Clinical trial NCT04779242
Conditions: Community-acquired Pneumonia Bacterial Pneumonia
Sponsor: Paratek Pharmaceuticals Inc
Start date: 2021-02-25; Completion date: 2024-03-27
Enrollment: 670 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 moxifloxacin in the treatment of adults with community-acquired bacterial pneumonia.

Detailed description:

Arms: arm 1: Omadacycline 100 mg IV; Omadacycline 300 mg PO (2 x 150 mg tablets); QD Dosing; 7-10 day duration. arm 2: Moxifloxacin 400 mg IV; Moxifloxacin 400 mg tablets; QD Dosing; 7-10 day duration
Interventions: intervention 1: Omadacycline intervention 2: Moxifloxacin
Intervention descriptions: intervention 1: IV for injection, oral tablets intervention 2: IV solution, oral tablets

Protocol documents:
Prot_000.pdf: 
Omadacycline 
Paratek Pharma, LLC 
Clinical Study Report:  PTK0796-CABP-19302 
Confidential and Proprietary 
 
16.1.1 Protocol and Amendments 
Version 5.0 (Dated 19-NOV-2020) 
Page 1 of 86


Clinical Trial Protocol: PTK0796-CABP-19302 
Study Title: 
A Phase 3b Randomized, Double-Blind, Multi-Center Study to 
Compare the Safety and Efficacy of Omadacycline IV/PO to 
Moxifloxacin IV/PO for Treating Adult Subjects with 
Community-Acquired Bacterial Pneumonia (CABP) 
Study Number: 
PTK0796-CABP-19302 
Study Phase: 
3b 
Product Name: 
Omadacycline (PTK 0796) 
IND Number: 
75,928 
73,431 
Indication: 
Community Acquired Bacterial Pneumonia 
Investigators: 
Multicenter 
Sponsor: 
Paratek Pharmaceuticals, Inc.  
75 Park Plaza, 4th Floor 
Boston, MA 02116 
1000 First Ave 
Suite 200 
King of Prussia, PA 19406 
Sponsor Contact: 
Tel: +1 617-275-0040 
Global Medical 
Monitor 
 MD 
Original Protocol Version 5: 
19-November-2020 
Confidentiality Statement 
 
The concepts and information contained in this document or generated during the study 
are considered proprietary and may not be disclosed in whole or in part without the 
expressed, written consent of Paratek Pharmaceuticals, Inc. 
The study was in accordance with the International Council on Harmonisation Harmonised 
Tripartite Guidelines for Good Clinical Practice. 
 
 
 
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Omadacycline 
Paratek Pharmaceuticals, Inc. 
PTK0796-CABP-19302-Version 5, 19-November-2020 
IND # 75,928 / IND #73,431 
 
 
Confidential and Proprietary 
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SYNOPSIS 
Sponsor: 
Paratek Pharmaceuticals, Inc.  
Name of Finished Product: 
Omadacycline for injection, 100 mg lyophilized vial drug product 
Omadacycline oral tablet, 150 mg 
Name of Active Ingredient: 
Omadacycline 
Study Title: 
A Phase 3b Randomized, Double-Blind, Multi-Center Study to Compare the Safety and 
Efficacy of Omadacycline IV/PO to Moxifloxacin IV/PO for Treating Adult Subjects with 
Community-Acquired Bacterial Pneumonia (CABP) 
Study Number: 
PTK0796-CABP-19302 
Study Phase: 3b 
Study Rationale: 
Omadacycline is an aminomethylcycline in the tetracycline class of antibiotics. NUZYRA™ 
(omadacycline) is available for both intravenous (iv) and oral (po) administration and has been 
approved by the United States (US) Food and Drug Administration (FDA) for the treatment of 
adult patients with community-acquired bacterial pneumonia (CABP) caused by susceptible 
microorganisms. 
Omadacycline is active in vitro against the most common CABP pathogens, including isolates 
resistant to currently marketed antibiotics. This study is intended to evaluate the safety and 
efficacy of iv and po omadacycline as compared to iv and po moxifloxacin in the treatment of 
adults with pneumonia patient outcomes research team (PORT) Risk Class III and IV CABP. 
Primary Objective: 
To demonstrate that iv to po omadacycline is non-inferior to iv to po moxifloxacin in the 
treatment of adults with PORT Risk Class III and IV CABP. 
Secondary Objectives: 
• To evaluate the safety of omadacycline in the treatment of adult subjects with 
CABP in the Safety population. 
• To evaluate the Clinical Response according to the identified causative pathogen. 
• To evaluate the pharmacokinetics (PK) of omadacycline in adult subjects with 
CABP. 
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Study Design: 
This is a randomized (1:1), active comparator controlled, double-blind, Phase 3 study comparing 
omadacycline and moxifloxacin in the treatment of adults with CABP (PORT Risk Class III and 
IV). Both iv and po phases of the study will be double-blind. 
Subjects will participate in the study for up to 37 days. Following a Screening period of up to 24 
hours, eligible subjects will be randomized to receive treatment. Subjects will be stratified by 
PORT Risk Class (III or IV) at Screening. 
Eligible subjects with a PORT Risk Class III or IV will be randomized to receive 7 to 10 days of 
iv treatment with the option to switch to po treatment beginning on Day 3. Subjects with 
bacteremia identified at Screening can receive up to 14 days of treatment. 
Switch to po will NOT be permitted until after the subject has completed at least 2 days of iv 
treatment. The decision to switch to po treatment will be made by the investigator; the subject 
should be considered clinically stable and meet all criteria for transition to a po regimen. 
Specifically, the subject must meet the following requirements and this should be noted in source 
documents and recorded on the electronic case report form (eCRF): 
• Temperature ≤ 37.8°C (100°F) 
• Heart rate ≤ 100 beats/minute 
• Respiratory rate (RR) ≤ 24 breaths/minute 
• Systolic blood pressure (SBP) ≥ 90 mm Hg 
• Oxygen saturation ≥ 90% as measured by pulse oximetry or partial pressure of 
arterial oxygen (PaO2) ≥ 60 mm Hg by arterial blood gas (ABG) 
• Normal (“absence of confusion”) or return to baseline mental status 
• Ability to maintain po intake. 
Subjects may receive iv treatment in certain outpatient centers in circumstances where the 
principal site investigator has identified that sufficient resources are available to complete all 
study procedures as defined in the protocol and the sponsor or sponsor’s designee has reviewed 
and approved the process for outpatient iv test article administration. 
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Eligible subjects will be randomized to one of the following treatment groups. 
Group 
Test Article 
Study Day 
1 
Study Day 
2 
Study Days 
3 to 10a 
1 
Omadacycline 
200 mg iv QD 
or 100mg iv 
100 mg iv 
100 mg iv or 300 mg po 
 
 
BID 
 
 
2 
Moxifloxacin 
400 mg iv 
400 mg iv 
400 mg iv or 
400 mg po 
BID = twice a day dosing, iv = intravenous, po = per oral, PORT = pneumonia patient outcomes research 
team, QD = once a day dosing. 
a 
The total duration of treatment for subjects is 7-10 days, with up to 14 days of treatment for subjects 
with bacteremia. 
 
