


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x 
Did not die of any cause up to PTE. 
Investigator-determined ‘clinical failure at PTE’ is defined by any of the following: 
x 
Lack of resolution or near resolution of most baseline ABSSSI symptoms and signs, 
x 
New signs, symptoms, or complications attributable to the ABSSSI, 
x 
No post-baseline surgical procedure through PTE, to treat the infection that was not 
already planned at baseline, 
x 
Inter-current non-protocol specified antibacterial therapy administered for the 
treatment of the primary ABSSSI lesion or might have potential antibiotic activity 
directed toward the Gram-positive pathogens implicated in the ABSSSI, or 
x 
Died of any cause up to PTE. 
Investigator-determined ‘Indeterminate at PTE’ is defined as: 
x 
Study data are unavailable for evaluation of efficacy for any reason (e.g., missing 
data, lost to follow-up).  
The following overall assessment of clinical response based on the Investigator’s 
Assessment will be determined at the PTE Visit based on the following rules.   
Table 4: Overall Assessment of Clinical Response  
Investigator's Assessment of Clinical Response 
 
 
 
EOT Visit 
PTE Visit 
Overall Assessment of Clinical 
Response at PTE Visit 
Success 
Success 
Success 
Success 
Failure 
Failure 
Success 
Indeterminate 
Indeterminate 
Failure 
Success 
Failure 
Failure 
Failure 
Failure 
Failure 
Indeterminate 
Failure 
Indeterminate 
Success 
Indeterminate 
Indeterminate 
Failure 
Failure 
Indeterminate 
Indeterminate 
Indeterminate 
 


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8.1.4 Investigator Assessment of Clinical Response at Late Follow-up (LFU) 
Investigator-determined ‘sustained clinical success’ at LFU is defined as no new signs or 
symptoms of primary ABSSSI after PTE, while ‘clinical relapse/failure’ is defined as new or 
worsened signs or symptoms of primary ABSSSI after PTE. All cases of ‘clinical 
relapse/failure’ will be queried to ensure that an antibiotic was taken. If study data is 
unavailable for evaluation of efficacy for any reason (e.g., missing data, lost to follow-up) 
then the result is ‘indeterminate’. For analysis purposes, the worst assessment at EOT, PTE, 
or LFU will be summarized at LFU, where Failure is a worse outcome than an Indeterminate 
result. For example, if the responses are Success, Failure, and Indeterminate at EOT, PTE, 
and LFU, then the worst assessment of Failure will be summarized at LFU. 
8.1.5 Composite Assessment of Clinical Outcome (CACO) 
The CACO will be programmatically determined from the programmatic assessment of early 
clinical response at the EA visit and the Overall Assessment of Clinical Response at PTE 
based on the Investigator’s assessment of clinical response at PTE as identified in Table 5. 
 
Table 5: Composite Assessment of Clinical Outcome 
Early Clinical Response 
at EA Visit 
Overall Assessment of Clinical 
Response at PTE Visit 
Composite Assessment of  
Clinical Outcome (CACO) 
Responder 
Success 
Success 
Responder 
Failure 
Failure 
Responder 
Indeterminate 
Indeterminate 
Nonresponder 
Success 
Failure 
Nonresponder 
Failure 
Failure 
Nonresponder 
Indeterminate 
Failure 
Indeterminate 
Success 
Indeterminate 
Indeterminate 
Failure 
Failure 
Indeterminate 
Indeterminate 
Indeterminate 
EA = early assessment; PTE = post therapy evaluation 
 
 


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8.2 
Microbiologic Response  
 
8.2.1 Per-Pathogen Microbiological Response at EOT and PTE Visits 
Pathogen microbiological outcome categories are: eradication, presumed eradication, 
persistence, presumed persistence, and indeterminate and these as defined in the following 
table. Favorable microbiological outcomes include eradication or presumed eradication. 
Unfavorable microbiological outcomes include persistence or presumed persistence and are 
defined in Table 6.  
Table 6:  Pathogen Microbiological Response at EOT and PTE Visits 
Eradication 
An adequate source specimen (from ABSSSI site and/or blood) 
demonstrates absence of the original screening/baseline pathogen(s). If 
there is a positive blood sample at screening/baseline, the last blood 
sample on or prior to the referenced visit (*) must be a negative. 
Presumed 
eradication 
An adequate source specimen was not available to culture and the 
subject was assessed as a clinical success by the Investigator at the 
referenced visit (*). If there is a positive blood sample at screening/ 
baseline but there is no post-baseline blood sample available and the 
subject was assessed a clinical success by the Investigator at the 
referenced visit (*), then categorize as presumed eradication. 
Persistence 
An adequate source specimen demonstrates continued presence of the 
original baseline pathogen(s)  (i.e., presence of original baseline 
pathogen cultured from the site of ABSSSI  or blood) at the referenced 
visit (*). 
Presumed 
persistence 
An adequate source specimen was not available to culture from site of 
ABSSSI or blood and the subject was assessed as a clinical failure by 
the Investigator at the referenced visit (*). 
Indeterminate 
An adequate source specimen was not available to culture from site of 
ABSSSI or blood and the subject’s clinical response was assessed as 
indeterminate at the referenced visit (*). 
Note: Should EA or Day 7 pathogen results of ‘no growth’ be present for a subject, but no 
subsequent pathogens captured for the same subject, then the ‘no growth’ (i.e. eradication) 
results will be carried forward to EOT and PTE. 


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(*) the term referenced visit is EOT when defining the Pathogen Microbiological Response at 
EOT, and is PTE when defining the Pathogen Microbiological Response at PTE. 
 
8.2.2 Per-Subject Microbiological Response at PTE and Overall Assessment at PTE 
In order for a subject to have a favorable per-subject microbiological response, the outcome 
for each baseline pathogen must be favorable (eradicated or presumed eradicated). In order 
for a subject to have an unfavorable per-subject microbiological response, the outcome for 
any baseline pathogen must be unfavorable (persistence, presumed persistence). 
The proportion of subjects with a favorable microbiological response is defined as: 
𝑃𝑀𝑖𝑐𝑟𝑜 𝐹𝑎𝑣 𝑅𝑒𝑠𝑝=
(# 𝑠𝑢𝑏𝑗𝑒𝑐𝑡𝑠 𝑤𝑖ℎ 𝑒𝑟𝑎𝑑𝑖𝑐𝑎𝑡𝑖𝑜𝑛 𝑜𝑟 𝑝𝑟𝑒𝑠𝑢𝑚𝑒𝑑 𝑒𝑟𝑎𝑑𝑖𝑐𝑎𝑡𝑖𝑜𝑛)
𝐴𝑙𝑙 𝑠𝑢𝑏𝑗𝑒𝑐𝑡𝑠 (𝑖𝑛𝑐𝑙𝑢𝑑𝑖𝑛𝑔 𝑖𝑛𝑑𝑒𝑡𝑒𝑟𝑚𝑖𝑛𝑎𝑡𝑒𝑠)
 
The overall assessment of microbiological response will be implemented using responses at 
the EOT and PTE visits as identified in Table 7 
 
Table 7: Overall Assessment of Microbiological Response 
Microbiologic Response 
EOT Visit 
PTE Visit 
Overall Microbiologic 
Response at PTE 
Favorable 
Favorable 
Favorable 
Favorable 
Unfavorable 
Unfavorable 
Favorable 
Indeterminate 
Indeterminate 
Unfavorable 
Favorable 
Unfavorable 
Unfavorable 
Unfavorable 
Unfavorable 
Unfavorable 
Indeterminate 
Unfavorable 
Indeterminate 
Favorable 
Indeterminate 
Indeterminate 
Unfavorable 
Unfavorable 
Indeterminate 
Indeterminate 
Indeterminate 
Favorable is defined as eradication or presumed eradication. 
Unless otherwise specified, all summaries of microbiological response are based on the 
overall microbiologic response at PTE. 
 
