Clinical trial NCT02877927
Conditions: Bacterial Infections Skin Structures and Soft Tissue Infections
Sponsor: Paratek Pharmaceuticals Inc
Start date: 2016-08-01; Completion date: 2017-06-06
Enrollment: 735 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the safety and efficacy of omadacycline as compared to linezolid in the treatment of adults with acute bacterial skin and skin structure infections.

Detailed description:

Arms: arm 1: Omadacycline tablets arm 2: Linezolid tablets
Interventions: intervention 1: Omadacycline intervention 2: Linezolid
Intervention descriptions: intervention 1: po tablets intervention 2: po tablets

Protocol documents:
Prot_000.pdf: 
Omadacycline (PTK 0796) 
PTK0796-ABSI-16301 – Version 3.0 
 IND 73,431 
22-NOV-2016 
 IND 75,928 
Confidential and Proprietary 
Page 1 of 79 
Paratek Pharma, LLC 
PROTOCOL PTK0796-ABSI-16301 
Study Title 
A Phase 3 Randomized, Double-Blind, Multi-Center Study to 
Compare the Safety and Efficacy of Oral Omadacycline to Oral 
Linezolid for Treating Adult Subjects with Acute Bacterial Skin and 
Skin Structure Infection (ABSSSI)  
IND Number: 
73,431 and 75,928 
Protocol Number: 
PTK0796-ABSI-16301 
Indication: 
Acute Bacterial Skin and Skin Structure Infection 
Phase: 
3 
Investigational 
Product: 
Omadacycline (PTK 0796) 
Dose Form: 
Oral  
Sponsor: 
Paratek Pharma, LLC 
A wholly-owned subsidiary of Paratek Pharmaceuticals, Inc. 
75 Park Plaza, 4th Floor 
Boston, MA 02116 USA 
1000 First Ave 
Suite 400 
King of Prussia, PA, 19406 
P.O. Box 120828 
Boston, MA 02111 
Tel:  +1 617-275-0040 
Protocol Version: 
Version 3.0 
Date: 
22-NOV-2016 
NCT02877927


Omadacycline (PTK 0796) 
 
PTK0796-ABSI-16301 – Version 3.0 
 IND 73,431 
22-NOV-2016 
 IND 75,928 
 
Confidential and Proprietary 
Page 2 of 79 
Paratek Pharma, LLC 
TABLE OF CONTENTS 
TABLE OF CONTENTS .....................................................................................................2 
LIST OF IN-TEXT TABLES ..............................................................................................6 
LIST OF APPENDICES ......................................................................................................6 
 
DISCLOSURE STATEMENT ..........................................................................................7 
1
 
CONTACTS ......................................................................................................................8 
2
2.1 
Emergency Contacts ................................................................................................8 
2.2 
Additional Contacts .................................................................................................8 
 
SPONSOR SIGNATURE ..................................................................................................9 
3
 
INVESTIGATOR AGREEMENT...................................................................................10 
4
 
LIST OF ABBREVIATIONS ..........................................................................................11 
5
 
DEFINITIONS .................................................................................................................14 
6
 
PROTOCOL SYNOPSIS.................................................................................................15 
7
 
STUDY FLOWCHART ..................................................................................................23 
8
 
INTRODUCTION ...........................................................................................................26 
9
9.1 
Background ............................................................................................................26 
 STUDY OBJECTIVES ....................................................................................................28 
10
10.1 
Primary Objectives .................................................................................................28 
10.2 
Secondary Objectives .............................................................................................28 
 STUDY DESIGN.............................................................................................................29 
11
11.1 
Description .............................................................................................................29 
11.2 
Rationale of Study Design .....................................................................................29 
11.3 
Rationale for Choice of Comparator ......................................................................29 
11.4 
Approximate Duration of Subject Participation ....................................................29 
11.5 
Approximate Duration of Study .............................................................................30 
11.6 
Approximate Number of Subjects .........................................................................30 
 SELECTION OF SUBJECTS..........................................................................................30 
12
12.1 
Inclusion Criteria ...................................................................................................30 
12.2 
Exclusion Criteria ..................................................................................................31 
12.3 
Screen Failures .......................................................................................................33 
 PRIOR AND CONCOMITANT TREATMENT ............................................................33 
13
13.1 
Prohibited Treatment .............................................................................................34 
 
Concomitant Medications That May Interact With Linezolid .....................34 
13.1.1
13.2 
Permitted Treatments .............................................................................................35 
 
Dressings ......................................................................................................35 
13.2.1
 
Topical Solutions .........................................................................................35 
13.2.2
 
Surgical Procedures .....................................................................................35 
13.2.3


Omadacycline (PTK 0796) 
 
PTK0796-ABSI-16301 – Version 3.0 
 IND 73,431 
22-NOV-2016 
 IND 75,928 
 
Confidential and Proprietary 
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 PROCEDURES................................................................................................................35 
14
14.1 
Visit Schedule and Assessments ............................................................................36 
14.2 
Screening Phase .....................................................................................................36 
 
Subject Demographics/Other Baseline Characteristics ...............................37 
14.2.1
14.2.1.1 
Medical History Relating to the Infection Under Study ....................37 
 
Physical Examination...................................................................................37 
14.2.2
 
Diagnosis of ABSSSI and Clinical Assessment of the Site of Infection .....37 
14.2.3
 
Assessment of Lesion Size...........................................................................38 
14.2.4
 
Subject Reported Outcomes .........................................................................38 
14.2.5
14.2.5.1 
Numerical Rating Scale for Pain ........................................................38 
14.2.5.2 
SF-36v2® Health Survey ....................................................................39 
 
Urine Tests ...................................................................................................39 
14.2.6
14.3 
Double-blind Treatment Phase ..............................................................................39 
 
Assessments While on Test Article .............................................................39 
14.3.1
14.3.1.1 
Treatment Phase .................................................................................40 
14.3.1.2 
Management While on Oral Test Article ...........................................41 
 
Permitted Dose Adjustments and Interruptions of Test Article ...................42 
14.3.2
14.4 
Follow-up Phase.....................................................................................................42 
14.5 
Total Volume of Blood Collected ..........................................................................42 
 TEST ARTICLE AND ADMINISTRATION .................................................................42 
15
15.1 
Test Article Administration ...................................................................................42 
 
Identity of the Investigational Product .........................................................43 
15.1.1
15.2 
Investigational and Comparator Test Article .........................................................43 
 
Investigational Test Article:  Omadacycline ................................................43 
15.2.1
 
Comparator Test Article:  Linezolid ............................................................43 
15.2.2
15.3 
Dose Selection Rationale .......................................................................................43 
15.4 
Subject Compliance ...............................................................................................44 
 SAFETY ..........................................................................................................................45 
16
16.1 
Physical Examinations ...........................................................................................45 
 
Vital Signs ....................................................................................................45 
16.1.1
 
Laboratory Evaluations ................................................................................46 
16.1.2
16.1.2.1 
Hematology ........................................................................................46 
16.1.2.2 
Clinical Chemistry .............................................................................47 
16.1.2.3 
Other Laboratory Tests ......................................................................47 
 
Safety Studies to be Performed Locally .......................................................47 
16.1.3
16.1.3.1 
Electrocardiogram (ECG) ..................................................................47 
16.1.3.2 
Pregnancy and Assessments of Fertility ............................................48 
16.1.3.3 
Blood Cultures ...................................................................................48 
16.1.3.4 
Additional Local Laboratory Tests ....................................................48 
 
Appropriateness of Safety Measurements ...................................................48 
16.1.4


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PTK0796-ABSI-16301 – Version 3.0 
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22-NOV-2016 
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 EFFICACY ......................................................................................................................48 
17
17.1 
Clinical Assessment of the Site of Infection ..........................................................49 
17.2 
Assessment of Lesion Size.....................................................................................49 
17.3 
Microbiological Assessment of the Site of Infection .............................................49 
17.4 
Assessment of Clinical Outcome ...........................................................................50 
 
Evaluation of the Infection Under Study at the Early Clinical Response 
17.4.1
Assessment ...................................................................................................51 
 
Clinical Evaluation of the Infection Under Study at EOT ...........................51 
17.4.2
 
Clinical Evaluation of the Infection Under Study at PTE............................52 
17.4.3
 OTHER ASSESSMENTS ...............................................................................................53 
18
18.1 
Resource Utilization ...............................................................................................53 
 PHARMACOKINETIC PLASMA SAMPLES FOR OMADACYCLINE 
19
CONCENTRATION ........................................................................................................53 
19.1 
Selection of Sites for PK Studies ...........................................................................53 
19.2 
Collection of PK Samples ......................................................................................53 
19.3 
Storing and Shipping of PK Samples.....................................................................54 
19.4 
Analysis of PK samples .........................................................................................54 
 OTHER BIOMARKERS .................................................................................................54 
20
 SAFETY MONITORING ................................................................................................54 
21
21.1 
Definitions..............................................................................................................54 
 
Adverse Events ............................................................................................54 
21.1.1
 
Serious Adverse Events ...............................................................................55 
21.1.2
 
Other Reportable Information ......................................................................56 
21.1.3
 
Overdose ......................................................................................................56 
21.1.4
 
Medication Errors ........................................................................................56 
21.1.5
21.2 
Recording and Reporting .......................................................................................57 
 
Serious Adverse Event Reporting ................................................................57 
21.2.1
 
Assessment of Relatedness ..........................................................................57 
21.2.2
 
Assessment of Severity ................................................................................58 
21.2.3
 
Laboratory Findings .....................................................................................58 
21.2.4
 
Worsening or Progression of Qualifying ABSSSI ......................................58 
21.2.5
 
Pregnancies ..................................................................................................59 
21.2.6
 DATA ANALYSIS ..........................................................................................................59 
22
22.1 
Analysis Populations ..............................................................................................59 
22.2 
Subject Demographics and Other Baseline Characteristics ...................................60 
22.3 
Treatments (Test Article, Rescue Medication, Other Concomitant Therapies, 
Compliance) ...........................................................................................................61 
22.4 
Primary Efficacy Analysis .....................................................................................61 


Omadacycline (PTK 0796) 
 
PTK0796-ABSI-16301 – Version 3.0 
 IND 73,431 
22-NOV-2016 
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Early Clinical Response Efficacy Variable ..................................................61 
22.4.1
 
Investigator’s Assessment of Clinical Response at PTE Efficacy Variable 61 
22.4.2
 
Statistical Model, Hypothesis, and Method of Analysis ..............................61 
22.4.3
 
Additional Analyses of the Primary Efficacy Outcomes .............................62 
22.4.4
22.5 
Analysis of Secondary Variables ...........................................................................63 
22.6 
Analysis of Additional Efficacy Variables ............................................................63 
22.7 
Safety Outcome Measures .....................................................................................64 
 
Adverse Events ............................................................................................64 
22.7.1
 
Vital Signs ....................................................................................................64 
22.7.2
 
Electrocardiograms ......................................................................................65 
22.7.3
 
Laboratory Tests ..........................................................................................65 
22.7.4
22.8 
Resource Utilization ...............................................................................................65 
22.9 
Pharmacokinetics ...................................................................................................65 
 
Population PK Modeling..............................................................................66 
22.9.1
22.10 Pharmacogenetics/Pharmacogenomics ..................................................................66 
22.11 Biomarkers .............................................................................................................66 
22.12 PK/PD ....................................................................................................................66 
22.13 Sample Size Calculation ........................................................................................67 
22.14 Interim Analyses ....................................................................................................67 
22.15 Handling of Missing Values/Censoring/Discontinuations .....................................68 
 SUBJECT IDENTIFICATION ........................................................................................68 
23
 TEST ARTICLE ACCOUNTABILITY, RECONCILIATION, AND RETURN ..........68 
24
24.1 
Supply, Storage and Tracking of Test Article .......................................................69 
 RANDOMIZATION AND BLINDING..........................................................................69 
25
25.1 
Treatment Assignment ...........................................................................................69 
25.2 
Dispensing the Test Article ....................................................................................70 
25.3 
Treatment Blinding ................................................................................................70 
25.4 
Emergency Unblinding of Treatment Assignment ................................................70 
 SUBJECT DISCONTINUATION OR WITHDRAWAL ...............................................71 
26
 STUDY SUSPENSION, TERMINATION, AND COMPLETION ................................72 
27
27.1 
Study Completion and Post-Study Test Article .....................................................72 
27.2 
Study Suspension or Termination ..........................................................................72 
 ETHICAL CONSIDERATIONS .....................................................................................73 
28
28.1 
Regulatory and Ethical Compliance ......................................................................73 
28.2 
Informed Consent Procedures ................................................................................73 
28.3 
Responsibilities of the Investigator and IRB/IEC/REB .........................................73 
 PROTOCOL ADHERENCE ...........................................................................................73 
29
29.1 
Protocol Amendments ............................................................................................74 


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PTK0796-ABSI-16301 – Version 3.0 
 IND 73,431 
22-NOV-2016 
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Confidential and Proprietary 
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 QUALITY CONTROL AND ASSURANCE .................................................................74 
30
 DIRECT ACCESS, DATA HANDLING, AND RECORD-KEEPING .........................74 
31
31.1 
Investigator ............................................................................................................74 
31.2 
Sponsor ..................................................................................................................74 
 SUBJECT INJURY .........................................................................................................75 
32
 PRESTUDY DOCUMENTATION .................................................................................75 
33
 RECORDS RETENTION ................................................................................................76 
34
 PUBLICATION POLICY ...............................................................................................76 
35
 REFERENCES (available upon request) .........................................................................77 
36
 
LIST OF IN-TEXT TABLES 
Table 1. Treatment Regimens for Oral Test Article..............................................................41 
Table 2. Oral Formulation .....................................................................................................43 
Table 3. Hematology Panel ...................................................................................................46 
Table 4. Clinical Chemistry Panel.........................................................................................47 
Table 5. Additional Laboratory Tests ...................................................................................47 
Table 6. Sample Size and Power Calculations ......................................................................67 
Table 7. Investigator’s Assessment of Clinical Response at PTE Determination Considering 
Missing Data ...........................................................................................................68 
 
LIST OF APPENDICES 
Appendix 1.  Allowed and Disallowed Prior Antibiotics ........................................................78 
Appendix 2.  Equations and Conversion Factors .....................................................................79 
 
 
 


Omadacycline (PTK 0796) 
 
PTK0796-ABSI-16301 – Version 3.0 
 IND 73,431 
22-NOV-2016 
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Confidential and Proprietary 
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Paratek Pharma, LLC 
 
DISCLOSURE STATEMENT 
1
Restricted Distribution of Documents 
This document contains information that is confidential and proprietary to the sponsor.  This 
information is being provided to you solely for the purpose of evaluating and/or conducting a 
clinical study for the sponsor.  You may disclose the contents of this document only to study 
personnel under your supervision, institutional review boards (IRBs)/independent ethics 
committees (IECs)/research ethics boards (REBs), or duly authorized representatives of 
regulatory agencies for this purpose under the condition that they maintain confidentiality.  The 
contents of this document may not be used in any other clinical study, disclosed to any other 
person or entity, and/or published without the prior written permission of the sponsor.  The 
foregoing shall not apply to disclosure required by any regulations; however, you will give 
prompt notice to the sponsor of any such disclosure.  All other nonpublic information provided 
by the sponsor and any information that may be added to this document also is confidential and 
proprietary to the sponsor and must be kept in confidence in the same manner as the contents of 
this document. 


Omadacycline (PTK 0796) 
 
PTK0796-ABSI-16301 – Version 3.0 
 IND 73,431 
22-NOV-2016 
 IND 75,928 
 
Confidential and Proprietary 
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Paratek Pharma, LLC 
 
CONTACTS 
2
2.1 
Emergency Contacts 
Name/Title:  Paul Eckburg, MD, Global Medical Monitor 
Phone (during business hours): 
 
Phone (after business hours):  
 
E-mail (not for emergencies):  
 
Address:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Name/Title: Stephen Villano, MD, Paratek Pharma, LLC, VP, Clinical and Medical Affairs 
Phone (during business hours): 
 
Phone (after business hours):  
 
E-mail (not for emergencies):  
 
Address:  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.2 
Additional Contacts 
Serious Adverse Event (SAE) contact information 
E-Mail: 
 
Fax: 
 
 


Omadacycline (PTK 0796) 
PTK0796-ABSI-16301 - Version 3.0 
22-NOV-2016 
3 
SPONSOR SIGNATURE 
IND 73,431 
IND 75,928 
I have read and approve this protocol. My signature, in conjunction with the signature of the 
investigator, confirms the agreement of both parties that the clinical study will be conducted in 
accordance with the protocol and all applicable laws and regulations including, but not limited 
to, the International Conference on Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) Guideline for Good Clinical Practice (GCP), the Code of 
Federal Regulations (CFR), and the ethical principles that have their origins in the Declaration of 
Helsinki. 
~ 
Stephen Villano, MD 
VP, Clinical and Medical Affairs 
Paratek Pharma, LLC 
Confidential and Proprietary 
Date of Signature 
(DD-MMM-YYYY) 
Page 9 of79 
Time 
(24-hour clock, time 
zone) 
Paratek Pharma. LLC 


Omadacycline (PTK 0796) 
 
PTK0796-ABSI-16301 – Version 3.0 
 IND 73,431 
22-NOV-2016 
 IND 75,928 
 
Confidential and Proprietary 
Page 10 of 79 
Paratek Pharma, LLC 
 
INVESTIGATOR AGREEMENT 
4
I have read the protocol (PTK0796-ABSI-16301) and agree to the following: 
The protocol contains all necessary details for carrying out this study;  
I will conduct the study as detailed in the protocol and will abide by all its provisions;  
I will conduct the study in compliance with the most current versions of International Conference 
on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human 
Use (ICH) Guidelines for Good Clinical Practice (GCP), all applicable government regulations 
and the requirements of the IRB/IEC/REB that approved the study. 
I will train and supervise all individuals delegated to assist me in conducting this study, including 
providing copies of the protocol and all pertinent information and discussing the material with 
them to ensure they are fully informed regarding the investigational product, the protocol and 
their responsibilities and obligations.  
I will use only the informed consent form (ICF) approved by PARATEK (or their designee) and 
by the IRB/IEC/REB responsible for this study.  
I will fulfill all requirements for submitting pertinent information to the IRB/IEC/REB and to 
PARATEK, including reportable serious adverse events (SAEs).  
I will provide PARATEK (or their designee) with access to any source documents from which 
case report form information may have been generated. 
I understand that the information in this protocol and the referenced Investigator’s Brochure is 
confidential and that its disclosure to any third parties (other than those involved in approving or 
conducting the study) is prohibited.  I will take the necessary precautions to protect this 
information from loss, inadvertent disclosure or access by third parties.  
I will complete the study within the time designated.  
My signature, in conjunction with the signature of the sponsor, confirms the agreement of both 
parties that the clinical study will be conducted in accordance with the protocol and all 
applicable laws and regulations including, but not limited to, the ICH Guideline for GCP, the 
Code of Federal Regulations (CFR), and the ethical principles that have their origins in the 
Declaration of Helsinki. 
Nothing in this document is intended to limit the authority of a physician to provide emergency 
medical care under applicable regulations.  
 
 
Investigator Signature 
 Date of Signature 
(DD-MMM-YYYY) 
 Time (24-hour clock, 
time zone) 
 
  
  
Investigator Name and Title (print) 
  
  


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PTK0796-ABSI-16301 – Version 3.0 
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LIST OF ABBREVIATIONS 
5
ABSSSI 
acute bacterial skin and skin structure infection 
ACM 
all-cause mortality 
AE 
adverse event 
AIDS 
Acquired Immune Deficiency Syndrome 
ALT 
alanine aminotransferase 
AP 
alkaline phosphatase 
AST 
aspartate aminotransferase 
AUC 
area under the (concentration/time) curve 
BMI 
body mass index 
BP 
blood pressure 
bpm 
beats per minute 
CABP 
community-acquired bacterial pneumonia 
cc 
cubic centimeter 
CD4 
cluster of differentiation 4 
CE 
clinically evaluable 
CFR 
Code of Federal Regulations 
CK 
creatine phosphokinase 
CI 
confidence interval 
Cmax 
maximum plasma concentration 
CrCL 
creatinine clearance 
CRF 
case report/record form 
CSA 
clinical study agreement 
CSR 
clinical study report 
cSSSI 
complicated skin and skin structure infection 
EC 
European Commission 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EMEA 
European Agency for the Evaluation of Medicinal Products 
EMA 
European Medicines Agency 
EOT 
end of treatment 
FDA 
Food and Drug Administration 
g 
gravity 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
β-hCG 
beta-human chorionic gonadotropin 
HDPE 
high-density polyethylene  
HIV 
Human Immunodeficiency Virus 
HPFB 
Canadian Health Products and Food Branch 


Omadacycline (PTK 0796) 
 
PTK0796-ABSI-16301 – Version 3.0 
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22-NOV-2016 
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HR 
heart rate 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IDSA 
Infectious Diseases Society of America 
IEC 
Independent Ethics Committee 
INR 
international normalized ratio 
IRB 
Institutional Review Board 
ITT 
intent-to-treat (population) 
IUD 
intrauterine device 
iv 
intravenous 
IxRS 
Interactive Voice Response System/Interactive Web Response System 
LC/MS/MS 
liquid chromatography/tandem mass spectrometry 
LDH 
lactate dehydrogenase 
MAO 
monoamine oxidase  
ME 
microbiologically evaluable  
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC 
minimum inhibitory concentration 
Micro-mITT 
microbiological modified intent-to-treat population 
mITT 
modified intent-to-treat population 
MRSA 
methicillin-resistant staphylococcus aureus 
NI 
non-inferiority  
PD 
pharmacodynamics 
PI 
principal investigator 
PK 
pharmacokinetics 
po 
per oral 
PT 
preferred term (MedDRA) 
PTE 
post therapy evaluation (test of cure)  
PVC 
polyvinyl chloride 
q12h 
every 12 hours 
q24h 
every 24 hours 
QTc 
corrected QT interval 
QTcB 
QTc Bazett’s correction formula 
QTcF 
QTc Fridericia’s correction formula 
REB 
Research Ethics Board 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis Software 
SBP 
systolic blood pressure 
SD 
standard deviation  


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SOC 
system organ class (MedDRA) 
spp 
species (pleural) 
ss 
steady state 
TEAE 
treatment-emergent adverse event 
TFL 
table, figure and listing 
TGA 
Therapeutic Goods Administration 
Tmax 
time to maximum plasma concentration 
ULN 
upper limit of normal  
US 
United States 
UTI 
urinary tract infection 
WBC 
white blood cells  
 


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DEFINITIONS 
6
Term 
Definition 
Regulation 
The term regulation refers to all applicable regulations, laws, and guidelines.  The 
regulations may be international, national, or local and may include but are not 
limited to the Code of Federal Regulations; the Good Clinical Practice:  Consolidated 
Guideline (Canada); the International Conference on Harmonisation Guideline for 
Good Clinical Practice; the Therapeutic Goods Administration Annotated 
International Conference on Harmonisation Guidelines (Australia); the World 
Medical Association Declaration of Helsinki:  Ethical Principles for Medical 
Research Involving Human Subjects. 
Regulatory agency 
The term regulatory agency refers to all health and regulatory agencies with 
oversight responsibility for the study.  These may be international, national, or local 
and may include but are not limited to the Australian Therapeutic Goods 
Administration (TGA), the Canadian Health Products and Food Branch (HPFB), the 
European Agency for the Evaluation of Medicinal Products (EMEA), the United 
States (US) Food and Drug Administration (FDA). 
Sponsor 
The term sponsor refers to, but is not limited to the Sponsor listed in the front of this 
document and any contract research organization that is being used for the study. 
Test article 
Any study drug, device, biologic agent, or comparator (including placebo) used in 
sponsor studies.  For test article accountability, this term applies to the above articles 
when they are required by the protocol and supplied (shipped) by the sponsor 
(including diluents such as sterile water for injection). 
Adverse event 
An adverse event (AE) is any untoward, undesired, or unplanned event in the form of 
signs, symptoms, disease, or laboratory or physiologic observations occurring in a 
person given a test article or in a clinical study.  


Omadacycline (PTK 0796) 
 
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PROTOCOL SYNOPSIS 
7
Study Title 
A Phase 3 Randomized, Double-Blind, Multi-Center Study to Compare the 
Safety and Efficacy of Oral Omadacycline to Oral Linezolid for Treating 
Adult Subjects with Acute Bacterial Skin and Skin Structure Infection 
(ABSSSI) 
Clinical Phase 
3 
Study Rationale 
Omadacycline, the first aminomethylcycline antibiotic, is a semi-synthetic 
derivative of the tetracycline class.  As a class, the tetracyclines have been 
in use for approximately 70 years.  They are well-tolerated, and have 
proven effective in the treatment of a variety of bacterial infections.  
Omadacycline has demonstrated activity against the most common 
ABSSSI pathogens, including methicillin-resistant Staphylococcus aureus 
(MRSA).  Omadacycline was evaluated in a Phase 2 study of 219 subjects 
with complicated skin and skin structure infection (cSSSI) and a 
sponsor-terminated Phase 3 study of 140 subjects with cSSSI.  
Omadacycline was well-tolerated and demonstrated efficacy similar to an 
established comparator (linezolid).  
In a global Phase 3 study comparing the safety and efficacy of intravenous 
(iv) and per oral (po) omadacycline to iv and po linezolid in the treatment 
of adult subjects with ABSSSI (PTK0796-ABSI-1108) omadacycline was 
non-inferior to linezolid and was well tolerated.  In addition, a global 
Phase 3 study is currently being conducted to evaluate the safety and 
efficacy of iv and po omadacycline compared to iv and po moxifloxacin in 
the treatment of adult subjects with community-acquired bacterial 
pneumonia (PTK0796-CABP-1200). 
This study is intended to evaluate the safety and efficacy of po 
omadacycline as compared to po linezolid in the treatment of adult subjects 
with ABSSSI.   
Study 
Objective(s) 
Primary objective: 
To demonstrate that omadacycline administered orally for 7 to 14 days is 
non-inferior to linezolid administered orally for 7 to 14 days in the 
treatment of adult subjects with ABSSSI known or suspected to be due to 
Gram-positive pathogens.  
Secondary objectives: 
• To evaluate the safety of omadacycline in the treatment of adult 
subjects with ABSSSI. 
• To evaluate the Clinical Response according to the identified 
causative pathogen. 
• To evaluate the pharmacokinetics (PK) of omadacycline in adult 
subjects with ABSSSI. 


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Study Design 
This is a randomized (1:1), active comparator-controlled, double-blind, 
double-dummy, Phase 3 study comparing omadacycline and linezolid for 
the treatment of adult subjects with ABSSSI that is known or suspected to 
be due to a Gram-positive pathogen(s).  The Schedule of Events for the 
study is shown in Section 8.  Enrollment of subjects with major abscess 
may be up to 30% of randomized subjects.  Enrollment of subjects who 
have received a single dose of an allowed short-acting antibiotic (see 
Appendix 1) within the 72 hours prior to randomization will be limited to 
no more than 25% of randomized subjects.   
Approximate 
Duration of 
Subject 
Participation  
Subjects will participate in the study for approximately 30 days.  
Following Screening, eligible subjects will be randomly assigned to 
receive 7 to 14 days of po treatment with either omadacycline or linezolid.  
A follow-up office visit will occur approximately 7 to 14 days after the last 
dose of test article and a follow-up telephone contact will occur 
approximately 30 to 37 days after the first dose of test article. 
Approximate 
Duration of Study 
The study is expected to be clinically complete in approximately 
12 months. 
Approximate 
Number of 
Subjects 
704 randomized subjects. 
Approximate 
Number of Study 
Centers 
50 sites.  
Diagnosis and 
Main Criteria for 
Inclusion 
1. Written and signed informed consent must be obtained before any 
assessment is performed.  
2. Male or female, age 18 years or older. 
3. Has a qualifying skin and skin structure infection.  All qualifying 
lesions must be greater than or equal to 75 cm2 in total surface area of 
contiguous involved tissue, calculated as the product of the maximum 
length (head-to-toe) multiplied by the maximum width (measured 
perpendicular to length) as measured by the investigator using a wound 
ruler.  Involved tissue is defined as tissue exhibiting clear evidence of 
one or more of the following:  erythema, edema or induration.  
The classification of qualifying infections is shown below. 
• Wound infection – an infection characterized by purulent drainage 
from a wound with surrounding erythema, edema, and/or 
induration extending at least 5 cm in the shortest distance from 
the peripheral margin of the wound.  
• Cellulitis/erysipelas – a diffuse skin infection characterized by 
spreading areas of erythema, edema, and/or induration.  
• Major abscess – an infection characterized by a collection of pus 
within the dermis or deeper with surrounding erythema, edema, 


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and/or induration extending at least 5 cm in the shortest distance 
from the peripheral margin of the abscess. 
4. Has evidence of a systemic inflammatory response within the 24 hours 
prior to randomization, as indicated by ONE of the following:   
• Elevated white blood cell (WBC) count (greater than or equal 
to 10,000 cells/mm3) or leukopenia (less than or equal 
to 4,000 cells/mm3) 
• Elevated immature neutrophils (greater than or equal to 15% band 
forms, see % bands calculation in Appendix 2) regardless of total 
peripheral white blood cell (WBC) count 
• Lymphatic involvement:  lymphangitis or lymphadenopathy that is 
proximal to and in a location that suggests drainage from the 
qualifying infection 
• Fever or hypothermia documented by the investigator 
(temperature greater than 38.0°C [100.4°F] or less than 36.0°C 
[95.5°F]) 
5. Females must have a negative pregnancy test at Screening and agree to 
comply with using an acceptable method of birth control (eg, 
abstinence, oral contraceptive, intrauterine device [IUD], barrier 
contraception [condom], tubal ligation, hysterectomy, bilateral 
oophorectomy, postmenopausal or vasectomized partner) from 
Screening through Post Therapy Evaluation (PTE).  Males must agree 
to use an acceptable method of birth control with female partner(s) and 
must not donate sperm from Screening through PTE. 
Main Criteria for 
Exclusion 
1. Has received 1 or more doses of a potentially effective systemic 
antibacterial treatment within the 72 hour period prior to randomization 
(a subject will be considered to have received a potentially effective 
systemic antibacterial treatment if the pathogen identified as causing 
the infection is shown to be susceptible to the antibacterial treatment 
given or, in the circumstance where a pathogen is not identified, if the 
antibacterial agent is approved for treatment of skin infections or is 
known to have activity against any of the leading Gram-positive causes 
of ABSSSI [eg, Staphylococcus aureus, Streptococcus species [spp.], 
Enterococcus spp.). EXCEPTION: Subjects may be eligible despite 
prior antibacterial therapy if they have been treated with a single dose 
of a short-acting, non-oxazolidinone antibacterial (ie, an antibacterial 
whose standard dosing regimen is more frequent than once per day, see 
list in Appendix 1).   
2. Has, for any reason, used a topical antibacterial agent(s) with specific 
antibacterial activity (eg, mupirocin, retapamulin, fusidic acid) 
continuously within the 72 hour period prior to randomization, if 
applied to the skin for greater than or equal to 72 hours. 
3. Infections where the outcome is strongly influenced by factors other 
than protocol-defined treatment and procedures, that require 
antibacterial treatment for greater than 14 days, are associated with 


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chronic skin lesions that may obscure determination of response even 
after successful bacterial eradication has been achieved, or are 
suspected or known to be caused by a pathogen resistant to either test 
article, eg: 
• chronic (persistently present greater than 3 months) lesions, ulcers 
or wounds (eg, cellulitis contiguous with a diabetic foot ulcer)  
• association with chronic dermatitis or any other chronic 
inflammatory skin lesion (eg, psoriasis, eczema) 
• burns 
• peri-rectal abscess (eg, buttock or perineal lesion likely to 
communicate with the rectum) or perineal infection 
• infected decubitus (pressure) ulcers 
• necrotizing fasciitis (infections with rapidly progressive 
destruction of tissue at or below the fascia) 
• life-threatening infections, ie, require emergency surgery for the 
treatment (eg, progressive gangrene) 
• infections in an area requiring surgery that in and of itself would 
cure the infection or remove the infected site (eg, amputation for 
vascular insufficiency) 
• infections associated with severe vascular insufficiency (eg, 
peripheral vascular disease) or acute occlusion expected to require 
immediate revascularization 
• infections associated with acute compartment syndrome expected 
to require extensive surgery to provide decompression 
• infections accompanied by confirmed or suspected contiguous 
bone or joint infection (eg, osteomyelitis, septic arthritis, bursitis) 
• bacteremic infections associated with an intravascular foreign 
body 
• infections accompanied by another confirmed or suspected 
infection requiring systemic antibiotic therapy (eg, endocarditis, 
other endovascular infection, meningitis, visceral abscess, 
intra-abdominal infection, pneumonia, urinary tract infection) 
• human or animal bites (infections associated with insect bites are 
NOT excluded) 
• myonecrosis 
• complicated by an immune deficiency in the subject (eg, ecthyma 
gangrenosum in a neutropenic subject) 
• infections associated with the presence of a foreign body (eg, 
wood, metal, plastic, etc.) if the foreign body cannot be removed 
within 24 hours of first dose of test article 
4. Inability to tolerate oral medication (eg, nausea, vomiting, diarrhea or 
any other condition that might impair ingestion or absorption of oral 
medication). 
5. Has known or is clinically suspected for one or more of the following 
prior to randomization: 


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• Alanine Aminotransferase (ALT) or Aspartate Aminotransferase 
(AST) greater than or equal to 3 times the Upper Limit of Normal 
(ULN),  
• total bilirubin greater than 1.5 times the ULN, or 
• evidence of end-stage liver disease (eg, ascites, hepatic 
encephalopathy) 
6. Has a known history of having experienced unstable cardiac disease 
(eg, unstable angina, myocardial infarction, acute congestive heart 
failure, unstable cardiac arrhythmia, etc.) within the 3 months prior to 
Screening. 
7. Requires any form of dialysis (eg, hemodialysis, peritoneal dialysis). 
8. History or evidence of severe renal disease or has a calculated 
creatinine clearance (CrCL) of less than 30 mL/min, using the 
Cockcroft-Gault equation (see equation in Appendix 2). 
9. Evidence of significant immunological disease determined by any of 
the following: 
• Current or anticipated neutropenia defined as less 
than 500 neutrophils/mm3 
• Known infection with Human Immunodeficiency Virus (HIV) and 
a cluster of differentiation 4 (CD4) count that is unknown or 
documented to be less than 200 cells/mm3 within the last year, or 
an Acquired Immune Deficiency Syndrome (AIDS)-defining 
illness 
10. The receipt of cancer chemotherapy, radiotherapy, or potent, 
non-corticosteroid immunosuppressant drugs (eg, cyclosporine, 
azathioprine, tacrolimus, immune-modulating monoclonal antibody 
therapy, etc.) within the 3 months prior to Screening, or the receipt of 
systemic corticosteroids for more than 14 days in the 30 days prior to 
Screening. 
11. Requires acute pharmacologic intervention to stabilize blood pressure 
and/or adequate tissue perfusion, OR has evidence of septic shock, 
defined by ALL of the following:   
• Fever or hypothermia documented by the investigator (temperature 
greater than 38.0°C [100.4°F] or less than 36.0°C [95.5°F]) 
• Heart rate greater than 90 beats/min (bpm) 
• Respiratory rate greater than 20 breaths/min 
• WBC greater than 12,000 cells/mm3 or less than 4,000 cells/mm3 
or greater than 10% immature (band) forms, see % bands 
calculation in Appendix 2, regardless of the total peripheral WBC 
count 
• Hypotension with systolic blood pressure (SBP) less 
than 90 mm Hg despite an iv fluid challenge of 20 to 30 cc/kg over 
a 30 minute period  
• Perfusion abnormalities that may include, but are not limited to, 
lactic acidosis (blood lactate concentration greater than or equal 