Refer to Appendix 1 for the summary of subject visits and assessments through end of treatment 
(EOT). 
Subjects will return to the study site for a Post Therapy Evaluation (PTE) 5 to 10 days after the 
last dose of test article. A Final Follow-up visit (Final Follow-up) will be conducted within 30 to 
37 days following 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 had an 
outcome of Clinical Success in the opinion of the investigator at EOT and PTE and had no 
adverse events (AEs) or clinically significant laboratory or electrocardiogram (ECG) 
abnormalities noted at or after the PTE visit. Otherwise, this assessment is to be performed with 
an in-person study visit. 
Rationale for Omadacycline Dose Regimen Selection: 
The dosing regimen of omadacycline selected for this study is based on the nonclinical and 
clinical experience to date, including in-vitro antibacterial activity, PK characteristics, clinical 
efficacy in prior studies, the overall safety and tolerability profile, and the FDA approved dosing 
regimen for CABP. 
Either a regimen of 200 mg iv omadacycline once or 100 mg iv omadacycline q12h on Day 1 
followed by 100 mg iv omadacycline administered once daily OR 300 mg po omadacycline once 
daily has been approved by US FDA for the treatment of adult patients with CABP caused by 
susceptible microorganisms. The FDA-approved treatment duration for omadacycline is 7 to 
14 days total. 
The duration for the iv to po regimen in this study will be 7 to 10 days with up to 14 days 
allowed for subjects with bacteremia identified at the Screening visit. This dosing regimen is 
supported by the efficacy observed in the previously completed CABP Phase 3 study, 
PTK0796-CABP-1200, where by Day 7 of treatment, > 80% of patients in the omadacycline 
treatment group had symptom improvement (as defined by the Early Clinical Response [ECR] 
endpoint) and had reached clinical stability. 
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Approximate Number of Subjects/Sites: 
Approximately 670 subjects will be enrolled at approximately 75 sites globally. 
Approximate Duration of the Study: 
The study is expected to be complete in approximately 24 months. 
Main Criteria for Inclusion: 
1. Written and signed informed consent must be obtained before any protocol specific 
assessment is performed. 
2. Male or female, aged 18 years or older. 
3. Has at least 3 of the following symptoms: 
• Cough 
• Production of purulent sputum 
• Dyspnea (shortness of breath) 
• Pleuritic chest pain 
4. Has at least TWO of the following abnormal vital signs: 
• Fever or hypothermia documented by the investigator (temperature > 38.0°C 
[100.4°F] or < 36.0°C [95.5°F]) 
• Hypotension with SBP < 90 mm Hg 
• Heart rate > 90 beats per minute (bpm) 
• RR > 20 breaths/minute 
5. Has at least 1 clinical sign or laboratory finding associated with CABP: 
• Hypoxemia (PaO2 < 60 mm Hg by ABG or oxygen saturation < 90% by pulse 
oximetry) 
• Physical examination findings of pulmonary consolidation (eg, dullness on 
percussion, bronchial breath sounds, or egophony) 
• An elevated total white blood cell (WBC) count (> 12,000 cells/mm3) or 
leucopenia (WBC < 4,000 cells/mm3) or elevated immature neutrophils (> 15% 
band forms) (regardless of total peripheral WBC count) 
6. Has disease categorized as being PORT Risk Class III or IV at Screening (see PORT Risk 
Class calculation in Appendix 5). 
7. Radiographically-confirmed pneumonia, ie, new or progressive pulmonary infiltrate(s) on 
chest X-ray (CXR) or chest computed tomography (CT) scan consistent with acute bacterial 
pneumonia within 48 hours prior to the first dose of test article. 
8. Is expected to require a minimum of at least 2 days of iv therapy for the initial treatment of 
CABP. 
9. Females must have a negative pregnancy test at Screening and agree to comply with using an 
acceptable method of birth control as per your local requirements (eg, abstinence, po 
contraceptive, intrauterine device [IUD], barrier contraception [condom], tubal ligation, 
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hysterectomy, bilateral oophorectomy, postmenopausal or vasectomized partner) from 
Screening through 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 dose(s) of a potentially effective systemic antibacterial treatment 
within the 72 hours prior to the first dose of test article (a subject will be considered to have 
received a potentially effective systemic antibacterial treatment if the pathogen identified as 
causing infection is shown to be susceptible to the antibacterial given or, in the circumstance 
where a pathogen is not identified, if the antibacterial agent is approved for treatment of 
pneumonia or is known to have activity against any of the leading causes of CABP [eg, 
Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus 
aureus, Legionella pneumophila]). EXCEPTION: Subjects (not exceeding 25% of the total 
study population) may be eligible despite prior antibacterial therapy if they have been treated 
with a single dose of a short-acting antibacterial (ie, an antibacterial whose standard dosing 
regimen is more frequent than once per day, see list in Appendix 4). 
2. Is known or suspected to have CABP caused by a pathogen that may be resistant to either test 
article (eg, Pseudomonas aeruginosa, Proteus spp., Morganella morganii, Providencia spp., 
Pneumocystis jiroveci, obligate anaerobes, mycobacteria, fungal pathogens). 
3. Suspected or confirmed empyema (a parapneumonic pleural effusion is not an exclusion 
criteria) or lung abscess. 
4. Confirmed or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 
infection based on local standard-of-care assessments available during Screening. 
5. Subjects who reside in a long-term care or subacute/intermediate healthcare facility (eg, 
nursing home) or a subject admitted with pneumonia following a recent hospitalization 
(overnight admission within 90 days prior to current admission). 
6. Has a known history of having experienced unstable cardiac disease (eg, unstable angina, 
myocardial infarction, acute congestive heart failure, unstable cardiac arrhythmia) within the 
3 months prior to Screening or presents with a tachyarrhythmia (excluding sinus 
tachycardia). 
7. Has a QT interval corrected for heart rate using Fridericia’s formula (QTcF) > 450 msec 
(males) or > 470 msec (females), are known to have long QT syndrome, use drugs of 
potential proarrhythmic or QT prolonging effect. 
8. Has other contraindications to receiving a systemic fluoroquinolone antibiotic, including 
confirmed or suspected peripheral neuropathy, tendon disorder, myasthenia gravis, cirrhosis, 
aortic aneurysm, or central nervous system (CNS) disorder that may predispose to seizures or 
lower the seizure threshold. 
9. History or evidence of severe renal disease or has a calculated creatinine clearance (CrCl) of 
< 30 mL/minute, using the Cockcroft-Gault equation (Appendix 2). Requires any form of 
dialysis (eg, hemodialysis, peritoneal dialysis). 
10. Significant immunological disease determined by any of the following: 
• Current or anticipated neutropenia defined as < 500 neutrophils/mm3 
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• Known infection with Human Immunodeficiency Virus (HIV) and a cluster of 
differentiation 4 (CD4) count that is unknown or documented to be 
< 200 cells/mm3 within the last year, or an Acquired Immune Deficiency Syndrome 
(AIDS)-defining illness 
11. The receipt of cancer chemotherapy, radiotherapy, or potent, non-corticosteroid 
immunosuppressant drugs (eg, cyclosporine, azathioprine, tacrolimus, immune- modulating 
monoclonal antibody therapy, etc) within the past 3 months, or the receipt of corticosteroids 
equivalent to or greater than 40 mg of prednisone per day or for more than 14 days in the 
prior 30 days (Appendix 2). Exception: Systemic corticosteroids administered within 24 
hours of randomization or any time after randomization as adjunctive therapy for the current 
episode of CABP (at any dosage) is allowed. 
12. Requires acute pharmacologic intervention to stabilize blood pressure (BP) and/or adequate 
tissue perfusion OR meets septic shock criteria (meets ALL of the following): 
• Meets at least 2 criteria for sepsis as defined by the quick Sequential Organ Failure 
Assessment (qSOFA) score: (a) Altered mental status with Glasgow Coma Scale 
(GCS) < 15, (b) RR ≥ 22 breaths per minute, and (c) SBP ≤ 100 mmHg 
• Despite adequate fluid resuscitation, persistent hypotension requiring vasopressors 
to maintain mean arterial pressure (MAP) ≥ 65 mmHg. 
• Serum lactate ≥ 2 mmol/L (serum lactate measurement is not required at Screening if 
any of the above septic shock criteria are not met) 
13. PORT Risk Class I, II, and V patients. 
14. Requires or expected to require Intensive Care Unit (ICU) admittance or invasive or non-
invasive ventilation. 
15. Known or suspected primary or metastatic neoplastic lung disease, aspiration 
pneumonia, active tuberculosis, cystic fibrosis, bronchiectasis, bronchial obstruction 
(eg, post-obstructive pneumonia), chronic neurological disorder preventing clearance of 
pulmonary secretions, or severe chronic obstructive pulmonary disease (COPD) (severe 
COPD is defined as known forced expiratory volume in 1 second [FEV1] < 50% of 
predicted in a patient with FEV1/forced vital capacity [FVC] < 70%; note that 
spirometry or pulmonary function testing is not required during Screening). 
16. Pregnant or nursing (breastfeeding) women. 
17. Has a history of hypersensitivity or allergic reaction (eg, anaphylaxis, urticaria, other 
significant reaction) to any tetracycline (eg, minocycline, doxycycline or tigecycline),to any 
fluoroquinolone or any of the components of the investigational product or comparator. 
18. Has a history of pseudotumor cerebri, or prior (within 2 weeks prior to Screening) or planned 
concomitant use of isotretinoin. 
19. Has a history of systemic lupus erythematosus or lupus-like syndrome. 
20. History of lactose intolerance, lactase deficiency, or glucose-galactose malabsorption. 
21. Has current evidence of pancreatitis. 
22. Use of other investigational drugs within 5 half-lives or 30 days prior to Screening, 
whichever is longer. 
23. Has previously been treated with omadacycline or previously enrolled in this study. 
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24. Any planned medical intervention that might interfere with the ability to comply with the 
study requirements. 
25. Has a life expectancy of less than or equal to 3 months or 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. 
Test Article; Dose; and Mode of Administration: 
Study Day 
Study Day 
Study Days 
Group 
Test Article 
1 
2 
3 to 10a 
1 
Omadacycline 
200 mg iv QD or 
100 mg iv BID 
100 mg iv 
100 mg iv or 300 mg po 
2 
Moxifloxacin 
400 mg iv 
400 mg iv 
400 mg iv or 
400 mg po 
BID = twice a day dosing, iv = intravenous, po = per oral, PORT = pneumonia patient outcomes 
research team, QD = once a day dosing. 
a 
The total duration of treatment for subjects is 7-10 days, with up to 14 days of treatment for subjects with 
bacteremia. 
 