 


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8.3 
Emergent Infections 
Microbiological definitions of superinfections or new infections are defined in Table 8. 
Table 8: Superinfections and New Infections 
Category 
Definition 
Superinfection 
Isolation of a new pathogen(s) (other than the original 
screening/baseline pathogen[s]) from the primary ABSSSI site (culture) 
which is accompanied by signs and symptoms of infection requiring 
alternative systemic antimicrobial therapy during the period up to and 
including EOT, based on the Investigator’s assessment of clinical 
response.  
New infection 
Isolation of a new pathogen(s) (other than the original 
screening/baseline pathogen[s]) from the primary ABSSSI site (culture) 
which is accompanied by signs and symptoms of infection requiring 
alternative systemic antimicrobial therapy after EOT, based on the 
Investigator’s assessment of clinical response. 
Abbreviations: ABSSSI= acute bacterial skin and skin structure infection; EOT = End of 
Therapy;  
8.4 
Safety Outcomes 
Safety will be assessed through the determination and recording of the occurrence of 
adverse events (AEs) and AEs of special interest including, but not limited to hematology 
related AEs and neuropathies, as well as by adverse changes in vital signs, ECG 
parameters, and laboratory data. Hematology evaluations, serum chemistries, and urinalysis 
will be performed at screening/baseline, EA, Day 7 (± 1 day), EOT (+ 1 day), and PTE. 
Additional safety events that occur after PTE will be assessed at LFU. Adverse events will 
be evaluated by relationship to study drug and severity. Serious adverse events (SAEs) will 
be identified. 
8.5 
Pharmacokinetic Outcomes 
Pharmacokinetic data will be collected at the time points specified in the protocol and details 
of the analysis of this data will be provided separately. 
 


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9 
Statistical Methods and General Considerations 
9.1 
Sample Size 
This study is not powered for inferential statistical analysis and the purpose is to allow for 
planning of future studies.  No formal comparisons between treatment groups will be 
conducted. Up to 200 (133 contezolid acefosamil : 67 linezolid) adult subjects with ABSSSI 
will be enrolled in this study. If the responder rate is 0.8 at EA using early clinical response 
in the contezolid acefosamil group, then 133 evaluable subjects results in a 95% confidence 
interval (CI) of (0.72, 0.86) for the responder rate. 
9.2 
Randomization and Masking 
Permuted block randomization using an interactive response system (IWRS) will be used to 
assign subjects (2:1) to contezolid acefosamil or linezolid. Randomization will be stratified by 
infection type. After informed consent has been obtained and study eligibility established, 
the study site’s Pharmacist or Pharmacist’s designee will obtain the subject number and the 
study drug assignment from a computer-generated randomization code via IWRS. A subject 
is considered randomized when the Pharmacist or Pharmacist’s designee receives the 
randomization number or study drug assignment. 
This is a double-blind study. Those blinded to study drug assignment include the Sponsor, 
Investigator, study statistician, clinical study personnel participating in subjects’ care or 
clinical evaluations, and the subjects. Those unblinded to study drug assignment include the 
pharmacy personnel, the unblinded study monitor, and the bioanalytical laboratory. Blinded 
personnel must not make any effort to determine which study drug therapy is being 
administered. Blinded personnel will remain blinded to study drug assignment until all 
subjects have completed the study and the database is locked. Procedures to ensure that 
the blind is maintained are detailed in the Sponsor, CRO, and Vendor Blinding plan, the 
Blinded Clinical Monitoring Plan, and the Site-Specific Blinding Plans. 
If study drug is determined not to be safe and tolerated, the study drug assignment for those 
subjects with a safety concern may be unblinded after discussion between the Investigator 
and Sponsor. The blind may also be broken in the case of a medical emergency requiring 
the Investigator to know the identity of the study drug to appropriately guide the subject’s 
medical management. Prior to any unblinding, the Investigator is strongly advised to discuss 
options with the Medical Monitor or appropriate Sponsor study personnel. If the blind is 


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broken for any reason and the Investigator was unable to contact the Sponsor before 
unblinding, the Investigator must notify the Sponsor as soon as possible, without revealing 
the subject’s study drug treatment assignment (unless important to the safety of subjects 
remaining in the study). All instances of unblinding will be thoroughly investigated and 
documented by the unblinded study monitor. 
After the database is locked and the SAP is final, and all analysis populations have been 
determined, the study will be unblinded. 
9.3 
Interim Analysis 
There is no formal interim analysis of efficacy or safety for this study and a Data Monitoring 
Committee (DMC) will not be utilized. 
9.4 
Standard Calculations 
Variables requiring calculation will be derived using the following formulas: 
x 
Baseline - A baseline value is the last non-missing value recorded prior to the first dose 
of study drug. For subjects who never get dosed, the screening measurements will be 
the baseline.  If an assessment has both a date and time that exactly match the date and 
time of first dose of study drug, the assessment will be counted as baseline.  
o Baseline pathogens however will include any pathogens identified from samples 
during the baseline/screening visit. If no pathogens are identified from these 
samples, then a Day 2 or 3 ABSSSI site sample can be used as baseline if the 
sample is considered acceptable. 
o In the event of missing baseline lesion measurements, a lesion size baseline 
measurement may include a measurement up to 6 hours after the first dose. 
x 
Change from baseline - Change from baseline will be calculated for each subject at the 
specified time point as the value at the specified time point minus that subject’s baseline 
value. 
x 
Study day – For a given date (date), the study day is calculated as days since the date 
of first dose of study drug (firstdose). 
 
Study day = date – firstdose + 1, where date ≥ firstdose  
 
Study day = date – firstdose, where date < firstdose 
x 
Days – Durations, expressed in days, between one date (date1) and another later date 
(date2) are calculated using the following formula: duration in days = (date2-date1+1). 


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x 
Body Mass Index (BMI) - BMI (kg/m2) = weight (kg) / [[height (cm)/100]2]. 
x 
Age, in years, will be computed as from the date of informed consent and the date of 
birth. 
9.5 
Handling of Missing Data 
All missing data and missing and partial dates for events occurring after randomization or for 
medications received after randomization will be queried for a value.  If no value can be 
obtained missing data will be handled as outlined below:  
All AEs with partial or missing dates and times will be considered treatment emergent unless 
a partial start date and/or time indicates the AE began prior to the start of study medication 
or a stop date indicates the AE ended prior to the start of study medication. 
The severity and causality assessment for adverse events should not be missing and will be 
queried for a value. Should there be missing data, adverse events with missing severity will 
be considered severe and adverse events with missing relationship to study drug will be 
considered related to study drug. 
Missing start and stop times for antibiotics will be queried for a value. If no value can be 
obtained but the site indicates the antibiotic was received (onset time) prior to the first dose 
of study drug, 00:01 will be used for the onset time. If the site also indicates that the end 
time was prior to the first dose of study drug, 00:01 will be used for end time. The actual 
value (blank) will be recorded on the e-CRF and will be used in the listings. 
All other (non-antibiotic) medications with partial or missing dates and times recorded on the 
concomitant medication eCRF will be considered concomitant unless a partial stop date and 
time clearly indicates it was stopped before the first dose of study treatment. 
For clinical and microbiological response, missing data will be handled as follows: 
x 
For the primary efficacy outcome measure (early clinical response at 48 to 72 hours): 
x 
The subject will have missing data if there is no lesion size measurement (either 
length or width) at the EA visit and will be defined as an indeterminate response. 
x 
If the time of administration of the first dose of study drug is missing, the subject will 
also be defined as an indeterminate response. 
For the Investigator’s assessment of clinical response:  


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x 
Subjects will be defined as an indeterminate if the Investigator cannot determine 
whether the subject is a clinical success or failure or if any data is missing to make a 
determination of failure or success. By definition, subjects with an indeterminate 
response are included in the denominator for analyses in the ITT, MITT, and micro-
ITT analysis sets, and thus, are considered failures; however subjects with an 
indeterminate response are excluded from the CE-EOT, CE-PTE, and ME 
Populations. 
For microbiologic response: 
x 
If no source specimen is obtained and the subject has an Investigator’s assessment 
of clinical response, the per-pathogen microbiological response is based on the 
Investigator’s assessment of clinical response; hence a per-pathogen microbiological 
response will be considered missing or indeterminate only if the clinical response is 
also missing or indeterminate.  
Missing values for other individual data points will remain as missing. Missing values will not 
be imputed and only observed values will be used in data analyses and presentations. 
Where individual data points are missing, categorical data will be summarized based on 
reduced denominators (i.e., only subjects with available data will be included in the 
denominators). 
9.6 
Comments on Statistical Analysis 
The following general comments apply to all statistical analyses and data presentations: 
x 
All listings will be sorted by subject number in ascending order. All relevant data 
captured on the case report forms (eCRFs) and external data sources, including 
specific descriptions of ‘other’ and comments fields will be included on the listings. 
x 
All summary tables will be presented by study drug. Summary tables presenting 
results by study visit will include all scheduled study visits using informative visit 
labels. 
x 
Continuous variables will be summarized using number (n), mean, standard 
deviation (SD), median, minimum, and maximum. Summaries of blood concentration 
will also include the geometric mean (GM) and coefficient of variation (CV). 
x 
Frequency counts and percentages will be reported for all categorical data.  