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to 4 mmol/L), oliguria, or acute alteration in mental status 
12. Pregnant or nursing (breastfeeding) women. 
13. Has a history of hypersensitivity or allergic reaction (eg, anaphylaxis, 
urticaria, other significant reaction) to any tetracycline (eg, 
minocycline, doxycycline or tigecycline) or to any oxazolidinone (eg, 
linezolid, tedizolid). 
14. Has a history of pseudotumor cerebri, or prior (within 2 weeks prior to 
Screening) or planned concomitant use of isotretinoin. 
15. Has a history of systemic lupus erythematosus or lupus-like syndrome. 
16. Has current evidence of pancreatitis. 
17. Has received a monoamine oxidase inhibitor within 14 days prior to 
Screening (eg, phenelzine, isocarboxazid, selegiline, moclobemide; 
which are typically used to treat depression or Parkinson's Disease). 
18. Use of other investigational drugs within 5 half-lives or within 30 days 
prior to Screening. 
19. Has previously been treated with omadacycline or previously enrolled 
in this study. 
20. Any planned medical intervention that might interfere with the ability 
to comply with the study requirements. 
21. Has any concomitant condition that, in the opinion of the investigator, 
is likely to interfere with evaluation of the response of the infection 
under study, determination of adverse events (AEs), or completion of 
the expected course of treatment.  
Prior and 
Concomitant 
Treatment 
No systemic prior or concomitant antibacterial therapy is allowed, other 
than a single dose of a short-acting antibacterial (see Exclusion Criterion 
number 1 and Appendix 1), within the 72 hours prior to randomization.  
No topical antibacterial therapy with a spectrum that is active against the 
known or potential infecting pathogen(s) responsible for the infection 
under study is allowed within the 72 hours prior to randomization or 
concomitantly through PTE.  No monoamine oxidase (MAO) inhibitors 
within 14 days prior to Screening or concomitantly through Final 
Follow-up.  All other medications not prohibited by the protocol and 
considered necessary for the subject’s welfare may be administered and/or 
continued under the supervision of the investigator. 
Test Article(s)  
Subjects will be randomized (1:1) to: 
• Omadacycline 
• Linezolid 
Dosage and 
Administration 
• Omadacycline 450 mg po every 24 hours (q24h) for 2 doses 
followed by 300 mg po q24h 
• Linezolid 600 mg po every 12 hours (q12h)  
Safety Evaluation 
• Adverse events (AEs) and Serious Adverse events (SAEs)  
• Physical examinations 
• Vital signs 


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• 12-lead electrocardiograms (ECGs) 
• Laboratory assessments 
• Pregnancy assessments 
Efficacy 
Evaluation 
• In order to satisfy different health authority requirements, the 
primary variables assessing efficacy will be tested with 2 response 
endpoints: 
• Successful Early Clinical Response (48 to 72 hours after the 
first dose of test article) defined as survival with a greater than 
or equal to 20% reduction of lesion size compared to 
Screening measurements without receiving any rescue 
antibacterial therapy 
• Successful Investigator’s Assessment of Clinical Response at 
the Post Therapy Evaluation (PTE) visit defined as survival 
after completion of a test article regimen, with resolution or 
improvement of signs and symptoms of infection to the extent 
that further antibacterial therapy is not necessary 
• Lesion size 
• Microbiology of the infection 
Health Outcomes 
Assessment 
• Resource utilization 
Pharmacokinetics 
• Population pharmacokinetic (PK) analysis 
Statistical 
Analysis 
A number of subject analysis populations have been defined for the various 
analyses of efficacy and safety, as follows: 
• The intent-to-treat (ITT) population will consist of all randomized 
subjects 
• The modified intent-to-treat (mITT) population will consist of all 
randomized subjects without a sole Gram-negative causative 
pathogen(s) at Screening 
• The clinically evaluable (CE) population will consist of all mITT 
subjects who received test article, have a qualifying ABSSSI, an 
assessment of outcome, and meet all other evaluability criteria 
detailed in the statistical analysis plan (SAP) 
• The microbiological modified intent-to-treat (micro-mITT) 
population will consist of subjects in the mITT population who 
have at least 1 Gram-positive causative pathogen(s) at Screening 
• The microbiologically evaluable (ME) population will include 
subjects in the CE population who have at least 1 Gram-positive 
causative pathogen(s) at Screening 
• The Safety population will consist of all randomized subjects who 
receive test article 
A 2-sided 95% confidence interval (CI) approach for the difference in the 


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rate of early clinical success in the mITT population (primary analysis for 
the United States [US] Food and Drug Administration [FDA]) will be used 
to test for non-inferiority (NI) of omadacycline arm compared to the 
linezolid arm.  For the primary analysis for the European Medicines 
Agency (EMA), 95% CIs for the difference in the rate of clinical success at 
PTE in the mITT and CE populations will be used to test for the NI of 
omadacycline arm compared to the linezolid arm.  
Safety will be assessed through the use of summary statistics and clinical 
review of reported AEs, changes in vital signs, ECGs and laboratory 
results obtained from blood and urine samples taken during the study.  
Rationale for 
Number of 
Subjects 
The study is designed to show NI in the primary efficacy outcome of Early 
Clinical Response at 48 to 72 hours following the first dose of test article 
in the mITT population.  An NI margin of 10% will be used for the 
analysis in the mITT population.  The NI margin was based on an analysis 
of the historical data regarding the treatment effect of antibiotics in 
ABSSSI. 
The sample size determination is based on ensuring sufficient power for 
the secondary efficacy analyses of Investigator’s Assessment of Clinical 
Response at PTE in the mITT and CE populations (co-primary efficacy 
outcomes for EMA) as well as the primary efficacy analysis of Early 
Clinical Response.  For the Early Clinical Response primary efficacy 
endpoint, assuming an outcome rate of 79% for both treatment groups, NI 
margin of 10%, 90% power and a 1-sided alpha of 0.025, using the sample 
size determination method of Farrington and Manning12, a total of 
704 subjects are required. 
Assuming an 85% outcome rate in both treatment groups, NI margin of 
10%, and a 1-sided alpha of 0.025, with a total of 704 subjects, there is 
more than 90% power to show NI for Investigator’s Assessment of clinical 
response at PTE in the mITT population.  With an evaluability rate of 80%, 
there will be 564 subjects in the CE population.  Assuming a 90% outcome 
rate in both treatment groups, NI margin of 10% and a 1-sided alpha of 
0.025, 564 subjects provides more than 90% power to show NI in the CE 
population. 
Ethical 
Considerations 
This study will be conducted in accordance with applicable laws and 
regulations including, but not limited to, the International Conference on 
Harmonisation of Technical Requirements for Registration of 
Pharmaceuticals for Human use (ICH) Guideline for Good Clinical 
Practice (GCP) and the ethical principles that have their origins in the 
Declaration of Helsinki.  The institutional review board (IRB)/independent 
ethics committee (IEC)/research ethics board (REB) must review and 
approve the protocol and informed consent form (ICF) before any subjects 
are enrolled.  The subject must be consented using the approved ICF 
before any procedures specified in the protocol are performed. 


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STUDY FLOWCHART 
8
Study Phase 
Screeninga 
Double-Blind Treatment Phase 
Follow-up Phase 
Study Dayb 
 
Day 1 
Day 2 
Day 3 
 (ECR 48-
72 hr after 
first dose) 
Day 7 
Day 10c 
EOTd 
PTEe 
Final  
Follow-upf 
Day 30-37 
Signed Informed Consentg 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical/surgical history and current medical 
conditions 
X 
 
 
 
 
 
 
 
Prior and concomitant medicationsh 
X 
X---------------------------------------------------------------------------------------------------X 
Clinical assessment of the site of infectioni 
X 
 
X 
X 
X 
X 
X 
X 
 
Assessment of lesion sizej 
X 
 
X 
X 
X 
X 
X 
X 
 
Diagnosis of ABSSSI and photograph of the 
lesion sitek 
X 
 
 
 
 
 
 
 
Numerical Rating Scale for pain at the primary 
lesion site 
X 
 
X 
 
 
X 
X 
 
SF-36v2® Health Survey 
X 
 
 
 
 
 
X 
 
Physical examinationl 
X 
 
 
 
 
 
X 
X 
 
Vital signs 
 
 
 
 
 
 
 
 
 
Respiratory rate 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Body temperature 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Blood pressure 
X 
Xm 
Xn 
Xn 
X 
X 
X 
X 
 
 
Pulse/heart rate 
X 
Xm 
Xn 
Xn 
X 
X 
X 
X 
 
12-lead ECGo 
X 
 
 
 
 
X 
  
 
Urine dipstick testp 
X 
 
 
 
 
 
 
 
Local urine or serum pregnancy testq 
X 
 
 
 
 
 
 
 
Central serum pregnancy testr 
X 
 
 
 
 
X 
X 
 
Hematologys 
Xt 
 
X 
X 
X 
X 
X 
 
Serum chemistrys 
Xt 
 
X 
X 
X 
X 
X 
 
Blood cultureu 
X 
As Clinically Indicated 
Xv 
Xv 
 


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Study Phase 
Screeninga 
Double-Blind Treatment Phase 
Follow-up Phase 
Study Dayb 
 
Day 1 
Day 2 
Day 3 
 (ECR 48-
72 hr after 
first dose) 
Day 7 
Day 10c 
EOTd 
PTEe 
Final  
Follow-upf 
Day 30-37 
Culture of infection site & Gram stain 
X 
As Clinically Indicated 
Xv 
Xv 
 
Adverse Eventsw 
X 
X-------------------------------------------------------------------------------------------------X 
Review of Inclusion and Exclusion 
Criteria/Randomization (if Eligible) 
X 
 
 
 
 
 
 
 
Test Article Administration and Accountabilityx 
 
Xy 
Xz 
Xaa 
X 
X 
 
 
 
Plasma samples (in heparin) for PK analysesbb 
 
 
X 
X 
 
 
 
 
 
Assessment of need to continue therapycc 
 
 
 
X 
X 
 
 
 
Investigator’s Assessment of Clinical Response 
 
 
 
 
 
X 
X 
 
ABSSSI = Acute Bacterial Skin and Skin Structure infection; AE = adverse event; β-hCG = beta – human Chorionic Gonadotropin; ECG = electrocardiogram; 
ECR = Early Clinical Response; eCRF = electronic case report form; EOT = end of treatment; ICF = informed consent form; PK = pharmacokinetics; PTE = post 
therapy evaluation; SAE = serious adverse event. 
a 
Following the signing of an ICF, all Screening evaluations, with the exception of the blood culture sample collection, should be completed within the 
24 hours prior to randomization. The blood culture sample collection should be completed within 24 hours prior to the first dose of test article. 
b 
Day 1 is the first day of test article administration.  Subsequent study days are consecutive calendar days. 
c 
A Day 10 visit should be conducted for subjects with treatment extending beyond 9 days, unless this visit coincides with the EOT visit. 
d 
To be conducted on the calendar day of, or within 2 days following the last dose of test article.  Should also be conducted for any subject who withdraws 
prematurely or terminates participation in the study before completion. 
e 
To be conducted 7 to 14 days after the subject’s last day of study therapy.   
f 
To be conducted 30 to 37 days after the first dose of test article.  The Final Follow-up assessment may be conducted via telephone contact or by another 
interactive technology for subjects who were considered to be Clinical Successes and had no AEs or clinically significant laboratory or ECG abnormalities 
noted at or after the PTE visit.  Otherwise, the visit must be conducted in person.   
g 
Written and signed ICF must be obtained before any assessment is performed. 
h 
Treatments that have been administered within the 7 days prior to the date of signing the ICF or during the Screening phase will be recorded in the eCRF.  
All medications and significant non-drug therapies (including physical therapy and blood transfusions) administered after the first dose of test article must be 
recorded in the eCRF. 
i 
Semi-quantitative description of infection features. Must be assessed within 48 to 72 hours after the first dose.  
j 
Measurement of the subject’s lesion by ruler length × width.  The Screening measurement must be collected within 4 hours prior to randomization. A lesion 
measurement must be completed within 48 to 72 hours after the first dose.  
k 
Diagnosis of the type of ABSSSI (wound infection, cellulitis/erysipelas or major abscess) and anatomical location.  A digital photograph of the infection site 
will be taken at Screening only. 
l 
A full physical examination will be completed at Screening; thereafter only changes from Screening measurements should be recorded as AEs in the eCRFs. 


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m 
Blood pressure and pulse rate should be measured within 30 min before, and approximately (± 15 minutes) 1 hour after and 3 hours after the completion of the 
first dose on Day 1. 
n 
Blood pressure and pulse rate should be measured within 30 min before, and approximately (± 15 minutes) 1 hour after and 3 hours after the completion of the 
odd numbered doses on Days 2 and 3. In the event that the subject takes the dose before arriving for the office visit, the site should collect the 1 and 3 hour post 
dose measurements if possible, if not then a single measurement should be made at any time during the visit and the date and time recorded.  
o 
A 12-lead ECG should be performed at screening, at the EOT visit, and as otherwise clinically indicated. 
p 
A urine dipstick test will be performed locally at Screening. 
q 
All women will have a local urine or serum pregnancy test at Screening. 
r 
All women will have blood collected for a serum β-hCG pregnancy test at the Central Laboratory at the Screening, EOT and PTE visits.   
s 
Blood will be collected for hematology (includes coagulation) and serum chemistry testing at the Central Laboratory at Screening and at the Day 3, Day 7, 
Day 10, EOT and PTE visits. 
t 
At the Screening visit, blood will be collected for local laboratory hematology and serum chemistry evaluations required for assessing subject eligibility. 
u 
If bacteria are isolated from blood cultures, repeat blood cultures should be collected. If subsequent blood cultures are also positive, repeat the blood cultures 
as necessary until negative blood cultures are obtained. 
v 
At the EOT and/or PTE visit, blood cultures and infection site specimen cultures and Gram stains should be obtained only for subjects who are clinical 
failures and require alternative antibacterial treatment for the infection under study. 
w 
A subject’s AEs and SAEs will be recorded and reported from signing of the ICF to the Final Follow-up assessment. 
x 
A 6 hour fast is required before and a 2 hour fast is required following  all odd numbered doses. The total duration of test article therapy for all subjects will be 
7 to 14 days.  Test article may be dispensed and reconciled by blinded personnel. Subjects will be asked to return all unused test article and packaging at each 
visit.  At the EOT visit subjects will return the test article packaging and site staff will perform accountability. 
y 
Subjects should receive their first dose of test article at the site within 4 hours after randomization.  
z 
Subjects should be instructed not to take the odd numbered dose on Day 2 until they return to the site for the Day 2 visit. 
aa 
Subjects should be instructed not to take the odd numbered dose on Day 3 until they return to  the site for the Day 3 visit.  
bb 
At selected sites, subjects who have agreed to participate in PK evaluation and have signed a separate PK evaluation consent form will have up to 4 blood 
samples collected between Days 2 and 3. The PK sample collection schedule for the individual subject will be provided by the Sponsor.  
cc 
At the investigator’s discretion, all therapy may be discontinued after the 7th day of treatment, when the infection is considered clinically cured (based on 
normalization of the clinical signs and symptoms of infection and the investigator’s clinical assessment that continued systemic antibacterial therapy is no 
longer needed).


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INTRODUCTION 
9
9.1 
Background 
The investigational product – omadacycline (formerly named PTK 0796) – is the first member of 
the aminomethylcycline class of antibiotics, which are semi synthetic derivatives of the 
tetracycline class.  As a class, the tetracyclines have been in use for approximately 70 years. 
They are well-tolerated, and have proven effective in the treatment of a variety of bacterial 
infections. Omadacycline is being developed for clinical use by both intravenous (iv) and 
per oral (po) administration. The targeted indications encompass community-acquired bacterial 
pneumonia (CABP), acute bacterial skin and skin structure infections (ABSSSI), and urinary 
tract infection (UTI). 
When first approved, the tetracyclines were an important component of the antibiotic 
armamentarium.  Their clinical use declined in subsequent years, due to the increasing 
prevalence of tetracycline resistance and the availability of effective alternative therapies.  
Over the past decade, Gram-positive bacteria with multi-drug resistance to a diverse range of 
antibiotics have emerged as a major treatment challenge.  Two developments raise the specter 
that currently available antibiotics may become even less useful for treatment of infections 
caused by Gram-positive organisms.  The first is the emergence of vancomycin resistance in 
Enterococcus species (spp.) and the subsequent transfer of those resistance elements to 
Staphylococcus aureus.  Although vancomycin-resistant Staphylococcus aureus have not become 
epidemiologically significant, their very existence raises concern because vancomycin has been 
the agent of choice for infections caused by resistant Gram-positive pathogens.  
The second important development is the appearance of community-acquired methicillin-
resistant Staphylococcus aureus (MRSA).1  These strains are increasingly becoming multi-drug 
resistant over time.  In many areas of the world, MRSA infections represent the majority of 
sporadic staphylococcal infections with community-onset.  These strains also have been 
associated with numerous outbreaks of localized (skin and skin structure) and invasive 
(bacteremic) infections. 
Omadacycline is very active in vitro against most Gram-positive pathogens.  It also exhibits 
activity against atypical pathogens (eg, Legionella spp.), and some anaerobic and Gram-negative 
pathogens.  The drug is active against strains expressing both mechanisms of tetracycline 
resistance as well as strains that are resistant to currently available antibiotics, including 
methicillin, vancomycin, erythromycin, and ciprofloxacin.2 
Omadacycline has been developed for both iv and po administration and to date over 
700 subjects have received one or both formulations in clinical studies.  Across the completed 
Phase 1 studies, more than 500 subjects were exposed to omadacycline. 
Single iv doses up to 600 mg and single po doses up to 600 mg have been investigated.  Multiple 
iv doses of 100 mg once daily and 200 mg once daily for up to 14 and 7 consecutive days, 
respectively, have been investigated.  Multiple po doses of 200 mg once daily and 300 mg once 
daily for up to 10 consecutive days have also been investigated.  In a Phase 2 study, 219 subjects 


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with complicated skin and skin structure infections (cSSSI) were treated with omadacycline 
(n = 111) or linezolid (n = 108); treatment was initiated with iv administration, with switch to po 
therapy at the discretion of the investigator.  In this study the total duration of study treatment 
was a mean of 10 and maximum of 20 days.  In a sponsor terminated Phase 3 study of similar 
design, 140 subjects with cSSSI were treated with omadacycline (n = 68) or linezolid (n = 72) 
for a mean of 10 and maximum of 20 days for omadacycline and 22 days for linezolid. 
In Phase 1 studies of iv administration, modest and reversible alanine aminotransferase (ALT) 
increases were seen, most notably with iv doses of 300 mg or greater.  Transient increases in 
heart rate (HR) were observed following administration of single and multiple doses of 
omadacycline, with a dose dependent mean increase of up to 15 to 20 beats per minute (bpm) 
compared to placebo.  The increases in HR were rarely reported as adverse events (AEs) and not 
associated with any other cardiac findings.  These increases were most evident within the 6 hours 
post-infusion.  Following po administration, an increased incidence of gastrointestinal (GI) AEs, 
particularly nausea, was noted in early studies, which were most notable at po doses of 400 mg 
or greater.  Of note, different po formulations evaluated in early studies (eg, capsule versus 
tablet) may have influenced the GI safety profile.  In Phase 1 studies there were no 
discontinuations due to drug-related AEs in any subject who received multiple doses of 
omadacycline. 
In the Phase 2 cSSSI study, the most frequently reported AEs were GI related occurring in 19% 
of omadacycline treated and 17% of linezolid-treated subjects.  Nausea and vomiting were 
reported in 10% and 5%, respectively, of omadacycline- treated subjects primarily during po 
treatment, compared to 7 and 4%, respectively, of linezolid-treated subjects. Premature 
discontinuation of treatment due to an AE was very infrequent, occurring in 0.9% of 
omadacycline subjects and 1.9% of linezolid subjects.  There was no pattern of adverse changes 
in laboratory safety parameters among subjects treated with omadacycline or linezolid.  In 
particular, there was no clinical or statistical difference between the treatment groups in ALT 
values or in other liver enzymes. 
An increase in mean HR was observed, but to a lesser extent than what was observed in Phase 
1 studies.  This effect was transient and no QT prolongation was observed, consistent with the 
negative findings from testing of omadacycline in a dedicated corrected QT interval (QTc) study.  
Three subjects treated with omadacycline had AEs of tachycardia; 1 other subject reported 
palpitations.  All 4 of these AEs were mild in intensity, all were assessed as either unrelated or 
unlikely related to test article, and none resulted in discontinuation of study treatment. 
In the sponsor-terminated Phase 3 cSSSI study, 140 subjects were treated prior to the sponsor’s 
decision to discontinue the study (due to changing regulations regarding the endpoints).  The 
overall incidence of reported AEs in this study was comparable between the 2 treatment groups.  
The most commonly reported AEs (greater than or equal to 10% frequency in either treatment 
group) were nausea (27% omadacycline, 26% linezolid), headache (24% omadacycline, 7% 
linezolid), vomiting (9% omadacycline, 15% linezolid), diarrhea (4% omadacycline, 18% 
linezolid), and dizziness (10% omadacycline, 8% linezolid).  Creatine phosphokinase (CK) 
elevation was reported in 9% of omadacycline treated subjects compared to 3% for linezolid.  
Alanine Aminotransferase increases were reported as AEs in 1 omadacycline subject (2%) 


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compared to 4 linezolid treated subjects (6%).  Rash was reported by 1 omadacycline subject 
(2%) and 6 linezolid subjects (8%).  Serious adverse events (SAEs) were experienced by 3 
omadacycline subjects (small bowel obstruction, large left pleural effusion, and worsening 
depression) and 1 linezolid subject (worsening right hand cellulitis). 
In a completed Phase 3 study comparing omadacycline and linezolid for the treatment of adults 
with ABSSSI (PTK0796-ABSI-1108), subjects started therapy with omadacycline 100 mg iv 
every 12 hours (q12h) for 2 doses then 100 mg iv every 24 hours (q24h), or linezolid 600 mg iv 
q12h.  Subjects could be switched to oral therapy (omadacycline 300 mg q24h or linezolid 600 
mg q12h) after a minimum of 3 days of iv therapy; the total treatment duration was 7-14 days.  
Study results showed that omadacycline was non-inferior to linezolid.  In the modified intent-to-
treat population (mITT, total N=627) for omadacycline versus linezolid, respectively, clinical 
success based on a reduction of lesion size at 48-72 hours after the first dose was 84.8% versus 
85.5% (95% confidence interval [CI]: -6.3, 4.9); clinical success based on investigator’s 
assessment of clinical response at 7-14 days after the last dose was 86.1% versus 83.6% (CI: -
3.2, 8.2).  Omadacycline was well tolerated: treatment-emergent adverse events (TEAEs) were 
reported in 48.3% versus 45.7%; serious TEAEs in 3.4% versus 2.5% and discontinuation due to 
TEAE in 1.9% versus 2.2% of omadacycline and linezolid treated subjects, respectively.  
In addition, a global Phase 3 study is currently being conducted to evaluate the safety and 
efficacy of iv and po omadacycline compared to iv and po moxifloxacin in the treatment of adult 
subjects with community-acquired bacterial pneumonia (PTK0796-CABP-1200). 
Please refer to the current version of the omadacycline Investigator's Brochure for additional 
information.2 
Omadacycline has demonstrated activity against the most common ABSSSI pathogens, including 
isolates resistant to standards of care.  This study is intended to evaluate the safety and efficacy 
of po omadacycline as compared to po linezolid in the treatment of adult subjects with ABSSSI. 
 STUDY OBJECTIVES 
10
10.1 Primary Objectives 
To demonstrate that omadacycline administered orally for 7 to 14 days is non-inferior to 
linezolid administered orally for 7 to 14 days in the treatment of adult subjects with ABSSSI 
known or suspected to be due to Gram-positive pathogens.  
10.2 Secondary Objectives 
• To evaluate the safety of omadacycline in the treatment of adult subjects with ABSSSI. 
• To evaluate the Clinical Response according to the identified causative pathogen. 
• To evaluate the pharmacokinetics (PK) of omadacycline in adult subjects with ABSSSI. 
 


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 STUDY DESIGN 
11
11.1 Description 
This is a randomized (1:1), double-blind, double-dummy, active comparator-controlled, Phase 3 
study comparing omadacycline and linezolid for the treatment of adult subjects with ABSSSI 
that is known or suspected to be due to a Gram-positive pathogen(s).  Enrollment of subjects 
with major abscess may be up to 30% of randomized subjects.  Enrollment of subjects who have 
received a single dose of an allowed short-acting antibiotic (see Appendix 1) within the 72 hours 
prior to randomization will be limited to no more than 25% of randomized subjects.  Subject 
randomization will be stratified across treatment groups by type of infection (wound infection, 
cellulitis/erysipelas or major abscess) and receipt of an allowed antibacterial therapy (see 
Appendix 1) in the 72 hours prior to randomization, as defined in the Interactive Voice Response 
System/Interactive Web Response System (IxRS) specifications and statistical analysis plan 
(SAP) (see Section 25.1).   
The study will consist of 3 protocol-defined phases:  Screening, Double-Blind Treatment and 
Follow-up.  All Screening evaluations, with the exception of the blood culture, should be 
completed within the 24 hours prior to randomization.  The blood culture should be completed 
within the 24 hours prior to the first dose of test article.  Subjects who meet inclusion criteria, 
and do not meet exclusion criteria will be randomly assigned to a treatment group, and should 
receive their first dose of test article at the site within 4 hours after randomization. 
11.2 Rationale of Study Design 
The study was designed in accordance with the United States (US) Food and Drug 
Administration (FDA)3 and European Medicines Agency (EMA)4,5 guidance on developing 
antimicrobial drugs for the treatment of ABSSSI, in addition to the guidelines of the Infectious 
Diseases Society of America (IDSA)6 and 2012 Update from the Biomarkers Consortium of the 
Foundation for the National Institutes of Health.7 
11.3 Rationale for Choice of Comparator 
The comparator drug, linezolid, is approved world-wide for the treatment of ABSSSI caused by 
Gram-positive pathogens and has an acceptable and well-defined safety profile.  Linezolid can be 
administered orally and has regulatory approval for the treatment of ABSSSI caused by 
Gram-positive pathogens including MRSA. 
11.4 Approximate Duration of Subject Participation   
Subjects will participate in the study for approximately 30 days.  Following Screening, eligible 
subjects will be randomly assigned to receive 7 to 14 days of po treatment with either 
omadacycline or linezolid.  A follow-up office visit will occur approximately 7 to 14 days after 
the last dose of test article, and a follow-up telephone contact will occur approximately 30 to 
37 days after the first dose of test article.  


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11.5 Approximate Duration of Study 
This study is expected to be clinically complete in approximately 12 months.  
11.6 Approximate Number of Subjects 
Approximately 704 subjects will participate in this study at approximately 50 sites.    
 SELECTION OF SUBJECTS 
12
Each subject must participate in the informed consent process and sign and date an institutional 
review board (IRB)/independent ethics committee (IEC)/research ethics board (REB) approved 
informed consent form (ICF) before any procedures specified in this protocol are performed. 
12.1 Inclusion Criteria 
To be eligible for randomization in this study, a subject must fulfill ALL of the following 
criteria:   
1. Written and signed informed consent must be obtained before any assessment is performed.   
2. Male or Female, age 18 years or older. 
3. Has a qualifying skin and skin structure infection.  All qualifying lesions must be greater than 
or equal to 75 cm2 in total surface area of contiguous involved tissue, calculated as the 
product of the maximum length (head-to-toe) multiplied by the maximum width (measured 
perpendicular to length) as measured by the investigator using a wound ruler.  Involved 
tissue is defined as tissue exhibiting clear evidence of one or more of the following:  
erythema, edema or induration.  
The classification of qualifying infections is shown below. 
• Wound infection – an infection characterized by purulent drainage from a wound with 
surrounding erythema, edema, and/or induration extending at least 5 cm in the 
shortest distance from the peripheral margin of the wound.  
• Cellulitis/erysipelas – a diffuse skin infection characterized by spreading areas of 
erythema, edema, and/or induration.  
• Major abscess – an infection characterized by a collection of pus within the dermis or 
deeper with surrounding erythema, edema, and/or induration extending at least 5 cm 
in the shortest distance from the peripheral margin of the abscess.  
4. Has evidence of a systemic inflammatory response within the 24 hours prior to 
randomization, as indicated by ONE of the following:   
• Elevated white blood cell (WBC) count (greater than or equal to 10,000 cells/mm3) or 
leukopenia (less than or equal to 4,000 cells/mm3) 
• Elevated immature neutrophils (greater than or equal to 15% band forms, see % bands 
calculation in Appendix 2) regardless of total peripheral WBC count 
• Lymphatic involvement:  lymphangitis or lymphadenopathy that is proximal to and in 
a location that suggests drainage from the qualifying infection 


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• Fever or hypothermia documented by the investigator (temperature greater 
than 38.0°C [100.4°F] or less than 36.0°C [95.5°F]) 
5. Females must have a negative pregnancy test at Screening and agree to comply with using an 
acceptable method of birth control (eg, abstinence, oral contraceptive, intrauterine device 
[IUD], barrier contraception [condom], tubal ligation, hysterectomy, bilateral oophorectomy, 
postmenopausal or vasectomized partner) from Screening through Post Therapy Evaluation 
(PTE).  Males must agree to use an acceptable method of birth control with female partner(s) 
and must not donate sperm from Screening through PTE. 
 
12.2 Exclusion Criteria 
Subjects fulfilling any of the following criteria are not eligible for inclusion in this study: 
1. Has received 1 or more doses of a potentially effective systemic antibacterial treatment 
within the 72 hour period prior to randomization (a subject will be considered to have 
received a potentially effective systemic antibacterial treatment if the pathogen identified as 
causing the infection is shown to be susceptible to the antibacterial treatment given or, in the 
circumstance where a pathogen is not identified, if the antibacterial agent is approved for 
treatment of skin infections or is known to have activity against any of the leading 
Gram-positive causes of ABSSSI [eg, Staphylococcus aureus, Streptococcus species [spp.] , 
Enterococcus spp.]). EXCEPTION: Subjects may be eligible despite prior antibacterial 
therapy if they have been treated with a single dose of a short-acting, non-oxazolidinone 
antibacterial (ie, an antibacterial whose standard dosing regimen is more frequent than once 
per day, see list in Appendix 1). 
2. Has, for any reason, used a topical antibacterial agent(s) with specific antibacterial activity 
(eg, mupirocin, retapamulin, fusidic acid) continuously within the 72 hour period prior to 
randomization, if applied to the skin for greater than or equal to 72 hours.   
3. Infections where the outcome is strongly influenced by factors other than protocol-defined 
treatment and procedures, that require antibacterial treatment for greater than 14 days, are 
associated with chronic skin lesions that may obscure determination of response even after 
successful bacterial eradication has been achieved, or are suspected or known to be caused by 
a pathogen resistant to either test article, eg: 
• Chronic (persistently present greater than 3 months) lesions, ulcers or wounds 
(eg, cellulitis contiguous with a diabetic foot ulcer) 
• association with chronic dermatitis or any other chronic inflammatory skin lesion 
(eg, psoriasis, eczema) 
• burns 
• peri-rectal abscess (eg, buttock or perineal lesion likely to communicate with the 
rectum) or perineal infection 
• infected decubitus (pressure) ulcers 
• necrotizing fasciitis (infections with rapidly progressive destruction of tissue at or 
below the fascia) 
• life-threatening infections, ie, require emergency surgery for the treatment 
(eg, progressive gangrene) 


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• infections in an area requiring surgery that in and of itself would cure the infection or 
remove the infected site (eg, amputation for vascular insufficiency) 
• infections associated with severe vascular insufficiency (eg, peripheral vascular 
disease) or acute occlusion expected to require immediate revascularization 
• infections associated with acute compartment syndrome expected to require extensive 
surgery to provide decompression 
• infections accompanied by confirmed or suspected contiguous bone or joint infection 
(eg, osteomyelitis, septic arthritis, bursitis) 
• bacteremic infections associated with an intravascular foreign body 
• infections accompanied by another confirmed or suspected infection requiring 
systemic antibiotic therapy (eg, endocarditis, other endovascular infection, 
meningitis, visceral abscess, intra-abdominal infection, pneumonia, urinary tract 
infection) 
• human or animal bites (infections associated with insect bites are NOT excluded) 
• myonecrosis 
• complicated by an immune deficiency in the subject (eg, ecthyma gangrenosum in a 
neutropenic subject) 
• infections associated with the presence of a foreign body (eg, wood, metal, plastic, 
etc.) if the foreign body cannot be removed within 24 hours of first dose of test article 
4. Inability to tolerate oral medication (eg, nausea, vomiting, diarrhea or any other condition 
that might impair ingestion or absorption of oral medication). 
5. Has known or is clinically suspected for 1 or more of the following prior to randomization: 
• Alanine Aminotransferase (ALT) or Aspartate aminotransferase (AST) greater than 
or equal to 3 times the Upper Limit of Normal (ULN),  
• total bilirubin greater than 1.5 times the ULN, or  
• evidence of end-stage liver disease (eg, ascites, hepatic encephalopathy) 
6. Has a known history of having experienced unstable cardiac disease (eg, unstable angina, 
myocardial infarction, acute congestive heart failure, unstable cardiac arrhythmia, etc.) 
within the 3 months prior to Screening. 
7. Requires any form of dialysis (eg, hemodialysis, peritoneal dialysis). 
8. History or evidence of severe renal disease or has a calculated creatinine clearance (CrCL) 
of less than 30 mL/min, using the Cockcroft-Gault equation (see equation in Appendix 2). 
9. Evidence of significant immunological disease determined by any of the following: 
• Current or anticipated neutropenia defined as less than 500 neutrophils/mm3 
• Known infection with Human Immunodeficiency Virus (HIV) and a cluster of 
differentiation 4 (CD4) count that is unknown or documented to be less 
than 200 cells/mm3 within the last year, or an Acquired Immune Deficiency 
Syndrome (AIDS)-defining illness 
10. The receipt of cancer chemotherapy, radiotherapy, or potent, non-corticosteroid 
immunosuppressant drugs (eg, cyclosporine, azathioprine, tacrolimus, immune-modulating 
monoclonal antibody therapy, etc.) within the 3 months prior to Screening, or the receipt of 
systemic corticosteroids for more than 14 days in the 30 days prior to Screening. 