Duration of Treatment: 
The total duration of therapy will be for a minimum of 7 and up to 10 days, with a total duration 
of up to 14 days for subjects with bacteremia identified at Screening. 
Pharmacokinetic Assessments 
Blood Collection (plasma): 
Blood samples will be collected and analyzed for omadacycline concentration at the following 
times: 
• Day 1, 2 to 3 hours after the start of infusion 1, regardless of once a day (QD) or twice a day 
(BID) dosing 
• ECR visit (Days 4 to 6), date and time of collection must be recorded in the eCRF 
Safety Assessments: 
• Physical examinations; 
• Vital signs (body temperature, BP, pulse rate, respiratory rate, pulse oximetry); 
• Laboratory tests (Hematology, serum chemistry, prothrombin time, urinalysis, SARS-CoV-
2); 
• 12-lead ECGs; 
• AEs, serious adverse events (SAEs), and mortality; 
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• Pregnancy assessments. 
Efficacy Assessments: 
• In order to satisfy different health authority requirements, the primary variables assessing 
efficacy will be tested with 2 response endpoints:  
o ECR Success (72 to 120 hours after first dose) will be determined programmatically and 
defined as survival with improvement in at least 2 of 4 subject symptoms (cough, sputum 
production, pleuritic chest pain, dyspnea), as assessed by the investigator, without 
deterioration in any of these 4 symptoms. 
o Investigator’s Assessment of Clinical Success at the PTE visit, defined as survival after 
completion of a test article regimen, with resolution of signs and symptoms of the 
infection to the extent that further antibacterial therapy is not necessary. 
• Assessment of signs and symptoms of CABP by the investigator. 
• Microbiological assessment of the infection. 
• Patient reported outcome assessment. 
• Clinical stability. 
Resource Utilization: 
• Hospital discharge. 
• Hospital re-admission. 
• Duration (days) and number of doses on iv therapy (test article) 
• Duration (days) and number of outpatient iv doses (test article) 
• Duration (days) and number of doses on po therapy (test article) 
• ER/ED and Physician visits. 
 
Statistical Methods: 
The following subject populations have been defined for the various analyses of efficacy and 
safety: 
• The intent-to-treat (ITT) population will consist of all randomized subjects. 
• The microbiological intent-to-treat (micro-ITT) population will consist of subjects in the ITT 
population who have at least 1 causative pathogen identified at Screening from culture of a 
respiratory specimen (eg, respiratory fluid obtained by bronchoalveolar lavage or 
bronchoscopy; pleural fluid obtained by thoracentesis; or expectorated or induced sputum 
meeting adequacy criteria), culture of blood, or from a culture-independent method (eg, 
positive urinary antigen test for Streptococcus pneumoniae or Legionella pneumophila, or 
positive serology for L. pneumophila, Mycoplasma pneumoniae or Chlamydophila 
pneumoniae). 
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• The clinically evaluable (CE) population will consist of all ITT subjects who received test 
article, have a qualifying CABP, an assessment of outcome, and meet all other evaluability 
criteria detailed in the Statistical Analysis Plan (SAP). 
• The microbiologically evaluable (ME) population will include subjects in the CE population 
who have at least 1 causative pathogen identified 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 rate of ECR success in 
the ITT population (primary analysis for the US FDA) will be used to test for non-inferiority 
(NI) of the omadacycline arm compared to the moxifloxacin 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 ITT and CE populations will be used to test for the NI of the omadacycline 
arm compared to the moxifloxacin arm.   
Safety will be assessed through the use of summary statistics and clinical review of reported 
AEs/SAEs, changes in vital signs, ECGs, and laboratory results obtained from blood samples 
taken during the study. 
Data Monitoring Committee (DMC):  
A DMC (independent of the sponsor) will provide ongoing monitoring of safety data. Data will 
be provided to the DMC as treatment A and treatment B. 
Rationale for Number of Subjects: 
This study is designed to have sufficient power for the primary efficacy analyses in for both the 
FDA and EMA regulatory authorities.  Based on data from study CABP-1200, it is reasonable to 
assume the rate of ECR success will be approximately 80% in both treatment groups.  With a NI 
margin of 10%, 1-sided alpha level of 0.025 and about 90% power and using the sample size 
determination method of Farrington and Manning, a total of 670 subjects are required.  For the 
Investigator's Assessment of Clinical Response at PTE endpoint (EMA co-primary endpoint) 
with 670 subjects in the ITT population, assuming an outcome rate of 85% in both treatment 
groups, NI margin of 10% and 1-sided alpha level of 0.025, there is 94.7% power to show NI.  
Assuming the evaluability rate for the CE population is 80%, an outcome rate of 80% in both 
treatment groups, NI margin of 10% and 1-sided alpha level of 0.025, there is 94.9% power to 
show NI in the CE population. 
 