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x 
Duration variables will be calculated using the general formula 
(end date - start date) +1. 
x 
If the reported value of a clinical laboratory parameter cannot be used in a statistical 
summary table (e.g., a character string is reported for a parameter of the numerical 
type), a coded value must be appropriately determined and used in the statistical 
analyses. In general, a value or lower and upper limit of normal range such as ‘<10’ 
or ‘≤ 5’ will be treated as ‘10’ or ‘5’ respectively, and a value such as ‘>100’ will be 
treated as ’100’. However, the actual values as reported in the database will be 
presented in data listings. 
x 
For all “by visit” safety tables (e.g., laboratory values, vital signs, ECGs), nominal 
visits will be summarized. In addition within tables that summarize changes from 
baseline, the minimum and maximum post-baseline values will be summarized to 
take unscheduled visits into account. 
x 
Version 9.4 (or higher) of SAS statistical software package will be used to provide 
all summaries, listings, graphs, and statistical analyses. 
The analyses described in this plan are considered a priori, in that they have been defined 
prior to database lock. Any analyses performed subsequent to this will be considered post-
hoc and exploratory. Post-hoc analyses will be labeled as such on the output and identified 
in the CSR. 
Sensitivity analysis to address potential unblinding event:  Any subjects for whom the blind 
may have been comprised will be examined further using sensitivity analyses. Additional 
details will be provided in the CSR. These analyses may include tabulations of adverse 
events, Programmatic Clinical Response at EA, and Overall assessment of clinical response 
at the PTE visit and these will be repeated with and without these subjects to assess any 
bias. 
10 Statistical Analyses 
10.1 Subject Disposition 
The number and percentage of subjects included in each of the analysis populations (ITT, 
MITT, Safety, Micro-ITT, CE-EOT, CE-PTE, ME) will be summarized by treatment group and 
the number of subjects screened and the reasons for screen failures will also be 


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summarized.  A table will summarize the reasons for exclusion from each population and a 
listing will be provided that indicates each subject’s inclusion/exclusion from the analysis 
population and the reason for exclusion from each analysis population.  
The number and percentage of subjects completing the study, prematurely discontinuing 
from study drug, and prematurely withdrawing from the study will be presented for each 
treatment group for the ITT, Safety, and CE- PTE populations. Reasons for premature 
discontinuation of study drug and/or premature withdrawal from the study as recorded on 
the e-CRF will be summarized (number and percentage) by treatment group. 
A listing of all subjects who prematurely discontinued from study drug or prematurely 
withdrew from the study will be presented, and the primary reason for discontinuation of 
study drug or withdrawal from the study will be provided. 
10.2 Demographics and Baseline Characteristics 
Demographic data and baseline characteristics will be presented by treatment group in the 
ITT, Safety, Micro-ITT, and CE- PTE analysis populations. A table will present the subject 
demographics (e.g., gender, age, ethnicity and race) and baseline characteristics (height, 
weight, and BMI) collected before the start of study drug. 
A demographic data listing, which includes the date the informed consent was signed, will 
also be provided. 
10.3 Medical and Surgical History 
Medical history will be coded using the Medical Dictionary of Regulatory Activities 
(MedDRA) classification, version 21.1. Medical history (skin infection related) and all other 
medical history and surgical history will be summarized separately for the ITT Population 
and Safety population by system organ class, preferred term, and treatment group. Subjects 
reporting the same system organ class or preferred term more than once will be counted 
only once for that system organ class and preferred term.  Relevant medical and surgical 
history for all prior and concurrent skin infections, previous history of ABSSSI (within 10 
years), current or recent IV drug use, chronic hepatic disease, concurrent secondary 
infection, history of diabetes mellitus, peripheral vascular disease or alcohol abuse will be 
identified if possible from the medical history terms and will be summarized treatment group 
for the ITT and Safety populations.   
A listing of medical and surgical history will be provided. 


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10.4 Baseline Disease Characteristics 
The primary disease diagnosis at baseline (cellulitis/erysipelas, wound infection, or major 
cutaneous abscess), location of infection, symptoms of infection, and size of infection 
(<=300 cm2, >300-600 cm2, >600-1000 cm2 and >1000 cm2) will be summarized by 
treatment group for the ITT, Micro-ITT, and CE-PTE Populations.  The location of infection 
will be categorized as follows:  head or face or neck, chest or shoulder or back or abdomen, 
groin or buttock, arm or hand (upper extremities), and leg or thigh or knee or lower leg or 
ankle or foot (lower extremities). 
Baseline information about each ABSSSI including mean infection area, mean infection area 
by disease diagnosis, and the signs and symptoms of disease will be summarized by 
treatment group for the ITT, Safety, and CE-PTE populations. 
10.5 Baseline Microbiology 
The number and percentage of subjects with each type of ABSSSI site specimen obtained, 
whether or not there was Gram stain, whether there was growth, whether there was culture 
grown, and the number of unique pathogens from the local laboratory will be provided by 
treatment group in the Micro-ITT and ME populations. Baseline blood specimen results from 
the local laboratory will be summarized similarly for the Micro-ITT and ME populations.  All 
ABSSSI site specimen and blood specimen Gram stain results will be listed. 
The pathogenic organisms identified by the central laboratory from the baseline blood 
culture or culture of the ABSSSI specimen will be presented. The number and percentage of 
subjects with Gram positive and Gram negative organisms will be presented by genus and 
species for the Micro-ITT and ME populations overall and by infection type. The same 
pathogen identified from both the blood and the ABSSSI culture will be counted only once in 
the summary. The pathogenic organisms identified at baseline from blood sample(s) will 
also be presented for the Micro-ITT and ME populations.  
The number and percentage of subjects with monomicrobial Gram-positive, polymicrobial 
Gram-positive, mixed (Gram positive and Gram negative) infections, will be presented by 
treatment group, and provided for specimens from blood or ABSSSI culture for both the 
Micro-ITT and ME populations. When per-subject counts of S. aureus are presented, 
subjects with both MRSA and MSSA are counted only once. 


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A listing will be provided that includes all baseline and post-baseline isolates obtained from 
the blood and primary ABSSSI site specimen and will indicate the type of specimen and 
pathogenic organism identified from both the local and central laboratories.  Gram stain 
results will also be listed. 
The minimum inhibitory concentration (MIC) of contezolid acefomacil to baseline pathogens 
from the primary ABSSSI site or blood culture will be summarized by genus, species and 
treatment group in the Micro-ITT and ME populations.  The MIC of linezolid will be 
summarized similarly.  
Summary Statistics (range, MIC50, MIC90) will be presented for the study drug received to 
baseline pathogens from the primary ABSSSI site or blood culture will be summarized by 
treatment group in the Micro-ITT and ME populations. MIC50 and MIC90 values will only be 
presented for a particular pathogen if there are >=10 pathogens identified within a treatment 
arm.  The MIC50 and MIC90 are the MICs required to inhibit the growth of 50% and 90% of 
organisms, respectively.  For subjects with more than one baseline pathogen of the same 
genus and species, the one with the highest MIC to study drug received will be selected for 
analysis; thus subjects are counted only once for that pathogen. If there is a tie, the MIC 
with the lowest disk diffusion (if applicable) to study drug received will be chosen. Otherwise, 
the highest accession number is chosen. 
10.6 Prior and Concomitant Medications  
All prescription medications and over-the-counter medications, including herbal, nutritional, 
and dietary supplements (e.g., any antacid, iron supplement, or multivitamin) administered 
within 2 weeks (14 days) prior to randomization and during the study between Day 1 and 
EOT will be documented in the eCRF. 
Verbatim terms on case report forms will be mapped to Anatomical/Therapeutic/Chemical 
(ATC) class and Generic Drug Names using the World Health Organization (WHODrug 
March/Sep 2018) dictionary. Anatomical Therapeutic Chemical Classification (ATC) level 4 
(fourth level indicates the chemical/therapeutic/pharmacologic subgroup) and 3 (third level 
indicates the therapeutic/pharmacologic subgroup). 
Prior medications are those medications taken before the first dose of study drug.  
Concomitant medications are those medications taken at the start of study drug or initiated 
after the initial dose of study drug, or medications that were initiated prior to the start of 