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11. Requires acute pharmacologic intervention to stabilize blood pressure (BP) and/or adequate 
tissue perfusion, OR has evidence of septic shock, defined by ALL of the following:   
• Fever or hypothermia documented by the investigator (temperature greater 
than 38.0°C [100.4°F] or less than 36.0°C [95.5°F])  
• Heart rate greater than 90 bpm  
• Respiratory rate greater than 20 breaths/min  
• WBC greater than 12,000 cells/mm3 or less than 4,000 cells/mm3 or greater than 10% 
immature (band) forms, see % bands calculation in Appendix 2, regardless of the total 
peripheral WBC count 
• Hypotension with systolic blood pressure (SBP) less than 90 mm Hg despite an iv 
fluid challenge of 20 to 30 cc/kg over a 30 minute period  
• Perfusion abnormalities that may include, but are not limited to, lactic acidosis (blood 
lactate concentration greater than or equal to 4 mmol/L), oliguria, or acute alteration 
in mental status 
12. Pregnant or nursing (breastfeeding) women. 
13. Has a history of hypersensitivity or allergic reaction (eg, anaphylaxis, urticaria, other 
significant reaction) to any tetracycline (eg, minocycline, doxycycline or tigecycline) or to 
any oxazolidinone (eg, linezolid, tedizolid). 
14. Has a history of pseudotumor cerebri, or prior (within 2 weeks prior to Screening) or planned 
concomitant use of isotretinoin. 
15. Has a history of systemic lupus erythematosus or lupus-like syndrome. 
16. Has current evidence of pancreatitis. 
17. Has received a monoamine oxidase (MAO) inhibitor within 14 days prior to Screening (eg, 
phenelzine, isocarboxazid, selegiline, moclobemide; which are typically used to treat 
depression or Parkinson's Disease). 
18. Use of other investigational drugs within 5 half-lives or within 30 days prior to Screening. 
19. Has previously been treated with omadacycline or previously enrolled in this study. 
20. Any planned medical intervention that might interfere with the ability to comply with the 
study requirements. 
21. Has any concomitant condition that, in the opinion of the investigator, is likely to interfere 
with evaluation of the response of the infection under study, determination of AEs, or 
completion of the expected course of treatment. 
 
12.3 Screen Failures 
Subjects who sign the ICF but withdraw or are withdrawn from the study before random 
assignment to double-blind treatment are defined as screen failures.  All screen failures should be 
recorded on the subject master list.  Limited information including reason for screen failure will 
be recorded on the electronic case report form (eCRF) or (IxRS) system for screen failures. 
 PRIOR AND CONCOMITANT TREATMENT 
13
Treatments that have been administered within the 7 days prior to the date of informed consent, 
or during the Screening phase, will be recorded in the eCRF.  The investigator is to instruct the 


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subject to notify the study site about any new medications he/she takes after the start of the test 
article.  All medications and significant non-drug therapies (including physical therapy and blood 
transfusions) administered after the subject starts treatment with test article must be listed in the 
eCRF (see Section 8).  In addition, for antibacterial agents, the dose, unit, frequency and route 
must be entered in the eCRF.  
13.1 Prohibited Treatment 
• Use of all non-study investigational medications or devices is prohibited during the 30 days 
prior to Screening through PTE.   
• Systemic antibacterial agents potentially effective for ABSSSI are prohibited for 72 hours 
prior to randomization through PTE, except as rescue therapy in cases of clinical failure.  A 
single dose of a short-acting potentially effective systemic antibacterial agent (see list in 
Appendix 1) administered within the 72 hours prior to randomization will be allowed for up 
to 25% of randomized subjects. 
• Any topical antibacterial agent applied to the infection site with a spectrum that is active 
against the known or potential infecting pathogen(s) responsible for the infection under study 
within the 72 hours prior to randomization through PTE. 
• MAO inhibitors.  Linezolid is a reversible non-selective inhibitor of MAO.  Therefore, 
subjects should not be enrolled who are either taking MAO inhibitors (eg, phenelzine, 
isocarboxazid), or have taken MAO inhibitors within 14 days prior to Screening.  MAO 
inhibitors are prohibited from 14 days prior to Screening through the Final Follow-up 
assessment. 
• Subjects will be instructed to avoid taking antacids and multivitamins containing multivalent 
cations (eg, aluminum, magnesium, calcium, bismuth, iron, or zinc) for 6 hours before and 
4 hours after all odd numbered doses. 
 
All other medications not prohibited by the protocol and considered necessary for the subject’s 
welfare may be administered and/or continued under the supervision of the investigator. 
 
Concomitant Medications That May Interact With Linezolid  
13.1.1
Adverse interactions between linezolid and serotonergic psychiatric medications, 
sympathomimetics, vasopressors, dopaminergic agents and dextromethorphan have been 
reported.  Subjects who receive any of these classes of drugs concurrent with test article must be 
monitored closely for elevated blood pressure and other manifestations of serotonin syndrome 
which could include mental changes (eg, confusion, hyperactivity, memory problems), muscle 
twitching, excessive sweating, shivering or shaking, diarrhea, trouble with coordination, and/or 
fever. 
All subjects will be instructed to avoid eating foods high in tyramine content while taking test 
article as recommended in the linezolid prescribing information. 
The full prescribing information for linezolid will be provided to the investigator under separate 
cover.  


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13.2 Permitted Treatments 
All other treatments not specified as prohibited are permitted during the study.  A single dose of 
a short-acting potentially effective systemic antibacterial agent (see list in Appendix 1) 
administered within the 72 hours prior to randomization will be allowed for up to 25% of 
randomized subjects.  Subjects requiring additional or alternative antibacterial therapy for the 
ABSSSI will be judged as Clinical Failures and test article will be discontinued.  Further 
treatment for their infection is at the discretion of the investigator or the subject’s health care 
provider and will be considered as a concomitant medication. 
Subjects should be encouraged to contact site personnel before starting any new treatment. 
For all treatments received by the subject during the study, relevant information must be 
recorded on the subject’s eCRF. 
 
Dressings 
13.2.1
Wounds may be covered with any sterile non-adherent type dressing (not containing any specific 
antibacterial agents) chosen by the investigator.  
 
Topical Solutions 
13.2.2
Topical solutions with nonspecific activity such as povidone iodine can be used during dressing 
changes and as part of local care to lesions.  However, solutions containing specific antibacterial 
agents (eg, mupirocin, retapamulin, fusidic acid) should not be used as part of the regimen 
involved in local infection site care. 
 
Surgical Procedures 
13.2.3
Adjunct surgical treatment is appropriate and necessary in many ABSSSIs.  At Screening, all 
subjects should be carefully evaluated and a determination should be made as to whether 1 or 
more procedures are indicated.  When indicated, planned procedures should be performed within 
24 hours and no later than 48 hours after start of test article.  The date and time of all planned or 
unplanned surgical procedures will be recorded.  
 PROCEDURES 
14
Written, signed, and dated informed consent will be obtained before any study-related 
procedures have been performed.  Upon signing the informed consent, the subject should then be 
assigned a study subject number.  AEs must be recorded from the time the ICF is signed.  
Subjects who have been pre-screened on the telephone but who do not sign an ICF will not be 
assigned a subject number.  The investigator will maintain a subject master list to document 
every subject who has signed an ICF.  A copy of this list should be retained in the investigator’s 
study files. 


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14.1 Visit Schedule and Assessments 
Refer to Section 8, for the study procedures and their time points. There are 3 protocol-defined 
phases of the study: Screening, Double-Blind Treatment, and Follow-up.  The study will have 
the following protocol-defined evaluations: 
• Day 1 visit 
• Day 2 visit 
• Day 3 visit (Early Clinical Response [ECR] must be conducted between 48 to 72 hours after 
the first dose of test article) 
• Day 7 visit  
• Day 10 visit (A Day 10 visit should be conducted for subjects with treatment extending 
beyond 9 days, unless this visit coincides with the End of Treatment visit) 
• End of Treatment (EOT):  to be conducted on the calendar day of, or within 2 days following 
the last dose of any test article.  If a subject withdraws prematurely or terminates 
participation in the study before completion, the EOT visit should be conducted 
• Post Therapy Evaluation (PTE):  to be performed 7 to 14 days after the subject’s last day of 
study therapy 
• Final Follow-up assessment:  Day 30 to 37 (after the first dose of test article) 
 
Subjects who discontinue study treatment prematurely should have the EOT visit and the 
procedures listed in Section 8, a PTE visit and a Final Follow-up assessment, if possible.  The 
site should also collect subject safety information through the Final Follow-up assessment. 
14.2 Screening Phase  
Due to the nature of the disease under study, the Screening phase should be completed within 
1 day (24 hour period).  The Screening phase will be used to establish subject eligibility and 
Baseline characteristics for each subject.  Subjects are eligible for Screening if they present with 
ABSSSI signs and symptoms.  Following the signing of an ICF, site personnel will collect the 
following information: 
• Demographics 
• Medical/surgical history and current medical conditions 
• Physical examination 
• Vital signs 
• Review of inclusion/exclusion criteria 
• Laboratory tests:  hematology, chemistry, urine tests, pregnancy test (for women only) 
• 12-lead electrocardiogram (ECG) 
• Concomitant medications (past 7 days) 
• AEs since the signing of the ICF 


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• Diagnosis of ABSSSI (cellulitis/erysipelas, wound infection, or major abscess), clinical 
assessment of the site of infection, and photograph of the infection site.  
• Assessment of lesion size 
• Numerical Rating Scale for pain at the primary infection site 
• SF-36v2® Health Survey 
• Microbiological assessments (blood culture, culture of the infection site, and Gram stains) 
 
Subject Demographics/Other Baseline Characteristics 
14.2.1
Subject demographic and Baseline characteristic data to be collected on all subjects include:  
date of birth, gender, race/ethnicity and childbearing potential.  Medical history/current medical 
condition data includes data until the signing of informed consent.  Whenever possible, 
diagnoses are to be recorded.  
The investigator will perform a comprehensive history and physical examination at the Screening 
evaluation with particular attention to items indicated below. 
14.2.1.1 
Medical History Relating to the Infection Under Study 
• Predisposing factors at the site of infection, eg, surgery, mechanical trauma, edema (acute or 
chronic), vascular insufficiency, prior infection, iv drug abuse 
• All systemic antimicrobials and topical treatments (prescription, over-the-counter) from onset 
of the infection will be recorded under concomitant medications 
• Procedures (eg, debridement, incision and drainage) performed within the week (7 days) 
prior to Screening, including surgical (operating room, procedure room) procedures, 
interventional radiology procedures and bedside procedures, but excluding routine wound 
care such as dressing changes will be collected 
• Surgical procedure history for surgical wound infections (within 30 days prior to Screening) 
 
Physical Examination 
14.2.2
At Screening, the physical examination will include the examination of general appearance, skin, 
neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, 
extremities, vascular and neurological.  If indicated based on medical history and/or symptoms, 
rectal, external genitalia, breast, and pelvic exams may be performed.  Height and body weight 
will be measured.   
Information for all physical examinations must be included in the source documentation at the 
study site.  Significant findings that are present prior to the start of test article must be included 
in the subject’s eCRF.   
 
Diagnosis of ABSSSI and Clinical Assessment of the Site of Infection 
14.2.3
At the Screening evaluation, the type of ABSSSI will be recorded:  wound infection, 
cellulitis/erysipelas or major abscess as defined in the inclusion criteria (see Section 12.1).  To 


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qualify, there must be greater than or equal to 75 cm2 in total surface area of contiguous involved 
tissue (ie, surrounding erythema, edema and/or induration).  
The anatomical location of the primary site of infection should be recorded.  For subjects with 
multiple non-contiguous areas of infection, the investigator will identify the most severely 
affected portion at Screening and designate that as the primary lesion site.  The investigator 
should note the presence and nature of any foreign body (eg, wood, metal, plastic, etc.) present at 
the site of infection.  Note that if the foreign body cannot be removed within 24 hours of 
initiation of test article the subject should not be enrolled in the study (see Exclusion criteria, 
Section 12.2).  
The investigator will examine the primary site of infection and record the following information 
on source documents and the eCRFs: 
• Presence of lymphadenopathy proximal to primary lesion site  
• Presence of lymphangitis proximal to primary lesion site  
• Presence of drainage from the primary lesion site and description (serous/serosanguineous, 
seropurulent, or purulent) 
Semi-quantitative (none, mild, moderate, severe) description of infection for the following 
features: 
• Tenderness 
• Edema 
• Erythema 
• Induration 
At the Screening evaluation the site of infection will be photographed using a digital camera 
provided by the sponsor; the subject number and date will be included in the field.  Instructions 
for lesion photographs will be provided to the investigator. 
 
Assessment of Lesion Size 
14.2.4
The Screening evaluation measurement of lesion size must be collected within 4 hours prior to 
randomization.  Surface area of lesions will be calculated by multiplying the head-to-toe 
maximum length of the total lesion and maximum width (perpendicular to maximum length) 
inclusive of contiguous involvement (erythema, edema and/or induration).  Investigator ruler 
measurements will be used to document the lesion size.  Instructions for ruler measurements will 
be provided to the investigator.  
 
Subject Reported Outcomes 
14.2.5
14.2.5.1 
Numerical Rating Scale for Pain 
At the Screening, Day 3 (ECR), EOT and PTE visits the subject will complete a numerical rating 
scale for pain8 at the primary ABSSSI lesion site. The numerical rating scale anchors will range 


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from 0 to 10, where 0 represents “No pain” and 10 represents “Pain as bad as you can imagine.” 
The subject will be asked to rate their pain at the primary site of infection under study: “Please 
rate your pain by circling the number that best describes the average pain caused by your primary 
skin infection over the last 24 hours, where 0 represents no pain and 10 represents pain as bad as 
you can imagine.”  
14.2.5.2 
SF-36v2® Health Survey 
At the Screening and PTE visits the subject will complete a SF-36v2® Health Survey (Medical 
Outcomes Trust, OptumTM). The SF-36v2® Health Survey asks 36 questions to measure 
functional health and well-being from the subject's point of view. It is a practical, reliable and 
valid measure of physical and mental health that can be completed in five to ten minutes. It is 
referred to as a generic health survey because it can be used across age (18 and older), disease, 
and treatment group, as opposed to a disease-specific health survey, which focuses on a 
particular condition or disease. 
 
Urine Tests 
14.2.6
A urine dipstick will be performed locally at Screening.  Urine dipstick results will be recorded 
on the eCRF.  A local urine (or serum) pregnancy test will be performed during Screening for all 
women and the results will be recorded on the eCRF. 
14.3 Double-blind Treatment Phase 
 
Assessments While on Test Article  
14.3.1
The double-blind treatment period is 7 to 14 days in duration.  Subjects who met inclusion 
criteria, and did not meet exclusion criteria will be randomly assigned to a treatment group, and 
should receive their first dose of test article at the site within 4 hours after randomization. 
The following assessments (see Section 8) will be done: 
• Vital signs 
• AEs and SAEs 
• Concomitant treatments 
• Assessment of lesion size and clinical assessment of the site of infection  
• Numerical Rating Scale for pain at the primary infection site 
• Microbiological assessments  
• Blood for Central Laboratory assessments: hematology, chemistry, pregnancy (for women 
only) 
• Test article administration and accountability 
• Assessment for need to continue therapy 
• Investigator’s assessment of clinical response 
 


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14.3.1.1 
Treatment Phase  
The study will employ a double-blind, double-dummy design using omadacycline placebo 
comparator tablets of matching size and shape to active omadacycline tablets and matching 
over-encapsulated placebo and over-encapsulated active linezolid tablets.  To maintain 
investigator and subject blinding, subjects on both arms will receive the same number of tablets 
as shown in Table 1. 
All doses of test article should be taken with water.  There are fasting requirements for 
administration of the odd numbered doses due to effects of food on oral omadacycline (see Table 
1).  These fasting requirements should be considered when determining the time of day when 
subjects will take their doses. 
In order to perform protocol-required procedures, Dose 1 and the odd numbered doses on Days 2 
and 3 should be taken at the site.  Ability to perform the study procedures and the fasting 
requirements for the odd numbered doses should be considered when determining when subjects 
visit the clinic on Days 2 and 3.   
On Day 1, Dose 1 will be administered after the completion of all required Screening and Day 1 
procedures and within 4 hours after randomization as outlined in Section 8.  On Day 1, a second 
dose should be taken provided that 1) it can occur a minimum of 8 hours after Dose 1, and 2) it 
can occur a minimum of 8 hours before the expected time of the next dose (ie, Dose 3); 
otherwise only Dose 1 should be taken that day.  Starting on Day 2, test article will be taken 
twice daily, with approximately 12 hours (at least 8 hours) separating each dose.  


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Table 1. 
Treatment Regimens for Oral Test Article 
Dosing 
 
Omadacycline Arm  
Linezolid Arm 
Dosing Condition 
Day 1 
Dose 1 
Three 150 mg 
omadacycline tablets and 
one over-encapsulated 
placebo tablet resembling 
linezolid  
Three placebo tablets 
resembling 
omadacycline and 
one over-encapsulated 
600 mg linezolid 
tablet   
Fasting a  
Dose 2 b 
One over-encapsulated 
placebo tablet resembling 
linezolid  
One over-encapsulated 
600 mg linezolid 
tablet  
No restrictions 
Day 2 
Dose 3 
Three 150 mg 
omadacycline tablets and 
one over-encapsulated 
placebo tablet resembling 
linezolid  
Three placebo tablets 
resembling 
omadacycline and 
one over-encapsulated 
600 mg linezolid 
tablet   
Fasting a 
Dose 4 
One over-encapsulated 
placebo tablet resembling 
linezolid  
One over-encapsulated 
600 mg linezolid 
tablet  
No restrictions 
Day 3 and all 
subsequent study 
days 
Dose 5 
and odd 
doses 
Two 150 mg omadacycline 
tablets and one over-
encapsulated placebo tablet 
resembling linezolid 
Two placebo tablets 
resembling 
omadacycline and 
one over-encapsulated 
600 mg linezolid 
tablet   
Fasting a 
Dose 6 
and even 
doses 
One over-encapsulated 
placebo tablet resembling 
linezolid  
One over-encapsulated 
600 mg linezolid 
tablet  
No restrictions 
a  Fasting: no food, antacids or multivitamins containing multivalent cations (eg, aluminum, magnesium, calcium, 
bismuth, iron, or zinc) or drink except water for at least 6 hours before dosing; after dosing, no food for 2 hours, no 
dairy products, antacids or multivitamins containing multivalent cations (eg, aluminum, magnesium, calcium, 
bismuth, iron, or zinc) for 4 hours 
b  On Day 1, Dose 2 should be taken provided that 1) it can occur a minimum of 8 hours after Dose 1 and 2) it can 
occur a minimum of 8 hours before the expected time of the next dose (ie, Dose 3); otherwise Dose 2 should be 
skipped.   
14.3.1.2 
Management While on Oral Test Article 
While the subject is receiving therapy, the investigator should assess the subject at the visits 
specified in Section 8 and choose ONE of the following actions: 
• Continue test article  
• Discontinue test article – this decision will prompt the EOT evaluation 
The date, time and decision of the investigator will be recorded on source documents and the 
information transferred to eCRFs by study site personnel. 


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The investigator may use the culture and susceptibility results from the local microbiology 
laboratory to help guide therapy; however, decisions to continue or discontinue test article should 
be based on clinical response rather than susceptibility results (as omadacycline susceptibility 
testing is not available at the local site).  If the ABSSSI is caused by a microorganism that is not 
susceptible to linezolid in vitro, the decision to continue or discontinue study treatment should be 
based on the subject's clinical course and the investigator’s clinical judgment.  These cases 
should be discussed with the Medical Monitor.  The rationale for this decision should be 
recorded in source documents. 
 
Permitted Dose Adjustments and Interruptions of Test Article 
14.3.2
None. 
14.4 Follow-up Phase 
Subjects will be evaluated at 2 visits after the completion of treatment:  at the PTE visit, 7 to 
14 days after the subject’s last day of study therapy, and at a Final Follow-up assessment, 30 to 
37 days after the first dose of treatment (see Section 8).  The Final Follow-up assessment may be 
conducted via telephone contact or by another interactive technology for subjects who were 
considered to be Clinical Successes and had no AEs or clinically significant laboratory or ECG 
abnormalities noted at or after the PTE visit.  Otherwise, this assessment is to be performed with 
an in person study visit. 
14.5 Total Volume of Blood Collected 
The total volume of blood collected from each subject will be approximately 80 mL. 
 TEST ARTICLE AND ADMINISTRATION 
15
Test articles will be supplied by Paratek Pharma, LLC (the sponsor).  Test articles will be labeled 
according to regulations. 
The test articles should be administered only to subjects who have provided informed consent 
and who meet all of the inclusion criteria and none of the exclusion criteria.  Once the test article 
has been assigned to a subject, it must not be reassigned to another subject. 
15.1 Test Article Administration 
Subjects will be randomized (1:1) to 1 of the following 2 treatment arms: 
• Investigational therapy:  omadacycline, 450 mg po every 24 hours (q24h) for 2 doses, 
followed by 300 mg po q24h.  Total treatment duration of 7 to 14 days.  
• Reference therapy:  linezolid, 600 mg po every 12 hours (q12h).  Total treatment duration of 
7 to 14 days.  
 


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Identity of the Investigational Product  
15.1.1
Table 2. 
Oral Formulation 
Name 
Omadacycline Tablet, 150 mg 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
15.2 Investigational and Comparator Test Article 
 
Investigational Test Article:  Omadacycline 
15.2.1
• 450 mg po q24h for 2 doses followed by 300 mg po q24h   
• Total treatment duration of 7 to 14 days 
 
Comparator Test Article:  Linezolid 
15.2.2
• 600 mg po q12h  
• Total treatment duration of 7 to 14 days 
15.3 Dose Selection Rationale 
The dosing regimen of omadacycline selected for this study is based on the totality of nonclinical 
and clinical experience to date, including in vitro antibacterial activity, PK characteristics, 
clinical efficacy in prior studies, and the overall safety and tolerability profile.  Key 
considerations in dose selection are summarized below: 
• Given the half-life of omadacycline (approximately 18 hours), if dosing were to occur 
once daily then several days of dosing would be required to reach steady-state plasma 
concentrations.  Consequently, dosing regimens typically include a “loading-dose” 
strategy to reach steady-state more rapidly. 


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• In a completed Phase 3 study comparing omadacycline and linezolid for the treatment of 
adults with ABSSSI (PTK0796-ABSI-1108), subjects started therapy with omadacycline 
100 mg iv q12h for 2 doses (ie, 2 doses on Day 1), then 100 mg iv q24h; after 3 days iv 
therapy subjects could be switched to oral therapy (300 mg po q24h).  As described in 
Section 9.1, omadacycline demonstrated good efficacy and tolerability in that study.   
• It has been demonstrated that omadacycline administered as a 100 mg iv dose is 
bioequivalent (based on plasma area under the curve [AUC]) to a 300 mg oral dose.  
Therefore, one approach to the dosing regimen for this oral-only treatment study was to 
start omadacycline treatment with oral doses considered bioequivalent to the iv doses 
used in the completed Phase 3 study (ie, 300 mg po q12h for 2 doses, then 300 mg po 
q24h). 
• Because of a known food effect, oral omadacycline should be administered in a fasted 
state.  While this restriction is considered manageable for once daily dosing, it was 
recognized that adherence to a fasting window surrounding two doses in a given day 
(such as that associated with a “loading-dose” of two separate doses on Day 1) would be 
challenging. 
• A recently completed Phase 1 study (PTK0796-MDPO-16105) evaluated multiple once 
daily oral regimens of omadacycline.  Preliminary results from that study showed that 
oral dosing regimens of 300 mg q24h and 450 mg q24h had similar and favorable 
tolerability profiles.  In addition, PK results based on that study and prior studies indicate 
that a regimen of 450 mg po q24h for 2 doses followed by 300 mg po q24h will achieve 
approximately the same steady state concentrations within the same time frame as a 
dosing regimen starting with 300 mg po q12h for 2 doses, then 300 mg po q24h.  In both 
regimens, a total of 900 mg oral omadacycline is administered over the first 2 days. 
• Therefore, in order to minimize the potential impact of food effects and maximize 
convenience with an oral dosing regimen that is expected to be well tolerated and achieve 
rapid target plasma concentrations, an omadacycline dosing regimen of entirely once 
daily dosing will be used (ie, 450 mg po q24h for 2 doses, then 300 mg po q24h).  Note 
that because the study is double-blind and linezolid is dosed twice-daily, all study 
subjects will be dosed twice-daily (with either active or placebo tablets), as detailed in 
Section 14.3.1.1. 
15.4 Subject Compliance  
Study personnel at the site, should monitor po test article compliance at each study visit, by 
comparing the returned test article with the dosing information reported in the subject charts and 
subject diaries.  Discrepancies should be resolved with the subject during the visit.  Compliance 
and any unresolved discrepancies will be documented in the source document and on the drug 
inventory record.  The test article eCRF should reflect the reconciled dosing information 
provided by the subject charts and subject diaries. 


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 SAFETY 
16
Any subject who receives test article will be included in the evaluation for safety. 
Safety is assessed by the following measures: 
• Physical examinations 
• AEs and SAEs 
• Vital signs 
• Laboratory assessments 
• 12-lead ECG 
• Pregnancy assessments  
 
16.1 Physical Examinations 
After Screening, a physical examination should be conducted on the study days indicated in 
Section 8. Any abnormalities or changes in intensity noted during the review of the body systems 
should be documented in the source documents.  If a new clinically significant finding occurs (ie, 
not noted at Screening) after the Screening exam, it must be captured as an AE.  In addition, 
resolution of any clinically significant abnormal findings that have been reported as an AE will 
be noted in the medical record and the AE eCRF. 
 
Vital Signs 
16.1.1
Vital signs include BP, pulse/heart rate, body temperature, and respiratory rate.  Vital signs 
should be recorded at all visits, with the exception of the Final Follow-up assessment (see 
Section 8).  
• In addition, blood pressure and pulse rate should be measured within 30 min before, and 
approximately (± 15 minutes) 1 hour after and 3 hours after the completion of the first dose 
on Day 1 
• Blood pressure and pulse rate should be measured within 30 min before, and approximately 
(± 15 minutes) 1 hour after and 3 hours after the completion of the odd numbered dose on 
Day 2 
• Blood pressure and pulse rate should be measured within 30 min before, and approximately 
(± 15 minutes) 1 hour after and 3 hours after the completion of the odd numbered dose on 
Day 3 
 
In the event that the subject takes the dose before arriving for the Day 2 or Day 3 office visit, the 
site should collect the 1 and 3 hour post dose measurements if possible, if not then a single 
measurement should be made at any time during the visit and the date and time recorded. 
 


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The subject’s vital signs should be captured after at least 5 minutes of rest while in a 
non-standing position (supine or semi-recumbent, head of bed from 0° to 90°).  Subsequent vital 
sign measurements should be captured in the same non-standing position. 
Systolic and diastolic blood pressure will be measured using an automated validated device, with 
an appropriately sized cuff.  
Pulse will be measured using an automated validated device, when available.  If not available, 
pulse will be measured manually.  
In addition to the above, BP and heart rate may be measured whenever clinically indicated at the 
discretion of the treating physician.  Any subject who experiences an AE of cardiac chest pain, 
palpitations, or tachyarrhythmia while on study should have an ECG and an evaluation by the 
investigator (see Section 16.1.3.1).   
Temperature will be obtained using an electronic (rapid reading) device whenever possible.  
Respiratory rate will be determined by observation. 
 
Laboratory Evaluations 
16.1.2
Blood samples for hematology, serum chemistry and coagulation (prothrombin time only) should 
be drawn at the Screening, Day 3, Day 7, Day 10, EOT, and PTE visits (see Section 8).  At 
Screening only, 1 sample will be analyzed at a local laboratory for confirmation of eligibility 
criteria and a second sample shipped to the Central Laboratory for analysis.  All other visits 
should have samples shipped to the Central Laboratory for analysis.  
The Central Laboratory will be used for safety analysis of all specimens collected.  Details on the 
collection tubes and containers, shipment of samples and reporting of results by the Central 
Laboratory are provided to investigators in the Central Laboratory manual.  
Because subject enrollment will not permit using Central Laboratory results to assess a subject’s 
meeting inclusion/exclusion criteria, it is expected that local laboratory testing will be used in 
circumstances where this testing is needed to assess a subject’s WBC count or differential, serum 
transaminase or bilirubin levels, serum creatinine or pregnancy testing (for women only).  
16.1.2.1 
Hematology 
The analytes listed in the table below (Table 3) will be measured at the Central Laboratory. 
Table 3. 
Hematology Panel 
Hematocrit  
Total red blood cell count  
Hemoglobin 
Mean cell hemoglobin 
Mean cell hemoglobin concentration 
Mean cell volume 
White blood cell count  
Platelet count  
White blood cell differential (as % cell counts) 
-Neutrophils  
-Lymphocytes  
-Monocytes  
-Eosinophils  
-Basophils  


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16.1.2.2 
Clinical Chemistry 
The analytes indicated in Table 4 below will be measured at the Central Laboratory. 
Table 4. 
Clinical Chemistry Panel 
Blood glucose  
Urea  
Creatinine 
Sodium 
Potassium 
Chloride 
Bicarbonate 
 
ALT 
AST 
AP 
Total bilirubin  
Total protein  
Magnesium  
Albumin  
 
LDH 
CK 
(CK isoenzyme testing as required) 
Calcium  
Phosphate  
Cholesterol  
Uric Acid 
GGT 
Amylase 
Lipase 
ALT = Alanine aminotransferase; AP = Alkaline phosphatase; AST = Aspartate aminotransferase; 
CK = creatine phosphokinase; GGT = gamma-glutamyl transpeptidase; LDH = Lactate dehydrogenase. 
16.1.2.3 
Other Laboratory Tests 
Table 5. 
Additional Laboratory Tests 
Category 
Test 
Note 
Coagulation 
INR  
Prothrombin time only  
Female endocrinology 
β-hCG (for 
women only) 
See Section 16.1.3.2 below.  Done both locally (urine) and 
centrally (serum)  
β-hCG = beta-human Chorionic Gonadotropin; INR = international normalized ratio. 
 
Safety Studies to be Performed Locally 
16.1.3
16.1.3.1 
Electrocardiogram (ECG) 
A standard 12-lead ECG should be obtained using equipment provided by the sponsor.  The ECG 
will be obtained after the subject has been in a semi-recumbent position for approximately 
10 minutes at the following times: 
• Screening 
• At the EOT visit  
• In any case in which a subject develops an AE of cardiac chest pain, palpitations, 
tachyarrhythmia or as otherwise clinically indicated (see Section 16.1.1) 
Reading and interpretation of the ECG will be performed centrally and provided to the 
investigator.  The investigator is responsible for reviewing interpretations and for retaining hard 
copies of the reports.   


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16.1.3.2 
Pregnancy and Assessments of Fertility 
All women will have a local urine or serum pregnancy test at the site at the Screening visit.  
Urine pregnancy test kits will be provided by the sponsor through the Central Laboratory.  If a 
positive urine or serum pregnancy test result is obtained at the site, the woman is not to be 
randomized.  A serum sample for β-hCG testing will be collected at the Screening visit and sent 
to the Central Laboratory for confirmation of the local urine or serum pregnancy test results.  
Serum samples for β-hCG testing at the Central Laboratory also will be collected at EOT and 
PTE.  If a positive β-hCG result is reported by the Central Laboratory after a woman is enrolled, 
test article administration should be discontinued (see Section 21.2.6). 
16.1.3.3 
Blood Cultures 
Two sets of blood cultures (1 set = 1 aerobic bottle + 1 anaerobic bottle) should be collected 
within the 24 hours prior to the first dose of test article.  Each set of blood cultures should be 
collected by direct venipuncture from independent body sites at least 15 minutes apart.  Blood 
cultures should be collected for subjects that are clinical failures at the EOT and/or PTE visit.  If 
bacteria are isolated from blood cultures, repeat blood cultures should be collected.  If 
subsequent blood cultures are also positive, repeat the blood cultures as necessary until negative 
blood cultures are obtained (see Section 8).  Blood culture isolates should be sent to the Central 
Laboratory (see Section 17.3). 
16.1.3.4 
Additional Local Laboratory Tests 
The investigator may order additional local laboratory tests consistent with his/her routine 
standard of care.  
 
Appropriateness of Safety Measurements 
16.1.4
The safety assessments selected are standard for this indication and subject population. 
 EFFICACY 
17
The following is a list of key assessments that will be performed: 
• Clinical assessment of the site of infection  
• Assessment of lesion size 
• Assessment of the need for adjunct surgical procedures 
• Microbiological assessment of the infection 
• Assessment of clinical response by the investigator 
• Assessment of all-cause mortality 
Each is described in further detail below. 


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17.1 Clinical Assessment of the Site of Infection  
The clinical assessment of the site of infection should be conducted at Screening and every 
scheduled evaluation with the exception of the Final Follow-up assessment (see Section 8).  A 
clinical assessment of the site of infection must be performed within 48 to 72 hours after the first 
dose.  The investigator will examine the primary site of infection and record the following 
information on source documents and the eCRFs: 
• Presence of drainage from the primary lesion site and description (serous/serosanguineous, 
seropurulent, or purulent) 
Semi-quantitative (none, mild, moderate, severe) description of infection for the following 
features: 
• Tenderness 
• Edema 
• Erythema 
• Induration 
17.2 Assessment of Lesion Size  
Lesion measurements by ruler should be performed by the Investigator at Screening, and every 
scheduled evaluation with the exception of the Final Follow-up assessment (see Section 8). 
Surface area of lesions will be calculated by multiplying the head-to-toe maximum length of total 
lesion and maximum width (perpendicular to maximum length) inclusive of contiguous 
involvement (erythema, edema and/or induration).  Investigator ruler measurements will be used 
to document lesion size.  Instructions for ruler measurements will be provided to the investigator. 
17.3 Microbiological Assessment of the Site of Infection 
At the Screening visit, material should be collected from the site of infection and submitted to 
site’s local microbiology laboratory for Gram stain and culture.  The type of specimen submitted 
will be recorded on source documents at the microbiology laboratory.  Laboratory reports on 
Gram stains should include a semi-quantitative description of the number of polymorphonuclear 
leukocytes per low power field (ie, 100×) and a description of bacteria seen.  
It is critical, especially at Screening, that the best possible specimen be obtained.  
As the site of infection responds to therapy, repeated cultures may not be clinically appropriate 
and/or there may be no material for culture.  At the EOT and/or PTE visit, infection site 
specimen cultures and Gram stains should be obtained only for subjects who are clinical failures 
and require alternative antibacterial treatment for the infection under study. 
The following types of specimens are considered acceptable in order of preference6: 


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• biopsy of involved cutaneous or subcutaneous tissue, preferably from the advancing margin 
of the lesion; 
• debrided tissue; 
• tissue scraping (using curette or scalpel);  
• needle aspirate of involved, nonpurulent cutaneous or subcutaneous tissue;  
• pus or infected tissue collected during an incision and drainage procedure; 
• pus aspirated into a syringe;  
• deep swab of purulent material (only if collected from infected tissue that has been incised or 
is draining). 
Surface swabs of wounds, inflamed skin, or drainage (including purulent material) are not 
acceptable and should not be submitted.  For subjects with cellulitis/erysipelas, a 
skin/subcutaneous tissue punch biopsy at the ‘leading edge’ (not the center) of the involved area 
is preferred.  If this cannot be done, a needle aspirate of the ‘leading edge’ of the cellulitic area 
should be performed. 
All specimens submitted to the site’s local laboratory are to be evaluated for aerobic and, where 
appropriate, anaerobic culture.  Culture results are to include a semi-quantitative description of 
the organisms on the primary culture plate and identification of all isolates to the level of genus 
and species.  Susceptibility testing for linezolid can be performed locally using a standard 
method chosen by the laboratory.  Results of this testing can be used by investigators along with 
clinical findings to help guide therapy. 
All bacterial isolates identified by the local laboratory from infection site specimens or blood 
will be submitted to the Central Laboratory for verification of genus and species and for 
standardized minimum inhibitory concentration (MIC) testing performed for omadacycline, 
linezolid and a panel of currently approved antibiotics.  In the event that local laboratory genus 
and species identification are not consistent with Central Laboratory results, a back-up isolate 
should be sent to the Central Laboratory. 
The investigator is to check the laboratory microbiology specimen results.  If there is evidence of 
a Gram-negative or anaerobic microorganism, or microorganism that is non-susceptible to 
linezolid, the decision to continue or discontinue test article and change the antibacterial regimen 
is made based on the investigator’s clinical judgment and should be recorded in the source 
documents. 
Details concerning Gram stains and cultures will be provided in the Clinical Microbiology 
Laboratory Manual. 
17.4 Assessment of Clinical Outcome 
Assessment of clinical outcome will occur at the Early Clinical Response assessment 
(programmatically), EOT, and PTE as described below. 