 
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TABLE OF CONTENTS 
SYNOPSIS .......................................................................................................................................2 
TABLE OF CONTENTS ...............................................................................................................11 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ................................................16 
1 
DISCLOSURE STATEMENT ...............................................................................................19 
1.1 
Restricted Distribution of Documents ...............................................................................19 
2 
CONTACTS ...........................................................................................................................19 
2.1 
Emergency Contacts ..........................................................................................................19 
2.2 
Additional Contacts ...........................................................................................................19 
3 
INTRODUCTION ..................................................................................................................20 
3.1 
Community-acquired Bacterial Pneumonia .......................................................................20 
3.2 
Omadacycline ....................................................................................................................20 
4 
STUDY OBJECTIVES ..........................................................................................................21 
4.1 
Primary Objective ..............................................................................................................21 
4.2 
Secondary Objectives .........................................................................................................21 
5 
INVESTIGATIONAL PLAN .................................................................................................22 
5.1 
Overall Study Description ..................................................................................................22 
5.2 
Rationale for Study Design ................................................................................................23 
5.3 
Rationale for Control Group ..............................................................................................23 
5.4 
Approximate Duration of Subject Participation ................................................................23 
5.5 
Approximate Duration of Study .........................................................................................23 
5.6 
Approximate Number of Subjects .....................................................................................23 
6 
STUDY POPULATION SELECTION ..................................................................................24 
6.1 
Study Population ................................................................................................................24 
6.2 
Inclusion Criteria ...............................................................................................................24 
6.3 
Exclusion Criteria ..............................................................................................................25 
6.4 
Screen Failures ...................................................................................................................27 
7 
STUDY TREATMENT(S) .....................................................................................................28 
7.1 
Treatments Administered ...................................................................................................28 
7.2 
Identity of the Investigational Product: Omadacycline .....................................................28 
7.3 
Comparator Test Article: Moxifloxacin .............................................................................29 
7.4 
Dose Selection Rationale ...................................................................................................29 
7.5 
Description of Treatments ..................................................................................................30 
7.6 
Test Article Administration ...............................................................................................30 
7.6.1 
Intravenous Treatment Phase .......................................................................................30 
7.6.2 
Selection and Timing of iv Dose for Each Subject ......................................................31 
7.6.3 
Management While on iv Test Article .........................................................................32 
7.6.4 
Investigator’s Decision to Continue or Discontinue Treatment ..................................32 
7.6.5 
Investigator’s Decision to Switch from iv to po Treatment .........................................33 
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7.6.6 
Oral Treatment Phase ...................................................................................................33 
7.6.6.1 
Management While on Oral Test Article ...............................................................34 
7.7 
Dose Adjustments and Interruptions of Test Article .........................................................34 
7.8 
Method of Assigning Patients to Treatment Groups ..........................................................34 
7.8.1 
Subject Numbering ......................................................................................................35 
7.9 
Dispensing Test Article......................................................................................................35 
7.10 
Blinding..............................................................................................................................35 
7.11 
Emergency Unblinding of Treatment Assignment ............................................................36 
7.12 
Prior & Concomitant Therapy ...........................................................................................37 
7.13 
Prohibited Therapy .............................................................................................................37 
7.13.1 
Concomitant Medications That May Interact With Moxifloxacin ..............................37 
7.14 
Permitted Treatments .........................................................................................................38 
7.15 
Treatment Compliance .......................................................................................................38 
7.16 
Packaging and Labeling .....................................................................................................38 
7.17 
Storage and Accountability ................................................................................................38 
7.18 
Investigational Product Retention at Study Site ................................................................38 
8 
STUDY PROCEDURES ........................................................................................................39 
8.1 
Informed Consent...............................................................................................................39 
8.2 
Subject Demographics/Other Baseline Characteristics .....................................................39 
8.3 
Medical History .................................................................................................................39 
8.4 
Physical Examination.........................................................................................................40 
8.5 
Vital Signs ..........................................................................................................................40 
8.6 
Electrocardiogram ..............................................................................................................40 
8.7 
Height and Weight .............................................................................................................41 
8.8 
Assessment of CABP Symptom Severity ..........................................................................41 
8.9 
Radiologic Evaluation of Pneumonia ................................................................................41 
8.10 
PORT Risk Class ...............................................................................................................41 
8.11 
SF-36v2® Health Survey ....................................................................................................41 
8.12 
Clinical Laboratory Tests ...................................................................................................42 
8.12.1 
Central Laboratory Parameters ....................................................................................42 
8.12.2 
Local Laboratory Parameters .......................................................................................42 
8.12.2.1 
Pregnancy Assessments .........................................................................................42 
8.12.2.2 
Blood Cultures .......................................................................................................43 
8.12.2.3 
Sputum and Urine Samples ....................................................................................43 
8.12.2.4 
SARS-CoV-2 Sample ............................................................................................43 
8.12.3 
Blood Volume ..............................................................................................................43 
8.13 
Efficacy Assessments .........................................................................................................43 
8.13.1 
Investigator’s Assessment of Clinical Response .........................................................43 
8.13.1.1 
Evaluation of the Infection Under Study at the Early Clinical Response 
Assessment .............................................................................................................44 
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8.13.1.2 
Investigator’s Assessment of Clinical Response at EOT .......................................45 
8.13.1.3 
Investigator’s Assessment of Clinical Response at PTE .......................................46 
8.13.2 
Clinical Stability ..........................................................................................................46 
8.14 
Microbiologic Response ....................................................................................................47 
8.14.1 
Respiratory Culture and Gram Stain ............................................................................47 
8.14.2 
Urine for Legionella pneumophila and Streptococcus pneumoniae Antigen 
Screening ....................................................................................................................48 
8.14.3 
Serology for Legionella pneumophila, Mycoplasma pneumoniae, and 
Chlamydophila pneumoniae Titers .............................................................................48 
8.15 
Pharmacokinetic Assessments ...........................................................................................48 
8.15.1 
PK Blood Collection and Processing ...........................................................................48 
8.15.2 
Storing and Shipping of PK Samples...........................................................................49 
8.16 
Adverse Events ..................................................................................................................49 
8.17 
Serious Adverse Events .....................................................................................................49 
8.18 
Other Reportable Information ............................................................................................50 
8.19 
Overdose ............................................................................................................................50 
8.20 
Medication Errors ..............................................................................................................51 
8.21 
Recording and Reporting ...................................................................................................51 
8.21.1 
Serious Adverse Event Reporting ................................................................................52 
8.21.2 
Assessment of Relatedness ..........................................................................................52 
8.21.3 
Assessment of Severity ................................................................................................52 
8.21.4 
Laboratory Findings .....................................................................................................53 
8.21.5 
Worsening or Progression of Disease Under Study .....................................................53 
8.22 
Pregnancies ........................................................................................................................53 
8.23 
Concomitant Medication Assessments ..............................................................................53 
8.24 
Subject Discontinuation or Withdrawal .............................................................................54 
9 
STUDY ACTIVITIES ............................................................................................................55 
9.1 
Screening Phase .................................................................................................................55 
9.2 
Double-blind Treatment Phase ..........................................................................................55 
9.3 
EOT Visit Procedures ........................................................................................................55 
9.4 
Follow-up Phase.................................................................................................................56 
9.4.1 
Post-therapy Evaluation Visit Procedures ...................................................................56 
9.4.2 
Final Follow-up ............................................................................................................56 
10 STUDY SUSPENSION, TERMINATION, AND COMPLETION .......................................56 
10.1 
Study Completion and Post-study Test Article ..................................................................56 
10.2 
Study Suspension or Termination ......................................................................................56 
11 QUALITY CONTROL AND ASSURANCE ........................................................................57 
12 PLANNED STATISTICAL METHODS ...............................................................................57 
12.1 
General Considerations ......................................................................................................57 
12.2 
Determination of Sample Size ...........................................................................................58 
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12.3 
Analysis Populations ..........................................................................................................59 
12.4 
Demographics and Other Baseline Characteristics ............................................................59 
12.5 
Treatments (Test Article, Rescue Medication, Other Concomitant Therapies, 
Compliance) ....................................................................................................................60 
12.6 
Primary Efficacy Analysis .................................................................................................60 
12.6.1 
Early Clinical Response Efficacy Variable ..................................................................60 
12.6.2 
Investigator’s Assessment of Clinical Response at PTE Efficacy Variable ................60 
12.6.3 
Statistical Model, Hypothesis, and Method of Analysis ..............................................61 
12.6.4 
Additional Analyses of Primary Efficacy Outcomes ...................................................62 
12.7 
Analysis of Secondary Variables .......................................................................................62 
12.8 
Analysis of Additional Efficacy Variables ........................................................................63 
12.9 
Safety Outcome Measures .................................................................................................64 
12.9.1 
Adverse Events ............................................................................................................64 
12.9.2 
Vital Signs ....................................................................................................................64 
12.9.3 
Electrocardiograms ......................................................................................................64 
12.9.4 
Laboratory Tests ..........................................................................................................64 
12.10 Resource Utilization ...........................................................................................................65 
12.11 Pharmacokinetics ...............................................................................................................65 
12.11.1 
Population PK Modeling..............................................................................................66 
12.12 Pharmacogenetics/Pharmacogenomics ..............................................................................66 
12.13 Biomarkers .........................................................................................................................66 
12.14 Pharmacokinetics/Pharmacodynamics ...............................................................................66 
12.15 Interim Analysis .................................................................................................................66 
12.16 Handling of Missing Values/Censoring/Discontinuations .................................................67 
12.17 Data Monitoring Committee ..............................................................................................67 
12.18 Clinical Events Committee ................................................................................................68 
13 ADMINISTRATIVE CONSIDERATIONS ..........................................................................68 
13.1 
Investigators and Study Administrative Structure .............................................................68 
13.2 
Institutional Review Board or Independent Ethics Committee Approval .........................68 
13.3 
Ethical Conduct of the Study .............................................................................................68 
13.4 
Patient Information and Consent .......................................................................................69 
13.5 
Direct Access, Data Handling, and Record Keeping .........................................................69 
13.5.1 
Investigator ..................................................................................................................69 
13.5.2 
Sponsor ........................................................................................................................69 
13.6 
Protocol Adherence ............................................................................................................69 
13.6.1 
Violations/Deviations ..................................................................................................69 
13.6.2 
Protocol Amendments ..................................................................................................70 
13.7 
Subject Injury .....................................................................................................................70 
13.8 
Pre-study Documentation...................................................................................................70 
13.9 
Retention of Data ...............................................................................................................71 
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13.10 Publication and Disclosure Policy .....................................................................................71 
14 REFERENCE LIST ................................................................................................................73 
LIST OF TABLES 
Table 1. 
Treatment Regimens for IV Test Article ...............................................................31 
Table 2. 
Treatment Regimens for Oral Test Article ............................................................34 
Table 3. 
Clinical Success Rates in CABP-1200 at ECR and PTE in PORT III and IV 
Subjects ..................................................................................................................58 
Table 4. 
Sample Size and Power Calculations .....................................................................59 
 