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study drug and continue to be taken after study drug is administered. (See the “Handling of 
Missing Data” section for details on handling in the event of missing medication dates.) 
The proportion of subjects who receive the following prior and concomitant medications will 
be summarized ATC level 3 class, preferred term, and treatment group: 
x 
Prior systemic or topical antibacterial medications taken prior to the first dose of 
study drug (ITT, and CE-PTE populations) 
x 
Concomitant systemic or topical antibacterial medications (excluding study drug) 
taken between time of the first administration of study drug on Day 1 and the EOT 
Visit (ITT, CE-EOT populations) and the PTE Visit (ITT, CE-PTE) 
x 
Prior non-antibacterial medications taken  (ITT, Safety populations) 
x 
Concomitant non-antibacterial medications (ITT, Safety Population) 
Subjects will be counted only once for an ATC class and preferred term. 
Receipt of systemic and topical antibacterial medications in the 96 hours prior to Dose 1 of 
study drug is an exclusion criterion. However, a listing will be provided of all antibacterial 
medications received in this time frame, and the reason for receiving, should subjects be 
enrolled having met this exclusion criterion. 
10.7 Study Drug Exposure and Compliance 
The active study drugs are contezolid acefosamil (IV and PO) and linezolid (IV and PO), 
which will be administered for a total of 10 to 14 days. Subjects may receive the IV 
formulations for the entire treatment duration or be switched to the PO formulations (after 
receiving at least 3 IV doses) to complete 10 to 14 days of treatment. All subjects will start 
with IV therapy, with either contezolid acefosamil 1500 mg IV x 1 dose followed by 1000 mg 
IV q12h (± 2 hours) or linezolid 600 mg IV q12h (± 2 hours), and all subjects will receive at 
least 3 total doses of IV study drug. For subjects who switch from IV to PO treatment, 2 
contezolid acefosamil capsules (each capsule containing 650 mg of contezolid acefosamil 
for a total of 1300 mg) or 2 linezolid capsules (each capsule containing 300 mg of linezolid 
for a total of 600 mg) will be administered PO q12h [± 2 hours]) to complete a total of 10 to 
14 days of treatment. 
By treatment group summaries will be provided for total number of doses, number of IV 
doses, and the number of PO doses in the ITT, Safety, and CE-PTE populations. 


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Duration of treatment is defined as the number of calendar days from when the subject first 
received study treatment until the day that they last received study treatment (IV or PO) and 
is calculated as (date of last dose – date of first dose +1).   
Compliance to study drug will be calculated based on the total number of doses taken, 
divided by the total number of expected doses, in the time period between the dates of the 
first and last doses of study drug. 
𝑪𝒐𝒎𝒑𝒍𝒊𝒂𝒏𝒄𝒆= 100 ∗(𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑜𝑠𝑒𝑠 𝑟𝑒𝑐𝑒𝑖𝑣𝑒𝑑 (𝐼𝑉 𝑜𝑟 𝑃𝑂))
(𝐸𝑥𝑝𝑒𝑐𝑡𝑒𝑑 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑜𝑠𝑒𝑠 (𝐼𝑉 𝑜𝑟 𝑃𝑂)) 
Descriptive statistics of percent compliance as well as the number and percentage of 
subjects at least 80% compliant by number of doses (IV or PO), will be provided by 
treatment group for the ITT, Safety, and CE-PTE populations.  
Descriptive statistics of study drug exposure by route of administration will also summarized 
by treatment group, for the ITT and Safety and CE-PTE populations. 
 
10.8 Efficacy Analyses 
For all efficacy analyses, subjects will be analyzed in the group to which they were 
randomized. By definition, subjects who receive the wrong study drug are not included in the 
CE and ME populations.  The primary and secondary efficacy analyses are identified in 
Table 9. 


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Table 9: Efficacy Analyses 
 
Efficacy Populations 
 
ITT 
MITT 
micro-
ITT 
CE-
EOT 
CE-
PTE 
ME 
Primary: 
 
 
 
 
 
 
Early clinical response at EA  
√ 
 
 
 
 
 
Secondary: 
 
 
 
 
 
 
Early clinical response at EA  
 
√ 
 
 
 
 
Early clinical response at EA (overall and by 
baseline pathogen) 
 
 
√ 
 
 
 
Percent reduction in lesion size at Day 7 
√ 
√ 
 
 
 
 
Investigator’s assessment of clinical response at 
EOT  
√ 
√ 
 
√ 
 
 
Investigator’s assessment of clinical response at 
PTE and LFU 
√ 
√ 
 
 
√ 
 
Per-subject microbiological response at PTE  
 
 
√ 
 
 
√ 
Per-pathogen microbiological response at PTE 
 
 
√ 
 
 
√ 
Investigators assessment of clinical response at PTE 
and LFU (overall and by baseline pathogen) 
 
 
√ 
 
 
√ 
CACO  
√ 
 
√ 
 
√ 
 
CACO = composite assessment of clinical outcome (combined outcome of early clinical response at EA and 
Investigator’s assessment of clinical response at PTE); CE = clinically evaluable; EA = early assessment; 
EOT = end of therapy; ITT = intent-to-treat; LFU = late follow-up; ME = microbiologically evaluable; MITT = 
modified intent-to-treat; micro-ITT = microbiological intent-to-treat; PTE = post therapy evaluation 
 
10.8.1  Primary Efficacy Analysis 
The primary efficacy analysis is an examination of the percentage of responders in the 
contezolid acefosamil treated group vs. the percentage of responders in the linezolid group 
at EA in the ITT population. This aligns with the FDA’s primary efficacy endpoint of interest 
in ABSSSI studies (reference 1). The number and percentage of responders, non-
responders and indeterminate responses will be summarized by treatment group and an 
exact 95% CI will be provided for the responder rates in each treatment group. The 
difference between the responder rates will be calculated and 95% CI for the difference 
between response rates will be calculated using a Wald continuity correction.  A summary 
of reasons for programmatic clinical failure and indeterminate response at the EA Visit will 


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also be provided. The reasons for failure and indeterminate will be summarized as well for 
the programmatic clinical response at EA in the ITT population. 
 
10.8.2 Secondary Efficacy Analysis 
Secondary efficacy analyses will include the following: early clinical response at EA in the 
MITT population, early clinical response at the EA visit by baseline pathogen and treatment 
group in the micro-ITT population and changes from baseline in the percent reduction in 
lesion area at Day 7 summarized in a continuous and categorical manner (≤10%, >10-20%, 
>20-50%, >50-75%, >75%), by treatment group in the ITT and MITT populations. 
 
The Investigator’s assessment of clinical response will be classified as described in sections 
8.1.2 and 8.1.3. The number of subjects with an Investigator’s assessment of clinical 
success, clinical failure, and indeterminate at EOT will be summarized for both treatment 
groups in the ITT, MITT and CE-EOT populations. Similarly, the Overall Assessment of 
Clinical Response based on the Investigator’s assessment at PTE and the Investigator’s 
assessment at LFU will also be summarized for both treatment groups in the ITT, MITT and 
CE-PTE populations. 
 
Note that, by definition, subjects with an indeterminate response will be excluded from 
summaries in the CE-EOT and CE-PTE populations. The 95% CI will be provided for the 
rate of clinical success for each treatment group. The 95% CI will also be provided for the 
difference in rates of success at EOT in the ITT and the CE-EOT populations. Similarly the 
95% CI will be provided for the difference in rates of success at PTE in the ITT and the CE-
PTE populations. The reasons for failure and indeterminate will be summarized as well for 
the clinical responses at EOT and PTE for the indicated populations as well as for the ITT 
and MITT populations. 
 
The Overall Assessment of Clinical Response based on the Investigator’s assessment at 
PTE and the Investigator’s assessment at LFU will also be summarized by baseline 
pathogen in the Micro-ITT and ME populations.  The Overall Assessment of Clinical 
response at PTE will also be summarized by the MIC of Linezolid and MIC of Contezolid 
Acefomacil by treatment group in the Micro-ITT and ME populations. 


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The durability of clinical response (rate of sustained clinical response and clinical 
relapse/failure and indeterminate) at LFU will be summarized by treatment group in the ITT, 
MITT and ME populations. 
 
The rates of success as assessed by the CACO as described in Section 8.1.5 will be 
summarized in the ITT, micro-ITT, and CE-PTE populations. 
 