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Evaluation of the Infection Under Study at the Early Clinical Response 
17.4.1
Assessment 
The formal determination of the response to therapy at the Early Clinical Response assessment 
(48 to 72 hours after the first dose of test article) will be done programmatically using lesion 
measurement values entered into the eCRF.  The investigator is not responsible for categorizing 
subjects as Clinical Success, Failure, or Indeterminate at the Early Clinical Response assessment.   
Clinical Success at the Early Clinical Response assessment will be defined as meeting all 3 of the 
following: 
• The subject is alive 
• The size of the primary lesion has been reduced greater than or equal to 20% compared to 
Screening measurements, without receiving any alternative (rescue) antibacterial therapy. 
• The subject does not meet any criteria for Clinical Failure or Indeterminate (see below for 
definitions) 
Clinical Failure will be defined as meeting any of the criteria below: 
• The size of the primary lesion has not been reduced by greater than or equal to 20% 
compared to Screening measurements 
• Investigator discontinued test article and indicated that the infection had responded 
inadequately such that alternative (rescue) antibacterial therapy was needed 
• The subject received antibacterial therapy that may be effective for the infection under study 
for a different infection from the one under study 
• The subject developed an AE that required discontinuation of test article prior to the Early 
Clinical Response assessment and alternative (rescue) antibacterial therapy was needed 
• Death prior to Early Clinical Response assessment 
 
Indeterminate  
The clinical response to test article could not be adequately inferred because: 
• Subject was not seen for Early Clinical Response assessment because they withdrew consent, 
were lost to follow-up, other reason (specify) 
• Other, specify 
 
Clinical Evaluation of the Infection Under Study at EOT  
17.4.2
At the EOT visit (on the day of or within 2 days following the last dose of test article), the 
investigator will indicate the clinical status of the infection under study as detailed below. 
Clinical Success at the End of Treatment assessment will be defined as meeting the following: 
• The subject is alive 


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• The infection is sufficiently resolved such that further antibacterial therapy is not needed.  
These subjects may have some residual changes related to infection requiring ancillary (ie, 
non-antibiotic) treatment, eg, bandages on a healing wound, debridement of uninfected tissue 
(ie, necrotic) 
Clinical Failure will be defined as meeting any of the criteria below, the primary reason for 
clinical failure will be designated: 
• Investigator discontinued test article and indicated that the infection had responded 
inadequately such that alternative (rescue) antibacterial therapy was needed 
• The subject received antibacterial therapy that may be effective for the infection under study 
for a different infection from the one under study 
• The subject developed an AE that required discontinuation of test article prior to completion 
of the planned test article regimen and alternative (rescue) antibacterial therapy was needed 
• Unplanned major surgical intervention (ie, procedures that would not normally be performed 
at the bedside) for the infection under study 
• The subject died before evaluation 
• Other, specify 
Indeterminate The clinical response to test article could not be adequately inferred.  The 
investigator will mark all that apply: 
• The subject was not seen for EOT assessment because they withdrew consent, were lost to 
follow-up, other reason (specify) 
• Other, specify 
 
Clinical Evaluation of the Infection Under Study at PTE 
17.4.3
At the Post Therapy Evaluation PTE visit (7 to 14 days after the subject’s last day of study 
therapy) the investigator will indicate ONE of the following outcomes relating to the primary 
infection under study:   
Clinical Success at the Post Therapy Evaluation assessment will be defined as meeting the 
following: 
• The subject is alive 
• The infection is sufficiently resolved such that further antibacterial therapy is not needed.  
These subjects may have some residual changes related to infection requiring ancillary (ie, 
non-antibiotic) treatment, eg, bandages on a healing wound, debridement of uninfected tissue 
(ie, necrotic) 
Clinical Failure will be defined as meeting any of the criteria below, the primary reason for 
clinical failure will be designated: 
• The infection required additional treatment with alternative (rescue) antibacterial therapy 


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• The subject received antibacterial therapy between EOT and PTE that may be effective for 
the infection under study for a different infection from the one under study 
• Unplanned major surgical intervention (ie, procedures that would not normally be performed 
at the bedside) for the infection under study between EOT and PTE 
• The subject died before evaluation 
• Other, specify 
Indeterminate The clinical response to test article could not be adequately inferred.  The 
investigator will mark all that apply: 
• The subject was not seen for PTE assessment because they withdrew consent, were lost to 
follow-up, other reason (specify) 
• Other, specify 
 OTHER ASSESSMENTS 
18
18.1 Resource Utilization 
The number of emergency room visits and hospitalizations including number of days 
hospitalized during the study period will be calculated. 
 PHARMACOKINETIC PLASMA SAMPLES FOR OMADACYCLINE 
19
CONCENTRATION 
19.1 Selection of Sites for PK Studies 
PK data will be analyzed using a population PK model.  In order to maximize the number of 
subjects who participate so that this analysis is optimal, during site selection the site’s ability to 
participate in the PK portion of the study will be assessed.  Not all sites will participate in the PK 
portion of the study.  To assure the quality and accuracy of the PK samples, samples will be 
obtained only from subjects participating at a center that has the appropriate facilities and 
capabilities and has been specifically trained by the sponsor.  
19.2 Collection of PK Samples 
At selected sites, subjects who have agreed to participate in PK evaluation and have signed a 
separate PK evaluation consent form will have blood samples collected for PK analysis.  PK 
samples will be collected using a sparse sampling method for the population PK model.  The 
number of samples and collection schedule will vary for individual subjects.  The sponsor will 
notify the site of the PK sample collection schedule for the individual subject.  Up to 4 blood 
samples will be collected per subject between Days 2 and 3 (see Section 8). 
The sponsor will provide heparin tubes for the collection of PK blood samples and will provide 
freezer tubes for storing the plasma.  Blood will be collected either by fresh venipuncture or via a 
cannula used SOLELY for that purpose. 


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The dates and times for all doses of test article and PK sample collections will be recorded.  The 
identification of the subject, sample number and the time of the sample collection to the nearest 
minute should be immediately recorded on the tube.  The tube will be centrifuged at 1500 × g for 
10 minutes; the separated plasma transferred in 2 equal aliquots into pre-labeled tubes; and the 
tubes frozen at -20ºC or colder within 60 minutes of collection.  The time the sample is frozen 
should be recorded to the nearest minute. 
19.3 Storing and Shipping of PK Samples 
After all of the PK samples from a single subject have been collected and frozen at -20ºC or 
colder, 1 sample from each time point can be batched together with corresponding complete 
sample sets from other subjects and be carefully packaged and shipped frozen at -20ºC or colder 
to the Central Laboratory.  Samples are to be shipped with sufficient dry ice to remain frozen 
during transit (up to a possible 4 day period).  The Central Laboratory will process these samples 
and forward them at -20ºC or colder to the Analytical Laboratory designated by the sponsor.  For 
each subject and time point, the remaining stored aliquots will be retained on-site at -20ºC or 
colder until released or requested by the sponsor. 
19.4 Analysis of PK samples 
The Analytical Laboratory will assay the samples for omadacycline using a specific, sensitive 
and validated Liquid Chromatography/Tandem Mass Spectrometry (LC/MS/MS) method 
approved by the sponsor. 
 OTHER BIOMARKERS 
20
None.  
 SAFETY MONITORING 
21
21.1 Definitions  
 
Adverse Events 
21.1.1
An AE is any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, 
or laboratory or physiologic observations occurring in a person given a test article or in a clinical 
study.  The event does not need to be causally related to the test article or clinical study.  An AE 
includes, but is not limited to, the following: 
• Any clinically significant worsening of a preexisting condition. 
• An AE occurring from overdose of a test article, whether accidental or intentional.  
Overdose is a dose greater than that specified in the protocol. 
• An AE occurring from abuse (eg, use for nonclinical reasons) of a test article 
• An AE that has been associated with the discontinuation of the use of a test article 


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Serious Adverse Events 
21.1.2
A SAE is an AE that: 
• Results in death 
• Is life-threatening (see below) 
• Requires hospitalization or prolongation of an existing hospitalization (see below) 
• Results in a persistent or significant disability or incapacity (see below) 
• Results in a congenital anomaly or birth defect 
• Additionally, important medical events that may not result in death, be life-threatening, 
or require hospitalization may be considered SAEs when, based on appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent any one (1) of the outcomes listed above in this definition.  
Examples of such events include allergic bronchospasm requiring intensive treatment in 
an emergency room or at home, blood dyscrasias or convulsions that do not result in 
hospitalization, or development of drug dependency or drug abuse. 
Life-threatening refers to immediate risk of death as the event occurred per the reporter.  A 
life-threatening experience does not include an experience, had it occurred in a more severe 
form, might have caused death, but as it actually occurred, did not create an immediate risk of 
death.  For example, hepatitis that resolved without evidence of hepatic failure would not be 
considered life-threatening, even though hepatitis of a more severe nature can be fatal.  
Similarly, an allergic reaction resulting in angioedema of the face would not be life-threatening, 
even though angioedema of the larynx, allergic bronchospasm, or anaphylaxis can be fatal. 
Hospitalization is official admission to a hospital.  Hospitalization or prolongation of a 
hospitalization constitutes criteria for an AE to be serious; however, it is not in itself considered 
an SAE.  In absence of an AE, a hospitalization or prolongation of a hospitalization should not 
be reported as an SAE by the participating investigator.  This is the case in the following 
situations: 
• The hospitalization or prolongation of hospitalization is needed for a procedure required 
by the protocol 
• The hospitalization or prolongation of hospitalization is part of a routine procedure 
followed by the center (eg, stent removal after surgery).  This should be recorded in the 
study file. 
• A hospitalization for a preexisting condition that has not worsened  
Disability is defined as a substantial disruption in a person’s ability to conduct normal life 
functions. 
If there is any doubt about whether the information constitutes an SAE, the information is treated 
as an SAE. 


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Other Reportable Information  
21.1.3
Certain information, although not considered an SAE, must be recorded, reported, and followed 
up as indicated for an SAE.  This includes: 
• Pregnancy exposure to a test article:  If a pregnancy is confirmed, use of the test article 
must be discontinued immediately.  Information about pregnancy exposure includes the 
entire course of pregnancy and delivery, and perinatal and neonatal outcomes, even if 
there are no abnormal findings.  Both maternal and paternal exposures are considered 
other reportable information.  For exposure involving the female partner of a male 
subject, the necessary information must be collected from the subject, while respecting 
the confidentiality of the partner. 
• Lactation exposure to a test article with or without an AE 
• Overdose of a test article as specified in this protocol with or without an AE 
• Inadvertent or accidental exposure to a test article with or without an AE 
 
Overdose 
21.1.4
Any administration of omadacycline of greater than 900 mg within a 24 hour period will be an 
overdose, regardless of whether the overdose is intentional or accidental, it is a reportable event 
and the sponsor must be notified within 1 business day.  Any administration of greater than 
3000 mg of linezolid within a 24 hour period will be an overdose.  In the event that a study 
subject takes an overdose of test article, the investigator may obtain the subject’s treatment 
assignment by contacting the IxRS.  IxRS will also provide a confirmation report of the drug 
assignment to site personnel.  The site personnel will retain this confirmation report. 
The physician managing the overdose may order any test he/she thinks is necessary to manage 
the subject properly. 
 
Medication Errors 
21.1.5
Medication errors are the result of administration or consumption of the wrong product, by the 
wrong subject, at the wrong time, and/or by the wrong administration route, due to human error.   
Medication errors include, but are not limited to, the following: 
• The administration and/or consumption of test article that has not been assigned to the 
subject 
• Administration of expired test article 
All AEs and SAEs must be handled as specified in this protocol whether or not they are 
associated with a medication error.  A medication error associated with an SAE (including 
overdose, inadvertent exposure, and/or accidental exposure) will be reported with the SAE on the 
SAE Report Form.  All other medication errors will be reported by faxing or e-mailing the 
Clinical Test Article Error Incident Report Form as indicated in the Emergency Contacts (see 
Section 2). 


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21.2 Recording and Reporting 
A subject’s AEs and SAEs will be recorded and reported from the signing of the ICF to the time 
of the Final Follow-up assessment.  The investigator must instruct the subject to report AEs and 
SAEs during this time period.  Reports of death within 30 days after the last contact with the 
subject will be reported to the sponsor and additional information relative to the cause of death 
will be sought and documented.   
All AEs and SAEs must be recorded on source documents.  All AEs and SAEs for subjects who 
receive a treatment assignment will be recorded in the eCRFs. 
The investigator must follow-up as medically necessary on all AEs and SAEs until the events 
have subsided, the condition has returned to Baseline, or in case of permanent impairment, until 
the condition stabilizes. 
AEs should be based on the signs or symptoms detected during the physical examination and on 
clinical evaluation of the subject.  In addition to the information obtained from those sources, the 
subject should be asked the following nonspecific question:  "How have you been feeling since 
your last visit?"  Whenever possible, AEs should be reported as a diagnosis rather than 
individual signs and symptoms.  If a definitive diagnosis is not possible, the individual signs and 
symptoms should be recorded using standard medical terminology. 
If an AE requires a surgical or diagnostic procedure, the illness leading to the procedure should 
be recorded as the AE, not the procedure itself. 
Death should be recorded in the eCRF as an outcome of an AE.  Any unanticipated risks to the 
subjects must be reported promptly to the IRB/IEC/REB.  
 
Serious Adverse Event Reporting 
21.2.1
All SAEs and follow-up information must be reported within 1 business day or 24 hours as 
required by local regulations by faxing a completed SAE Report Form to the fax number below 
or e-mailing a completed SAE Report Form to the email address below.  
Serious Adverse Event (SAE) contact information: 
E-Mail: 
 
Fax: 
 
 
 
Assessment of Relatedness 
21.2.2
The investigator will assess causality (ie, whether there is a reasonable possibility that test article 
caused the event) for all AEs and SAEs.  The relationship will be characterized using the 
following classification: 
• Not related: This relationship suggests that there is no association between test article and the 
reported event.  The event can be explained by other factors such as an underlying medical 


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condition, concomitant therapy, or accident, and no plausible temporal or biologic 
relationship exists between test article and the event. 
• Related: This relationship suggests that a definite causal relationship exists between test 
article administration and the AE, or there is a reasonable possibility that the event was 
caused by the study medication, and other conditions (concurrent illness, 
progression/expression of disease state, or concurrent medication reaction) do not appear to 
explain the event. 
AEs and SAEs also will be assessed for their potential relationship to the protocol.  A protocol-
related adverse event is one that is not related to the test article, but is considered by the 
investigator or the medical monitor (or designee) to be related to the research conditions, ie, 
related to the fact that a subject is participating in the study.  For example, a protocol-related AE 
may be an untoward event related to a medical procedure required by the protocol. 
 
Assessment of Severity 
21.2.3
The severity (or intensity) of an AE will be classified using the following criteria: 
• Mild: These events are usually transient, require minimal or no treatment, and do not 
interfere with the subject’s daily activities. 
• Moderate: These events result in a low level of inconvenience or concern with the therapeutic 
measures. Moderate events may cause some interference with normal functioning but pose 
no significant or permanent risk of harm. 
• Severe: These events interrupt a subject’s usual daily activity and may require systemic drug 
therapy or other treatment. Severe events are usually incapacitating. 
Changes in the severity of an AE should be documented as a new event to allow an assessment 
of the duration of the event at each level of intensity to be performed. 
 
Laboratory Findings 
21.2.4
Protocol-defined safety laboratory test results will be analyzed as part of specific laboratory 
safety analyses.  Additional laboratory test results at other time points may be available to the 
investigator as part of standard clinical practice.  Throughout the study, laboratory-related 
abnormalities should be recorded as AEs only if considered clinically significant, outside the 
range of expected values given the subject’s baseline assessments and clinical course, and not 
known to be part of another AE diagnosis. 
 
Worsening or Progression of Qualifying ABSSSI 
21.2.5
The skin infection that qualified the subject for entry in the study (“qualifying ABSSSI”) is 
unique because data regarding the progress of this infection are being captured as part of efficacy 
analyses.  Therefore, worsening or progression of the qualifying ABSSSI should be recorded as a 
clinical failure (as part of the efficacy assessment), rather than an AE, unless the 
worsening/progression also meets the criteria for a serious AE (in which case the event also 
should be reported as an SAE).  In contrast, any new or secondary infections that the investigator 


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considers to be distinct from the qualifying ABSSSI (eg, a secondary skin abscesses in a 
different anatomical location) should be reported as AEs in all cases, whether non-serious or 
serious. 
 
Pregnancies 
21.2.6
To ensure subject safety, each pregnancy in a subject on test article must be reported to the 
sponsor within 1 business day of learning of its occurrence.  Test article should be discontinued 
immediately and the pregnancy should be followed up to determine outcome, including 
spontaneous or voluntary termination, details of the birth, and the presence or absence of any 
birth defects, congenital abnormalities, or maternal and/or newborn complications. 
Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported by the 
investigator to the sponsor.  Pregnancy follow-up should be recorded on the same form and 
should include an assessment of the possible relationship to the test article of any pregnancy 
outcome.  Any SAE experienced during pregnancy must be reported on the SAE Report Form. 
 DATA ANALYSIS 
22
All analyses of data for this study will comply with International Conference on Harmonisation 
of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH-E9) and the 
sponsor’s guidance documents and standards.  Statistical analyses will be performed using 
Statistical Analysis Software (SAS). 
A SAP incorporating the sections below and with mock table, figure and listing (TFL) shells will 
be prepared prior to the start of the study and approved and finalized by the sponsor prior to 
database lock.  This plan will define populations for analysis, outline all data handling 
conventions and specify statistical methods to be used for analysis of safety and efficacy.  As a 
consequence of differing regulatory requirements for the choice of the primary efficacy outcome 
and statistical analyses, 2 separate SAPs will be prepared (FDA and EMA).  The sections below 
indicate the overall structure and approach of the analyses. 
Inferential statistical analyses of the primary and secondary outcomes will be conducted as 
outlined below.  Descriptive statistics, including the numbers and percentages for categorical 
variables, and the numbers, means, standard deviations (SD), medians, minimums, and 
maximums for continuous variables will be provided.  All comparisons will be for omadacycline 
versus linezolid.  Exploratory analyses may also be performed.  Listings of individual subject’s 
data will be produced.   
22.1 Analysis Populations 
A number of subject analysis populations have been defined for the various analyses of efficacy 
and safety, as follows: 
• The intent-to-treat (ITT) population will consist of all randomized subjects. 


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• The modified intent-to-treat (mITT) population will consist of all randomized subjects 
without a sole Gram-negative causative pathogen(s) at Screening.   
• The clinically evaluable (CE) population will consist of all mITT subjects who received test 
article, have a qualifying ABSSSI, an assessment of outcome, and meet all other evaluability 
criteria detailed in the SAP.   
• The microbiological modified intent-to-treat (micro-mITT) population will consist of 
subjects in the mITT population who have at least 1 Gram-positive causative pathogen(s) at 
Screening. 
• The microbiologically evaluable (ME) population will include subjects in the CE population 
who have at least 1 Gram-positive causative pathogen(s) at Screening.  
• The safety population will consist of all randomized subjects who receive test article.  
22.2 Subject Demographics and Other Baseline Characteristics 
Descriptive statistics, by treatment arm, will be provided for the following: 
• Subject disposition: 
• completed test article 
• discontinued test article by reason for discontinuation 
• completed study 
• discontinued study by reason for discontinuation 
• Protocol deviations 
• ABSSSI background information 
• Subject demographics:  age (years), gender, race/ethnicity, height (cm), weight (kg), 
Body Mass Index (BMI) (kg/m2) 
• Description and location of the primary site of the ABSSSI 
• type of infection 
• site of infection 
• area (length × width) of the lesion 
• presence of systemic signs of infection 
• severity of clinical signs and symptoms 
• culture source and type of specimen by specified Baseline pathogens isolated either 
from the ABSSSI site or from blood samples 
• Surgical procedures 
• Medical histories and continuing medical conditions 
Screening demographic and medical variables will be analyzed using a 2-sided Fisher’s exact 
test (for categorical variables) or a 2-sided Wilcoxon Rank Sum test (for ordinal and continuous 
variables).  


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22.3 Treatments (Test Article, Rescue Medication, Other Concomitant Therapies, 
Compliance) 
A listing will be provided that indicates the subject’s date and time of randomization, 
randomized treatment assignment, randomized infection type and receipt of allowed antibacterial 
therapy in the 72 hours prior to randomization stratum. 
The tablet count taken will be presented. 
The total number of days on study therapy will also be provided by treatment group. 
Prior medications, concomitant medications, separately for antibiotics and non-antibiotics will be 
summarized.  For prior and concomitant antibiotics the reason for receipt will be provided.   
22.4 Primary Efficacy Analysis 
For all efficacy analyses, subject data will be analyzed in the group to which the subject was 
randomized.  For the primary analyses for both the FDA and EMA, subjects will be analyzed in 
the stratum to which they were randomized (see Section 25.1). 
 
Early Clinical Response Efficacy Variable  
22.4.1
The Early Clinical Response can be Clinical Success, Clinical Failure and Indeterminate (defined 
in Section 17.4.1).  
An Indeterminate Response is included in the denominator for the calculation of the percentage 
of subjects with a Clinical Success in the mITT population and thus, is essentially considered as 
a Clinical Failure for the purpose of the primary analysis for the FDA.  
 
Investigator’s Assessment of Clinical Response at PTE Efficacy Variable  
22.4.2
This is defined as Investigator’s Assessment of Clinical Response at the PTE visit with outcomes 
of Clinical Success, Clinical Failure and Indeterminate (defined in Section 17.4.3) in the mITT 
population and Clinical Success and Clinical Failure in the CE population.  Subjects with a 
response of Clinical Failure at EOT will be defined as a Clinical Failure at PTE.  An 
Indeterminate Response is included in the denominator for the calculation of the percentage of 
subjects with a Clinical Success in the mITT population and thus, is essentially considered a 
Clinical Failure for the purpose of the primary analysis for the EMA. 
 
Statistical Model, Hypothesis, and Method of Analysis 
22.4.3
To demonstrate the efficacy of omadacycline is non-inferior to linezolid in the treatment of adult 
subjects with ABSSSI, the following hypothesis will be evaluated by analysis of the Clinical 
Success rates. 
The null hypothesis and alternate hypothesis for the Early Clinical Response endpoint will be 
assessed in the mITT population as follows: 


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Ho:  θT – θC ≤ -∆ 
Hai:  θT – θC > -∆  
Where the clinical success rate for the omadacycline regimen is θT and for linezolid is θC  
∆ is the non-inferiority (NI) margin and is 0.10.   
Similar null and alternative hypotheses can be set up with ∆ of 0.10 for the PTE endpoint.  For 
the Early Clinical Response (FDA) endpoint, a 2-sided 95% confidence interval (CI) approach 
for the difference of clinical success rates (using the point estimate of the difference:  
omadacycline response proportion minus linezolid response proportion) will be used to test for 
the NI of the omadacycline arm compared to the linezolid arm in the mITT population.  The 95% 
CI will be calculated using the unstratified method proposed by Miettinen and Nurminen.9  
Omadacycline will be considered non-inferior to linezolid if the lower bound of the CI is greater 
than -0.10. 
For Investigator’s Assessment of Clinical Response at PTE (EMA) primary efficacy analyses in 
both the mITT and CE populations, a 2-sided 95% CI approach for the difference of clinical 
success rates (using the point estimate of the difference:  omadacycline response proportion 
minus linezolid response proportion) will be used to test for the NI of the omadacycline arm 
compared to the linezolid arm.  The 95% CI will be calculated using the stratified (for the 
randomization stratification factors) method proposed by Miettinen and Nurminen.9  
Omadacycline will be considered non-inferior to linezolid if the lower bound of the CI is greater 
than -0.10. 
Early Clinical Response and Investigator’s Assessment of Clinical Response at PTE will be 
tested separately and are not co-primary endpoints.  The probability for approving an ineffective 
drug based on PTE efficacy is  2.5%, regardless of the result for the Early Clinical Response 
endpoint and vice versa.  An adjustment would only be required if winning on at least 1 endpoint 
would result in global approval which is not the case here.  In addition, no alpha adjustment is 
needed for the co-primary efficacy endpoints for the EMA (mITT and CE populations) since NI 
must be shown in both populations to conclude NI.  Hence there will be no adjustment for 
multiple endpoints. 
 
Additional Analyses of the Primary Efficacy Outcomes 
22.4.4
Additional and sensitivity analyses of the primary efficacy outcomes (Early Clinical Response 
and Investigator’s Assessment of Clinical Response at PTE) will be performed.  Analyses for the 
FDA primary efficacy outcome will be described here and in more detail in the SAP.  Analyses 
for the EMA primary efficacy outcome will be described in the SAP. 
If the null hypothesis of inferiority is rejected for the Early Clinical Response in the mITT 
population and the observed success response proportion for omadacycline is larger than the 
observed proportion for linezolid, a formal statistical analysis of superiority will be conducted.  
If the lower limit of the 2-sided 95% CI for the treatment difference is greater than 0%, 
omadacycline will be considered superior to linezolid. 


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The primary efficacy outcome will be assessed separately across the stratification factors of type 
of infection and receipt of allowed antibacterial therapy in the 72 hours prior to randomization 
stratum by treatment group.  For each type of infection stratum and each prior antibacterial 
therapy stratum, a 2-sided 95% CI for the observed difference in Early Clinical Response rates 
will be calculated for the mITT population.  Additional subgroup analyses of the primary 
efficacy outcome may be conducted as descriptive analyses.  
Sensitivity analyses include:  conducting an adjusted analysis of the primary efficacy outcome 
based on the randomized stratum and separately, based on the stratum the subject actually 
belongs, and conducting an analysis where all subjects with an Indeterminate response are 
considered Clinical Successes. 
22.5 Analysis of Secondary Variables 
Analyses for the FDA secondary outcomes will be described here and in more detail in the SAP.  
Analyses for the EMA secondary outcomes will be described in the SAP.  The number and 
percentage of subjects classified as a Clinical Success, Clinical Failure and Indeterminate by the 
Investigator’s Assessment at PTE in the mITT and CE populations (by definition subjects with 
an Indeterminate response are excluded from the CE population) will be calculated for each 
treatment group.  A 2-sided unadjusted 95% CI will be constructed for the observed difference in 
the clinical success rate using the method of Miettinen and Nurminen.9  For Investigator’s 
Assessment of Clinical Response at PTE in the mITT and CE populations the 2-sided 95% CI is 
for descriptive purposes only and no conclusion of NI will be made.   
The number and percentage of subjects in each treatment group in each response category for 
Early Clinical Response will be presented for the micro-mITT population.  The number and 
percentage of subjects who are classified as a Clinical Success and Clinical Failure by the 
investigator at the PTE visit in the ME population will be calculated.  Two-sided unadjusted 95% 
CI will be constructed for the observed difference in the clinical success rates using the method 
of Miettinen and Nurminen.9 
The number and percentage of subjects with an Early Clinical Response of success and an 
Investigator’s Assessment of Clinical Response at PTE of Clinical Success by pathogen 
(including Gram-negative causative pathogens and MRSA) will be provided in the micro-mITT 
and ME populations.  
22.6 Analysis of Additional Efficacy Variables 
Additional efficacy analyses will be conducted to support the efficacy findings of the primary 
and secondary outcomes.  CIs will be determined for descriptive purposes, but no conclusions of 
NI will be made.  
The number and percentage of subjects classified as an Early Clinical Success, Clinical Failure 
and Indeterminate at 48 to 72 hours after the first dose of test article in the ITT population will 
be calculated.  A 2-sided unadjusted 95% CI will be constructed for the observed difference in 
the Clinical Success rate using the method of Miettinen and Nurminen. 9  


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The number and percentage of subjects classified as a Clinical Success, Clinical Failure and 
Indeterminate by the Investigator’s Assessment at EOT in the mITT and CE populations (by 
definition subjects with an Indeterminate response are excluded from the CE population) will be 
calculated for each treatment group.  A 2-sided unadjusted 95% CI will be constructed for the 
observed difference in the clinical success rate using the method of Miettinen and Nurminen.9 
Descriptive summaries, including change from baseline where appropriate, of the clinical signs 
and symptoms (tenderness, edema, erythema, induration and drainage), complete resolution of 
the clinical signs and symptoms, temperature, ABSSSI lesion measurements (including absolute 
and percentage reduction in lesion area, eg, 0 to < 5%, 5 to < 10%, 10 to < 20%, ≥ 20%, etc., as 
detailed in the SAP), and systemic signs by study visit will be presented.   
All-cause mortality (ACM) at 15 and 30 days after the first dose of test article will be 
summarized in the ITT population.  Subjects who are lost to follow-up will be considered 
deceased for this analysis.  A 2-sided unadjusted 95% CI for the observed difference in mortality 
rates will be calculated for ACM. 
The per-subject and per-pathogen microbiologic outcomes will be provided for the micro-mITT 
and ME populations at the EOT and PTE visits.  Two-sided unadjusted 95% CIs will be provided 
for the difference in per-subject microbiological favorable outcome rates.   
A concordance analysis of Early Clinical Response and Investigator’s Assessment of Clinical 
Response at PTE in the mITT analysis set will also be presented. 
22.7 Safety Outcome Measures 
Safety variables include the incidence rate of AEs, change in vital signs, ECG parameters and 
laboratory test results obtained during the course of the study.  For safety analyses for both the 
FDA and EMA, subjects will be analyzed according to the treatment actually received.  
 
Adverse Events 
22.7.1
Summary tables will be provided for all treatment-emergent adverse events (TEAEs).  A TEAE 
is defined as an AE with a start date and time on or after the first dose of test article.  AEs will be 
coded using the Medical Dictionary for Regulatory Activities (MedDRA) and will be 
summarized by presenting the number and percentage of subjects having each TEAE for each 
treatment group by system organ class (SOC) and preferred term (PT).  Additional tabulations 
will provide summaries by SOC and PT of subjects experiencing SAEs, severe TEAEs, TEAEs 
judged to be related to test article, TEAEs leading to discontinuation of test article, and TEAEs 
of special interest. 
 
Vital Signs 
22.7.2
The following variables will be analyzed descriptively: 
• Vital signs (systolic and diastolic BP, pulse rate, body temperature, respiratory rate), 
including change from Screening by visit 


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• Clinically notable vital signs (meeting predefined criteria as specified in the SAP) by visit 
Subjects with notable vital signs data will be listed. 
 
Electrocardiograms 
22.7.3
ECG data (RR interval, PR interval, QRS interval, QTc, QTc Bazett’s Correction Formula 
[QTcB], and QTc Fridericia’s Correction Formula [QTcF]) will be summarized descriptively at 
each scheduled evaluation, as noted in Section 8, and for the overall worst post-Screening value.  
Changes from Screening at each visit that a 12-lead ECG is obtained will also be provided.  An 
outlier analysis will be conducted based on the worst post-Screening value.  
 
Laboratory Tests 
22.7.4
The following variables will be analyzed descriptively: 
• Laboratory variables by visit 
• Change from Screening of laboratory variables by visit 
• Clinically notable laboratory values (meeting predefined criteria specified in the SAP) by 
visit 
Listings of individual subject laboratory data will be generated.  Values meeting predefined 
criteria for being clinically notable will be flagged within the listings. 
22.8 Resource Utilization 
The following are the variables relating to resource utilization.  Data for resource utilization will 
be collected through the Final Follow-up visit. 
• Hospitalizations including number of days hospitalized 
• number of emergency room visits  
Descriptive statistics for the resource utilization parameters will be provided by treatment group 
for the purpose of health economic evaluation.  
22.9 Pharmacokinetics 
Population PK analysis will be conducted to characterize PK parameters.  A population PK data 
set including subjects with 1 or more quantified omadacycline concentration determinations will 
be constructed from the dates and times of the doses and blood samples along with all the 
bioanalytical determinations and subject background information.  If the actual date or time for a 
blood sample or dose is missing, the related bioanalytical determination of the PK concentration 
will be excluded from all analyses.  Omadacycline concentrations below the limit of 
quantification will be treated as missing data in summary statistics and for the calculation of PK 
parameters. 


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Variables including age (years), body weight (kg), gender, and race/ethnicity along with other 
covariates previously determined to be important will be incorporated into the population PK 
database.  Based on the subjects in the population analysis data set, descriptive summaries at 
Screening for these variables will be reported.  Outliers may be excluded from the analysis.  
These will be determined by a scatter plot of the observed concentration versus time post dose 
reported.  The distribution of the number of samples contributed per subject to the model-based 
analysis will be tabulated.  Also, simple summary descriptive statistics for the concentration of 
samples by study day or week will be computed. 
 
Population PK Modeling 
22.9.1
Results from Phase 1 studies indicate that omadacycline PK is linear and that following 
intravenous infusion, plasma concentration-time profiles show a 3-compartmental disposition.  
Therefore, the probable structural PK model would be a 3-compartment model with zero order 
input for iv infusion and first order input for po administration.  This PK model contains the 
parameters clearance, volume of distribution, bioavailability and absorption rate constant.  The 
associated population models are nonlinear mixed-effects models.  The population model adds 
random effects and covariates for the PK parameters in order to recognize differences among 
individuals and similarities across observations corresponding to the same subject.  At the time 
of the population modeling, previously reported structural PK models will be considered first.  A 
residual error model combining additive error and proportional error will also be initially 
considered.  Simplifications (eg, fewer random affects or an alternative residual error model) 
may be appropriate if the diagnostics for the model suggest false convergence.  Additional 
covariates will be investigated graphically (gender, race/ethnicity, age) as part of the model 
diagnostics and some may be retained in the final model and additional ones in a competing 
model to deliver estimates of arguably insignificant effects.  Scatter plots of the observed 
concentrations versus population-estimated and individually estimated concentrations will be 
used as part of the overall assessment of the overall quality of the fit.  During modeling, the 
broad principles outlined by the FDA10 will be followed. 
The individual model-based exposure measures at steady state (area under the curve [AUC]0-24,ss, 
time to maximum plasma concentration [Tmax,ss], maximum plasma concentration [Cmax,ss]) will 
be computed and summarized. 
22.10 Pharmacogenetics/Pharmacogenomics 
Pharmacogenetics/pharmacogenomics studies are not planned as part of this protocol. 
22.11 Biomarkers 
Not applicable. 
22.12 PK/PD 
The relationship between omadacycline exposure and response (efficacy and safety) will be 
examined as appropriate for the data.  A population PK model will be used to calculate 
individual subject AUCs and, subsequently, possible AUC/MIC breakpoints. 