LIST OF APPENDICES 
 
Schedule of Events .................................................................................................74 
 
Equations and Conversion Factors .........................................................................77 
 
Community-acquired Bacterial Pneumonia Subject Symptom Severity Guidance 
Framework for Investigator Assessment ...............................................................78 
 
Allowed and Disallowed Prior Antibiotics ............................................................79 
 
PORT Risk Class Calculation ................................................................................81 
 
Sponsor Signature ..................................................................................................84 
 
Investigator’s Signature .........................................................................................85 
 
 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
ABG 
arterial blood gas 
AE 
adverse event 
AIDS 
acquired immune deficiency syndrome 
ACM 
all-cause mortality 
β-hCG 
serum β-human chorionic gonadotropin 
BID 
twice a day dosing 
BP 
blood pressure 
bpm 
beats per minute 
CABP 
community-acquired bacterial pneumonia 
CD4 
cluster of differentiation 4 
CE 
clinically evaluable 
CFR 
Code of Federal Regulations 
CI 
confidence interval 
CNS 
central nervous system 
COPD 
chronic obstructive pulmonary disease 
CrCl 
creatinine clearance 
CRF 
case report form 
CSA 
clinical study agreement 
CSR 
clinical study report 
CT 
computed tomography 
CXR 
chest X-ray 
DMC 
data monitoring committee 
EC 
ethics committee 
ECG 
electrocardiogram 
ECR 
Early Clinical Response 
eCRF 
electronic case report form 
ED 
emergency department 
EMA 
European Medicines Agency 
EOT 
end of treatment 
ER 
emergency room 
FDA 
Food and Drug Administration 
FEV1 
forced expiratory volume in 1 second 
FVC 
forced vital capacity 
GCP 
good clinical practice 
GCS 
Glasgow Coma Scale 
HIV 
human immunodeficiency virus 
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ICF 
informed consent form 
ICH 
International Council on Harmonisation 
ICU 
Intensive Care Unit 
IEC 
independent ethics committee 
IND 
investigational new drug 
IRB 
institutional review board 
ITT 
intent-to-treat 
IUD 
intrauterine device 
iv 
intravenous 
IxRS 
interactive voice/web response system 
LPF 
low power field 
MAP 
mean arterial pressure 
ME 
microbiologically evaluable 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC 
minimum inhibitory concentration 
micro-ITT 
microbiological intent-to-treat 
NI 
non-inferiority 
OTC 
over-the-counter 
PaO2 
partial pressure of arterial oxygen 
PI 
principal investigator 
PK 
pharmacokinetics 
po 
per oral 
PORT 
pneumonia patient outcomes research team 
PT 
preferred term 
PTE 
post-therapy evaluation 
q24h 
every 24 hours 
q12h 
every 12 hours 
QD 
once a day dosing 
qSOFA 
quick Sequential Organ Failure Assessment 
QTc 
corrected QT interval 
QTcB 
QTc Bazzett’s Correction Formula 
QTcF 
QTc Fridericia’s Correction Formula 
REB 
research ethics board 
RR 
respiratory rate 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SAS 
Statistical Analysis Software 
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SBP 
systolic blood pressure 
SOC 
system organ class 
TEAE 
treatment-emergent adverse event 
TFL 
tables, figures, and listings 
US 
United States 
USP 
United States Pharmacopeia 
USPI 
United States Prescribing Information 
WBC 
white blood cell (count) 
 
 
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1 DISCLOSURE STATEMENT 
1.1 
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. 
2 CONTACTS 
2.1 
Emergency Contacts 
Name/Title: 
 MD  
 
Medical Monitor 
Phone (during business hours): 
Phone (after business hours): 
E-mail (not for emergencies): 
mailto:Address: 
 
 
Name/Title: 
 MD  
 
Vice President, Medical and Scientific Strategy 
Phone (during business hours): 
Phone (after business hours): 
E-mail (not for emergencies): 
 
Address: 
1000 First Avenue, Suite 200 
 
King of Prussia, PA 19406 
2.2 
Additional Contacts 
SAE contact information E-Mail: 
 