10.8.3 Additional Efficacy Analysis 
Early clinical response at the EA visit will also be summarized by ABSSSI type in the ITT 
and MITT populations.  Also early clinical response at EA will be summarized by pathogen 
and baseline MIC of contezolid acefosamil and linezolid, by treatment in the Micro-ITT and 
ME populations.   
 
Overall assessment of clinical response at PTE will also be summarized by ABSSSI type in 
the ITT, MITT and CE-PTE populations.  Also the overall assessment of clinical response at 
PTE will be summarized by pathogen and baseline MIC of contezolid acefosamil and 
linezolid, by treatment in the Micro-ITT and ME populations. 
 
10.8.4 Microbiological Outcomes 
The number and percentage of subjects with favorable, unfavorable, and indeterminate 
microbiological responses will be summarized at PTE in the micro-ITT and ME populations. 
A 2-sided exact 95% CI will be constructed for the percentage of subjects with favorable 
response and a 95% CI will be calculated for the difference in the per-subject favorable 
microbiological response using a Wald continuity correction. 
Microbiologic response will  be summarized by baseline pathogen and treatment at the PTE 
visit for each pathogen isolated at baseline from the primary ABSSSI site or from blood in 
the micro-ITT and ME populations.  
A listing will be provided that presents the subjects with a superinfection or a new infection. 
 


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10.9 Safety Analyses 
All safety analyses will be conducted in the Safety population.   
10.9.1 Adverse Events 
Verbatim descriptions of AEs will be coded using Version 21.1 of MedDRA. Summary tables 
will be provided for all treatment-emergent adverse events (TEAEs). A treatment-emergent 
AE is defined as any AE that newly appeared, increased in frequency, or worsened in 
severity following initiation of study drug and up through the last study visit or evaluation, or 
an SAE that occurs during or after the first administration of study drug up through 30 days 
after the final administration of study drug.  
An overall summary of AEs will include number and percentage of subjects in each 
treatment group who experienced at least one AE of the following categories: any AE, any 
TEAE, any drug-related TEAE (defined as possibly, probably or definitely related to study 
drug), any severe or life-threatening TEAE, any serious TEAE (SAE), any drug-related SAE, 
any SAE leading to death, and any TEAE leading to premature discontinuation of study drug 
and any SAE leading to premature study drug discontinuation. 
The number and percentage of subjects reporting a TEAE in each treatment group will be 
tabulated by system organ class and preferred term; by system organ class, preferred term, 
and severity (mild, moderate, and severe/life-threatening/death); and by system organ class, 
preferred term, and relationship (unrelated [defined as unrelated or unlikely related to study 
drug] or related to study drug). In addition, all TEAEs will also be summarized by system 
organ class and preferred term separately based on whether the TEAE started while the 
subject received IV or oral study drug (select AE tables only). 
Summary tables will be presented alphabetically by system organ class and preferred term 
within system organ class. For all analyses of TEAEs, if the same AE (based on preferred 
term) is reported for the same subject more than once, the AE is counted only once for that 
preferred term and at the highest severity and strongest relationship to study drug.  
The number and percentage of subjects reporting a SAE and reporting a TEAE leading to 
premature discontinuation of study drug in each treatment group will be summarized by 
system organ class and preferred term. 


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The incidence of TEAEs that occur in at least 2% of subjects in either treatment group will 
be summarized by preferred term and treatment group, sorted by decreasing frequency in 
the contezolid acefosamil group. 
In addition, all AEs (including non-TEAEs), serious AEs (SAEs) , and TEAEs leading to 
study drug discontinuation will be provided in listings.  AEs of special interest will also be 
summarized by treatment groups. 
10.9.2 Laboratory Values 
Summaries of laboratory data will include hematology, chemistry, coagulation and C-
reactive protein laboratory parameters. Laboratory parameters will be presented in 
alphabetic order with the following exceptions: differentials of white blood cell (WBC) counts 
will be presented following the WBC results, and chemistry parameters will first be grouped 
by organ class (renal, liver, electrolytes, and other) and presented alphabetically within each 
of these classes, as shown in Table 10. 
Table 10:  Laboratory Parameters 
Renal 
 
Creatinine 
Blood urea nitrogen 
Liver 
 
Alkaline phosphatase 
ALT 
AST 
Bilirubin direct 
Bilirubin total 
GGT 
LDH 
Electrolytes 
 
Bicarbonate 
Calcium 
Chloride 
Magnesium 
Potassium 
Sodium 
Other 
 
Albumin 
Cholesterol (total) 
Creatine kinase 
Glucose, nonfasting 
Phosphorus 
Total protein 
Uric acid 
 
Several analyses of the laboratory data will be presented. Descriptive statistics (based on SI 
units) for chemistry, hematology, and coagulation values and the change from baseline will 
be summarized by treatment group at Day 1, EA, Day 7, EOT, and PTE visits, and for the 


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overall minimum and maximum post-baseline values (which includes unscheduled visits). 
Change from baseline will be calculated for each subject at the specified time point as the 
value at the specified time point minus the baseline value. 
For subjects with missing central laboratory results at baseline, the local baseline results will 
be used after transformation to centralized local baseline results. On a per laboratory test 
basis, the local baseline result will be normalized using the local laboratory range.  The 
normalized local baseline result will be converted to a centralized local baseline result using 
the range for the central laboratory test. This transformation (Normalization and 
Centralization) is defined as follows, where NRL is the Normal Range Low and NRH is the 
Normal Range High: 
Normalized Local Baseline Result = 
    (Local Baseline Result – Local NRL) / (Local NRH – Local NRL)   
Centralized Local Baseline Result =  
     Normalized Local Baseline Result * (Central NRH – Central NRL) + Central NRL 
Toxicity grade will be determined based on the modified DMID criteria (Appendix B). Shift 
tables will be presented to show the number of subjects with a chemistry or hematology 
laboratory value with a grade of 1, 2, 3 or 4 at baseline versus the worst post-baseline value. 
Post-baseline substantially abnormal clinical laboratory values will also be summarized. For 
hematology, where substantially abnormal is defined as <75% of the lower limit of normal 
(LLN) (<50% of ANC) for values normal at baseline, and <75% of the LLN (<50% for ANC) 
and of baseline for values abnormal at baseline.  For chemistry substantially abnormal is 
defined as 2 x the ULN for values normal at baseline and 2 x the ULN and 2 x the baseline. 
The number and percentage of subjects with elevated liver function assessments will also 
be summarized by visit using the following categories: >3-5 xULN, >5-10 xULN, and >10 
xULN, where ULN is the upper limit of normal. 
A listing will be presented identifying all subject records meeting the substantially abnormal 
hematology, chemistry criteria. This same listing will also contain any abnormal liver function 
records that meet Hy’s law criteria, which is: AST or ALT > 3xULN, alkaline phosphatase 
<=2xULN, and total bilirubin >1.5xULN.   


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A general detailed subject listing of all laboratory data collected during the study will be 
provided. Laboratory values outside normal limits will be identified in the subject data listings 
with flags for low (L) and high (H) as will laboratory values that meet the clinically notable 
thresholds (CN). 
 
10.9.3 Vital Signs 
Blood pressure (systolic and diastolic), respiration rate, heart rate, and temperature will be 
summarized using descriptive statistics by treatment group at each time point at which they 
were measured. Descriptive statistics of the change from baseline to each post-baseline 
time visit will also be provided.  
The number and percentage of subject abnormal values, identified by the threshold levels 
provided in Table 11, will be summarized by treatment group.  Only subjects with both 
baseline and post-baseline values will be summarized for diastolic blood pressure increases 
Table 11: Abnormal Vital Threshold Values 
Vital Sign 
Threshold 
Diastolic blood pressure 
> 20 mmHg increase from baseline 
Systolic blood pressure 
≥ 140 mmHg 
Heart rate 
< 60 beats/min 
Heart rate 
> 120 beats/min 
Temperature 
>102.3 F 
All vital signs will also be provided in by-subject listings.  
 
10.9.4 Electrocardiogram 
ECGs will be recorded in triplicate at each visit, where all three measurements are taken 
within a 15 minute period. The mean of available triplicate values will be calculated and 
reported for each time point. If there are no triplicate values, the mean of the duplicate or 
single value will be used. Descriptive statistics for central ECG parameters of RR interval, 
PR interval, QRS duration, QT interval, and QTcF interval, as well as the changes from 
baseline will be presented by treatment group at each scheduled visit. 