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22.13 Sample Size Calculation 
The study is designed to show NI in the primary efficacy outcome of Early Clinical Response at 
48 to 72 hours following the first dose of test article in the mITT population.  An NI margin of 
10% will be used for the analysis in the mITT population.  The NI margin was based on an 
analysis of the historical data regarding the treatment effect of antibiotics in ABSSSI. 
In the po study of tedizolid versus linezolid, the rates of Early Clinical Response were 79% in 
both treatment arms in the ITT population.11  Thus, an outcome rate of 79% in the mITT 
population was used for determination of the sample size.  For the Early Clinical Response 
primary efficacy endpoint, assuming an outcome rate of 79% for both treatment groups, NI 
margin of 10%, 90% power and a 1-sided alpha of 0.025, using the sample size determination 
method of Farrington and Manning,12 a total of 704 subjects are required.   
The rates of clinical success based on the Investigator’s Assessment at PTE were 86% in the ITT 
population and 95% in the CE population for linezolid, in the recent po clinical study in ABSSSI 
subjects.11  To be conservative, outcome rates of 85% in the mITT and 90% in the CE population 
are used for the sample size determination.  Assuming an 85% outcome rate in both treatment 
groups, NI margin of 10%, and a 1-sided alpha of 0.025, with a total of 704 subjects, there is 
more than 90% power to show NI for Investigator’s Assessment of Clinical Response at PTE in 
the mITT population.  With an evaluability rate of 80%, there will be 564 subjects in the CE 
population.  Assuming a 90% outcome rate in both treatment groups, NI margin of 10% and a 
1-sided alpha of 0.025, 564 subjects provides more than 90% power to show NI in the CE 
population. 
Thus, a total of 704 subjects provide sufficient power for the primary efficacy analyses for both 
the FDA and EMA regulatory authorities.  A summary of the sample size calculations and 
assumptions is provided in Table 6. 
Table 6. 
Sample Size and Power Calculations 
 
Primary Efficacy Outcome 
FDA 
(Early Clinical Response) 
Primary Efficacy Outcome EMA 
(Investigator’s Assessment of Clinical Response at 
PTE) 
Population 
mITT 
mITT 
CE 
N 
704 
704 
564 
Outcome Rate 
79% 
85% 
90% 
Evaluability Rate 
N/A 
N/A 
80% 
Power 
90% 
96% 
97% 
CE = clinically evaluable; EMA = European Medicines Agency; FDA = United States Food and Drug 
Administration; mITT = modified intent-to-treat; N = number; N/A = not applicable; PTE = post therapy evaluation. 
 
22.14 Interim Analyses 
No interim analyses of efficacy are planned. 


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22.15 Handling of Missing Values/Censoring/Discontinuations 
Missing values will not be imputed for primary and secondary efficacy and safety analyses 
(except as detailed in the SAP for missing dates) and only observed values will be used in data 
analyses and presentations.  For the primary efficacy outcome measure, if any data field needed 
to determine the response is missing the subject will be assigned an Indeterminate response.  For 
analyses of the primary efficacy outcome, subjects with an Indeterminate response are included 
in the denominator, and thus, are considered Clinical Failures.  A sensitivity analysis of the 
primary efficacy outcome will be conducted in which subjects with an Indeterminate response 
are considered Clinical Successes.   
For the secondary outcome measure of Investigator’s Assessment of Clinical Response at PTE in 
the mITT population (co-primary for the EMA analysis), subjects with missing data are assigned 
an Indeterminate response.  Subjects with an Indeterminate response are included in the 
denominator, and thus, are considered failures.  Table 7 provides a summary of the handling of 
missing/indeterminate outcomes for the Investigator’s Assessment of Clinical Response at PTE. 
Table 7. 
Investigator’s Assessment of Clinical Response at PTE Determination 
Considering Missing Data   
EOT Visit 
PTE Visit 
Overall Assessment of Clinical Response at 
PTE (Investigator’s Assessment) 
Missing/indeterminate 
Success 
Indeterminate 
Missing/indeterminate 
Failure 
Failure 
Missing/indeterminate 
Missing/indeterminate 
Indeterminate 
Success 
Missing/indeterminate 
Indeterminate 
Failure 
Missing/indeterminate 
Failure 
EOT = end of treatment; mITT = modified intent-to-treat population; PTE = post therapy evaluation. 
For the analysis in the mITT analysis set of Investigator’s Assessment of Clinical Response at PTE, indeterminate 
responses are included in the denominator and are thus considered clinical failures. 
Missing data are handled in a similar manner for the outcome of microbiological response at PTE.   
 SUBJECT IDENTIFICATION 
23
Each subject in the study is assigned a unique subject number and must keep that number 
throughout the study even if he/she transfers to another site.  A subject who discontinues 
participation or is withdrawn before receiving a treatment assignment code, and who re-enrolls at 
a later time will be assigned a new subject number and recorded as rescreened.  The investigator 
must maintain a subject master log of all subjects.  
 TEST ARTICLE ACCOUNTABILITY, RECONCILIATION, AND 
24
RETURN 
The investigator must maintain a complete and current dispensing and inventory record that has 
been supplied by the sponsor.   


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All unused test articles must be returned in the original containers or destroyed at the site with 
approval of the sponsor.  Test articles can only be returned or destroyed after the sponsor has 
performed accountability.  Test article return/destruction must be documented.   
24.1 Supply, Storage and Tracking of Test Article 
Test article must be received at the study site by a designated person, handled and stored safely 
and properly, and kept in a secured location to which only the investigator and designated staff 
have access.  Upon receipt, the test article should be stored according to the instructions 
specified on the drug labels.  Storage conditions must be adequately monitored and appropriate 
temperature logs maintained as source data. 
The designated study personnel must maintain an accurate record of the shipment and dispensing 
of test articles in the study specific medication accountability ledger.  Test article supplies are 
completely blinded.  Monitoring of oral medication accountability will be performed by the field 
monitor during site visits and at the completion of the study.  Subjects will be asked to return all 
unused test article and packaging at each visit and at the end of the study, last study visit or at the 
time of test article discontinuation.  
At the conclusion of the study, and as appropriate during the course of the study, with instruction 
from the sponsor, the designated study personnel will destroy on site or return all unused test 
articles, packaging, drug labels, and send a copy of the completed medication accountability 
ledger to the monitor or to the address provided to the investigator. 
 RANDOMIZATION AND BLINDING 
25
25.1 Treatment Assignment 
All eligible subjects will be randomized via an IxRS that assigns them to 1 of the treatment arms 
(in a 1:1 ratio).  The site delegate will contact the IxRS (via phone or web) after confirming that 
the subject fulfills all the inclusion criteria and none of the exclusion criteria.  The IxRS will 
assign a test article to the subject based on a computer-generated randomization schedule.  The 
randomization will be a blocked randomization sequence stratified by type of infection (wound 
infection, cellulitis/erysipelas or major abscess) and receipt of an allowed antibacterial therapy 
(see Appendix 1) in the 72 hours prior to randomization as defined in the IxRS specifications and 
SAP.  Subjects randomized into the study will be assigned the treatment corresponding to the 
next available number in the respective stratum of the computer-generated randomization 
schedule.  The subject is considered randomized when the IxRS provides the test article 
assignment, regardless of whether the subject actually receives any medication.  Enrollment of 
subjects with major abscess will be capped at 30% of the subjects randomized.  Enrollment of 
subjects who have received an allowed antibacterial therapy in the 72 hours prior to 
randomization will be capped at 25% of the subjects randomized.   


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25.2 Dispensing the Test Article 
Each study site will be supplied by the sponsor with the investigational product and comparator.  
Test articles will be supplied to the sites in kits that contain active omadacycline tablets or 
matched placebo tablets, and active linezolid over-encapsulated tablets or matched placebo over-
encapsulated tablets.  Oral test article supplies are completely blinded and blinded study 
personnel can conduct storage, dispensation, and reconciliation.  The IxRS will instruct the 
designated study personnel as to the appropriate test article kit to be administered. The study 
coordinator/staff will instruct the subject on the use of po test article.   
25.3 Treatment Blinding 
The investigator and sponsor will be blinded to treatment arm assignments throughout the study.  
The sponsor designee (eg, study statistical team, IxRS vendor, etc.) will have a designated 
randomization administrator who will maintain the randomization codes in accordance with 
standard operating procedures to ensure the blind is properly maintained, and that only sponsor 
personnel who require knowledge of treatment assignments will be unblinded (eg, staff involved 
in maintaining the randomization codes or SAE reporting).  
The study will follow a double-dummy design.  Subjects assigned to omadacycline will receive 
active omadacycline tablets and over-encapsulated linezolid placebo tablets.  Subjects assigned 
to the linezolid arm will receive omadacycline placebo tablets and over-encapsulated active 
linezolid tablets.  
Randomization data are kept strictly confidential until the time of database lock and unblinding 
at the end of the study.  
All eCRFs must be completed, entered and checked; all safety laboratory results must have been 
reported; all AEs must have been fully characterized (eg, relationship to test article determined) 
and coded; and all queries must have been resolved prior to database lock and unblinding.  
Determination of inclusion in the analysis populations, characterization of protocol deviations as 
major/minor and final approval of the SAP will also be completed prior to database lock. 
Plasma samples for subjects receiving omadacycline may be analyzed during the course of the 
study.  To permit the sponsor to review the drug concentration data prior to locking the dataset 
and without unblinding, any PK data provided prior to unblinding will be re-coded by the 
bioanalytic laboratory to avoid revealing the individual subject numbers. 
Unblinding is only to occur in the case of subject emergencies (see Section 25.4) and at the 
conclusion of the study. 
25.4 Emergency Unblinding of Treatment Assignment 
Emergency unblinding should only be undertaken when it is essential to treat the subject safely 
and efficaciously.  Most often, test article discontinuation and knowledge of the possible 
treatment assignments are sufficient to treat a study subject who presents with an emergency 
condition.  It is encouraged for the investigator, when contemplating unblinding, to contact the 


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sponsor or sponsor’s designated Medical Monitor or designee to confirm the need to unblind, 
prior to unblinding.  However, if required, the investigator can unblind without consulting the 
Medical Monitor. 
Emergency code breaks are performed using the IxRS.  When the investigator contacts the 
system to unblind a subject, he/she must provide the requested subject identifying information 
and confirm the necessity to unblind the subject.  The investigator will then receive details of the 
drug treatment for the specified subject and a fax or e-mail confirming that the treatment 
assignment of the subject was unblinded.  The system will automatically inform the sponsor’s 
monitor for the site and the sponsor that the code has been broken. 
It is the investigator’s responsibility to ensure that there is a procedure in place to allow access to 
the IxRS code break information in case of emergency.  The investigator will inform the subject 
how to contact his/her backup in cases of emergency when he/she is unavailable.  The 
investigator will provide protocol number, test article name if available, subject number, and 
instructions for contacting the sponsor (or any entity to which it has delegated responsibility for 
emergency code breaks) to the subject in case emergency unblinding is required at a time when 
the investigator and backup are unavailable. 
In the event of a medical emergency in which the investigator judges that the subject cannot be 
managed safely without unblinding, the investigator may obtain the treatment allocation directly 
from the research pharmacist.  All steps outlined above will be followed, including contacting 
the Medical Monitor as soon as possible and not more than 24 hours afterwards.  It will be the 
responsibility of all study personnel to ensure that, except for the above procedure, investigator 
blinding is maintained until after study completion. 
 SUBJECT DISCONTINUATION OR WITHDRAWAL  
26
Reasons why a subject may discontinue or be withdrawn from the study include, but are not 
limited to, AE, subject request, protocol violation, subject noncompliance, and study termination 
by the sponsor.  Subjects may voluntarily withdraw from the study for any reason at any time.  
Subjects are considered withdrawn from the study if they state an intention to withdraw, or fail to 
return for visits, or become lost to follow-up for any other reason.  If premature withdrawal from 
the study occurs for any reason, the investigator should determine the primary reason for a 
subject’s premature withdrawal from the study and record this information on the eCRF. 
Subjects who discontinue study treatment (unless that subject withdraws informed consent) 
should NOT be considered withdrawn from the study.  The date and primary reason for 
discontinuation of study treatment should be recorded in source documents.  Subjects who 
discontinue the study treatment should have the EOT visit and the procedures listed for that visit 
in Section 8, a PTE visit and a Final Follow-up Assessment, if possible.  The site should also 
collect subject safety information through the Final Follow-up assessment.   
Site personnel should also contact the IxRS to register the subject’s discontinuation from test 
article.   


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For subjects who are lost to follow-up, the investigator should show "due diligence" by 
documenting in the source documents steps taken to contact the subject, eg, dates of telephone 
calls, registered letters, etc. 
Subjects who are prematurely withdrawn from the study will not be replaced by an equal number 
of newly enrolled subjects. 
 STUDY SUSPENSION, TERMINATION, AND COMPLETION 
27
27.1 Study Completion and Post-Study Test Article 
A subject will have successfully completed the study after the planned test article regimen has 
been administered, and all assessments and visits have been made.  Visits include the final 
follow-up visit (Final Follow-up).  The study will be completed when the last subject has either 
discontinued or completed the Final Follow-up visit.   
No long-term follow-up of subjects is planned, with the exception of pregnancies, as described in 
Section 21.2.6, and SAEs described in Section 21.2. 
Sites will be notified by either the Sponsor or IxRS to stop enrollment when the desired number 
of treated subjects have been enrolled.  Subjects already consented will be allowed to continue in 
the study. 
Upon study completion, the investigator will provide the sponsor, IRB/IEC/REB, and regulatory 
agency with final reports and summaries as required by regulations.  The investigator must 
submit a written report to the sponsor and the IRB/IEC/REB within 3 months after the 
completion or termination of the study. 
27.2 Study Suspension or Termination 
The sponsor may suspend or terminate the study or part of the study at any time for any reason.  
Should this be necessary, subjects should be seen as soon as possible and treated as described in 
Section 26 for prematurely withdrawn subjects.  The investigator may be informed of additional 
procedures to be followed in order to ensure that adequate consideration is given to the 
protection of the subject’s interests.  The investigator will be responsible for informing 
Institutional Review Boards (IRBs) and/or Ethics Committees (ECs) of the early termination of 
the study. 
If the investigator suspends or terminates the study, the investigator will promptly inform the 
sponsor and the IRB/IEC/REB and provide them with a detailed written explanation.  Subjects 
should be seen as soon as possible and treated as described in Section 26 for prematurely 
withdrawn subjects.  The investigator will also return all test articles, containers, and other study 
materials to the sponsor. 


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 ETHICAL CONSIDERATIONS 
28
28.1 Regulatory and Ethical Compliance 
This clinical study was designed and shall be implemented and reported in accordance with the 
ICH Harmonized Tripartite Guideline for Good Clinical Practice (GCP), with applicable local 
regulations (including European Directive 2001/20/EC, United States [US] Code of Federal 
Regulations [CFR] Title 21, and Japanese Ministry of Health, Labor, and Welfare), and with the 
ethical principles laid down in the Declaration of Helsinki. 
28.2 Informed Consent Procedures 
The investigator will provide for the protection of the subjects by following all applicable 
regulations.  These regulations are available upon request from the sponsor.  The ICF must be 
reviewed by the sponsor and approved by the IRB/IEC/REB. 
Before any procedures specified in the protocol are performed, a subject must: 
• Be informed of all pertinent aspects of the study and all elements of informed consent  
• Be given time to ask questions and time to consider the decision to participate 
• Voluntarily agree to participate in the study 
• Sign and date an IRB/IEC/REB approved ICF 
28.3 Responsibilities of the Investigator and IRB/IEC/REB 
The protocol and the proposed ICF must be reviewed and approved by a properly constituted 
IRB/IEC/REB before study start.  A signed and dated statement that the protocol and ICF have 
been approved by the IRB/IEC/REB must be given to the sponsor before study initiation.  Prior 
to study start, the investigator is required to sign a protocol signature page confirming his/her 
agreement to conduct the study in accordance with these documents and all of the instructions 
and procedures found in this protocol, and to give access to all relevant data and records to the 
sponsor monitors, auditors, designated agents of the sponsor, IRBs/IECs/REBs, and regulatory 
authorities as required.  If an inspection of the clinical site is requested by a regulatory authority, 
the investigator must inform the sponsor immediately that this request has been made. 
 PROTOCOL ADHERENCE 
29
Investigators ascertain they will apply due diligence to avoid protocol deviations.  Under no 
circumstances should the investigator contact the sponsor or its agents to request approval of a 
protocol deviation, as no authorized deviations are permitted.  If the investigator feels a protocol 
deviation would improve the conduct of the study this must be considered a protocol 
amendment, and unless such an amendment is agreed upon by the sponsor and approved by the 
IRB/IEC/REB, it cannot be implemented.  All significant protocol deviations will be recorded 
and reported in the clinical study report (CSR). 


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29.1 Protocol Amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by the sponsor, Health Authorities where required, and the IRB/IEC/REB.  
Only amendments that are required for subject safety may be implemented prior to 
IRB/IEC/REB approval.  Notwithstanding the need for approval of formal protocol amendments, 
the investigator is expected to take any immediate action required for the safety of any subject 
included in this study, even if this action represents a deviation from the protocol.  In such cases, 
the sponsor should be notified of this action and the IRB/IEC/REB at the study site should be 
informed within 10 working days. 
 QUALITY CONTROL AND ASSURANCE 
30
The sponsor performs quality control and assurance checks on all clinical studies that it sponsors.  
Before enrolling any subjects in this study, sponsor personnel and the investigator review the 
protocol, the Investigator’s Brochure, the case report forms (CRFs) and instructions for their 
completion, the procedure for obtaining informed consent, and the procedure for reporting AEs 
and SAEs.  A qualified representative of the sponsor monitors the conduct of the study by 
visiting the site and by contacting the site by telephone and e-mail.  During these site visits, 
information recorded in the CRFs is verified against source documents. 
 DIRECT ACCESS, DATA HANDLING, AND RECORD-KEEPING 
31
31.1 Investigator 
The investigator will permit study-related monitoring, audits, IRB/IEC/REB review, and 
regulatory inspections by providing direct access to source data and documents. 
All information will be recorded on source documents.  All required data will be recorded in the 
eCRFs. 
If an investigator retires, relocates, or otherwise withdraws from conducting the study, the 
investigator must notify the sponsor to agree upon an acceptable storage solution.  Regulatory 
agencies will be notified with the appropriate documentation. 
An updated form 1572 will be filed with the sponsor for any changes in the study personnel 
reported in the current form 1572. 
31.2 Sponsor 
The data is entered into an electronic database via eCRFs.  The Sponsor Medical Monitor 
reviews the data for safety information.  The data is reviewed for completeness and logical 
consistency.  Automated validation checks identify missing data, out-of-range data, and other 
data inconsistencies.  The central safety and microbiology data will be processed electronically.  
Requests for data clarification are forwarded to the investigative site for resolution. 


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 SUBJECT INJURY 
32
In general, subject to specific provisions in the clinical study agreement (CSA), if a subject is 
injured as a direct result of a test article, the sponsor will pay for reasonable and necessary 
medical treatment for the injury, to the extent that such expenses are not covered by the subject’s 
medical insurance, a government program, or other responsible third party.  If laws or 
regulations of the locality in which the study is taking place require additional payment of 
expenses, the sponsor shall comply with such laws or regulations.  Where applicable, the sponsor 
has taken specific national insurance. 
 PRESTUDY DOCUMENTATION 
33
The investigator must provide the sponsor with the following documents BEFORE enrolling any 
subjects: 
• Completed and signed form 1572 
• All applicable country-specific regulatory forms 
• Current signed and dated curricula vitae for the investigator, sub-investigators, and other 
individuals having significant investigator responsibility who are listed on the form 1572 or 
equivalent, or the clinical study information form 
• Copy of the IRB/IEC/REB approval letter for the protocol and informed consent.  All 
advertising, recruitment, and other written information provided to the subject must be 
approved by the IRB/IEC/REB.  Written assurance of continuing approval (at least annually) 
as well as a copy of the annual progress report submitted to the IRB/IEC/REB must also be 
provided to the sponsor.   
• Copy of the IRB/IEC/REB-approved informed consent document to be used 
• Where applicable, a list of the IRB/IEC/REB members and their qualifications, and a 
description of the committee’s working procedure 
• Copy of the protocol sign-off page signed by the investigator 
• Fully executed CSA 
• Where applicable, a financial disclosure form 
• A written document containing the name, location, certification number, and date of 
certification of the laboratories to be used for laboratory assays and those of other facilities 
conducting tests.  This document should be returned along with the statement of investigator 
form.  The sponsor must be notified if the laboratory is changed or if any additional 
laboratory is to be used.  
• List of normal laboratory values and units of measure for all laboratory tests required by the 
protocol.  This is required for each laboratory to be used during the study.  The sponsor must 
be notified if normal values or units of measurement change. 
 


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 RECORDS RETENTION 
34
The investigator shall retain and preserve 1 copy of all data generated in the course of the study, 
specifically including but not limited to those defined by GCP as essential, for the longer of:  (a) 
2 years after the last marketing authorization for the investigational test article has been approved 
or the sponsor has discontinued its research with respect to such investigational test article or (b) 
such longer period as required by applicable global regulatory requirements.  At the end of such 
period, the investigator shall notify the sponsor in writing of its intent to destroy all such 
material.  The sponsor shall have 30 days to respond to the investigator’s notice, and the sponsor 
shall have a further opportunity to retain such materials at the sponsor’s expense. 
 PUBLICATION POLICY 
35
The sponsor assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov.  In addition, upon study completion and 
finalization of the study report, the results of this study will be either submitted for publication 
and/or posted in a publicly accessible database of clinical study results. 
Upon completion of the study, the investigator may publish the results in recognized (refereed) 
scientific journals subject to the provisions of the CSA.  Unless otherwise specified in the CSA, 
the following process shall occur: 
The institution and Principal Investigator (PI) shall not publish or present data from an individual 
study center until the complete multi-center study has been presented in full or for 2 years after 
the termination of the multi-center study, whichever occurs first.  Subsequent publications must 
refer to the multi-center findings.  Thereafter, if the PI expects to participate in the publication of 
data generated from this site, the institution and PI shall submit reports, abstracts, manuscripts, 
and/or other presentation materials to the sponsor for review before submission for publication or 
presentation.  The sponsor shall have 60 days to respond with any requested revisions, including, 
without limitation, the deletion of confidential information.  The PI shall act in good faith upon 
requested revisions, except that the PI shall delete any confidential information from such 
proposed publication.  The PI shall delay submission of such publication or presentation 
materials for up to an additional 90 days in order to have a patent application(s) filed. 


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 REFERENCES (AVAILABLE UPON REQUEST) 
36
 
1. David MZ, Daum RS. 2010. Community-Acquired Methicillin-Resistant Staphylococcus 
aureus:  Epidemiology and Clinical Consequences of an Emerging Epidemic. Clin. 
Microbiol. Rev. 23(3):616-87. 
2. Paratek Pharmaceuticals, Inc. 2016 Omadacycline/PTK 0796 Investigator's Brochure, 
Edition 9.0. 
3. FDA. 2013. Guidance for Industry:  Acute Bacterial Skin and Skin Structure Infections:  
Developing Drugs for Treatment. CDER. 
4. EMA. 2011. Guideline on the evaluation of medical products indicated for treatment of 
bacterial infections. European Medicines Agency. CPMP/EWP/558/95 rev 2. 
5. EMA. 2013. Addendum to the guideline on the evaluation of medicinal products indicated 
for treatment of bacterial infections (CPMP/EWP/558/95 Rev 2), European Medicines 
Agency. EMA/CHMP/351889/2013.] 
6. Stevens DL, Bisno AL, Chambers HF, Dellinger EP, Goldstein EJC, Gorbach SL, 
Hirschmann JV, Kaplan SL, Montoya JG, Wade JC. 2014. 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. 59:10-52. 
7. Talbot GH, Powers JH, Fleming TR, Siuciak JA, Bradley J, Boucher H on behalf of the 
CABP-ABSSSI Project Team. 2012. Progress on Developing Endpoints for Registrational 
Clinical Trials of Community-Acquired Bacterial Pneumonia and Acute Bacterial Skin and 
Skin Structure Infections:  Update From the Biomarkers Consortium of the Foundation for 
the National Institutes of Health. Clin. Infect. Dis. 55:1114-21. 
8. McCaffery, M, Beebe, A. 1993. Pain: Clinical Manual for Nursing Practice. Baltimore: V.V. 
Mosby Company. 
9. Miettinen O, Nurminen M. 1985. Comparative Analysis of Two Rates. Statistics in Medicine 
4:213-26. 
10. FDA. 1999. Guidance for Industry, Population Pharmacokinetics. Center for Drug Evaluation 
and Research, U.S. Department of Health and Human Services February 1999. 
11. Prokocimer P, De Anda C, Fang E, Mehra P, Das A. 2013. Tedizolid Phosphate vs Linezolid 
for Treatment of Acute Bacterial Skin and Skin Structure Infections: The ESTABLISH-
1 Randomized Trial. JAMA. 309:559-69. 
12. Farrington CP, Manning G. 1990. Test Statistics and Sample Size Formulae for Comparative 
Binomial Trials with Null Hypothesis of Non-zero Risk Difference or Non-unity Relative 
Risk Statistics in Medicine 9:1447-54. 
 


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Appendix 1.  Allowed and Disallowed Prior Antibiotics 
Allowed Antibiotics 
(One dose within 72 hours prior to randomization*) 
Disallowed Antibiotics 
Penicillins 
Amoxicillin 
Nafcillin 
Benzathine/Penicillin-G Procaine 
Amoxicillin-Clavulanate 
Oxacillin 
 
Amoxicillin-Sulbactam 
Penicillin-G or -V 
 
Ampicillin 
Piperacillin 
 
Ampicillin-Sulbactam 
Piperacillin-Tazobactam 
 
Dicloxacillin 
Ticarcillin-Clavulanate 
 
Cephalosporins 
Cefaclor 
Cefpodoxime 
Cefixime (400 mg) 
Cefadroxil 
Cefprozil 
Ceftriaxone 
Cefazolin 
Ceftaroline 
Cefdinir 
Ceftazidime 
Cefepime 
Ceftibuten 
Cefixime (200 mg) 
Cefuroxime 
Cefditoren 
Cephalexin 
Cefotaxime 
Loracarbef 
Carbapenems 
Doripenem 
Imipenem 
Meropenem 
Ertapenem 
Glycopeptides 
Televancin 
Dalbavancin 
Vancomycin 
Oritavancin 
Fluoroquinolones 
Ciprofloxacin 
Levofloxacin 
Moxifloxacin 
Macrolides 
Clarithromycin 
Erythromycin 
Azithromycin 
Clarithromycin XL 
Tetracyclines 
Doxycycline (100 mg) 
Minocycline 
Doxycycline (200 mg) 
Minocycline Extended Release 
Tigecycline 
Oxazolidinones 
 
Linezolid  
Tedizolid 
Miscellaneous 
Clindamycin 
Metronidazole 
Trimethoprim-sulfamethoxazole/Co-trimoxazole 
 
*Prior (within 72 hours prior to randomization) administration of potentially effective systemic antibacterial therapy 
is an exclusion criterion; however, subjects may be eligible for the study despite prior antimicrobial therapy if they 
received a single dose of a short-acting systemic antibiotic within 72 hours prior to randomization.  For the purposes 
of this protocol, short-acting is defined as having a dosage frequency of more than once a day.  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. 


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Appendix 2.  Equations and Conversion Factors 
1. Cockcroft-Gault equation to calculate creatinine clearance (CrCL) (relevant to Exclusion 
Criterion number 8): 
 
(140-age[yrs]) * weight [kg] * (Z) 
Z = 1.0, if Male 
Z = 0.85, if Female 
Cr [mg/dL] * 72 
 
2. mm3 = µL 
 
3. cc = mL 
 
4. Conversion of immature neutrophils (band) forms in K/µL or K/mL to % bands (relevant to 
Inclusion Criterion number 4 and Exclusion Criterion number 11): 
[(bands K/µL)/(total WBC K/µL)] × 100 = % bands 
Or 
[(bands K/mL)/(total WBC K/mL)] × 100 = % bands 
 
 

SAP_001.pdf: 
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Statistical Analysis Plan:  PTK0796-ABSI-16301 - Version 1.0 
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Statistical Analysis Plan:  PTK0796-ABSI-16301 
Study Title: 
A Phase 3 Randomized, Double-Blind, Multi-Center Study to 
Compare the Safety and Efficacy of Oral Omadacycline to 
Oral Linezolid for Treating Adult Subjects with Acute 
Bacterial Skin and Skin Structure Infection (ABSSSI) 
Study Number: 
PTK0796-ABSI-16301 
Study Phase:  
3 
Sponsor: 
Paratek Pharma, LLC 
A wholly-owned subsidiary of Paratek Pharmaceuticals, Inc. 
75 Park Plaza, 4th Floor 
Boston, MA 02116 USA 
Tel:  +1 617-275-0040 
1000 First Ave 
Suite 400 
King of Prussia, PA 19406 
P.O. Box 120828 
Boston, MA 02111 
Version 
Final 1.0 
Date: 
May 24, 2017 
Confidentiality Statement 
This document contains confidential and proprietary information, and is not to 
be distributed to any third party. 
NCT02877927 


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1 TABLE OF CONTENTS 
1 
TABLE OF CONTENTS .........................................................................................................2 
LIST OF TABLES ...........................................................................................................................4 
LIST OF APPENDICES ..................................................................................................................4 
2 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ...........................................5 
3 
INTRODUCTION ....................................................................................................................6 
4 
TRIAL OBJECTIVES ..............................................................................................................7 
4.1 
Primary Objectives ...............................................................................................................7 
4.2 
Secondary Objectives ...........................................................................................................7 
5 
STUDY DESIGN CONSIDERATIONS ..................................................................................8 
5.1 
Study Design ........................................................................................................................8 
5.1.1 
Sample Size ....................................................................................................................8 
5.1.2 
Randomization and Masking .........................................................................................9 
5.2 
Efficacy Measures ..............................................................................................................10 
5.2.1 
Primary Efficacy Outcome ..........................................................................................10 
5.2.2 
Secondary Efficacy Outcomes .....................................................................................11 
5.2.2.1 
Investigator’s Assessment of Clinical Response ...................................................11 
5.2.2.2 
Microbiologic Outcomes .......................................................................................14 
5.3 
Safety Measures .................................................................................................................17 
5.4 
Pharmacokinetic Parameters ..............................................................................................17 
6 
STUDY POPULATIONS .......................................................................................................18 
6.1 
Analysis Populations ..........................................................................................................18 
6.1.1 
Intent-to-Treat (ITT) Population ..................................................................................18 
6.1.2 
Safety Population .........................................................................................................18 
6.1.3 
Modified Intent-to-Treat (mITT) Population ...............................................................18 
6.1.4 
Microbiological Modified Intent-to-Treat (micro-mITT) Population .........................18 
6.1.5 
Clinically Evaluable (CE) Populations ........................................................................20 
6.1.5.1 
Diagnosis of ABSSSI .............................................................................................20 
6.1.5.2 
Prior Antibiotic Therapy ........................................................................................21 
6.1.5.3 
Concomitant Antibiotic Therapy ...........................................................................21 
6.1.5.4 
Concomitant Surgical Procedures ..........................................................................22 
6.1.5.5 
Test Article Therapy ..............................................................................................22 
6.1.5.6 
Clinical Outcome Assessment ...............................................................................23 
6.1.5.7 
Baseline Medical Events ........................................................................................23 
6.1.6 
Microbiologically Evaluable (ME) Populations ..........................................................24 
6.2 
Evaluability Review Team .................................................................................................24 
6.2.1 
Membership and Responsibilities ................................................................................24 
6.2.2 
Process for Determining Inclusion in Populations .......................................................24 
6.3 
Subgroups ..........................................................................................................................25 
7 
CHANGES IN CONDUCT OR PLANNED ANALYSES FROM THE PROTOCOL .........26 


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8 
OVERALL STATISTICAL CONSIDERATIONS ................................................................27 
8.1 
General Conventions ..........................................................................................................27 
8.2 
Baseline Definition ............................................................................................................27 
8.3 
Handling of Missing Data ..................................................................................................28 
8.4 
Interim Analysis .................................................................................................................29 
8.5 
Pooling Strategy for Study Sites ........................................................................................29 
8.6 
Visit Windows/Unscheduled Visits ...................................................................................29 
9 
STATISTICAL ANALYSIS METHODS ..............................................................................31 
9.1 
Subject Disposition ............................................................................................................31 
9.2 
Demographics and Baseline Characteristics ......................................................................31 
9.2.1 
Baseline Microbiology .................................................................................................33 
9.2.2 
Primary Site Procedures and Care ...............................................................................34 
9.3 
Treatment Compliance and Exposure ................................................................................34 
10 EFFICACY PARAMETERS..................................................................................................36 
10.1 
Primary Analysis ................................................................................................................36 
10.2 
Sensitivity and Additional Analyses of the Primary Efficacy Outcome ............................37 
10.3 
Secondary Analysis ............................................................................................................38 
10.4 
Additional Analyses ...........................................................................................................38 
10.5 
Interim Analysis .................................................................................................................41 
10.6 
Subgroup Analyses ............................................................................................................41 
11 SAFETY AND TOLERABILITY ..........................................................................................42 
11.1 
Adverse Events ..................................................................................................................42 
11.2 
Vital Signs ..........................................................................................................................43 
11.3 
Electrocardiogram ..............................................................................................................44 
11.4 
Laboratory Values ..............................................................................................................44 
11.5 
Physical Examinations .......................................................................................................46 
12 RESOURCE UTILIZATION ANALYSES ...........................................................................47 
13 OTHER RELEVANT DATA ANALYSES/SUMMARIES ..................................................48 
13.1 
Protocol Deviations ............................................................................................................48 
13.2 
Prior and Concomitant Medications ..................................................................................48 
14 REFERENCES .......................................................................................................................50 
15 APPENDICES ........................................................................................................................51 
 


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LIST OF TABLES 
Table 1. 
Sample Size and Power Calculations .......................................................................9 
Table 2.  
Investigator's Assessment of Clinical Response ....................................................13 
Table 3.  
Per-Pathogen Microbiological Response Definitions at the EOT and PTE Visits 14 
Table 4.  
Per-Pathogen Microbiologic Response ..................................................................15 
Table 5. 
Per-Subject Microbiologic Response .....................................................................16 
Table 6. 
Microbiological Response Definitions:  Superinfection or New Infection ...........17 
Table 7.  
Scheduled Study Visits ..........................................................................................30 
Table 8.  
Criteria for Treatment Emergent Clinically Notable Vital Signs ..........................43 
Table 9.  
Laboratory Parameters and Organ Class ................................................................45 
 
LIST OF APPENDICES 
Appendix 1 Schedule of Events .....................................................................................................52 
Appendix 2 Summary of Efficacy Analyses ..................................................................................55 
Appendix 3 Adverse Event and Prior/Concomitant Medication Date Imputations .......................56 
Appendix 4 Directionality of Worst Laboratory Parameters .........................................................57 
Appendix 5 Modified Division of Microbiology and Infectious Diseases Adult Toxicity Table .58 
 


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2 LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ABSSSI 
acute bacterial skin and skin structure infection 
ACM 
all-cause mortality 
AE 
adverse event 
BMI 
body mass index 
CE 
clinically evaluable 
CI 
confidence interval 
eCRF 
electronic case report form 
EMA 
European Medicines Agency 
EOT 
end of treatment 
FDA 
Food and Drug Administration 
I&D 
Incision and drainage 
IND 
Investigational New Drug  
IRB 
Institutional Review Board 
IV 
intravenous 
IxRS 
Interactive Response System 
ME 
microbiologically evaluable 
MedDRA 
Medical Dictionary for Regulatory Activities 
Mg 
milligram 
MIC 
minimum inhibitory concentration 
Micro-mITT 
microbiological modified intent to treat 
mITT 
modified intent to treat 
NDA 
New Drug Application 
NI 
non-inferior 
NSAIDs 
nonsteroidal anti-inflammatory drugs 
PD 
pharmacodynamic 
PK 
pharmacokinetic 
PO 
orally 
PR 
interval from the P wave (atrial contraction or depolarization) to the onset 
of the Q wave in the measurement of electrical activity of the 
myocardium 
PTE 
post therapy evaluation 
QTc 
QT, corrected 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
standard deviation 
TEAE 
treatment emergent adverse event 
US 
United States 


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3 INTRODUCTION 
This document presents the Statistical Analysis Plan (SAP) for the protocol 
PTK0796-ABSI-16301, “A Phase 3 Randomized, Double-Blind, Multi-Center Study to Compare 
the Safety and Efficacy of Oral Omadacycline to Oral Linezolid for Treating Adult Subjects with 
Acute Bacterial Skin and Skin Structure Infection (ABSSSI).”  The statistical plan described is 
an a priori plan and no unblinded analysis prior to the preparation of this plan has been 
conducted.  This SAP summarizes the study design and objectives, and provides details of the 
outcome definitions and statistical methods that will be used to analyze the data from protocol 
PTK0796-ABSI-16301.   
The study has been designed to address both the Food and Drug Administration (FDA) and 
European Medicines Agency (EMA) regulatory requirements; however, a separate SAP will be 
developed to address the different primary efficacy outcome and analyses for the EMA.  While 
the EMA supports the assessment of clinical response by the Investigator at a Post Therapy 
Evaluation (PTE) visit (which is scheduled to occur 7 to 14 days after the last dose of test article) 
as the primary endpoint, the FDA guidelines require using an earlier primary endpoint (48 to 
72 hours after the first dose of test article) based on reduction in lesion area. 