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3 INTRODUCTION 
3.1 
Community-acquired Bacterial Pneumonia 
Community-Acquired Bacterial Pneumonia (CABP) is a leading cause of morbidity and 
mortality in the United States (US) and throughout the world.1 Four to 6 million cases of CABP 
occur per year in the US, resulting in 10 million physician visits, 600,000 hospitalizations, and 
tens of thousands of deaths. The total cost of CABP to the annual US health care budget exceeds 
$10 billion (in 2007-adjusted dollars).2 Furthermore, there is increasing resistance to antibiotics 
among common pathogens, with a resulting critical need for new antibiotics.3 Bacterial resistance 
to the most frequently prescribed, currently available antibiotics has limited their potential to 
treat infections, which prevents their use as a first-line empiric monotherapy.  Methicillin-
resistant Staphylococcus aureus and multi-drug resistant Streptococcus pneumoniae in the 
community have posed treatment challenges because of resistance to penicillins (resistance rate 
100% for both), cephalosporins (100% and 11%, respectively, for ceftriaxone), macrolides (83% 
and 86%, respectively, for azithromycin/erythromycin), and quinolones (73% and 2%, 
respectively, for levofloxacin), in CABP. In addition, the growing concern about, “collateral 
damage” associated with use of quinolone and beta-lactam class antibiotics further underscores 
the need for new antibiotic treatment options for CABP.4  Failure of therapy due to resistance 
will continue to contribute to the morbidity and mortality of CABP and treatment failures of mild 
disease will result in increased hospitalizations and contribute to increased healthcare costs. 
3.2 
Omadacycline 
The investigational product, omadacycline (formerly named PTK 0796), is the first member of 
the aminomethylcycline class of antibiotics, which are semisynthetic 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. 
NUZYRA™ (omadacycline) has been approved by the US Food and Drug Administration 
(FDA) for the treatment of adult patients with CABP caused by susceptible microorganisms. 
Omadacycline has demonstrated activity against the most common CABP pathogens, including 
isolates resistant to older antibiotics. This study is intended to evaluate the safety and efficacy of 
intravenous (iv) and oral (po) omadacycline as compared to iv and po moxifloxacin in the 
treatment of pneumonia patient outcomes research team (PORT) Risk Class III and IV adults 
with CABP. 
Please refer to the current version of the Investigator's Brochure or the NUZYRA™ 
(omadacycline) United States Prescribing Information (USPI) for additional information on 
omadacycline.5 
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4 STUDY OBJECTIVES 
4.1 
Primary Objective 
The primary objective of this study is: 
• To demonstrate that iv to po omadacycline is non-inferior to iv to po moxifloxacin in the 
treatment of adults with PORT Risk Class III and IV CABP. 
4.2 
Secondary Objectives 
The secondary objectives of this study are: 
• To evaluate the safety of omadacycline in the treatment of adults with CABP in the Safety 
population. 
• To evaluate the Clinical Response according to the identified causative pathogen. 
• To evaluate the pharmacokinetics (PK) of omadacycline in adults with CABP. 
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5 INVESTIGATIONAL PLAN 
5.1 
Overall Study Description 
This is a randomized (1:1), active comparator controlled, double-blind, Phase 3 study comparing 
omadacycline and moxifloxacin in the treatment of adults with CABP (PORT Risk Class III and 
IV). Both iv and po phases of the study will be double-blind. 
Subjects will participate in the study for up to 37 days. Following a Screening period of up to 
24 hours, eligible subjects will be randomized to receive treatment. Subject randomization will 
be stratified by PORT Risk Class (III or IV), and by receipt of an allowed antibacterial therapy 
(see Appendix 4) in the 72 hours prior to study treatment.  
Eligible subjects with a PORT RISK Class III or IV will be randomized to receive 7 to 10 days 
of iv treatment with the option to switch to po treatment on Day 3. Subjects with bacteremia 
identified at Screening can receive up to 14 days of treatment. Switch to po will NOT be 
permitted until after the subject has completed at least 2 days of iv treatment. The decision to 
switch to po treatment will be made by the investigator; the subject should be considered 
clinically stable and meet all criteria for transition to a po regimen. Specifically, the subject must 
meet the following requirements and this should be noted in source documents and recorded on 
the electronic case report form (eCRF): 
• Temperature ≤ 37.8°C (100°F) 
• Heart rate ≤ 100 beats/minute 
• Respiratory rate (RR) ≤ 24 breaths/minute 
• Systolic blood pressure (SBP) ≥ 90 mm Hg 
• Oxygen saturation ≥ 90% as measured by pulse oximetry or partial pressure of arterial 
oxygen (PaO2) ≥ 60 mm Hg by arterial blood gas (ABG) 
• Normal (“absence of confusion”) or return to baseline mental status 
• Ability to maintain po intake. 
Eligible subjects will be randomized to one of the following treatment groups: 
Study Day 
Study Day 
Study Days 
Group 
Test Article 
1 
2 
3 to 10a 
1 
Omadacycline 
200 mg iv QD or 
100 mg iv BID 
100 mg iv 
100 mg iv or 300 mg po 
2 
Moxifloxacin 
400 mg iv 
400 mg iv 
400 mg iv or 
400 mg po 
BID = twice a day dosing, iv = intravenous, po = per oral, PORT = pneumonia patient outcomes research 
team, QD = once a day dosing. 
a 
The total duration of treatment for subjects is 7-10 days, with up to 14 days of treatment for subjects 
with bacteremia. 
 