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For centrally collected QTcF values, a distribution showing counts and percentages for the 
maximum increase post-baseline to EOT will be provided using the following categories:  <0, 
≥1 - <30 msec, ≥30 - <60 msec, ≥60 - <90 msec, >=90 msec. Actual QTcF visit values will 
also be summarized using counts and percentages for the following categories: ≤ 450, > 450 
- ≤ 480, >480 - ≤ 500, and >500 msec). 
A listing of central and local electrocardiogram data will also be provided and will include the 
tracing results of normal, abnormal and clinically significant status for these measurements. 
10.9.5 Physical Examinations 
Physical examination results will be presented in by-subject listings. 
10.9.6 Basic Ophthalmoscopy Exams and Visual Fields 
Descriptive statistics for basic ophthalmoscopy and visual field parameters at baseline and 
EOT visit will be presented by treatment group. Snellen visual acuity scores will be 
categorized as identified in the Table 12 below. A summary table of this visual acuity score 
data will be created that includes the number and percentage of subjects in each treatment 
group with the following Snellen vision category changes from baseline to each visit: 
x 
Improvement or no change in both eyes 
x 
Improvement in one eye and worsening by 1 Snellen category in the other eye 
x 
Improvement in one eye and worsening by 2 or more Snellen categories in the other 
eye 
x 
Worsening by 1 Snellen category in both eyes 
x 
Worsening by 1 Snellen category in one eye and worsening by 2 or more Snellen 
categories in the other eye 
x 
Worsening by 2 or more Snellen categories in both eyes 
If subjects require corrective eyewear for vision, then only subjects who did not wear 
corrective eyewear for both visits or who did wear corrective eyewear for both visits will be 
included in summary tables. Baseline is defined as the Snellen measurement prior to the 
first dose of study drug. 


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Table 12: Ranges of Visual Acuity Loss 
Vision Category 
Snellen Decimal 
Examples of possible Snellen 
Ratios 
Normal Vision 
≥0.8 
20/12, 20/15, 20/20, 20/25 
Near-Normal Vision 
<0.8 and ≥0.32 
20/30, 20/40, 20/60 
Moderate Low Vision 
<0.32 and ≥0.125 
20/70, 20/80, 20/100 
Severe Low Vision 
<0.125 and ≥0.05 
20/200, 20/400 
Profound Low Vision or Worse 
than Profound Low Vision 
<0.05 
NA 
Note: All Snellen ratios will be converted to “Snellen Decimals.” For example, 20/12=1.67 
and 20/15=1.33. These categories of vision loss are definedbased on as report prepared for 
the International Council of Opthalmology (See reference 2). 
All Snellen examination scores, basic ophthalmoscopy exams, and visual field data will be 
provided in a by-subject listing. 
 
10.9.7 Pharmacokinetic Analyses 
These will not be summarized or listed here, as the PK analysis and related deliverables for 
plasma concentrations, metabolite concentrations, and PK parameters, will be produced by 
a different vendor. 
 
 
 
10.9.8 Protocol Deviations 
A listing of all protocol deviations will be provided. Protocol deviations will also be reviewed 
by the Sponsor and categorized into general categories such as:  
x 
Eligibility criteria not met 
x 
Study drug administration error 
x 
Randomization error 


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x 
Non-compliant visit schedule 
x 
Non-compliant study procedure 
x 
Non-compliant informed consent process 
x 
Other 
The number of subjects with at least one protocol deviation, the number of subjects with a 
minor protocol deviation, the number of subjects with a major (or important) deviation, and 
the number of subjects with at least one deviation in each category will be presented by 
treatment group for the ITT Population. A major (or important) deviation is defined as one 
that potentially affects the efficacy and/or safety analyses and will be determined by a 
review by the Sponsor.  
11 Deviations from the Protocol 
The SAP and the population definition sections of the protocol specify that the Clinically 
Evaluable populations include subjects who “did not receive any potentially-effective 
systemic antibacterial therapies other than protocol specified study drug(s) between Day 1 
and timepoint for assessment (except for adjunctive aztreonam or in cases of treatment 
failure)…”; however Figure 2 of the protocol incorrectly omits inclusion of the word 
“potentially”. 
The protocol EA visit window is 48-72 hours (after the first dose of study drug), but the 
window is extended to the lower bound of 46 hours. 
 
12 Reference List 
1. Food and Drug Administration, Center for Drug Evaluation and Research. Guidance 
for Industry - Acute Bacterial Skin and Skin Structure Infections: Developing Drugs 
for 
Treatment. 
Oct 
2013. 
Available 
at: 
http://www.fda.gov/downloads/Drugs/.../Guidances/ucm071185.pdf 
2. Visual Standards-Aspects and Ranges of Vision Loss with Emphasis on Population 
Surveys.  Report prepared for International Council of Ophthalmology at the 29th 
International Congress of Ophthalmology Sydney, Australia, April 2002. 
(http://www.icoph.org/downloads/visualstandardsreport.pdf) 


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Appendix A) Schedule of Events 
The calendar day on which the first dose of study drug is administered is Day 1. 
Procedure or Assessment 
Screening/ 
Baseline1 
(≤ 24 hrs 
of first 
dose) 
Study Treatment Period 
PTE5 
LFU6 
Day 12 
Day 2 
EA3 
(48-72 
hours) 
Day 7 
(± 1 day) 
EOT4  
(+ 1 day) 
7-14 Days 
After EOT 
21-28 Days  
After EOT 
Informed consent7 
X 
 
 
 
 
 
 
 
Medical/surgical history  
X 
 
 
 
 
 
 
 
Prior and concomitant therapy8 
X 
X 
X 
X 
X 
X 
X 
X 
Examination, measurement, and signs 
and symptoms of ABSSSI9 
X10 
 
 
X 
X 
X 
X 
 
Document primary ABSSSI lesion by 
digital photography11 
X10 
 
 
X 
X 
X 
 
 
Investigator’s assessment of clinical 
response 
 
 
 
 
 
X 
X 
X 
Activity assessment12 
X 
 
 
 
 
X 
X 
X 
Complete physical examination13 
X10 
 
 
 
 
X 
 
 
Focused physical examination14 
 
 
 
X 
X 
 
X 
 
Vital signs15 
X10 
 
 
X 
X 
X 
X 
 
12-Lead ECG16 
X10 
X17 
 
X 
 
X 
X 
 
Height and weight 
X 
 
 
 
 
 
 
 
Adverse events18 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory tests19 
X10 
 
 
X 
X 
X 
X 
 
Serology tests 20 
X 
 
 
 
 
 
 
 


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Procedure or Assessment 
Screening/ 
Baseline1 
(≤ 24 hrs 
of first 
dose) 
Study Treatment Period 
PTE5 
LFU6 
Day 12 
Day 2 
EA3 
(48-72 
hours) 
Day 7 
(± 1 day) 
EOT4  
(+ 1 day) 
7-14 Days 
After EOT 
21-28 Days  
After EOT 
Pregnancy test21 
X10 
 
 
 
 
X 
 
 
Estimate CrCl22 
X 
 
 
 
 
 
 
 
PK samples23 
 
X 
X 
 
 
X 
 
 
ABSSSI specimen Gram stain and 
culture24 
X10 
 
 
X 
X 
X 
X 
 
Blood cultures25 
X10 
 
 
X 
X 
X 
X 
 
Randomization26 
 
X 
 
 
 
 
 
 
Administration of study drug  
(10 to 14 days)27 
 
X 
X 
X 
X 
X 
 
 
ABSSSI = acute bacterial skin and skin structure infection; β–HCG = beta-human chorionic gonadotropin; CrCl = creatinine clearance; CRP = c-reactive protein; EA = early 
assessment; ECG = electrocardiogram; EOT = end of therapy; eRT = eResearch Technologies; LFU = late follow-up; PK = pharmacokinetic; PTE = post therapy evaluation; 
UA = urinalysis. 
1. 
Screening/baseline assessments must occur within 24 hours prior to first administration of study drug. 
2. 
Day 1 is the first day of study drug administration; subsequent study days are consecutive calendar days. 
3. 
Perform EA assessments at 48 to 72 hours after the start of the first dose of IV study drug. 
4. 
Perform EOT assessments on the last calendar day of study drug (+ 1 day). Subjects who prematurely discontinue study drug or withdraw from the study should have all 
EOT assessments performed on the day of discontinuation of study drug or withdrawal from the study (+ 1 day). 
5. 
Perform PTE assessments 7 to 14 days after EOT. 
6. 
Perform LFU assessments 21 to 28 days after EOT. If the subject has improved to the point that they have returned to their usual premorbid activity (work/school), and if 
the primary site has little or no pain, swelling, redness, or purulent/seropurulent drainage at PTE, the LFU visit may be performed over the telephone. 
7. 
Written informed consent must be obtained prior to initiating any study assessment or procedure. 
8. 
Record all prior medications taken within 2 weeks prior to randomization; record all concomitant medications between Day 1 and EOT, and only concomitant 
antimicrobial agents and concomitant medications taken for an AE between EOT and LFU. 
9. 
Direct evaluation of signs and symptoms of ABSSSI by the Investigator at EA, Day 7, EOT, and PTE; assessments include manual measurement of the primary ABSSSI 
lesion size (longest length and perpendicular width) with a ruler provided by the Sponsor (Protocol Section8.1). 
10. Procedures that must be repeated on Day 1 prior to dosing if they were collected > 24 hours prior to first administration of study drug. 