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4 TRIAL OBJECTIVES 
4.1 
Primary Objectives 
The primary objective of this study is to demonstrate that omadacycline administered orally for 
7 to 14 days is non-inferior to linezolid administered orally for 7 to 14 days in the treatment of 
adult subjects with ABSSSI known or suspected to be due to Gram-positive pathogens.   
4.2 
Secondary Objectives 
The secondary objectives are as follows: 
• To evaluate the safety of omadacycline in the treatment of adult subjects with ABSSSI  
• To evaluate the Clinical Response according to the identified causative pathogen 
• To evaluate the pharmacokinetics (PK) of omadacycline in adult subjects with ABSSSI 


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5 STUDY DESIGN CONSIDERATIONS 
5.1 
Study Design 
This is a randomized (1:1), double-blind, double-dummy, active comparator-controlled, Phase 3 
study comparing omadacycline and linezolid for the treatment of adults with ABSSSI that is 
known or suspected to be due to a Gram-positive pathogen(s).  Enrollment of subjects with major 
abscess may be up to 30% of randomized subjects.  Enrollment of subjects who have received a 
single dose of an allowed short-acting antibiotic within the 72 hours prior to randomization will 
be limited to no more than 25% of randomized subjects.  Subject randomization will be stratified 
across treatment groups by type of infection (wound infection, cellulitis/erysipelas or major 
abscess) and receipt of an allowed antibacterial therapy in the 72 hours prior to randomization.   
Screening evaluations, with the exception of the blood culture, will be performed within 24 hours 
prior to randomization.  The blood culture should be completed within the 24 hours prior to the 
first dose of test article.  The day of the first dose of test article is defined as Day 1 and the day 
prior is Day -1; there is no Day 0.  The study will have the following protocol-defined 
evaluations: 
• Day 1, 2, 3, 7, 10 (A Day 10 visit should be conducted for subjects with treatment extending 
beyond 9 days, unless this coincides with the End of Treatment [EOT] visit.) 
• EOT Visit:  to be conducted on the calendar day of, or within 2 days following the last dose 
of any test article.  If a subject withdraws prematurely or terminates participation in the study 
before completion, the EOT Visit should be conducted. 
• PTE Visit:  to be performed 7 to14 days after the subject’s last day of study therapy. 
• Final Follow-up assessment:  Day 30 to 37 (after the first dose of test article). 
 
A detailed Schedule of Study Procedures is provided in Appendix 1.  
5.1.1 
Sample Size 
The study is designed to show NI in the primary efficacy outcome of Early Clinical Response at 
48 to 72 hours following the first dose of test article in the modified Intent to Treat (mITT) 
population.  An NI margin of 10% will be used for the analysis in the mITT population.  The NI 
margin was based on an analysis of the historical data regarding the treatment effect of 
antibiotics in ABSSSI. 
In the po study of tedizolid versus linezolid, the rates of Early Clinical Response (ECR) were 
79% in both treatment arms in the ITT population1.  Thus, an outcome rate of 79% in the mITT 
population was used for determination of the sample size.  For the ECR primary efficacy 
endpoint, assuming an outcome rate of 79% for both treatment groups, NI margin of 10%, 90% 
power and a 1-sided alpha of 0.025, using the sample size determination method of Farrington 
and Manning2, a total of 704 subjects are required.   


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The rates of clinical success based on the Investigator’s Assessment at PTE were 86% in the ITT 
population and 95% in the CE population for linezolid, in the recent po clinical study in ABSSSI 
subjects1.  To be conservative, outcome rates of 85% in the mITT and 90% in the CE population 
are used for the sample size determination.  Assuming an 85% outcome rate in both treatment 
groups, NI margin of 10%, and a 1-sided alpha of 0.025, with a total of 704 subjects, there is 
more than 90% power to show NI for Investigator’s Assessment of Clinical Response at PTE in 
the mITT population.  With an evaluability rate of 80%, there will be 564 subjects in the CE 
population.  Assuming a 90% outcome rate in both treatment groups, NI margin of 10% and a 
1-sided alpha of 0.025, 564 subjects provides more than 90% power to show NI in the CE 
population. 
Thus, a total of 704 subjects provide sufficient power for the primary efficacy analyses for both 
the FDA and EMA regulatory authorities.  A summary of the sample size calculations and 
assumptions is provided in Table 1. 
Table 1. 
Sample Size and Power Calculations 
 
Primary Efficacy Outcome 
FDA 
(Early Clinical Response) 
Primary Efficacy Outcome EMA 
(Investigator’s Assessment of Clinical Response at 
PTE) 
Population 
mITT 
mITT 
CE 
N 
704 
704 
564 
Outcome Rate 
79% 
85% 
90% 
Evaluability Rate 
N/A 
N/A 
80% 
Power 
90% 
96% 
97% 
CE = clinically evaluable; EMA = European Medicines Agency; FDA = United States Food and Drug 
Administration; mITT = modified intent-to-treat; N = number; N/A = not applicable; PTE = post therapy 
evaluation. 
 
5.1.2 
Randomization and Masking  
All eligible subjects will be randomized via an Interactive Response System (IxRS) that assigns 
them to 1 of the treatment arms (in a 1:1 ratio).  The site delegate will contact the IxRS (via 
phone or web) after confirming that the subject fulfills all the inclusion criteria and none of the 
exclusion criteria.  The IxRS will assign a test article to the subject based on a 
computer-generated randomization schedule.  The randomization will be a blocked 
randomization sequence stratified by type of infection (wound infection, cellulitis/erysipelas or 
major abscess) and receipt of an allowed antibacterial therapy in the 72 hours prior to 
randomization (yes or no).  Subjects randomized into the study will be assigned the treatment 
corresponding to the next available number in the respective stratum of the computer-generated 
randomization schedule.  The subject is considered randomized when the IxRS provides the test 
article assignment by providing a kit number (ie, completes a randomization transaction), 
regardless of whether the subject actually receives any medication.  Enrollment of subjects with 
major abscess will be capped at 30% of the subjects randomized.  Enrollment of subjects who 
have received an allowed antibacterial therapy in the 72 hours prior to randomization will be 
capped at 25% of the subjects randomized.   


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5.2 
Efficacy Measures 
5.2.1 
Primary Efficacy Outcome 
The primary outcome measure is Early Clinical Response at 48 to 72 hours (defined 46 hours 
to < 73 hours) after the first dose of test article in the mITT population.  If more than one 
assessment of lesion size is done in the 46 to 72 hour time window, the latest will be used. 
The primary outcome will be determined programmatically based on data recorded on the eCRF 
as follows: 
Clinical Success will be defined as meeting all 3 of the following: 
• The subject is alive 
• The size of the primary lesion has been reduced ≥ 20% compared to Screening 
measurements, without receiving any rescue antibacterial therapy 
• The subject does not meet any criteria for Clinical Failure or Indeterminate (see below for 
definitions) 
 
Clinical Failure will be defined as meeting any of the criteria below: 
• The size of the primary lesion has not been reduced by ≥ 20% compared to Screening 
measurements 
• Investigator discontinued test article and indicated that the infection had responded 
inadequately such that alternative (rescue) antibacterial therapy was needed 
• The subject received antibacterial therapy that may be effective for the infection under study 
for a different infection from the one under study up through the assessment of Early Clinical 
Response (ie, lesion size) or if no assessment was done in the 46 to 72 hour time window, up 
through 72 hours after the first dose of test article. 
• The subject developed an AE that required discontinuation of test article prior to the Early 
Clinical Response assessment and alternative (rescue) antibacterial therapy was needed or if 
no assessment was done in the 46 to 72 hour time window, up through 72 hours after the first 
dose of test article. 
• Death prior to Early Clinical Response assessment or if no assessment of Early Clinical 
Response (ie, lesion size) was done in the 46 to 72 hour time window, up to 72 hours after 
the first dose of test article. 
 
Indeterminate The clinical response to test article could not be adequately inferred because: 
• Subject was not seen for Early Clinical Response assessment because they withdrew consent, 
were lost to follow-up, or other specified reason 
• Other specified reason 


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Subjects with missing data such that a response cannot be determined will be considered an 
indeterminate response.  Since indeterminates are included in the denominator of the calculation 
of Early Clinical Success, these subjects are essentially Early Clinical Failures.  For the mITT 
population, the proportion of mITT subjects with an Early Clinical Success is defined using the 
following formula: 
Number of subjects with an Early Clinical Success 
Number of subjects with an Early Clinical Failure + Number of subjects  
with a response of Indeterminate + Number of subjects with an Early Clinical Success 
 
5.2.2 
Secondary Efficacy Outcomes 
5.2.2.1 
Investigator’s Assessment of Clinical Response 
The investigator will make an assessment of Clinical Response at the EOT and PTE visits, based 
on the definitions below.  The secondary efficacy outcome is the overall assessment of clinical 
response at PTE (derived from the investigator assessments at the EOT and PTE visits) in the 
mITT and CE-PTE populations as defined in Table 2. 
5.2.2.1.1 
EOT Visit 
At the EOT visit (on the day of or within 2 days following the last dose of test article), the 
investigator will indicate the clinical status of the infection under study as detailed below. 
Clinical Success at the EOT assessment will be defined as meeting the following: 
• The subject is alive 
• The infection is sufficiently resolved such that further antibacterial therapy is not needed.  
These subjects may have some residual changes related to infection requiring ancillary (ie, 
non-antibiotic) treatment, eg, bandages on a healing wound, debridement of uninfected tissue 
(ie, necrotic) 
 
Clinical Failure will be defined as meeting any of the criteria below: 
• Investigator discontinued test article and indicated that the infection had responded 
inadequately such that alternative (rescue) antibacterial therapy was needed 
• The subject received antibacterial therapy that may be effective for the infection under study 
for a different infection from the one under study 
• The subject developed an AE that required discontinuation of test article prior to completion 
of the planned test article regimen and alternative (rescue) antibacterial therapy was needed 
• Unplanned major surgical intervention (ie, procedures that would not normally be performed 
at the bedside) for the infection under study 
• The subject died before evaluation 


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• Other specified reason as indicated on the eCRF. 
 
Indeterminate The clinical response to test article could not be adequately inferred:  
• The subject was not seen for EOT assessment because they withdrew consent, were lost to 
follow-up, or other specified reason 
• Other specified reason 
 
5.2.2.1.2 
PTE Visit 
At the PTE Visit (7 to 14 days after the subject’s last day of study therapy) the investigator will 
indicate one of the following outcomes relating to the primary infection under study:   
Clinical Success at the Post Therapy Evaluation assessment will be defined as meeting the 
following: 
• The subject is alive 
• The infection is sufficiently resolved such that further antibacterial therapy is not needed.  
These subjects may have some residual changes related to infection requiring ancillary (ie, 
non-antibiotic) treatment, eg, bandages on a healing wound, debridement of uninfected tissue 
(ie, necrotic) 
 
Clinical Failure will be defined as meeting any of the criteria below:  
• The infection required additional treatment with alternative (rescue) antibacterial therapy 
• The subject received antibacterial therapy between EOT and PTE that may be effective for 
the infection under study for a different infection from the one under study 
• Unplanned major surgical intervention (ie, procedures that would not normally be performed 
at the bedside) for the infection under study between EOT and PTE 
• The subject died before evaluation 
• Other specified reason 
 
Indeterminate The clinical response to test article could not be adequately inferred:  
• The subject was not seen for PTE assessment because they withdrew consent, were lost to 
follow-up, or other specified reason  
• Other specified reason 
 
Overall Clinical Response at PTE (based on the investigator’s assessment) is determined as 
follows (Table 2) from the investigator's assessments at the EOT and PTE Visits: 


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Table 2.  
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 
EOT = end of treatment; PTE = post-therapy evaluation. 
 
For the mITT population, the proportion of mITT subjects with a Clinical Success is defined 
using the following formula (where the denominator adds to the total number of subjects in the 
mITT population): 
Number of subjects with Clinical Success 
(Number of subjects with Clinical Success + Number of subjects with a Clinical 
Failure + Number of subjects with an Indeterminate response) 
 
By definition, subjects in the CE-EOT and CE-PTE populations cannot have an Indeterminate 
response.  Thus, for the CE-EOT and CE-PTE populations, the proportion of subjects with a 
Clinical Success is defined using the following formula: 
Number of subjects with Clinical Success 
(Number of subjects with Clinical Success + Number of subjects with a Clinical 
Failure) 
 
 


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5.2.2.2 
Microbiologic Outcomes 
Microbiological response definitions for the evaluations performed at the EOT and PTE Visits 
and analyzed in the micro-mITT and ME populations are presented in Table 3 below.  At the 
EOT and/or PTE visit, infection site specimen cultures and Gram stains should be obtained only 
for subjects who are clinical failures and require alternative antibacterial treatment for the 
infection under study. 
If a subject has the same pathogen (ie, same genus and species) identified from both an ABSSSI 
and blood specimen, a microbiological response is determined for each of the pathogens.  For 
tables summarizing microbiologic response for pathogens from the ABSSSI or blood specimen, 
if the same pathogen is isolated from both an ABSSSI and blood specimen, the worst response is 
summarized.  The microbiologic response for the ABSSSI pathogen is based on the pathogen 
isolated from the EOT or PTE specimen, if a specimen was collected.  The microbiologic 
response for the blood pathogen is based on the blood sample collected at EOT or PTE, or if a 
sample was not collected at the post-baseline visit, the blood sample collected prior to and 
closest to the visit.   
Table 3.  
Per-Pathogen Microbiological Response Definitions at the EOT and PTE 
Visits 
Term 
Definition 
Eradication 
Absence of original baseline pathogen 
Presumed Eradication 
No source specimen to culture in a subject assessed with a clinical success 
by the Investigator 
Persistence 
Continued presence of the original baseline pathogen 
Presumed Persistence 
No source specimen to culture in a subject assessed with a clinical failure 
by the Investigator 
Indeterminate 
The subject’s clinical response is indeterminate or other circumstance that 
precludes a microbiological evaluation 
EOT = end of treatment; PTE = post-therapy evaluation. 
 
Microbiological outcomes are further categorized as favorable, unfavorable and indeterminate.  
Favorable microbiological outcomes are defined as eradication or presumed eradication.  
Unfavorable microbiological outcomes are defined as persistence or presumed persistence.  
Microbiological response will be derived using electronic microbiology data from the central 
laboratory (or local laboratory if central data are not available) and from pathogen determination 
provided by the sponsor for each baseline isolate.   
Overall microbiological response at PTE is determined as follows (Table 4) from the 
microbiological responses at the EOT and PTE Visits: 


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Table 4.  
Per-Pathogen 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 
Note:  Favorable is defined as eradication or presumed eradication.  Unfavorable is defined as persistence or 
presumed persistence.   
EOT = end of treatment; PTE = post-therapy evaluation. 
 
Per-subject responses will be based on per-pathogen outcomes.  To have an overall per-subject 
favorable microbiologic response, the outcome for each baseline pathogen must be favorable 
(eradicated or presumed eradicated).  If the outcome for any pathogen is unfavorable (persistence 
or presumed persistence), the subject will be considered to have an unfavorable per-subject 
microbiologic response.  Subjects with an indeterminate response for all pathogens will be 
considered to have an indeterminate per-subject microbiologic response.  If the same pathogen is 
isolated from both the blood and the ABSSSI site culture, the worst outcome will be used to 
determine per-subject microbiologic response.  Superinfections will not be considered in the 
microbiological response.  Microbiological response from worst to best are as follows:  
persistence, presumed persistence, indeterminate, presumed eradication and eradication. 
The overall per-subject microbiologic response at PTE is determined from the per-subject 
microbiologic responses at the EOT and PTE Visits as follows (Table 5): 


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Table 5. 
Per-Subject Microbiologic Response 
EOT Visit 
PTE Visit 
Overall Microbiologic Response at 
PTE 
Favorable 
Favorable 
• 
Eradication 
• 
Presumed Eradication 
Favorable 
• 
Eradication 
• 
Presumed Eradication 
Favorable 
Unfavorable 
• 
Persistence 
• 
Presumed Persistence 
Unfavorable 
• 
Persistence 
• 
Presumed Persistence 
Favorable 
Indeterminate 
Indeterminate 
Unfavorable 
• 
Persistence 
• 
Presumed Persistence 
Favorable 
Unfavorable 
• 
Persistence 
• 
Presumed Persistence 
Unfavorable 
• 
Persistence 
• 
Presumed Persistence 
Unfavorable 
• 
Persistence 
• 
Presumed Persistence 
Unfavorable 
• 
Persistence 
• 
Presumed Persistence 
Unfavorable 
• 
Persistence 
• 
Presumed Persistence 
Indeterminate 
Unfavorable 
• 
Persistence 
• 
Presumed Persistence 
Indeterminate 
Favorable 
Indeterminate 
Indeterminate 
Unfavorable 
• 
Persistence 
• 
Presumed Persistence 
Unfavorable 
• 
Persistence 
• 
Presumed Persistence 
Indeterminate 
Indeterminate 
Indeterminate 
Note:  Favorable is defined as eradication or presumed eradication.  Unfavorable is defined as persistence or 
presumed persistence.   
EOT = end of treatment; PTE = post-therapy evaluation. 
 
For the microbiological modified intent to treat (micro-mITT) population, the proportion of 
subjects with a favorable microbiological response is defined using the following formula (where 
the denominator adds to the total number of subjects in the micro-mITT population): 
Number of subjects with eradication + Number of subjects with presumed eradication 
(Number of subjects with eradication + Number of subjects with presumed 
eradication + Number of subjects with persistence + Number of subjects with 
presumed persistence + Number of subjects with indeterminate response) 
 
By definition, the microbiological evaluable (ME) populations (ME-EOT and ME-PTE) must 
have sufficient information to determine the outcome and thus, excludes subjects with 
indeterminate responses.  For the ME analysis set, the proportion of subjects with a 
microbiological response is defined using the following formula: 
Number of subjects with eradication + Number of subjects with presumed eradication 
(Number of subjects with eradication + Number of subjects with presumed 
eradication + Number of subjects with persistence + Number of subjects with 
presumed persistence) 
 


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Microbiological response definitions of superinfection and new infection are presented in 
Table 6 below:  
Table 6. 
Microbiological Response Definitions:  Superinfection or New Infection 
Term 
Definition 
Superinfection 
Isolation of a non-baseline ABSSSI pathogen from the primary ABSSSI 
site or blood while the subject is on test article (ie, during test article 
administration, Day 1 to EOT) and the subject has worsening or new signs 
or symptoms of the primary ABSSSI (ie, the subject is deemed a clinical 
failure by the investigator) 
New infection 
Isolation of a non-baseline ABSSSI pathogen from a post-treatment (ie, 
after EOT) culture from the primary ABSSSI site or blood in a subject with 
worsening or new signs or symptoms of the primary ABSSSI (ie, the 
subject is deemed a clinical failure by the investigator) 
ABSSSI = acute bacterial skin and skin structure infection. 
 
For subjects with multiple microbiological samples taken either during test article administration 
(for determination of superinfection) or after test article administration (for determination of new 
infection) all cultures will be used in the analysis.   
5.3 
Safety Measures 
The safety parameters include AEs, clinical laboratory evaluations, vital signs, and ECG 
findings.  AEs will be coded using the Medical Dictionary of Regulatory Activities (MedDRA) 
Version 17.1 or higher to the System Organ Class and Preferred Term levels.   
5.4 
Pharmacokinetic Parameters 
The concentration of omadacycline will be obtained from plasma samples.  Refer to the 
pharmacokinetic analysis plan for further details.   


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6 STUDY POPULATIONS 
6.1 
Analysis Populations 
6.1.1 
Intent-to-Treat (ITT) Population 
The ITT population will consist of all randomized subjects regardless of whether or not the 
subject received test article.  A subject is considered randomized when the IxRS provides the test 
article assignment by providing the kit number (ie, completes a randomization transaction).  
6.1.2 
Safety Population 
The Safety population will consist of all randomized subjects who receive test article.  All safety 
analyses will be conducted in this analysis set.   
6.1.3 
Modified Intent-to-Treat (mITT) Population 
The mITT population will consist of all randomized subjects without a baseline sole 
Gram-negative ABSSSI pathogen.  Pathogen determination is described in Section 6.1.4. 
6.1.4 
Microbiological Modified Intent-to-Treat (micro-mITT) Population  
The micro-mITT population will consist of all subjects in the mITT population who have at least 
one Gram-positive causative bacterial pathogen identified from a blood culture or from a culture 
of a microbiological sample obtained from the primary ABSSSI site at baseline using a valid 
sampling technique.  Pathogen determination is 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 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.  The central laboratory identification of genus and species is used for analysis 
unless no central determination exists in which case the local laboratory determination is used.  If 
the central lab does not speciate the pathogen but the local/regional lab does speciate the 
pathogen, the Sponsor will make the final determination as to which pathogen identification is 
used for analysis.   
An acceptable ABSSSI site specimen obtained via a valid sampling technique is defined as one 
obtained from a biopsy of involved cutaneous or subcutaneous tissue preferably from the 
advancing margin of the lesion, debrided tissue, tissue scraping (using curette or scalpel), needle 
aspirate of involved, nonpurulent cutaneous or subcutaneous tissue, pus or infected tissue 
collected during an incision and drainage procedure, pus aspirated into a syringe or a deep swab 
of purulent material (only if collected from infected tissue that has been incised or is draining).  
Surface swabs of wounds, inflamed skin or drainage (including purulent material) are not 
considered valid sampling techniques.  If more than one baseline ABSSSI site sample was 
obtained using a valid sampling technique or more than one baseline blood sample was obtained, 
isolates from all samples will be reviewed for pathogen determination.   


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For subjects that have ABSSSI and blood specimens collected per protocol, baseline is defined 
as either Day –1 or 1.  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, a 
Day 2 or 3 microbiological sample can be used as baseline if the sample is considered 
acceptable.  If acceptable ABSSSI site and/or blood samples are obtained on both Study Days -1 
and 1, all isolates will be reviewed for pathogen determination.   
The 3 categories of pathogen classification are as follows: 
1. Always a pathogen:  If isolated from the culture of the ABSSSI, the following are always 
considered a pathogen: 
• Monomicrobial infections caused by 
o Staphylococcus aureus - isolates will be reviewed by oxacillin susceptibility results 
(methicillin resistant - MRSA and methicillin susceptible - MSSA) and MRSA and 
MSSA will be considered distinct pathogens. 
o Group A, B, C and G β–hemolytic streptococci (ie, Streptococcus agalactiae, 
Streptococcus dysgalactiae, Streptococcus pyogenes, etc.) 
o Streptococcus anginosus group (eg, Streptococcus anginosus, Streptococcus 
intermedius, Streptococcus constellatus) 
o Enterococcus faecalis - isolates will be reviewed by vancomycin susceptibility results 
(vancomycin resistant Enterococcus faecalis and vancomycin susceptible 
Enterococcus faecalis) and these will be considered distinct pathogens. 
o Enterococcus faecium - isolates will be reviewed by vancomycin susceptibility results 
(vancomycin resistant  Enterococcus faecium and vancomycin susceptible 
Enterococcus faecium) and these will be considered distinct pathogens. 
o Staphylococcus lugdunensis 
o Gram positive anaerobes isolated from a major abscess or wound infection 
• Polymicrobial infection consisting of any combination of Staphylococcus aureus, Group 
A, B, C and G β –hemolytic streptococci and Streptococcus anginosus group 
2. Never a pathogen:  If isolated from the culture of the ABSSSI, the following are never a 
pathogen:  
• Corynebacterium spp. 
• Bacillus spp. 
• Diphtheroids 
• Micrococcus spp. 
• Propionibacterium spp. 
• Actinomyces spp. 
• Actinobaculum spp. 
• Porphyromonas spp. 


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• All coagulase-negative staphylococci with the exception of S. lugdunensis (eg, S. capitis, 
S. caprae, S. cohnii, S. condiment, S. epidermidis, S. haemolyticus, S. hominis, S. 
saprophyticus, S. sciuri, S. simulans, S. warneri, S. xylosus)   
• Gram positive anaerobes isolated from cellulitis/erysipelas 
• Candida spp., Aspergillus spp., or other fungi 
3. Case-by case review:  The following organisms will be assessed on a case-by-case basis via 
manual review by the Sponsor.  If needed, subject clinical (eg, type of infection, type of 
specimen, subject underlying conditions, etc.) and microbiological information (eg, amount 
of culture growth, etc.) will be used to assist in determining if the isolate is a pathogen.   
• Monomicrobial infection with an organism not listed in #1 or #2 above 
• Polymicrobial infections (infections with ≥ 2 pathogens) will be reviewed on a case-by-
case basis, except as noted above for always a pathogen.  
• All organisms isolated from a blood culture 
• All Gram-negative organisms 
 
6.1.5 
Clinically Evaluable (CE) Populations 
Two CE analysis sets will be defined; the CE-EOT and the CE-PTE.  To be included in the CE-
EOT and the CE-PTE populations, subjects must be in the mITT population.  Subjects will be 
included in or excluded from the CE analysis sets based on the additional criteria listed below.   
6.1.5.1 
Diagnosis of ABSSSI 
To be included in the CE-EOT and CE-PTE populations, subjects must meet the following 
protocol defined inclusion criteria that describe the ABSSSI: 
Inclusion Criterion 3:  Has a qualifying skin and skin structure infection.  All qualifying lesions 
must be greater than or equal to 75 cm2 in total surface area of contiguous involved tissue, 
calculated as the product of the maximum length (head-to-toe) multiplied by the maximum width 
(measured perpendicular to length) as measured by the investigator using a wound ruler.  
Involved tissue is defined as tissue exhibiting clear evidence of one or more of the following:  
erythema, edema, or induration.  
The classification of qualifying infections is shown below: 
a. Wound infection – an infection characterized by purulent drainage from a wound with 
surrounding erythema, edema, and/or induration extending at least 5 cm in the 
shortest distance from the peripheral margin of the wound.  
b. Cellulitis/erysipelas – a diffuse skin infection characterized by spreading areas of 
erythema, edema, and/or induration.  
c. Major abscess – an infection characterized by a collection of pus within the dermis or 
deeper that is accompanied by erythema, edema and/or induration extending at least 
5 cm of in the shortest distance from the peripheral margin of the abscess.  
 


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Inclusion Criterion 4:  Has evidence of a systemic inflammatory response within the 24 hours 
prior to randomization, as indicated by ONE of the following:   
a. Elevated white blood cell (WBC) count (greater or equal to 10,000 cells/mm3) or 
leukopenia (less than or equal to 4,000 cells/mm3) 
b. Elevated immature neutrophils (greater than or equal to 15% band forms) regardless 
of total peripheral WBC count 
c. Lymphatic involvement:  lymphangitis or lymphadenopathy that is proximal to and in 
a location that suggests drainage from the qualifying infection 
d. Fever or hypothermia documented by the investigator (temperature greater 
than 38.0°C [100.4°F] or less than 36.0°C [95.5°F]) 
 
6.1.5.2 
Prior Antibiotic Therapy 
Subjects will be excluded from the CE populations if they meet either of the prior antibiotic 
exclusion criteria: 
Exclusion Criterion 1:  Has received 1 or more doses of a potentially effective systemic 
antibacterial treatment within the 72-hour period prior to randomization (a subject will be 
considered to have received a potentially effective systemic antibacterial treatment if the 
pathogen identified as causing the infection is shown to be susceptible to the antibacterial 
treatment given or, in the circumstance where a pathogen is not identified, if the antibacterial 
agent is approved for treatment of skin infections or is known to have activity against any of the 
leading Gram-positive causes of ABSSSI (eg, Staphylococcus aureus, Streptococcus species 
[spp.], Enterococcus spp.]).  EXCEPTION:  Subjects may be eligible despite prior antibacterial 
therapy if they have been treated with a single dose of a short-acting, non-oxazolidinone 
antibacterial (ie, an antibacterial whose standard dosing regimen is more frequent than once per 
day, see list in Appendix 1 of the protocol). 
Exclusion Criterion 2:  Has, for any reason, used a topical antibacterial agent(s) with specific 
antibacterial activity (eg, mupirocin, retapamulin, fusidic acid) continuously within the 72-hour 
period prior to first dose of test article, if applied to the skin for greater than or equal to 72 hours. 
6.1.5.3 
Concomitant Antibiotic Therapy 
Subjects who receive any systemic concomitant antibiotic therapy from the first dose of test 
article through the EOT visit and through the PTE visit with a spectrum of activity against the 
known or potential Gram-positive infecting pathogen(s) responsible for the infection under study 
will be excluded from the CE-EOT and CE-PTE populations, respectively, unless the subject 
receives the antibiotic therapy for treatment of the ABSSSI due to insufficient therapeutic effect 
of the test article. 
Subjects who receive a systemic concomitant antibiotic that is not effective against the Gram-
positive baseline pathogen, or if no Gram-positive pathogen is isolated and the antibiotic does 
not have Gram-positive activity, will be included in the CE-EOT and CE-PTE populations.   
In addition, subjects who have any topical antibacterial agent applied to the infection site (except 
for antibiotic/antiseptic-coated dressing applied to the clean postsurgical wound) with a spectrum 


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that is active against the known or potential infecting pathogen(s) responsible for the infection 
under study from the first dose of test article through the EOT or PTE visits, will be excluded 
from the CE-EOT and CE-PTE populations, respectively.   
Antimicrobials that will not interfere with the course of the ABSSSI are allowed and do not 
affect inclusion in the CE populations, eg, metronidazole, norfloxacin, nalidixic acid, pipemedic 
acid, oral vancomycin, antifungals, antivirals or topical antibiotics used for decontamination or 
in places other than the primary lesion. 
6.1.5.4 
Concomitant Surgical Procedures 
Subjects who receive an unplanned major surgical procedure for the infection under study (ie, 
procedures that would not normally be performed at the bedside, such as amputation or major 
incision and drainage performed in an operating room) will be defined as a clinical failure for the 
clinical response at the EOT and PTE Visits and thus, will be included in the CE populations.   
Minor bedside procedures such as debridement, aspiration puncture, excision with or without 
skin grafting and wound cleaning/lavage will generally be acceptable and will not exclude a 
subject from the CE populations.  All other surgical procedures performed after the first dose of 
test article will be reviewed by the Sponsor to determine whether the procedure potentially 
confounds the outcome and whether the subject should be excluded from either the CE-EOT or 
CE-PTE populations.   
6.1.5.5 
Test Article Therapy 
Subjects must meet all of the following to be included in the CE populations: 
• Received test article and the correct test article based on the randomization assignment 
• Study personnel involved in the assessment of efficacy remained blinded to study treatment, 
unless a treatment limiting adverse event occurred which required emergency unblinding.   
• Subject was at least 80% compliant with the dosing regimen. 
• Evaluable failure:  The subject received at least 2 doses of active test article (omadacycline 
group) or at least 4 doses of active test article (linezolid group) and the investigator classifies 
the subject as a Clinical Failure at the EOT Visit (CE-EOT population) or the overall Clinical 
Response (based on the investigator's assessment) at the PTE Visit (CE-PTE population) is 
Clinical Failure. 
• Evaluable success:  The subject received at least 3 doses of active test article (omadacycline 
group) at least 6 doses of active test article (linezolid group) and the investigator classifies 
the subject as a Clinical Success at the EOT Visit (CE-EOT population) or the overall 
Clinical Response (based on the investigator's assessment) at the PTE Visit (CE-PTE 
population) is Clinical Success.  
 


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6.1.5.6 
Clinical Outcome Assessment 
Subjects must meet the following to be included in the CE populations: 
• For the CE-EOT population: 
o Completed the investigator’s assessment of clinical response (ie, was not deemed an 
indeterminate outcome) at the EOT visit, and  
o The EOT visit occurred on the day of, or within 2 days following the last dose of test 
article.    
• For the CE-PTE population: 
o The overall Clinical Response (based on the investigator's assessment) at the PTE Visit is 
not Indeterminate.   
o The PTE Visit occurred 7 to 14 days after the last dose of test article, unless the subject 
was considered to be a Clinical Failure based on the investigator’s assessment at the EOT 
visit.   
 
6.1.5.7 
Baseline Medical Events 
Subjects will be excluded from the CE populations if the investigator has documented in the 
eCRF that they meet any one of the following protocol-defined exclusion criteria at baseline 
(ie, prior to randomization):  
Exclusion Criterion 3:  Infections where the outcome is strongly influenced by factors other than 
protocol-defined treatment and procedures, that require antibacterial treatment for greater than 
14 days, are associated with chronic skin lesions that may obscure determination of response 
even after successful bacterial eradication has been achieved, or are suspected or known to be 
caused by a pathogen resistant to either test article, eg: 
• Chronic (persistently present greater than 3 months) lesions, ulcers or wounds (eg, cellulitis 
contiguous with a diabetic foot ulcer) 
• association with chronic dermatitis or any other chronic inflammatory skin lesion (eg, 
psoriasis, eczema) 
• burns 
• peri-rectal abscess (eg, buttock or perineal lesion likely to communicate with the rectum) or 
perineal infection 
• infected decubitus (pressure) ulcers 
• necrotizing fasciitis (infections with rapidly progressive destruction of tissue at or below the 
fascia) 
• life-threatening infections, ie, require emergency surgery for the treatment (eg, progressive 
gangrene) 
• infections in an area requiring surgery that in and of itself would cure the infection or remove 
the infected site (eg, amputation for vascular insufficiency) 


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• infections associated with severe vascular insufficiency (eg, peripheral vascular disease) or 
acute occlusion expected to require immediate revascularization 
• infections associated with acute compartment syndrome expected to require extensive 
surgery to provide decompression 
• infections accompanied by confirmed or suspected contiguous bone or joint infection (eg, 
osteomyelitis, septic arthritis, bursitis) 
• bacteremic infections associated with an intravascular foreign body 
• infections accompanied by another confirmed or suspected infection requiring systemic 
antibiotic therapy (eg, endocarditis, other endovascular infection, meningitis, visceral 
abscess, intra-abdominal infection, pneumonia, urinary tract infection) 
• human or animal bites (infections associated with insect bites are NOT excluded) 
• myonecrosis 
• complicated by an immune deficiency in the subject (eg, ecthyma gangrenosum in a 
neutropenic subject) 
• infections associated with the presence of a foreign body (eg, wood, metal, plastic, etc.) if the 
foreign body cannot be removed within 24 hours of first dose of test article 
 
Exclusion 4:  Inability to tolerate oral medication (eg, nausea, vomiting diarrhea or any other 
condition that might impair ingestion or absorption of oral medication) 
Exclusion 19:  Has been previously treated with omadacycline or previously enrolled in this 
study. 
 