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Subjects will return to the study site for a Post Therapy Evaluation (PTE) 5 to 10 days after the 
last dose of test article. A Final Follow-up visit (Final Follow-up) will be conducted within 30 to 
37 days following 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 Success in the opinion of the investigator at end of treatment (EOT) 
and PTE and had no adverse events (AEs) or clinically significant laboratory or 
electrocardiogram (ECG) abnormalities noted at or after the PTE visit. 
Otherwise, this assessment is to be performed with an in-person study visit. 
Refer to the Schedule of Events (Appendix 1) for a complete summary of subject visits and 
assessments. 
5.2 
Rationale for Study Design 
The study was designed in accordance with the FDA 6 and European Medicines Agency (EMA)7 
guidance on developing antimicrobial drugs for the treatment of CABP, in addition to the 
guidelines created jointly by the Infectious Diseases Society of America and the American 
Thoracic Society. 
5.3 
Rationale for Control Group 
Moxifloxacin (400 mg iv every 24 hours [q24h] with the option to transition to 400 mg po q24h) 
was chosen as the comparator given the wide acceptance of fluoroquinolone monotherapy as a 
safe, first-line option for treating subjects with CABP. Moxifloxacin provides a broad spectrum 
of activity against respiratory pathogens that are causative agents of CABP, including typical 
(eg, Streptococcus pneumoniae) and atypical (eg, Legionella, Chlamydophila, and Mycoplasma 
spp.) pathogens, with a similar spectrum of activity to that of omadacycline. Like omadacycline, 
moxifloxacin has both iv and po formulation options and is administered once daily. 
5.4 
Approximate Duration of Subject Participation 
Subjects will participate in the study for up to 37 days. Eligible subjects will be randomly 
assigned to receive to 7 to 10 days of iv/po treatment of either omadacycline or moxifloxacin. 
Subjects with bacteremia confirmed from local blood culture drawn at Screening can receive up 
to 14 days of treatment. Subjects will return to the site for an EOT visit on the day of or within 2 
days following the last dose of test article. Subjects will return to the study site for a PTE 5 to 10 
days after the last dose of test article. A Final Follow-up assessment will be conducted within 30 
to 37 days following the first dose of test article. 
5.5 
Approximate Duration of Study 
The study is expected to be clinically complete in approximately 24 months. 
5.6 
Approximate Number of Subjects 
Approximately 670 subjects will be enrolled at approximately 75 sites globally. 
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6 STUDY POPULATION SELECTION 
Each subject must participate in the informed consent process and sign and date an 
IRB/IEC/REB approved informed consent form (ICF) before any procedures specified in this 
protocol are performed. 
6.1 
Study Population 
Approximately 670 patients will be enrolled at approximately 75 sites globally. Subjects will be 
randomized in a 1:1 ratio. 
6.2 
Inclusion Criteria 
Each subject must meet all of the following criteria to be enrolled in this study: 
1. Written and signed informed consent must be obtained before any protocol specific 
assessment is performed. 
2. Male or female, aged 18 years or older. 
3. Has at least 3 of the following symptoms: 
• Cough 
• Production of purulent sputum 
• Dyspnea (shortness of breath) 
• Pleuritic chest pain 
4. Has at least TWO of the following abnormal vital signs: 
• Fever or hypothermia documented by the investigator (temperature > 38.0°C [100.4°F] 
or < 36.0°C [95.5°F]) 
• Hypotension with SBP < 90 mm Hg 
• Heart rate > 90 beats per minute (bpm) 
• RR > 20 breaths/minute 
5. Has at least 1 clinical sign or laboratory finding associated with CABP: 
• Hypoxemia (PaO2 < 60 mm Hg by ABG or oxygen saturation < 90% by pulse oximetry) 
• Physical examination findings of pulmonary consolidation (eg, dullness on percussion, 
bronchial breath sounds, or egophony) 
• An elevated total white blood cell (WBC) count (> 12,000 cells/mm3) or leucopenia 
(WBC < 4,000 cells/mm3) or elevated immature neutrophils (> 15% band forms) 
(regardless of total peripheral WBC count) 
6. Has disease categorized as being PORT Risk Class III or IV at Screening (see PORT Risk 
Class calculation in Appendix 5). 
7. Radiographically-confirmed pneumonia, ie, new or progressive pulmonary infiltrate(s) on 
chest X-ray (CXR) or chest computed tomography (CT) scan consistent with acute bacterial 
pneumonia within 48 hours prior to the first dose of test article. 
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8. Is expected to require a minimum of at least 2 days of iv therapy for the initial treatment of 
CABP. 
9. Females must have a negative pregnancy test at Screening and agree to comply with using an 
acceptable method of birth control as per your local requirements (eg, abstinence, po 
contraceptive, intrauterine device [IUD], barrier contraception [condom], tubal ligation, 
hysterectomy, bilateral oophorectomy, postmenopausal or vasectomized partner) from 
Screening through 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. 
6.3 
Exclusion Criteria 
Patients who meet any of the following exclusion criteria will be excluded from the study: 
1. Has received 1 or more dose(s) of a potentially effective systemic antibacterial treatment 
within the 72 hours prior to the first dose of test article (a subject will be considered to have 
received a potentially effective systemic antibacterial treatment if the pathogen identified as 
causing infection is shown to be susceptible to the antibacterial given or, in the circumstance 
where a pathogen is not identified, if the antibacterial agent is approved for treatment of 
pneumonia or is known to have activity against any of the leading causes of CABP [eg, 
Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus 
aureus, Legionella pneumophila]). EXCEPTION: Subjects (not exceeding 25% of the total 
study population) may be eligible despite prior antibacterial therapy if they have been treated 
with a single dose of a short-acting antibacterial (ie, an antibacterial whose standard dosing 
regimen is more frequent than once per day, see list in Appendix 4). 
2. Is known or suspected to have CABP caused by a pathogen that may be resistant to either test 
article (eg, Pseudomonas aeruginosa, Proteus spp., Morganella morganii, Providencia spp., 
Pneumocystis jiroveci, obligate anaerobes, mycobacteria, fungal pathogens). 
3. Suspected or confirmed empyema (a parapneumonic pleural effusion is not an exclusion 
criteria) or lung abscess. 
4. Confirmed or suspected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 
infection based on local standard-of-care assessments available during Screening. 
5. Subjects who reside in a long-term care or subacute/intermediate healthcare facility (eg, 
nursing home) or a subject admitted with pneumonia following a recent hospitalization 
(overnight admission within 90 days prior to current admission). 
6. Has a known history of having experienced unstable cardiac disease (eg, unstable angina, 
myocardial infarction, acute congestive heart failure, unstable cardiac arrhythmia) within the 
3 months prior to Screening or presents with a tachyarrhythmia (excluding sinus 
tachycardia). 
7. Has a QT interval corrected for heart rate using Fridericia’s formula (QTcF) > 450 msec 
(males) or > 470 msec (females), are known to have long QT syndrome, use drugs of 
potential proarrhythmic or QT prolonging effect. 
8. Has other contraindications to receiving a systemic fluoroquinolone antibiotic, including 
confirmed or suspected peripheral neuropathy, tendon disorder, myasthenia gravis, cirrhosis, 
aortic aneurysm, or central nervous system (CNS) disorder that may predispose to seizures or 
lower the seizure threshold. 
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9. History or evidence of severe renal disease or has a calculated creatinine clearance (CrCl) of 
< 30 mL/minute, using the Cockcroft-Gault equation (Appendix 2).  Requires any form of 
dialysis (eg, hemodialysis, peritoneal dialysis). 
10. Significant immunological disease determined by any of the following: 
• Current or anticipated neutropenia defined as < 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 < 200 cells/mm3 
within the last year, or an Acquired Immune Deficiency Syndrome (AIDS)-defining 
illness 
11. The receipt of cancer chemotherapy, radiotherapy, or potent, non-corticosteroid 
immunosuppressant drugs (eg, cyclosporine, azathioprine, tacrolimus, immune- modulating 
monoclonal antibody therapy, etc) within the past 3 months, or the receipt of corticosteroids 
equivalent to or greater than 40 mg of prednisone per day or for more than 14 days in the 
prior 30 days (Appendix 2). Exception: Systemic corticosteroids administered within 24 
hours of randomization or any time after randomization as adjunctive therapy for the current 
episode of CABP (at any dosage) is allowed. 
12. Requires acute pharmacologic intervention to stabilize blood pressure (BP) and/or adequate 
tissue perfusion OR meets septic shock criteria (meets ALL of the following): 
• Meets at least 2 criteria for sepsis as defined by the quick Sequential Organ Failure 
Assessment (qSOFA) score: (a) Altered mental status with Glasgow Coma Scale (GCS) 
< 15, (b) RR ≥ 22 breaths per minute, and (c) SBP ≤ 100 mmHg 
• Despite adequate fluid resuscitation, persistent hypotension requiring vasopressors to 
maintain mean arterial pressure (MAP) ≥ 65 mmHg 
• Serum lactate ≥ 2 mmol/L (serum lactate measurement is not required at Screening if any 
of the above septic shock criteria are not met) 
13. PORT Risk Class I, II, and V patients. 
14. Requires or expected to require Intensive Care Unit (ICU) admittance or invasive or non- 
invasive ventilation. 
15. Known or suspected primary or metastatic neoplastic lung disease, aspiration pneumonia, 
active tuberculosis, cystic fibrosis, bronchiectasis, bronchial obstruction (eg, post- 
obstructive pneumonia), chronic neurological disorder preventing clearance of pulmonary 
secretions, or severe chronic obstructive pulmonary disease (COPD) (severe COPD is 
defined as known forced expiratory volume in 1 second [FEV1] < 50% of predicted in a 
patient with FEV1/forced vital capacity [FVC] < 70%; note that spirometry or pulmonary 
function testing is not required during Screening). 
16. Pregnant or nursing (breastfeeding) women. 
17. Has a history of hypersensitivity or allergic reaction (eg, anaphylaxis, urticaria, other 
significant reaction) to any tetracycline (eg, minocycline, doxycycline or tigecycline), to any 
fluoroquinolone or any of the components of the investigational product or comparator. 
18. Has a history of pseudotumor cerebri, or prior (within 2 weeks prior to Screening) or planned 
concomitant use of isotretinoin. 
19. Has a history of systemic lupus erythematosus or lupus-like syndrome. 
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20. History of lactose intolerance, lactase deficiency, or glucose-galactose malabsorption. 
21. Has current evidence of pancreatitis. 
22. Use of other investigational drugs within 5 half-lives or 30 days prior to Screening, 
whichever is longer. 
23. Has previously been treated with omadacycline or previously enrolled in this study. 
24. Any planned medical intervention that might interfere with the ability to comply with the 
study requirements. 
25. Has a life expectancy of less than or equal to 3 months or 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. 
6.4 
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 eCRF or interactive voice/web response system (IxRS) system for screen 
failures. Screen failure subjects may be re-screened at the discretion of the investigator and in 
consultation with the medical monitor as needed. Any subject who discontinues participation or 
is withdrawn before receiving a treatment assignment, and who is re-screened at a later time will 
be assigned a new subject number and recorded as re-screened. 
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7 STUDY TREATMENT(S) 
7.1 
Treatments Administered 
Test articles will be supplied by Paratek Pharmaceuticals, Inc. (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. 
Following a Screening period of up to 24 hours, eligible subjects will be randomly assigned a 
dosing regimen of omadacycline or moxifloxacin. Intravenous treatment will be double-blind 
and oral treatment will be double-blind and double-dummy. 
7.2 
Identity of the Investigational Product: Omadacycline 
Intravenous Formulation (Omadacycline) 
 
Name 
Omadacycline 
Administration 
Please reference Section 7.6 
 
Oral Formulation (Omadacycline) 
Name 
Omadacycline , 150 mg 
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Preparation and 
handling 
No special requirements 
Administration 
Please reference Section 7.6 
 