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11. Document the primary ABSSSI lesion via digital photography at screening/baseline, EA, Day 7, and EOT using the digital camera provided by the Sponsor (Protocol 
Section 8.3). 
12. At screening/baseline, record if the subject’s premorbid activities (work/school) are compromised. At subsequent visits, record the date the subject returned to premorbid 
level of activity (work/school), as applicable. 
13. Perform a complete physical examination (i.e., general appearance, head, ears, eyes [including basic Snellen visual acuity and visual field testing], nose, throat, dentition, 
thyroid, chest [heart, lungs], abdomen, skin/soft tissues, neurological, extremities, back, neck, musculoskeletal, lymph nodes) at screening/baseline and EOT. 
14. Perform a limited, symptom directed physical examination as clinically indicated at EA, Day 7, and PTE. 
15. Record vital signs (heart rate, blood pressure, respiratory rate, and temperature) at screening/baseline, EA, Day 7, EOT, and PTE. If > 1 temperature is measured within a 
calendar day, record the highest daily temperature measured. Vital signs will be collected prior to collection of blood laboratory samples. Oral or rectal temperatures are 
acceptable; the site of measurement will be collected in the eCRF. 
16. Obtain triplicate ECGs within a 15-minute period, each separated by at least 1 minute, at screening/baseline, Day 1 (predose and postdose), EA, EOT, and PTE. ECGs 
will be collected prior to collection of blood laboratory (including PK) samples. The time of prior dose of study drug and relationship of time of ECG to dose must be 
documented All ECGs will be performed on ECG machines provided by eRT and will be sent to eRT for central reading. 
17. Within 1 hour prior to start of IV infusion (unless screening/baseline ECG is performed in triplicate and is within 1 hour prior to start of IV infusion) and another within 
2 hours after completion of IV infusion. 
18. Adverse events are collected between written informed consent and LFU. During the LFU phone call, symptoms related to possible relapse of ABSSSI will be evaluated 
as part of the safety assessment. 
19. Perform safety laboratory tests, including hematology, chemistry, and coagulation tests, UA, and CRP, at screening/baseline, EA, Day 7, EOT, and PTE. Include urine 
microscopy if UA is positive for red blood cells, WBCs, or protein (Protocol Appendix 4). Samples for screening/baseline tests will be drawn and sent to local laboratory 
(to confirm eligibility) and central laboratory. All subsequent laboratory tests will be drawn and sent to the central laboratory. 
20. Serology tests include Anti-HBcAg anti-HBsAg, HBsAg, HCV Ab, HIV Ab (Protocol Appendix 4) 
21. Females of childbearing potential up to 2 years postmenopause must have a serum or urine β–HCG pregnancy test at baseline and EOT (otherwise, females must be 
surgically sterile, i.e., have had a tubal ligation, hysterectomy, or bilateral oophorectomy). Male and female subjects must agree to comply with using a highly effective 
form of birth control (see Protocol Section 10.3 from baseline through LFU. If the pregnancy test is positive at the EOT visit, or if a female partner of a male subject 
becomes pregnant, follow the reporting requirements in Protocol Section 10.3. 
22. Calculate estimated CrCl using screening/baseline height (m), actual weight (kg), and serum creatinine (Protocol Section 7.1). 
23. Obtain PK samples as follows (Protocol Section 11):   
x 
One sample after 1st IV dose, between 0.5 to 2 hrs after the end of the 1st infusion;  
x 
Three samples with the 3rd IV dose: obtain a 1st blood sample within 2 hours before the 3rd IV dose (trough level), a 2nd blood sample between 0.5 and 3 hours 
after the end of the 3rd IV dose,and a 3rd blood sample between 4 and 11 hours after the end of 3rd IV dose, but before the 4th dose (IV or PO);  
x 
Three samples at EOT: obtain 1 blood sample within 2 hours before the last dose (IV or PO). If the last dose is given PO: obtain 1 blood sample between 1.5 to 4 
hours after the last dose and obtain 1 additional sample between 5 to 12 hours after the last dose. If the last dose is given IV: obtain 1 blood sample between 
0.5 and 3 hours after the end of the last infusion and obtain 1 additional sample between 4 and 11 hours after the end of the last infusion. 
24. Obtain appropriate ABSSSI site specimen from all subjects at screening/baseline, and perform Gram stain and culture at the local laboratory (Protocol Section 8.2Error! 
Reference source not found.). The ABSSSI site specimen should be obtained before administration of antibacterial therapy whenever possible. Repeat post-
screening/baseline ABSSSI specimen culture and Gram stain at subsequent visits only if clinically indicated (e.g., the subject is deemed a clinical failure or if purulence 
and discharge from the ABSSSI site continues after screening/baseline). 


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25. Two sets of blood cultures (each set consists 1 aerobic and 1 anaerobic blood culture bottle from 2 separate venipuncture sites) will be collected from all subjects, 
regardless of location of management (inpatient or outpatient) (Protocol Section 8.2). The blood cultures should be obtained before administration of antibacterial 
therapy, whenever possible. Blood cultures must be repeated every 3 days (± 1 day) if the previous blood culture was positive, or at any time after screening/baseline if 
clinically indicated. 
26. Verify that the subject meets all study inclusion and exclusion criteria before randomization on Day 1. 
27. Subjects receive study drug q12h (± 2 hours) for 10-14 days. On Day 1, the first dose of study drug should be administered as quickly as possible after eligibility criteria 
are met. Subjects will receive the first 3 doses of study drug intravenously and then may switch to oral study drug if the primary ABSSSI lesion has not increased in area 
from the screening/baseline assessment and the Investigator determines that the subject has sufficient PO intake of food and drink to safely support the administration of 
PO doses of antibiotics. 
 
 
 
 


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Appendix B) Division of Microbiology and Infectious Diseases Adult Toxicity Table 
The DMID Adult Toxicity Table (November 21, 2007) was modified to exclude the clinical component of the toxicity grading because 
clinical signs and symptoms related to abnormal laboratory values are not collected in this study. In addition, Grade 0 was added to 
the table so that shifts from normal could be analyzed. For toxicity grades based on a multiple of the ULN, the normal range from the 
central laboratory will be applied. For toxicity grades based on fixed values, the grades will be assigned regardless of the normal 
actual range values from the central laboratory. For example, a hemoglobin value of 10.0 gm/dL will be assigned a grade of 1 
toxicity, even if the lower limit of normal from the laboratory was 9.8 gm/dL. 
 