6.1.6 
Microbiologically Evaluable (ME) Populations 
The ME-EOT and ME-PTE populations will consist of all subjects in both the micro-mITT and 
the CE-EOT and CE-PTE populations, respectively.   
6.2 
Evaluability Review Team 
6.2.1 
Membership and Responsibilities 
The Evaluability Review Team (ERT) 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.  ERT members will be blinded to 
treatment assignment and will review the data concurrent with the conduct of the study.  The 
ERT will be conducted in accordance with the ERT process documents.   
6.2.2 
Process for Determining Inclusion in Populations 
Inclusion into the ITT and Safety populations will be determined programmatically from the 
eCRF data.  Inclusion into the CE populations will be determined programmatically from the 


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eCRF data and the manual review conducted by the ERT.  The ERT may review subject data to 
confirm that population criteria are satisfied.   
Inclusion into the mITT and micro-mITT population will be determined programmatically by 
incorporating the outcome of the review of the isolates by the ERT.  The ERT will determine 
whether each isolate (baseline and post-baseline) is considered a pathogen based on a review of 
information from baseline samples including infection type, type of specimen, and local and 
central laboratory genus and species identification.  Inclusion into the ME populations will be 
determined programmatically.   
Review of data, Sponsor determination of evaluability, and final subject population classification 
will be performed in a blinded manner prior to database lock and unblinding with the exception 
of those criteria requiring the subject's actual treatment assignment (for example, the requirement 
for the subject to have received the correct test article per the randomization assignment).  For 
the criteria requiring the subject's actual treatment assignment, population determination will be 
completed programmatically after unblinding. 
6.3 
Subgroups 
Analyses of Early Clinical Response and the overall assessment of Clinical Response at the PTE 
Visit (based on the investigator’s assessment)  will be conducted (as described in Section 10.6) 
for subgroups defined by the randomization stratification factors:  infection type 
(cellulitis/erysipelas, wound infection and major abscess) and receipt of an allowed antibacterial 
therapy in the 72 hours prior to randomization (yes or no).  Analyses of Early Clinical Response 
will also be conducted in the following subgroups:  clinical site (sites that enroll less than 
10 subjects per group will be grouped together), bacteremic subjects, subjects meeting the 
systemic inflammatory response syndrome (SIRS) criteria at baseline, size of lesion (≤ 300 cm2, 
> 300 to 600 cm2, > 600 to 1000 cm2, and > 1000 cm2), receipt of a nonsteroidal anti-
inflammatory drug (NSAID) from the first dose of test article through to the assessment of Early 
Clinical Response,  receipt of an operative incision and drainage (I&D) from the first dose of test 
article through to the assessment of Early Clinical Response and IV drug use vs no IV drug use .  
SIRS is defined as having 2 or more of the following criteria:  temperature < 36o C or > 38o C, 
heart rate > 90 bpm, respiratory rate > 20 bpm, or WBC count < 4000 cells/mm3 or > 12,000 
cells/mm3 or > 10% bands.   
Exploratory analyses in other subgroups may also be conducted.   


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7 CHANGES IN CONDUCT OR PLANNED ANALYSES FROM THE 
PROTOCOL 
There are no changes to the analyses as detailed in the protocol. 


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8 OVERALL STATISTICAL CONSIDERATIONS 
8.1 
General Conventions 
The following general comments apply to all statistical analyses and data presentations: 
• Summaries will include frequency and percentages for categorical data; frequency and 
median for ordinal data; and frequency, mean, standard deviation, and median, minimum and 
maximum for quantitative data.   
• Duration variables will be calculated using the general formula (end date - start date) + 1.  
• 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.  
• If the reported value of a clinical laboratory parameter cannot be used in a statistical 
summary table (eg, 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.  Data will be 
reviewed on an ongoing basis in a blinded manner to assess the frequency of occurrence of 
laboratory parameters reported as a character string. 
• Individual subject listings of all data represented on the eCRFs will be provided to facilitate 
the investigation of tabulated values and to allow for the clinical review of all efficacy and 
safety parameters. 
• Version 9.3 (or higher) of SAS® statistical software package will be used to provide all 
summaries, listings, graphs, and statistical analyses.   
 
8.2 
Baseline Definition 
In general, baseline is defined as the value closest to but prior to the initiation of test article 
administration.  If no test article is received, baseline is defined as the value closest to but prior 
to randomization.  
For pathogen determination, baseline is defined as either Day –1 or 1.  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, a Day 2 or 3 microbiological sample 
can be used as baseline if the sample is considered acceptable.  If no test article is received, for 
pathogen determination, study day is defined based on date of randomization. 
For analyses of vital signs and ECGs, if no value is available prior to the initiation of test article 
administration, a value within 2 hours after initiation of test article administration can be used as 
baseline. 


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8.3 
Handling of Missing Data 
Missing data will be handled as outlined below:  
• All missing and partial dates for adverse events or for medications received after 
randomization will be queried for a value.  If no value can be obtained, substitutions will be 
made as detailed in Appendix 3.  These substitutions will be used in calculations; however, 
the actual value recorded on the eCRF will be used in all listings. 
• Missing start and stop times for prior and concomitant 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 test article, 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 test article, 00:01 will be used for end time.  
The actual value (blank) will be recorded on the eCRF and will be used in the listings. 
• Missing times for lesion measurements will be queried for a value.  If minutes are not 
available, the time will be recorded to the closest hour.   
• If the time of the outpatient dose of test article on Day 1 is missing, it will be imputed to 
23:59. 
• If no value can be obtained for all other times for events and assessments occurring after 
randomization, the time will not be imputed but will remain missing.   
• The severity and causality assessment for adverse events cannot be missing.  Missing data 
will be queried for a value.   
 
For clinical and microbiological response, missing data will be handled as follows: 
• For the primary outcome measure (Early Clinical Response at 48 to 72 hours): 
o The subject will be considered to have missing data if there is no lesion size measurement 
(either length or width) at either baseline or 46 to 72 hours after the first dose of test 
article.  Subjects with missing data will be defined as an Indeterminate response which is 
essentially a Clinical Failure for the primary analysis (mITT and ITT populations).   
o If the time of administration of the first dose of test article is missing, the subject will be 
defined as an Indeterminate response which is essentially a Clinical Failure for the 
primary analysis (mITT and ITT populations). 
• For the secondary outcome measures (investigator’s assessment of Clinical Response at the 
EOT and PTE Visits): 
o Subjects will be defined as an Indeterminate if the investigator cannot determine whether 
the subject is a Clinical Success or Failure at the EOT or PTE Visits or the subject has a 
missing response.  By definition, subjects with an Indeterminate response are included in 
the denominator for analyses in the mITT and micro-mITT populations, and thus, are 
considered Clinical Failures.  Subjects with an Indeterminate response are excluded from 
the CE-EOT, CE-PTE, ME-EOT and ME-PTE populations.   


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• For microbiologic response: 
o 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 (ie, the response is a presumed response).  
A per-pathogen microbiological response at the EOT Visit or PTE Visit will be 
considered Indeterminate only if the Clinical Response at EOT or PTE is also 
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 (ie, only subjects with available data will be included in the 
denominators).   
 
8.4 
Interim Analysis 
An interim analysis to assess efficacy or safety is not planned.   
8.5 
Pooling Strategy for Study Sites 
Data will be pooled across sites for all efficacy and safety analyses.  An analysis of the primary 
(Early Clinical Response) and secondary (Investigator assessment of clinical response) efficacy 
outcomes will be conducted by site.  Sites that enroll less than 10 subjects per arm will be pooled 
together for the by site analysis. 
8.6 
Visit Windows/Unscheduled Visits 
For the primary efficacy outcome, if more than one assessment of the lesion size is done in the 
46-72 hour window, the latest will be used.  For secondary and additional efficacy outcomes, the 
data collected at the EOT and PTE Visits, regardless of when these occur will be utilized in the 
analysis in the mITT population.  The CE and ME populations exclude subjects with a visit 
occurring outside the window allowed per protocol. 
For each safety outcome, analyses will utilize assessments occurring during the scheduled visit 
windows (provided in Table 7).  Thus, if a subject has a visit outside the scheduled visit window, 
for example, a PTE Visit occurred 20 days after the subject's last day of therapy, the assessment 
will not be summarized with the PTE Visit but will be considered an unscheduled assessment.  If 
a subject does not have an assessment at a scheduled visit and an unscheduled assessment was 
taken within the window for the time point (for example, 7 to 14 days after the subject's last day 
of therapy for PTE), these assessments will be summarized in the by time point analyses.  If 
more than one measurement is taken during the visit window, the value taken on the scheduled 
visit will be utilized or if no scheduled visit was done, the first (earliest) measurement in the visit 
window will be used.  If more than one measurement is taken on the same day, the assessment 
closest to the start of the dose will be used for on treatment values and the last measurement on 
the day will be used for post-treatment values.  For worst overall post-baseline analyses, all 
assessments including those obtained from unscheduled visits will be included.   


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Table 7.  
Scheduled Study Visits 
Study Visit 
Study Day 
Notes 
Baseline 
Day -1 or Day 1 
Except where indicated, last measurement prior to the first dose 
of test article.  Screening assessments are to be taken within 
24 hours prior to the first dose of test article.  If no test article is 
taken, the date and time of randomization is used in place of the 
first dose of test article. 
On Treatment (note:  
analysis visit will be 
each Study Day) 
Day 1, Day 2, Day 3, 
Day 7, Day 10 
The Day 3 visit is to occur within 46 to 72 hours after the first 
dose of study drug and thus, may occur on Study Day 4.  
A Day 10 visit is will be conducted for subjects with treatment 
extending beyond 9 days, unless this visit coincides with the 
EOT Visit. 
EOT 
 
Within 2 days following the last dose of test article 
PTE 
 
7 to 14 days after the subject's last day of therapy 
Final Follow-up (FU) 
Day 30 to 37 
30 to 37 days after the start of the first dose of test article 
Study Day is calculated relative to the first dose of test article (Day 1); there is no Day 0 – the day prior to the first 
dose of test article is Day -1.  If no test article is taken, study day is calculated relative to the date of 
randomization. 
 


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9 STATISTICAL ANALYSIS METHODS 
9.1 
Subject Disposition 
The number of Screen Failures and reason for screen failure will be presented overall.  A listing, 
grouped by stratum, will be provided that indicates the subject's date and time of randomization, 
randomized treatment assignment, randomization number, kit number(s), block number, 
randomized infection type, and prior antibiotic stratum (receipt of an allowed antibacterial 
therapy in the 72 hours prior to randomization - yes or no). 
The number of subjects included in each of the analysis populations (ie, ITT, Safety, mITT, 
micro-mITT, CE-EOT, CE-PTE, ME-EOT and ME-PTE) will be summarized by treatment 
group.  A table will summarize the reasons for exclusion from each population and a listing will 
be provided that indicates each subject’s inclusion in/exclusion from the populations and the 
reason for exclusion from each of the populations.   
A listing will be provided of randomized subjects who did not meet all inclusion/exclusion 
criteria, and which criteria were not met.  The number and percentage of subjects completing the 
study (defined as receiving at least one dose of test article and returning for all of the EOT, PTE 
and FU visits), not completing the study, missing each of the EOT and PTE Visits, and 
prematurely discontinuing from test article will be presented for each treatment group and 
overall for the ITT, mITT, and CE-PTE populations (by definition, a subject in the CE-PTE 
population cannot have missed the PTE Visit, unless the subject was a clinical failure at the EOT 
Visit).  Reasons for premature discontinuation of test article, not completing the study, and for 
missing each of the visits, as recorded on the eCRF will be summarized (number and percentage) 
by treatment group.  Percentages of subjects discontinued from test article and not completing 
the study will be compared between treatment groups using Fisher’s exact test.  A listing of all 
subjects who prematurely discontinued from test article or not completing the  study will be 
presented, and the primary reason for discontinuation of test article or not completing  the study 
will be provided.   
9.2 
Demographics and Baseline Characteristics 
Except where indicated, demographic data and baseline characteristics will be presented by 
treatment group for the Safety, mITT, micro-mITT, and CE-PTE populations.  A table will 
present the subject demographics (eg, gender, age, ethnicity, and race) and baseline 
characteristics (height, weight, BMI, and renal function).  Age will be calculated from the date of 
birth to the informed consent date and will be summarized as a continuous variable and 
categorized (18 to 45 years, > 45 to 65 years, > 65 to 75 years and > 75 years).  Renal function 
will be categorized as normal (creatinine clearance [CrCl] > 80 mL/min), mild renal impairment 
(CrCl > 50 to 80 mL/min), moderate renal impairment (CrCl 30 to 50 mL/min) and severe renal 
impairment (CrCl < 30 mL/min).  Creatinine clearance will be calculated from the local 
laboratory data and will be determined from the Cockcroft-Gault equation: 
(140-age[yrs])*weight [kg]* (Z) 
Z = 1.0, if Male 
Z = 0.85, if Female 
Cr [mg/dL] * 72 
 


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 Differences between treatment groups will be analyzed using Fisher’s exact test for 
dichotomous variables (gender, ethnicity, and race) and the Wilcoxon Rank Sum test for 
continuous variables (age, height, weight, and BMI).   
The number and percentage of subjects with reported ABSSSI relevant medical history (relevant 
surgical procedure that resulted in the primary infection, recent trauma that resulted in the 
primary infection, iv drug abuse, prior ABSSSI, association of ABSSSI with chronic skin 
lesions, concurrent secondary ABSSSI lesions, diabetes mellitus [based on the MedDRA higher 
level term “Diabetes mellitus (incl subtypes)”], hepatitis C [based on the MedDRA preferred 
terms of “Hepatitis C” and/or “Chronic Hepatitis C” ], infection result of vascular insufficiency 
or edema, and peripheral artery disease) will be summarized by treatment group for the mITT 
and CE-PTE populations.  Differences between treatment groups in the percent of subjects with 
each relevant medical history will be determined using Fisher’s exact test.  Other medical and 
surgical history will be coded using MedDRA and summarized based on MedDRA system organ 
class and treatment group for the mITT and Safety populations.  The number and percentage of 
subjects with a history of diabetes mellitus and hepatitis C  will be presented by treatment group 
in the Safety population. 
Listings will be provided of those subjects who were randomized to the wrong ABSSSI type of 
infection stratum and wrong prior antibiotic stratum.  The type of infection listing will provide 
the subject ID, treatment group, randomized type of infection and actual (as recorded on the 
eCRF) type of infection.  The prior antibiotic listing will provide the subject ID, treatment group, 
randomization date and time, randomized prior antibiotic stratum, preferred term of prior 
antibiotic, start and stop date/time of prior antibiotic, hours prior to randomization, dose and 
frequency of the antibiotic. 
Descriptive statistics of the primary infection site will be provided for the mITT and CE-PTE 
populations.  These include type of ABSSSI infection (cellulitis/erysipelas, major abscess, 
wound infection) and anatomical site (categorized as scalp, neck, face, chest, abdomen, back, 
groin, hand, foot, shoulder, buttock, axillary, arm, leg, elbow and knee).   Lesion measurements 
(length, width and area of erythema, edema and/or induration, and for subjects with wounds and 
abscesses, the shortest measurement from peripheral margin), local signs and symptoms 
(tenderness, edema, erythema, induration, and drainage [none, serous/serosanguineous, 
seropurulent, and purulent]), and systemic signs (lymphadenopathy proximal to primary lesion 
site, presence of lymphangitis proximal to primary lesion site, WBC count ≥ 10,000 cells/mm3 or 
≤ 4000 cells/mm3, ≥ 15% immature neutrophils, temperature [as a continuous variable and 
defined as fever/no fever at baseline > 38.0°C, hypothermia < 36.0°C]) will be summarized by 
treatment group.  The percentage of subjects meeting the systemic inflammatory response 
syndrome (SIRS) criteria at baseline will also be provided (yes vs no).  SIRS is defined as having 
2 or more of the following criteria:  temperature < 36°C or > 38°C, heart rate > 90 bpm, 
respiratory rate > 20 bpm, or WBC count < 4000 cells/mm3 or > 12,000 cells/mm3 
or > 10% bands.  Descriptive statistics of baseline lesion area and a summary of the local signs 
and symptoms will also be provided by treatment group separately by type of ABSSSI infection 
(actual as recorded on the eCRF.  Differences between treatment groups will be analyzed using 
Fisher’s exact test for dichotomous variables and the Wilcoxon Rank Sum test for ordinal and 
continuous variables.   


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For those subjects with a concurrent secondary ABSSSI, a summary or listing (depending on the 
number of subjects with a concurrent secondary ABSSSI) of the lesion type and organisms 
isolated will be provided by treatment group.   
9.2.1 
Baseline Microbiology 
The microbiological assessment of the primary ABSSSI site specimen by the local laboratory 
will be summarized by treatment group for the mITT population.  A frequency distribution of the 
specimen collection method, the number and percentage of subjects with no growth and growth 
will  be presented.   
The pathogenic organisms identified from the baseline blood culture or culture of the primary 
ABSSSI site will be presented.  The number and percentage of subjects with Gram-positive 
organisms (aerobes and anaerobes) and with Gram-negative organisms (aerobes and anaerobes) 
will be presented by genus and species for the micro-mITT and ME populations.  The same 
pathogen identified from both the blood and the culture of the ABSSSI will be counted only once 
in the summary.  In addition, the number and percentage of subjects with mono-microbial Gram-
positive and poly-microbial infections (Gram-positive only and mixed infections (Gram-positive 
and Gram-negative) will be provided overall and by type of infection (micro-mITT population 
only)  
The percentage of subjects with a positive blood culture by pathogenic organism will be 
provided for the micro-mITT and ME populations.  The number and percentage of subjects with 
a Gram-positive organism (aerobes and anaerobes) and with a Gram-negative organism (aerobes 
and anaerobes) will be presented by genus and species.  
A listing will be provided that includes all baseline and post-baseline isolates obtained from the 
blood and ABSSSI site specimen and will indicate the type of specimen and pathogenic 
organism.   
Several tables providing minimum inhibitory concentration (MIC) data will be provided for the 
micro-mITT and ME populations:  
• The MIC distribution to omadacycline and linezolid, across treatment groups 
• The MIC distribution to the test article received, by treatment group 
• MIC summary statistics (ie, range, MIC50, and MIC90) to the test article received.  The MIC 
range will be provided for all baseline pathogens.  The MIC50 and MIC90 will be provided 
only for those pathogens isolated at least 10 times in a treatment group.   
 
The distribution of disk diffusion zone diameters (mm) will be provided for the test article 
received, by treatment group. 
In all microbiology analyses, the following apply: 
• If there are multiple specimens (of the same sample type) from the same time-point where 
the same pathogen is isolated, only the pathogen with the highest MIC to the test article 


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received will be used.  If the pathogens have the same MIC to test article received, the one 
with the lowest accession number will be used.  The Gram's stain associated with the selected 
pathogen will be utilized for analysis. 
• If the same pathogen is identified from the blood and ABSSSI sample, for tables providing 
MIC or disk diffusion data, the pathogen with the highest MIC to the test article received will 
be used.  
• MRSA and MSSA are considered distinct pathogens. 
• Vancomycin susceptibility is provided for all Enterococcus spp. defined as pathogens.  
Vancomycin resistant and vancomycin susceptible isolates of each species are considered 
distinct pathogens (ie, vancomycin resistant E. faecalis and vancomycin susceptible 
E. faecalis are distinct) 
• When per-subject counts of Staphylococcus aureus are presented, subjects with both MRSA 
and MSSA are counted only once. 
• When per-subject counts of Enterococcus spp. pathogens are presented, subjects with both 
vancomycin susceptible and vancomycin resistant isolates of the same species are counted 
only once. 
 
9.2.2 
Primary Site Procedures and Care 
Any procedures on the primary ABSSSI site will be recorded on the eCRF.  All ABSSSI site 
procedures (eg, bedside I&D, operative I&D, aspiration, debridement, re-exam of the lesion in 
operating room, skin graft, incision without grafting, wound cleaning/lavage, amputation, 
interventional radiology, other) will be presented on a by subject listing.  The percentage of 
subjects receiving each type of surgical procedure prior to the first dose of test article, from the 
first dose of test article through to the assessment of Early Clinical Response (Safety and mITT 
population), from the first dose of test article through to the EOT Visit (Safety, mITT and 
CE-EOT populations), and through to the PTE Visit (Safety, mITT and CE-PTE populations) 
will be presented by treatment group.  The reasons for the surgical procedures from first dose of 
test article through the PTE Visit will also be provided for the mITT population. 
9.3 
Treatment Compliance and Exposure 
Exposure summary by treatment group will be presented for the Safety, mITT, and CE-PTE 
populations.  The distribution of subjects by the total number of days on therapy (1 to 3, 4 to 6, 7 
to 10, 11 to 12, 13 to 14 and > 14 days) will be presented as will descriptive statistics for the total 
number of days on therapy.   
Treatment compliance is defined as the number of active tablets actually received divided by the 
number of active tablets expected (× 100) over the time period defined by the first and last dose 
date.  The last dose date is the last day the subject is expected to receive test article based on the 
length of therapy determined by the Investigator or the actual last date the subject took test 
article, if s/he prematurely discontinued test article due to treatment failure or an adverse event.  
Dose 2 can be missed per protocol if it cannot be taken a minimum of 8 hours after Dose 1 and a 
minimum of 8 hours before the expected time of Dose 3.  Descriptive statistics for treatment 


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compliance and the number and percentage of subjects at least 80% compliant will be presented 
by treatment group for the mITT and Safety populations.   
A summary of compliance with the pre- and post-dose fasting requirements will also be 
provided.  The percent fasting compliance will be determined  based on the total doses taken 
where fasting is required.  The percentage of subjects who were < 50%, 50% to < 80%, and 80% 
to 100% compliance with the pre-dose and post-dose fasting requirements will be summarized 
for the mITT and Safety populations. 


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10 EFFICACY PARAMETERS 
For all efficacy analyses, subjects will be analyzed in the group to which they were randomized.  
By definition, subjects who receive the wrong test article are not included in the CE-EOT, 
CE-PTE, ME-EOT and ME-PTE populations.  Subjects who are randomized to the wrong 
infection type or prior antibiotic stratum will be analyzed in the stratum to which they were 
randomized, unless otherwise stated.  A summary of the efficacy analyses is provided in 
Appendix 2. 
10.1 Primary Analysis 
The primary efficacy analyses will be based on the mITT population.  The non-inferiority test 
will be a 1-sided hypothesis test performed at the 2.5% level of significance.  This 
non-inferiority test will be based on the lower limit of the 2-sided 95% confidence interval (CI).  
The primary efficacy outcome is the percentage of subjects with an Early Clinical Success at 
48 to 72 hours after the first dose of test article.   
The number and percentage of subjects in each treatment group defined as an Early Clinical 
Success, Clinical Failure and Indeterminate (subjects with missing data or who are lost to follow-
up) will be tabulated, as will the overall category combining Clinical Failure and Indeterminate.  
The null and alternative hypotheses are as follows: 
∆
−
≤
−
2
1
0 :
p
p
H
 and 
∆
−
>
−
2
1
1 :
p
p
H
, 
 
where p1 is the primary efficacy outcome rate in the omadacycline treatment group, p2 is the 
primary efficacy outcome rate in the linezolid treatment group, and Δ is the non-inferiority 
margin of 10%. 
To test the null hypothesis, a 2-sided 95% CI for the observed difference in primary outcome 
rates (omadacycline treatment group minus linezolid treatment group) will be calculated for the 
mITT population.  If the lower limit of the 95% CI for the difference in the mITT population 
exceeds –10%, then the null hypothesis will be rejected and the non-inferiority of omadacycline 
to linezolid will be declared.   
The 2-sided 95% CI for non-inferiority testing based on the difference of Early Clinical Success 
rates at 48 to 72 hours after the first dose of test article, will be computed using the method 
proposed without stratification by Miettinen and Nurminen3.  For notation purposes, assume 
1 represents the omadacycline group (Group 1) and 2 represents the linezolid group (Group 2).   
Based on Miettinen and Nurminen, the 2-sided 95% CI is given by the roots for 
2
1
p
p
RD
−
=
 of 
the following equation: 
V
RD
p
p
2
2
1
2
)
ˆ
ˆ
(
−
−
=
α
χ
 
 


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where 
2
α
χ is the cut point of size α  from the chi-square distribution (
2
α
χ =3.84 for 2-sided 95% 
CI); RD is the difference between the 2 true rates (
2
1
p
p
RD
−
=
); 
1ˆp  = the observed average 
proportion in Group 1; 
2ˆp  = the observed average proportion in Group 2; and 
1
)
~
1(
~
)
~
1(
~
2
1
2
1
2
2
2
1
1
1
−
+
+




−
+
−
=
n
n
n
n
n
p
p
n
p
p
V
 
 
where 
1
n = number of subjects in Group 1; 
2
n = number of subjects in Group 2; 
RD
p
p
+
=
2
1
~
~
; 
and 
2
~p  is the maximum likelihood estimate for 
2
p  as a function of RD  and under the constraint 
RD
p
p
+
=
2
1
. 
As stated above, the 2-sided 95% CI for the difference in rates is given by the roots for 
2
1
p
p
RD
−
=
 from the equation above, but this equation does not allow for explicit solution for
RD .  Therefore, a numerical algorithm will be used to obtain the 2 roots (CI) for RD .  This CI 
approach corresponds to the non-inferiority test (a p-value approach) proposed by Farrington and 
Manning2.   
The reasons for Clinical Failure and reasons for Indeterminate response will be summarized by 
treatment group.   
10.2 Sensitivity and Additional Analyses of the Primary Efficacy Outcome 
Sensitivity analyses of the primary outcome include:  
• Determination of the 95% CI adjusted for infection type and receipt of prior antibiotics.  If 
there are < 20 subjects within a stratum and treatment group, or there is a 0 count within a 
stratum for a treatment group and outcome, wound and abscess will be combined.  If the 
combining of the infection types is not sufficient to complete the adjusted analysis, the prior 
antibiotic strata will be combined into one group.  The 95% CI interval will be computed 
using the stratified methodology of Miettinen and Nurminen.  Cochran-Mantel-Haenszel 
weights will be used for the stratum weights in the calculation of the CI as follows, where 
i
n1  = number of subjects in Group 1 in the ith stratum; 
i
n2 = number of subjects in Group 2 in 
the ith stratum: 
i
i
i
i
i
n
n
n
n
W
2
1
2
1
+
=
 
• The second sensitivity analysis of the primary outcome will consider all subjects who are lost 
to follow-up prior to a lesion size assessment from 46 to 72 hours or have missing data as an 
Early Clinical Success (these subjects are considered Indeterminates and analyzed as Clinical 
Failures in the primary analysis).   
• A multiple imputation analysis using a Markov chain Monte Carlo full data imputation will 
be used to define missing data.  Fifty data sets will be created using this technique in which 
type of infection (cellulitis/erysipelas, major cutaneous abscess and wound infection), prior 
receipt of antibiotics (yes and no), infection result of IV drug use, (yes and no) and baseline 


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lesion area (≤ 300 cm2, > 300 to 600 cm2, > 600 to 1000 cm2, and > 1000 cm2) are included 
as predictive variables.   
 
10.3 Secondary Analysis 
The number and percentage of subjects in each treatment group with a Clinical Success, Clinical 
Failure, and Indeterminate for the overall assessment of Clinical Response at the PTE Visit 
(based on the investigator’s assessment) will be reported for the mITT and CE-PTE populations 
(by definition CE-PTE subjects cannot have a response of Indeterminate).  Two-sided 95% CIs 
will be constructed for the observed differences in the Clinical Success rate using the method of 
Miettinen and Nurminen without stratification.  The 95% CIs are for descriptive purposes only 
and no conclusion of NI will be made.  The reasons for Clinical Failure will be summarized by 
treatment group.   
The number and percentage of subjects in each treatment group in each response category for 
Early Clinical Response will be presented for the micro-mITT population.  The number and 
percentage of subjects who are classified as a Clinical Success and Clinical Failure based on the 
overall assessment of Clinical Response at the PTE Visit (based on the investigator's assessment) 
in the ME-PTE population will be calculated.  Two-sided 95% CI without stratification will be 
constructed for the observed difference in the Clinical Success rates using the method of 
Miettinen and Nurminen. 
Early Clinical Response and the overall assessment of Clinical Response at the PTE Visit by 
baseline pathogen will be determined as the proportion of subjects with a Clinical Success, for 
each pathogen isolated at baseline for the blood culture or the culture of the ABSSSI site.  The 
number and percentage of subjects in each treatment group with a Clinical Success (based on 
Early Clinical Response and investigator's assessment of response) will be tabulated per 
pathogen for the micro-mITT and ME-PTE (for investigator’s assessment only) populations.  
Early Clinical Response and the overall assessment of Clinical Response at the PTE Visit in the 
micro-mITT and ME populations will also be provided by mono-microbial and poly-microbial 
infections (Gram-positive only and mixed infections [Gram-positive and Gram-negative]). 
10.4 Additional Analyses 
Additional efficacy analyses will be conducted to support the efficacy findings of the primary 
and secondary outcomes.  CIs will be determined for descriptive purposes, but no conclusions of 
NI will be made. 
Clinical Outcomes 
The number and percentage of subjects classified as an Early Clinical Success, Clinical Failure 
and Indeterminate at 48 to 72 hours after the first dose of test article in the ITT population will 
be calculated.  A 2-sided 95% CI without stratification will be constructed for the observed 
difference in the Clinical Success rate using the method of Miettinen and Nurminen. 
The number and percentage of subjects classified as a Clinical Success, Clinical Failure and 
Indeterminate by the investigator’s assessment at EOT in the mITT and CE-EOT populations (by 


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definition subjects with an Indeterminate response are excluded from the CE-EOT population) 
will be calculated for each treatment group.  A 2-sided 95% CI without stratification will be 
constructed for the observed difference in the clinical success rate using the method of Miettinen 
and Nurminen. 
A summary (number and percentage of subjects) of the shift from baseline to each visit (Day 2, 
Day 3, Day 7, Day 10, EOT and PTE Visits) in the clinical signs and symptoms (presence of 
drainage, tenderness, edema, erythema, induration) of the ABSSSI will be presented by treatment 
group for the mITT and CE-PTE populations.  The number and percentage of subjects with 
resolution of all clinical signs and symptoms that were present at baseline will be presented for 
each visit throughout the study.  The assessment of the systemic signs will also be summarized at 
each time point these were measured.  This includes descriptive statistics of the WBC count, 
temperature and immature neutrophils as continuous variables, percentage of subjects with a 
WBC count ≥ 10,000 cells/mm3 or < 4000 cells/mm3, fever (defined as temperature > 38°C), 
> 15% neutrophils, presence of lymphadenopathy proximal to primary lesion site and presence of 
lymphangitis proximal to the primary lesion site. 
Descriptive statistics of the primary infection site measurements (surface area [length x width]) 
will also be provided at each visit the infection site was measured for the mITT populations.  The 
measurement at the visit, the absolute change from baseline, and the percent change from 
baseline will be provided at each visit.  The percent change from baseline will be categorized as, 
< 0% (any increase), and decreases of 0 to < 5%, 5 to < 10%, 10 to < 15%, 15 to < 20%, 
20 to < 30%, 30 to < 40%, 40 to < 50% and 50% to 100%.   
All-cause mortality (ACM) at 30 days after randomization will be summarized in the ITT 
population.  Subjects who are lost to follow-up will be excluded from this analysis.  
Descriptive statistics of temperature will be provided for each visit temperature was measured 
for the mITT and CE-PTE population.  The measurement at the visit and the absolute change 
from baseline will be provided at each visit, as will the percentage of subjects who have a 
temperature ≤ 37.8°C.   
A concordance analysis of the primary efficacy outcome (Early Clinical Response at 48 to 
72 hours) with the overall assessment of Clinical Response at the PTE Visit (based on the 
investigator's assessment) and the investigator’s assessment of Clinical Response at the EOT 
Visit will be conducted in the mITT population.  A concordance analysis of per-subject 
microbiological response and the investigator’s assessment of Clinical Response at the EOT 
Visit will be conducted in the micro-mITT population. 
For the micro-mITT and ME populations, the number and percentage of subjects with an Early 
Clinical Success (only micro-mITT population), with an assessment of Clinical Success (based 
on the investigator's assessment) at the EOT Visit (micro-mITT and ME-EOT populations) and 
an overall assessment of Clinical Success at the PTE Visit (based on investigator's assessment, 
micro-mITT and ME-PTE populations), will be tabulated by baseline MIC to omadacycline and 
linezolid by pathogen (for those pathogens occurring at least 5 times in one of the treatment 
groups) and treatment group. 


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Microbiological Outcomes 
The per-subject microbiological response at the EOT and PTE Visits in the micro-mITT, ME-
EOT (EOT Visit only) and ME-PTE (PTE-Visit only) populations will be determined to support 
the clinical findings.  The number and percentage of subjects classified with a favorable 
(eradication and presumed eradication) and unfavorable (persistence, presumed persistence, and 
indeterminate) microbiological response (by definition, indeterminates are excluded from the 
ME population) will be tabulated for both treatment groups.  A 2-sided 95% CI without 
stratification will be constructed for the observed difference in the per-subject favorable 
microbiological response rate between the omadacycline and linezolid groups using the method 
of Miettinen and Nurminen.   
Per-subject microbiological response at the PTE Visit in the micro-mITT and ME-PTE 
populations will also be provided by mono-microbial and poly-microbial infections 
(Gram-positive only and mixed infections [Gram-positive and Gram-negative]).   
Microbiologic response by baseline pathogen will be determined as the proportion of subjects 
with a favorable microbiological response (eradication or presumed eradication) at the EOT and 
PTE Visits for each pathogen isolated at baseline from the blood culture or culture of the 
ABSSSI site.  The number and percentage of subjects in each treatment group with a 
microbiologically favorable outcome will be tabulated for the micro-mITT, ME-EOT (EOT 
Visit) and ME-PTE (PTE Visit) populations.  Favorable microbiologic response by baseline 
pathogen will also be summarized separately for pathogens obtained from the blood culture (ie, 
for bacteremic subjects) for the micro-mITT population. 
Microbiological categories for pathogens identified after baseline assessment are superinfection 
and new infection.  The number and percentage of subjects with a superinfection or new 
infection will be presented by treatment group.  A listing will be provided that presents the 
subjects with a superinfection and new infection including the type of specimen and pathogen.   
Decreasing susceptibility of a pathogen is defined as a 4-fold increase from baseline to any 
subsequent study time point in the MIC of the test article received.  The number and percentage 
of subjects in the micro-mITT population with a pathogen showing decreasing susceptibility will 
be tabulated for each treatment group.  In addition, a table will list all subjects in each treatment 
group with a pathogen showing decreasing susceptibility, including the type of specimen, 
pathogen, and MIC values.  Additional exploratory microbiological analyses may be conducted.   
Subject Reported Outcomes 
At the Screening, Day 3, EOT and PTE visits the subject will complete a numerical rating scale 
for pain4 (average pain over the last 24 hours) at the primary ABSSSI lesion site.  The numerical 
rating scale anchors will range from 0 to 10, where 0 represents “No pain” and 10 represents 
“Pain as bad as you can imagine.” Descriptive statistics of the numerical rating scale for pain at 
each time point and the change from baseline for each time point will be provided by treatment 
group for the mITT population.   


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At the Screening and PTE visits the subject will complete a SF-36v2® Health Survey (Medical 
Outcomes Trust, OptumTM).  The SF-36v2® Health Survey asks 36 questions to measure 
functional health and well-being from the subject's point of view.  The SF-36v2® Health Survey 
consists of 8 scaled scores (vitality, physical functioning, bodily pain, general health perceptions, 
physical role functioning, emotional role functioning, social role functioning, and mental health) 
which are weighted sums of the questions in their section.  Each scale is transformed into a 0 to 
100 scale with the lower the score the more disability.  There are 2 composite scores:  physical 
and mental.  Descriptive statistics for the composite scores and each subscale will be provided 
for baseline, the PTE visit and the change from baseline by treatment group for the mITT 
population. 
Subject reported outcomes will be analyzed independently from other data collected in the study.   
10.5 Interim Analysis 
No interim analysis of efficacy or safety is planned.   
10.6 Subgroup Analyses 
The primary analysis (ECR) results will be assessed separately across infection type and prior 
antibiotic stratum by treatment group for both the as randomized strata and the actual strata as 
indicated on the eCRF.  For each infection type stratum, and each prior antibiotic stratum, a 
2-sided 95% CI for the observed difference in the early clinical success rates will be calculated 
for the mITT population.  If a clinically meaningful treatment group-by-infection type or 
treatment group-by-prior antibiotic result in the opposite direction of the overall result is noted, 
an inferential test may be performed as a descriptive statistic.   
Additional subgroup analyses of the primary efficacy outcome will also be conducted for 
descriptive purposes.  These include, but are not limited to clinical site, bacteremic subjects, 
subjects with SIRS,  size of lesion (≤ 300 cm2, > 300 to 600 cm2, > 600 to 1000 cm2, and 
> 1000 cm2), receipt of NSAIDs from first dose of test article through the assessment of early 
clinical response, and receipt of an operative incision and drainage.  Two-sided 95% CIs for the 
observed difference in the early clinical success rates will be calculated for the mITT analysis set 
for each subgroup as descriptive analyses.  Exploratory analyses in other subgroups may also be 
conducted.   
Results of the overall assessment of Clinical Response at the PTE Visit (based on the 
investigator’s assessment at the EOT and PTE Visits) will also be assessed across infection type 
and prior antibiotic by treatment group for both the as randomized strata and the actual strata as 
indicated on the eCRF.  Separately for each infection type stratum and for each prior antibiotic 
stratum, 2-sided 95% CIs for the observed difference in clinical response in the mITT and 
CE-PTE populations will be calculated.  If a clinically meaningful treatment group-by-infection 
type or treatment group-by-prior antibiotic result in the opposite direction of the overall result is 
noted, an inferential test may be performed as a descriptive statistic.   


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11 SAFETY AND TOLERABILITY 
All safety analyses will be conducted in the Safety population.  Subjects who receive the wrong 
test article for their entire course of treatment will be analyzed in the group based on the drug 
received.  If a subject receives both omadacycline and linezolid, the subject will be analyzed in 
the omadacycline arm regardless of the amount of omadacycline received or the randomized 
treatment assignment.  Safety parameters include adverse events (AEs), vital signs, 
electrocardiogram (ECG) parameters and clinical laboratory parameters.  
11.1 Adverse Events 
Verbatim descriptions of AEs will be coded using Version 17.1 or higher of MedDRA.  
Summary tables will be provided for all treatment-emergent adverse events (TEAEs) but all AEs 
will be provided in a listing.  A treatment-emergent AE is defined as any AE that newly 
appeared, increased in frequency, or worsened in severity on or after the initiation of active test 
article.  An AE is considered treatment emergent if the AE start date and time is on or after the 
start date and time of the first dose of active test article.  If time of the AE is missing and it 
occurred on the same date as the first dose of active test article, the AE will be defined as 
treatment emergent.  If the start date of the AE is partial or missing and it cannot be determined 
if the AE occurred prior to or after the first dose of test article, the AE should be defined as 
treatment emergent. 
An overall summary of AEs will include the number of subjects who experienced at least one AE 
of the following categories:  any AE, any TEAE, any drug-related TEAE, any severe TEAE, any 
serious TEAE, any drug-related SAE, any serious TEAE leading to death, any TEAE leading to 
premature discontinuation of test article, any TEAE leading to premature discontinuation from 
the study, any TEAE leading to dose interruption of test article, and any serious TEAE leading to 
premature discontinuation of test article.   
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); and by system organ class, preferred term, and 
relationship (unrelated or related to test article).  The incidence of TEAEs will be summarized by 
preferred term and treatment group, sorted by decreasing frequency in the omadacycline group, 
for all TEAES, related TEAEs, serious TEAEs and TEAEs leading to test article discontinuation.  
The incidence of serious TEAEs and TEAEs leading to premature discontinuation of test article, 
will be summarized by system organ class and preferred term.  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 
test article.   
TEAEs occurring (ie, with a start date and time) during the time period subjects are on treatment 
will be summarized by system organ class and preferred term. 
In addition, all AEs (including non-TEAEs), serious TEAEs, and TEAEs leading to 
discontinuation of test article will be provided in listings by treatment group, study site, subject, 
verbatim term, MedDRA system organ class and preferred term, start and end date, seriousness 


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flag, severity, relationship to test article, relationship to study protocol, action taken with test 
article, non-test article action taken and outcome.   
For subjects with a TEAE of nausea (based on the MedDRA preferred term), the total number of 
nausea events, descriptive statistics of the study day of onset of all nausea events, and descriptive 
statistics for the duration (in days) of all nausea events, will be presented by treatment group. 
11.2 Vital Signs 
Blood pressure (systolic and diastolic), respiratory rate and pulse/heart rate will be summarized 
using descriptive statistics at the following time points:  baseline, Day 1, Day 2, Day 3, Day 7, 
Day 10, the EOT visit and PTE visit, but not the final Follow-up Visit.  Pulse rate and blood 
pressure will be summarized for the following additional time points:  a) 30 minutes before, 1 
hour after and 3 hours after the completion of the first dose on Day 1, and b) 30 minutes before 
and 1 hour after and 3 hours after the completion of the odd numbered doses on Days 2 and 3.  In 
the event the subject takes the dose before arriving at the office visit,  the site should collect the 
1 and 3 hour post dose measurements, if possible.  If not then a single measurement at any time 
during the visit should be obtained.  
Descriptive statistics of the change from baseline to each post-baseline time point will also be 
provided.  Baseline is defined as the value closest to but prior to the initiation of test article 
administration.  If no value is available prior to the initiation of test article administration, a 
value within 2 hours after initiation of test article administration can be used as baseline.  The 
change from baseline to the minimum and maximum post-baseline values (including any 
unscheduled post-baseline assessments) will also be summarized by treatment group. 
Figures (line graphs) of value and change from baseline for systolic and diastolic blood pressure, 
and heart rate by time point will also be provided by treatment group. 
Post-baseline vital signs will be defined as clinically notable (CN) if they meet 1) the criterion 
value or 2) meet both the criterion value and the change from baseline criterion listed in Table 8.  
The incidence of CN vital signs will be summarized by time point and treatment group, and will 
be listed and flagged in by-subject listings.  The overall post-baseline incidence of CN values for 
each vital sign parameter, which includes values from unscheduled post-baseline visits, will also 
be summarized.  A listing will also be provided of subjects with a CN vital sign and will list all 
values for a vital sign noted as CN. 
Table 8.  
Criteria for Treatment Emergent Clinically Notable Vital Signs 
Vital Sign Parameter 
Flag 
Criterion Value 
Change from Baseline 
Systolic Blood Pressure 
(mmHg) 
High (CH) 
≥ 180 
Increase of ≥ 20 mmHg 
Low (CL) 
≤ 90 
Decrease of ≥ 20 mmHg 
Diastolic Blood Pressure 
(mmHg) 
High (CH) 
≥ 105 
Increase of ≥ 15 mmHg 
Low (CL) 
≤ 50 
Decrease of ≥ 15 mmHg 
Heart Rate (bpm) 
High (CH) 
≥ 120 
Increase of ≥ 15 bpm 
Low (CL) 
≤ 50 
Decrease of ≥ 15 bpm 
 


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11.3 Electrocardiogram 
A central vendor with readers blinded to treatment assignment will perform the reading of the 
ECGs.  The central ECG results will be used for the statistical analyses.   
Descriptive statistics for ECG parameters (heart rate, RR interval, PR interval, QRS interval, QT 
interval, and QTc interval) at baseline and at the EOT Visit, and the change from baseline will be 
presented by treatment group.  The QTc interval will be presented by both the Bazett (QTcB = 
QT/(RR)½) and the Fridericia (QTcF = QT/(RR)⅓) corrections.  The change from baseline to the 
minimum and maximum post-baseline values (including EOT and any unscheduled post-baseline 
assessments) will also be summarized by treatment group.  Baseline is defined as the value 
closest to but prior to the initiation of test article administration.  If no value is available prior to 
the initiation of test article administration, a value within 2 hours after initiation of test article 
administration can be used as baseline. 
The number and percentage of subjects with any post-baseline (including EOT and any 
unscheduled post-baseline assessments) increase in QTcF and any post-baseline increase of 
> 30 msec or > 60 msec in QTcF will be summarized by treatment group.  The number and 
percentage of subjects with a baseline QTcF ≤ 450 msec and with a post-baseline QTcF of 
> 450 msec and with a baseline QTcF ≤ 500 and with a post-baseline QTcF of > 500 msec will 
also be summarized by treatment group.  The number and percentage of subjects with a post-
baseline increase in QTcF of > 30 msec resulting in a post-baseline QTcF of > 450 msec or 
> 500 msec will also be summarized by treatment group.  A listing will also be provided of 
subjects with a QTcF that meets one of the criteria listed above and will list all QTcF values for 
the subject. 
The distribution of QTcF values (≤ 450 msec, > 450 to ≤ 480 msec, > 480 to ≤ 500 msec, 
and > 500 msec) at each time point and the distribution of change from baseline in QTcF values 
at EOT (0 or less [no increase], 1 to 29 msec, 30 to 60 msec, and > 60 msec) will be summarized 
by treatment group.   
11.4 Laboratory Values 
Summaries of laboratory data will include hematology, chemistry and coagulation (INR only) 
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 9. 


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Table 9.  
Laboratory Parameters and Organ Class 
Organ Class 
Laboratory Parameter 
Renal 
Creatinine 
Renal 
Urea 
Liver 
Alkaline phosphatase (ALP) 
Liver 
ALT 
Liver 
AST 
Liver 
Total Bilirubin  
Liver 
GGT 
Electrolytes 
Bicarbonate 
Electrolytes 
Calcium 
Electrolytes 
Chloride 
Electrolytes 
Magnesium 
Electrolytes 
Potassium 
Electrolytes 
Sodium 
Other 
Albumin 
Other 
Amylase 
Other 
Blood glucose 
Other 
Cholesterol 
Other 
CK 
Other 
CK isoenzyme 
Other 
LDH 
Other 
Lipase 
Other 
Phosphate 
Other 
Total protein 
Other 
Uric acid 
 
Baseline is defined as the central lab value closest to and prior to the first dose of test article.  If 
no central lab value is available prior to the first dose of test article the local lab value that is 
closest to and prior to the first dose of test article will be used as baseline.  For by visit analyses, 
central lab values will be used unless no central lab value was obtained in the visit window.  In 
this case, local lab values will be used for the by visit analyses.  All lab values (central and local) 
are used for determination of the overall worst post-baseline value. 
Several analyses of the laboratory data will be presented.  Descriptive statistics (based on SI 
units) for chemistry and hematology values and the change from baseline will be summarized by 
treatment group at each time point (Day 3 [+ 1 day], Day 7 [+1 day], Day 10 [+1 day], EOT visit 
and PTE visit), and for the overall worst value post-baseline (which includes unscheduled visits).  
Appendix 4 provides the directionality of the worst values for each laboratory parameter. 
Clinically notable laboratory values will be determined based on the modified Division of 
Microbiology and Infectious Diseases (DMID) criteria in Appendix 5.  Shift tables will be 
presented to show the number of subjects with a laboratory value with a grade of 0, 1, 2, 3 or 4 at 
baseline versus the value at each visit and the worst post-baseline value.  Number and percentage 
of subjects with at least a 2 grade increase from baseline (based on DMID criteria) will be 
summarized by treatment arm.  Percentages for each laboratory test will be based on the number 
of subjects with a baseline and post-baseline evaluation of the specific laboratory test.  A listing 


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will be provided which gives all laboratory results for a given laboratory test for subjects who 
have at least a 2 grade increase from baseline.  
The number and percentage (based on the number of subjects with a normal level at baseline) of 
subjects in each treatment group with an elevated transaminase level (> 3 × ULN, > 5 × ULN, 
and >10 × ULN), an elevated bilirubin level (>1.5 × ULN and >2 × ULN) will be presented by 
study visit.  A table will list all subjects with any post-baseline ALT or AST > 3x ULN or total 
bilirubin >1.5 x ULN.  The table will provide the AST, ALT, total bilirubin and alkaline 
phosphatase value for each subject at each time point laboratory values were entered.  A listing 
of subjects who meet the laboratory criteria for Hy’s law will also be provided.  The laboratory 
criteria for Hy’s law is defined as 1) ALT or AST > 3 × ULN, ALP ≤ 2.0 × ULN, and total 
bilirubin > 1.5 x ULN and 2) ALT or AST > 3 × ULN, ALP ≤ 2.0 × ULN, and total bilirubin 
> 2 × ULN. 
Detailed subject listings of all laboratory data (local and central laboratory data) collected during 
the study will be provided, including calculated creatinine clearance (using the Cockcroft-Gault 
equation).  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). 
11.5 Physical Examinations 
Subject listings of all physical examination results by body system will be provided.  Any 
changes from baseline will be recorded as adverse events. 


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12 RESOURCE UTILIZATION ANALYSES 
Descriptive statistics of the following resource utilization parameters will be provided by 
treatment group: 
• Number of hospitalizations for the ABSSSI from the first dose of study drug through the FU 
Visit. 
• For those subjects who had at least one hospitalization, the number of days in the hospital 
from date of admission for the ABSSSI until discharge. 
 


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13 OTHER RELEVANT DATA ANALYSES/SUMMARIES 
13.1 Protocol Deviations  
A listing of all protocol deviations will be provided.  Deviations will also be reviewed by the 
sponsor and categorized into general categories such as:  randomization, at least one inclusion 
criterion not met, at least one exclusion criteria met, study procedures/visits not done, study visit 
outside window, use of prohibited medications or treatments, consent-IRB compliance issues, 
etc.  The sponsor will also categorize the protocol deviations as major and minor.  Review of 
protocol deviations will be conducted and finalized prior to unblinding the database.  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 protocol deviation, and the number of 
subjects with at least one major protocol deviation in each category will be presented by 
treatment group for the ITT population.  A major deviation is defined as one that potentially 
affects the efficacy and/or safety analyses.   
13.2 Prior and Concomitant Medications 
All medications taken within 7 days prior to the date of informed consent through the Final 
Follow-up Visit will be recorded on the e-CRF.  Prior medications will be summarized by 
WHODRUG (Version 01-Dec-2014 ) Anatomical Therapeutic Chemical Classification (ATC) 
level 3 (third level indicates the therapeutic/pharmacologic subgroup) and generic medication 
name.  Medications are considered prior if taken prior to the first dose of test article or if their 
start date is unknown.  Subjects will be counted only once for an ATC class and generic 
medication name.  Concomitant medications taken during and after the study treatment period 
will be similarly summarized.  Medications are considered concomitant if taken on or after the 
first dose of test article, or if their stop date is unknown or marked as continuing.   
The proportion of subjects who receive the following prior and concomitant medications will be 
summarized by treatment group: 
• Systemic and topical antibacterial medications taken within 7 days prior to first dose of test 
article and the reasons for receipt (mITT and CE-PTE populations) 
• Systemic single dose, short-acting, non-oxazolidinone antibacterial taken within 72 hours 
prior to randomization 
• Systemic and topical antibacterial medications (excluding test article) taken between first 
dose of test article and the EOT Visit (CE-EOT population) and the reasons for receipt 
(mITT and CE-EOT populations) 
• Systemic and topical antibacterial medications (excluding test article) taken between first 
dose of test article and the PTE Visit (CE-PTE population) and the reasons for receipt (mITT 
and CE-PTE populations) 
• Non-antibacterial medications taken 7 days prior to informed consent through the first dose 
of test article (mITT and Safety populations)  


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• Non-antibacterial medications taken from the first dose of test article through the Final 
Follow-up Visit (mITT and Safety populations) 


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14 REFERENCES 
 
1 Prokocimer P, De Anda C, Fang E, Mehra P, Das A. 2013. Tedizolid Phosphate vs Linezolid 
for Treatment of Acute Bacterial Skin and Skin Structure Infections: The ESTABLISH-1 
Randomized Trial. JAMA. 309:559-69. 
2 Farrington CP, Manning G. Test statistics and sample size formulae for comparative binomial 
trials with null hypothesis of non-zero risk difference or non-unity relative risk. Stat Med. 1990 
Dec;9(12):1447-54. 
3 Miettinen O, Nurminen M. Comparative analysis of two rates.  Statistics in Medicine.  
1985;4(2):213-26. 
4 McCaffery, M, Beebe, A. 1993. Pain: Clinical Manual for Nursing Practice. Baltimore: V.V. 
Mosby Company. 


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15 APPENDICES 


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Appendix 1 Schedule of Events 
Study Phase 
Screeninga 
Double-Blind Treatment Phase 
Follow-up Phase 
Study Dayb 
 
Day 1 
Day 2 
Day 3 
 (ECR 48-
72 hr after 
first dose) 
Day 7 
Day 10c 
EOTd 
PTEe 
Final  
Follow-upf 
Day 30-37 
Signed Informed Consentg 
X 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
Medical/surgical history and current medical 
conditions 
X 
 
 
 
 
 
 
 
Prior and concomitant medicationsh 
X 
X---------------------------------------------------------------------------------------------------X 
Clinical assessment of the site of infectioni 
X 
 
X 
X 
X 
X 
X 
X 
 
Assessment of lesion sizej 
X 
 
X 
X 
X 
X 
X 
X 
 
Diagnosis of ABSSSI and photograph of the 
lesion sitek 
X 
 
 
 
 
 
 
 
Numerical Rating Scale for pain at the primary 
lesion site 
X 
 
X 
 
 
X 
X 
 
SF-36v2® Health Survey 
X 
 
 
 
 
 
X 
 
Physical examinationl 
X 
 
 
 
 
 
X 
X 
 
Vital signs 
 
 
 
 
 
 
 
 
 
Respiratory rate 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Body temperature 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Blood pressure 
X 
Xm 
Xn 
Xn 
X 
X 
X 
X 
 
 
Pulse/heart rate 
X 
Xm 
Xn 
Xn 
X 
X 
X 
X 
 
12-lead ECGo 
X 
 
 
 
 
X 
  
 
Urine dipstick testp 
X 
 
 
 
 
 
 
 
Urine pregnancy testq 
X 
 
 
 
 
 
 
 
Serum pregnancy testr 
X 
 
 
 
 
X 
X 
 
Hematologys 
Xt 
 
X 
X 
X 
X 
X 
 
Serum chemistrys 
Xt 
 
X 
X 
X 
X 
X 
 
Blood cultureu 
X 
As Clinically Indicated 
Xv 
Xv 
 
Culture of infection site & Gram stain 
X 
As Clinically Indicated 
Xv 
Xv 
 
Adverse Eventsw 
X 
X-------------------------------------------------------------------------------------------------X 


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Study Phase 
Screeninga 
Double-Blind Treatment Phase 
Follow-up Phase 
Study Dayb 
 
Day 1 
Day 2 
Day 3 
 (ECR 48-
72 hr after 
first dose) 
Day 7 
Day 10c 
EOTd 
PTEe 
Final  
Follow-upf 
Day 30-37 
Review of Inclusion and Exclusion 
Criteria/Randomization (if Eligible) 
X 
 
 
 
 
 
 
 
Test Article Administration and Accountabilityx 
 
Xy 
Xz 
Xaa 
X 
X 
 
 
 
Plasma samples (in heparin) for PK analysesbb 
 
 
X 
X 
 
 
 
 
 
Assessment of need to continue therapycc 
 
 
 
X 
X 
 
 
 
Investigator’s Assessment of Clinical Response 
 
 
 
 
 
X 
X 
 
ABSSSI = Acute Bacterial Skin and Skin Structure infection; AE = adverse event; β-hCG = beta – human Chorionic Gonadotropin; ECG = electrocardiogram; 
ECR = Early Clinical Response; eCRF = electronic case report form; EOT = end of treatment; ICF = informed consent form; PK = pharmacokinetics; PTE = post 
therapy evaluation; SAE = serious adverse event. 
a 
Following the signing of an ICF, all Screening evaluations, with the exception of the blood culture sample collection, should be completed within the 
24 hours prior to randomization.  The blood culture sample collection should be completed within 24 hours prior to the first dose of test article. 
b 
Day 1 is the first day of test article administration.  Subsequent study days are consecutive calendar days. 
c 
A Day 10 visit should be conducted for subjects with treatment extending beyond 9 days, unless this visit coincides with the EOT visit. 
d 
To be conducted on the calendar day of, or within 2 days following the last dose of test article.  Should also be conducted for any subject who withdraws 
prematurely or terminates participation in the study before completion. 
e 
To be conducted 7 to 14 days after the subject’s last day of study therapy.   
f 
To be conducted 30 to 37 days after the first dose of test article.  The Final Follow-up assessment may be conducted via telephone contact or by another 
interactive technology for subjects who were considered to be Clinical Successes and had no AEs or clinically significant laboratory or ECG abnormalities 
noted at or after the PTE visit.  Otherwise, the visit must be conducted in person.   
g 
Written and signed ICF must be obtained before any assessment is performed. 
h 
Treatments that have been administered within the 7 days prior to the date of signing the ICF or during the Screening phase will be recorded in the eCRF.  
All medications and significant non-drug therapies (including physical therapy and blood transfusions) administered after the first dose of test article must be 
recorded in the eCRF. 
i 
Semi-quantitative description of infection features.  Must be assessed within 48 to 72 hours after the first dose.  
j 
Measurement of the subject’s lesion by ruler length × width.  The Screening measurement must be collected within 4 hours prior to randomization.  A lesion 
measurement must be completed within 48 to 72 hours after the first dose.  
k 
Diagnosis of the type of ABSSSI (wound infection, cellulitis/erysipelas or major abscess) and anatomical location.  A digital photograph of the infection site 
will be taken at Screening only. 
l 
A full physical examination will be completed at Screening; thereafter only changes from Screening measurements should be recorded as AEs in the eCRFs. 
m 
Blood pressure and pulse rate should be measured within 30 min before, and approximately (± 15 minutes) 1 hour after and 3 hours after the completion of the 
first dose on Day 1. 


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n 
Blood pressure and pulse rate should be measured within 30 min before, and approximately (± 15 minutes) 1 hour after and 3 hours after the completion of the 
odd numbered doses on Days 2 and 3.  In the event that the subject takes the dose before arriving for the office visit, the site should collect the 1 and 3 hour post 
dose measurements if possible, if not then a single measurement should be made at any time during the visit and the date and time recorded.  
o 
A 12-lead ECG should be performed at screening, at the EOT visit, and as otherwise clinically indicated. 
p 
A urine dipstick test will be performed locally at Screening. 
q 
All women will have a local urine pregnancy test at Screening. 
r 
All women will have blood collected for a serum β-hCG pregnancy test at the Central Laboratory at the Screening, EOT and PTE visits.   
s 
Blood will be collected for hematology (includes coagulation) and serum chemistry testing at the Central Laboratory at Screening and at the Day 3, Day 7, 
Day 10, EOT and PTE visits. 
t 
At the Screening visit, blood will be collected for local laboratory hematology and serum chemistry evaluations required for assessing subject eligibility. 
u 
If bacteria are isolated from blood cultures, repeat blood cultures should be collected.  If subsequent blood cultures are also positive, repeat the blood 
cultures as necessary until negative blood cultures are obtained. 
v 
At the EOT and/or PTE visit, blood cultures and infection site specimen cultures and Gram stains should be obtained only for subjects who are clinical 
failures and require alternative antibacterial treatment for the infection under study. 
w 
A subject’s AEs and SAEs will be recorded and reported from signing of the ICF to the Final Follow-up assessment. 
x 
A 6 hour fast is required before and a 2 hour fast is required following  all odd numbered doses.  The total duration of test article therapy for all subjects will be 
7 to 14 days.  Test article may be dispensed and reconciled by blinded personnel.  Subjects will be asked to return all unused test article and packaging at each 
visit.  At the EOT visit subjects will return the test article packaging and site staff will perform accountability. 
y 
Subjects should receive their first dose of test article at the site within 4 hours after randomization.  
z 
Subjects should be instructed not to take the odd numbered dose on Day 2 until they return to the site for the Day 2 visit. 
aa 
Subjects should be instructed not to take the odd numbered dose on Day 3 until they return to  the site for the Day 3 visit.  
bb 
At selected sites, subjects who have agreed to participate in PK evaluation and have signed a separate PK evaluation consent form will have up to 4 blood 
samples collected between Days 2 and 3.  The PK sample collection schedule for the individual subject will be provided by the Sponsor.  
cc 
At the investigator’s discretion, all therapy may be discontinued after the 7th day of treatment, when the infection is considered clinically cured (based on 
normalization of the clinical signs and symptoms of infection and the investigator’s clinical assessment that continued systemic antibacterial therapy is no 
longer needed). 


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Appendix 2 Summary of Efficacy Analyses  
 
48-72 Hours Post First Dose 
End of Treatment Visit 
(EOT) 
Post Therapy Evaluation 
Visit (PTE) 
ITT 
ECR  
 
 
mITT 
ECR (primary efficacy ) 
IA  
IA  
Micro-mITT 
ECR  
ECR (by pathogen) 
ECR (by pathogen and MIC) 
Micro (by subject) 
Micro (by pathogen) 
IA (by pathogen) 
IA (by pathogen and MIC) 
Micro (by subject) 
Micro (by pathogen) 
CE-EOT 
 
IA  
 
CE-PTE 
 
 
IA  
ME-EOT 
 
Micro (by subject) 
Micro (by pathogen) 
 
ME-PTE 
 
 
IA  
IA (by pathogen) 
IA (by pathogen and MIC) 
Micro (by subject) 
Micro (by pathogen) 
ECR = Early Clinical Response; IA = Investigator Assessment of Response. 


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Appendix 3 Adverse Event and Prior/Concomitant Medication Date Imputations 
Adverse Event Start/Stop Date Imputation  
Imputation Rules for Partial Dates (D = day, M = month, Y = year) 
Parameter 
Missing 
Additional Conditions 
Imputation 
Start date 
for AEs 
 
D 
M and Y same as M and Y of first dose of test article 
Date of first dose of test article 
M and/or Y not same as date of first dose of test article 
First day of month 
D and M 
Y same as Y of first dose of test article 
Date of first dose of test article 
Y prior to Y of first dose of test article but same as Y of 
screening date 
Date of screening date 
D, M, Y 
None - date completely missing 
Date of first dose of test article 
Stop date 
for AEs 
 
D 
M and Y same as M and Y of last dose of test article 
Date of last dose of test article 
M and/or Y not same as date of last dose of test article 
Use last day of month 
D and M 
Y same as Y of last dose of test article 
Date of last dose of test article 
Y not same as Y of last dose of test article 
Use Dec 31 
D, M, Y 
None - date completely missing 
No imputation, but assume ongoing 
Note:  In all cases, if an estimated start date is after a complete stop date, use the first day of the stop date month. 
Similarly, if the estimated stop date is before a complete or imputed start date, use the last day of the start day month. 
In all cases, if it cannot be determined if the adverse event occurred prior to or after the first dose of test article, the adverse 
event should be defined as treatment emergent. 
 
Prior and Concomitant Medication Start Date Imputation  
Parameter 
Type of 
Medication 
Imputation 
Start date for 
con meds  
Non-
Antibacterial  
If it cannot be determined whether or not the start date of a medication (non-
antibacterial) is prior to the first dose of test article, it will be assumed that the 
medication was received prior to the first dose of test article  
Antibacterial 
Missing start dates for antibacterials will be queried for a value.  If it cannot be 
determined whether or not the start date of an antibacterial is prior to the first dose of 
test article, it will be assumed that the medication was received prior to the first dose 
of test article unless the indication notes that the medication was received after the 
first dose of test article. 
Stop date for con 
meds  
Non-
Antibacterial 
If it cannot be determined whether or not the stop date of a medication (non-
antibacterial) is after the first dose of test article, it will be assumed that the 
medication was received after the first dose of test article 
 
Antibacterial 
Missing stop dates for antibacterials will be queried for a value.  If it cannot be 
determined whether or not the stop date of an antibacterial is after the first dose of 
test article, it will be assumed that the medication was received after the first dose of 
test article unless the indication notes that the medication was received prior to the 
first dose of test article.  If it cannot be determined whether the antibacterial was 
received prior to the assessment of Early Clinical Reponse, the EOT and/or the PTE 
Visit, the antibacterial will be assumed to have been received through the PTE Visit. 
 


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Appendix 4 Directionality of Worst Laboratory Parameters 
Laboratory Test 
Parameter 
Worst Value 
Hematology 
Hematocrit 
Lowest value 
 
Hemoglobin 
Lowest value 
 
Red blood cell count 
Lowest value 
 
Mean cell hemoglobin 
Lowest value 
 
Mean cell hemoglobin concentration 
Lowest value 
 
Mean cell volume 
Lowest value 
 
White blood cell count 
Lowest value 
 
Platelets 
Lowest value 
 
Neutrophils  
Lowest value 
 
Lymphocytes  
Lowest value 
 
Monocytes  
Lowest value 
 
Eosinophils 
Highest value 
 
Basophils  
Lowest value 
Chemistry 
Albumin  
Lowest value 
 
Alkaline phosphatase 
Highest value 
 
Alanine aminotransferase ALT/SGPT) 
Highest value 
 
Amylase 
Highest value 
 
Aspartate aminotransferase (AST/SGOT) 
Highest value 
 
Urea 
Highest value 
 
Bicarbonate  
Lowest value 
 
Calcium 
Both highest value and lowest value 
 
Cholesterol  
Highest value 
 
Chloride  
Both highest value and lowest value 
 
Creatinine 
Highest value 
 
Creatine kinase (CK) 
Highest value 
 
Gamma-glutamyl transpeptidase (GGT) 
Highest value 
 
Blood glucose 
Both highest value and lowest value 
 
Lactate dehydrogenase (LDH) 
Highest value 
 
Lipase 
Highest value 
 
Magnesium  
Both highest value and lowest value 
 
Phosphate 
Both highest value and lowest value 
 
Potassium 
Both highest value and lowest value 
 
Sodium 
Both highest value and lowest value 
 
Total bilirubin 
Highest value 
 
Total protein 
Lowest value 
 
Uric acid 
Highest value 
Coagulation 
International normalized ratio (INR) 
Highest value 


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Appendix 5 Modified Division of Microbiology and Infectious Diseases Adult Toxicity 
Table 
The DMID Adult Toxicity Table (21-Nov-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.  The grades for several parameters including enzymes were 
modified to ensure that any possible numeric value can be categorized appropriately (eg, for 
creatinine, Grade 3 is defined as “>1.5-3.0×ULN” instead of “1.6-3.0×ULN”). 
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.   
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 or < 
1,000 
COAGULATION  
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Prothrombin time 
(PT) (sec) 
≤1 x ULN 
1.01-1.25 x 
ULN 
1.26-1.5 x ULN 
1.51 x 3.0 x 
ULN 
> 3 x ULN 
Activated partial 
thromboplastin time 
(aPTT) (sec) 
Increased 
≤ ULN 
1.01 - 1.66 x 
ULN 
1.67 - 2.33 x 
ULN 
2.34 - 3 x 
ULN 
International 
normalized ratio 
(INR) 
Increased 
≤ ULN 
> 1 - 1.5 x ULN 
> 1.5 - 2.5 x 
ULN 
> 2.5 x ULN 
 
 


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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) 
≥ 65 
55-64 
40-54 
30-39 
< 30  
Hyperglycemia (mg/dL) 
(nonfasting and regardless 
of prior history of 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)* 
≤ 10.5 
10.6-11.5 
11.6-12.5 
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) 
≥ 2.5 
2.0-2.4 
1.5-1.9 
1.0-1.4 
< 1.0 
Hyperbilirubinemia (total 
bilirubin) 
< 1.1×ULN 
1.1-1.5×ULN 
> 1.5-
2.5×ULN 
> 2.5-5×ULN 
> 5×ULN 
Urea 
< 1.25×ULN 
1.25-2.5×ULN 
> 2.5-5×ULN 
> 5-10×ULN 
>10×ULN 
Hyperuricemia (uric acid) 
(mg/dL) 
< 7.5 
7.5–10.0 
10.1–12.0 
12.1–15.0 
> 15.0 
Creatinine 
< 1.1×ULN 
1.1-1.5×ULN  
> 1.5-
3.0×ULN 
> 3.0-6×ULN 
> 6×ULN  
*The DMID toxicity table reports hyperglycemia detected in nonfasting specimens obtained from subjects with 
no prior diabetes. 
 
ENZYMES 
 
Grade 0  
Grade 1  
Grade 2  
Grade 3  
Grade 4  
AST (SGOT) 
< 1.25×ULN 
1.25-2.5×ULN 
> 2.5-5×ULN 
> 5-10×ULN 
> 10×ULN 
ALT (SGPT) 
< 1.25×ULN 
1.25-2.5×ULN 
> 2.5-5×ULN 
> 5-10×ULN 
> 10×ULN 
GGT 
< 1.25×ULN 
1.25-2.5×ULN 
> 2.5-5×ULN 
> 5-10×ULN 
> 10×ULN 
Alkaline 
Phosphatase 
< 1.25×ULN 
1.25-2.5×ULN 
> 2.5-5×ULN 
> 5-10×ULN 
> 10×ULN 
Amylase 
< 1.1×ULN 
1.1-1.5×ULN 
> 1.5-2.0×ULN 
> 2.0-5.0×ULN 
> 5.0×ULN 
Lipase 
< 1.1×ULN 
1.1-1.5×ULN 
> 1.5-2.0×ULN 
> 2.0-5.0×ULN 
> 5.0×ULN 
* Calcium corrected for albumin = [0.8 x (normal albumin - subject's albumin)] + serum Ca level 
Where normal albumin = 4 g/dl, albumin is in g/dL and calcium is in mg/dL