ENZYMES 
 
 
 
Grade 0  
 
Grade 1  
 
Grade 2  
 
Grade 3  
 
Grade 4  
AST (SGOT) 
<1.25xULN 
1.1-2.0xULN 
2.0-3.0xULN 
3.0-8.0xULN 
>8.0xULN 
ALT (SGPT) 
<1.25xULN 
1.1-2.0xULN 
2.0-3.0xULN 
3.0-8.0xULN 
>8.0xULN 
GGT 
<1.25xULN 
1.1-2.0xULN 
2.0-3.0xULN 
3.0-8.0xULN 
>8.0xULN 
Alkaline Phosphatase 
<1.25xULN 
1.1-2.0xULN 
2.0-3.0xULN 
3.0-8.0xULN 
>8.0xULN 
 
 
HEMATOLOGY 
 
 
 
Grade 0  
 
Grade 1  
 
Grade 2  
 
Grade 3  
 
Grade 4  
Hemoglobin (gm/dL) 
>10.5 
9.5-10.5 
8.0-9.4 
6.5-7.9 
<6.5 
Absolute Neutrophil Count 
(count/mm3) 
>1500 
1000-1500 
750-999 
500-749 
<500 
Platelets (count/mm3) 
≥100,000 
75,000-99,999 
50,000-74,999 
20,000-49,999 
<20,000 
WBCs (count/mm3) 
1000-10,999 
11,000-12,999 
13,000-14,999  
15,000-30,000 
>30,000 
% Polymorphonuclear Leucocytes 
+ Band Cells 
d80% 
>80%-90% 
>90–95% 
>95% 
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CHEMISTRY 
 
 
 
Grade 0  
 
Grade 1  
 
Grade 2  
 
Grade 3  
 
Grade 4  
Hyponatremia (mEq/L) 
>135 
130-135 
123-129 
116-122 
<116  
Hypernatremia (mEq/L) 
<146 
146-150 
151-157 
158-165 
>165  
Hypokalemia (mEq/L) 
>3.4 
3.0-3.4 
2.5-2.9 
2.0-2.4 
<2.0 
Hyperkalemia (mEq/L) 
<5.6 
5.6-6.0 
6.1-6.5 
6.6-7.0 
>7.0 
Hypoglycemia (mg/dL) 
t65 
55-64 
40-54 
30-39 
<30  
Hyperglycemia (mg/dL) (nonfasting 
and no prior diabetes)* 
<116 
116-160 
161-250 
251-500 
>500  
Hypocalcemia (mg/dL) (corrected 
for albumin) 
>8.4 
8.4-7.8 
7.7-7.0 
6.9-6.1 
<6.1 
Hypercalcemia (mg/dL) (correct for 
albumin) 
d10.5 
10.6-11.5 
11.6-1.5 
12.6-13.5 
>13.5 
Hypomagnesemia (mEq/L) 
>1.4 
1.4- 1.2 
1.1-0.9 
0.8-0.6 
<0.6 
Hypophosphatemia (mg/dL) 
t2.5 
2.0-2.4 
1.5-1.9 
1.0-1.4 
 
<1.0 
 
 
 
 
 
 
Hyperbilirubinemia (when 
accompanied by any increase in 
other liver function test) 
<1.1xULN 
1.1 - <1.25xULN 
1.25 - <1.5xULN 
1.5 – 1.75xULN 
> 1.75xULN 
Hyperbilirubinemia (when other 
liver function are in the normal 
range) 
<1.1xULN 
1.1 - <1.5xULN 
1.5 - <2.0xULN 
2.0 – 3.0xULN 
> 3.0xULN 
BUN 
<1.25xULN 
1.25-2.5xULN 
2.6-5xULN 
5.1-10xULN 
>10xULN 
Hyperuricemia (uric acid) (mg/dL) 
<7.5 
7.5–10.0 
10.1–12.0 
12.1–15.0 
>15.0 
Creatinine 
<1.1xULN 
1.1-1.5xULN  
1.6-3.0xULN 
3.1-6xULN 
>6xULN  
* The DMID toxicity table reports hyperglycemia detected in nonfasting specimens obtained from subjects with no prior diabetes.   


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Appendix C) Safety Laboratory Tests 
 
Hematology: 
x 
Hemoglobin 
x 
Hematocrit 
x 
Erythrocyte count 
x 
Leukocyte count (WBCs) 
x 
Neutrophils 
x 
Lymphocytes 
x 
Monocytes 
o Eosinophils 
o Basophils 
o Platelets 
 
Coagulation: 
x 
Prothrombin time/International normalized 
ratio (PT/INR) 
x 
Partial thromboplastin time 
x 
Activated partial thromboplastin time (aPTT) 
 
Urinalysis: 
x 
Specific gravity 
x 
pH 
x 
Protein 
x 
Glucose 
x 
Ketones 
x 
Bilirubin 
x 
Occult blood 
x 
Nitrites 
x 
Urobilinogen 
x 
Leukocyte esterase 
 
Urine Microscopy:a 
x 
WBCs 
x 
Red blood cells 
x 
Casts 
x 
Bacteria 
x 
Crystals 
Chemistry (Serum Concentrations): 
x 
Glucose 
x 
Calcium 
x 
Albumin 
x 
Total protein 
x 
Sodium 
x 
Potassium 
x 
Bicarbonate 
x 
Chloride 
x 
Urea nitrogen 
x 
Creatinine 
x 
Alkaline phosphatase 
x 
Alanine aminotransferase 
x 
Aspartate aminotransferase 
x 
Total and direct bilirubin 
x 
Magnesium 
x 
Lactate dehydrogenase 
x 
Phosphorus 
x 
Uric Acid 
x 
Creatine kinase 
x 
Gamma-glutamyl transferase 
x 
Indirect bilirubin 
x 
Cholesterol 
x 
Triglycerides 
x 
β-Human chorionic gonadotropin for females 
x 
C-reactive protein (CRP) 
 
SCREENING/BASELINE ONLY: 
x 
Creatinine clearance 
x 
Anti-HBcAg (anti-hepatitis B core antigen) 
x 
Anti-HBsAg (anti-hepatitis B surface 
antigen) 
x 
HBsAg (hepatitis B surface antigen) 
x 
HCV Ab (hepatitis C antibody) 
x 
HIV Ab (human immunodeficiency virus 
antibody) 
a 
Performed if UA is positive for red blood cells, WBCs, or protein. 
 
 


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Appendix D) Allowed Prior Antibiotics 
 
Allowed Antibiotics 
(One dose within 96 hours prior to randomization) 
Disallowed Antibiotics 
Penicillins: 
Amoxicillin 
Nafcillin 
NONE 
Amoxicillin-Clavulanate 
Oxacillin 
 
Amoxicillin-Sulbactam 
Penicillin-G 
 
Ampicillin 
Penicillin-V 
 
Ampicillin-Sulbactam 
Piperacillin 
 
Dicloxacillin 
Piperacillin-Tazobactam 
 
Cephalosporins: 
Cefaclor 
Cefpodoxime  
Ceftriaxone 
Cefadroxil 
Cefprozil  
 
Cefazolin 
Ceftaroline  
 
Cefdinir 
Ceftazidime 
 
Cefepime 
Ceftibuten 
 
Cefixime  
Cefuroxime 
 
Cefditoren  
Cephalexin 
 
Cefotaxime  
Loracarbef 
 
Carbapenems: 
Doripenem 
Ertapenem 
Imipenem 
 
Meropenem 
 
Glycopeptides: 
Televancin 
Dalbavancin 
Vancomycin 
Oritavancin 
Fluoroquinolones: 
Ciprofloxacin 
Levofloxacin 
 
Moxifloxacin 
Macrolides: 
Clarithromycin 
Erythromycin 
Azithromycin 
Clarithromycin XL  
Tetracyclines: 
Doxycycline 
Minocycline 
Minocycline Extended 
Release 
Miscellaneous: 
Clindamycin 
Metronidazole 
Trimethoprim-sulfamethoxazole/Co-trimoxazole 
Daptomycin 
Oxazolidinones: 
NONE 
Linezolid 
Tedizolid 
 
 
 


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Appendix E) Local Signs and Symptoms of ABSSSI 
Local signs and symptoms will be assessed for the primary ABSSSI site. 
The Investigator is to provide a categorical assessment and comparison to baseline of the 
following parameters using the scale below: 
Parameter 
Absent 
Mild 
Moderate 
Severe 
Erythema 
None 
Pink 
Red 
Fiery red 
Swelling/edema 
None 
Swelling just apparent  
on casual inspection  
(up to 2 mm of pitting) 
Marked swelling  
(≤ 4 mm of pitting) 
Maximal swelling  
(> 4 mm of pitting) 
Localized warmth 
None 
Slightly warm 
Warm 
Hot 
Tenderness on 
palpation 
None 
Slight or mild tolerable 
discomfort on palpitation 
Uncomfortable with  
light palpitation or 
pressure 
Intolerable by even a  
mild stimulus such as  
sheet touching 
Drainage 
None 
Serous 
Seropurulent  
Purulent 
Fluctuance 
None 
Present 
Not applicable 
Not applicable 
Induration 
None 
Present 
Not applicable 
Not applicable