7.3 
Comparator Test Article: Moxifloxacin 
Intravenous Formulation (Moxifloxacin) 
Name 
Moxifloxacin 
Excipients 
Sodium chloride, USP, glycine, Water for Injection, USP, disodium edetate, and 
hydrochloric acid for pH adjustment. 
How supplied 
Single-use ready-to use 250 mL flexibags as a sterile, preservative free, 0.8% sodium 
chloride solution of moxifloxacin hydrochloride (equivalent to 400 mg moxifloxacin). 
Storage 
Store at 25°C (77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F). Do not store 
below 15°C (59°F). 
Preparation and 
handling 
No special requirements 
Please refer to Pharmacy Manual for additional information. 
Administration 
Please reference Section 7.6 
 
Oral Formulation (Moxifloxacin) 
Name 
Moxifloxacin Tablet, 400 mg 
Excipients 
Microcrystalline cellulose, mannitol, silica colloidal anhydrous, sodium starch 
glycolate, hydroxypropyl cellulose, talc, magnesium stearate, and film coat 
(polyvinyl alcohol, titanium dioxide, macrogol, iron oxide yellow, iron oxide red, 
and talc).  Tablet is over-encapsulated with a Size 000 Swedish Orange hard gelatin 
capsule (red iron oxide and titanium dioxide).  
How supplied 
High-Density Polyethylene (HDPE) bottles with induction seal, child resistant closure 
and desiccant 
Storage 
Store at 25°C (77°F). Excursions permitted to 15°C to 30°C (59°F to 86°F) 
Preparation and 
handling 
No special requirements 
Administration 
Please reference Section 7.6 
 
7.4 
Dose Selection Rationale 
The dosing regimen of omadacycline selected for this study is based on the nonclinical and 
clinical experience to date, including in vitro antibacterial activity, PK characteristics, clinical 
efficacy in prior studies, the overall safety and tolerability profile, and the FDA approved dosing 
regimen for CABP. 
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Either a regimen of 200 mg iv omadacycline once daily or 100 mg iv omadacycline every 
12 hours (q12h) on Day 1 followed by 100 mg iv omadacycline administered once daily OR 
300 mg po omadacycline once daily has been approved by US FDA for the treatment of adult 
patients with CABP caused by susceptible microorganism. The FDA-approved treatment 
duration for omadacycline is 7 to 14 days total. 
The duration for the iv to po regimen in this study will be 7 to 10 days, with up to 14 days 
allowed for subjects with bacteremia at the Screening visit. The shorter regimen is supported by 
the efficacy observed in the previously completed CABP Phase 3 study, PTK0796-CABP-1200 
where by Day 7 of treatment, > 80% of patients in the omadacycline treatment group had 
symptom improvement (as defined by the Early Clinical Response [ECR] endpoint) and had 
reached clinical stability. 
7.5 
Description of Treatments 
Subjects will be randomized to 1 of the following treatment groups: 
Study Day 
Study Day 
Study Days 
Group 
Test Article 
1 
2 
3 to 10a 
1 
Omadacycline 
200 mg iv QD or 
100 mg iv BID 
100 mg iv 
100 mg iv or 300 mg po 
2 
Moxifloxacin 
400 mg iv 
400 mg iv 
400 mg iv or 
400 mg po 
BID = twice a day dosing, iv = intravenous, po = per oral, PORT = pneumonia patient outcomes research team, 
QD = once a day dosing. 
a 
The total duration of treatment for subjects is 7-10 days, with up to 14 days of treatment for subjects with 
bacteremia identified at Screening. 
 
7.6 
Test Article Administration 
7.6.1 
Intravenous Treatment Phase 
The iv-treatment phase (minimum 2 days) will follow a double-blind, double-dummy design for 
omadacycline and moxifloxacin. Infusions of 100 mg omadacycline or matched placebo will be 
administered continuously, without interruptions, over 30 minutes (± 5 minutes). On Day 1, if 
QD dosing is selected, the 200 mg infusion of omadacycline or matched placebo will be 
administered continuously, without interruptions, over 60 minutes (± 5 minutes). On Day 1 of iv 
treatment, if twice a day dosing (BID) was selected, subjects on the moxifloxacin treatment arm 
will receive an additional placebo infusion to match the t = 12 h infusion. Infusions of 
moxifloxacin or matched placebo will be administered continuously, without interruptions, over 
60 minutes (± 5 minutes). 
The first dose of test article should be administered within 4 hours of randomization. All infusion 
start and stop times are to be recorded in the source documents and on the eCRF. Because the 
color of the test article and placebo infusions are different, all infusion bags and iv tubing will be 
covered with materials provided by the sponsor (as described in the Pharmacy Manual) so that 
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subjects and blinded study personnel will not know the identity of the test article being 
administered. Subjects in each study arm will receive the same infusion volumes with the same 
blinded administration instructions. All iv infusions will be administered by qualified blinded 
personnel. However, unblinded personnel may administer the iv infusions provided they will not 
be performing any efficacy assessments. If gravity administration is not the standard of care, then 
an infusion pump may be used. If an infusion pump is used, then an unblinded administrator will 
be required. Subjects may receive iv treatment in certain outpatient centers in circumstances 
where the principal site investigator has identified that sufficient resources are available to 
complete all study procedures as defined in the protocol and the sponsor or sponsor’s designee 
has reviewed and approved the process for outpatient iv test article administration. 
Please refer to Table 1 for more detail on the Treatment regimens for iv dosing. 
Table 1. 
Treatment Regimens for IV Test Article 
Infusion 
Timepointa 
Infusion 
Number 
Omadacycline Armb,c 
Moxifloxacin Armb,c 
1 
 
2 
omadacycline 100 mg in 
100 mL NS 
250 mL NS placebo 
100 mL NS placebo  
 
moxifloxacin 400 mg in 250 mL 
0.8% saline 
t = 0 h 
 
OR 
1 
omadacycline 200 mg in 
100 mL NS 
2 
250 mL NS placebo 
t = 12 h 
(Only for BID 
dosing Day 1) 
1 
omadacycline 100 mg in 
100 mL NS 
100 mL NS placebo 
t = 24 h 
1 
 
2 
omadacycline 100 mg in 
100 mL NS 
250 mL NS placebo 
100 mL NS placebo  
 
moxifloxacin 400 mg in 250 mL 
0.8% saline 
t = 48 h, then 
q24h 
1 
 
2 
omadacycline 100 mg in 
100 mL NS 
250 mL NS placebo 
100 mL NS placebo  
 
moxifloxacin 400 mg in 250 mL 
0.8% saline  
BID = twice a day dosing, NS = Normal saline (0.9% sodium chloride) for injection, t = time. 
a 
See Section 7.6.2 for allowed adjustments in iv dosing schedules. 
b 
All 100 mg in 100 mL infusions of omadacycline or 100 mL NS placebo are administered 
continuously over 30 minutes (± 5 minutes). On Day 1, if QD dosing is selected, the 200 mg in 
100 mL infusion of omadacycline or matched placebo will be administered continuously, without 
interruptions, over 60 minutes (± 5 minutes). 
c 
All 250 mL infusions of moxifloxacin or 250 mL NS placebo are administered continuously over 
60 minutes (± 5 minutes). 
 
7.6.2 
Selection and Timing of iv Dose for Each Subject 
To facilitate study enrollment at all times of the day and permit subjects to be “shifted” to a more 
practical dosing schedule consistent with hospital schedules, a provision is made for limited 
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adjustment of the dosing interval. Specifically, infusion times may be adjusted up to ± 2 hours 
per infusion interval until the desired administration schedule is achieved. 
Once the desired start of infusion time is determined, subsequent infusions should be “anchored” 
to that time. That is, thereafter, the start of infusion should be within ± 1 hour of the specified 
target infusion time. 
7.6.3 
Management While on iv Test Article 
While the subject is receiving iv therapy, the investigator will assess the subject daily and choose 
one of the following outcomes based on the overall clinical response of the subject: 
• Continue iv test article 
• Assess for po test article using the protocol defined criteria (after a minimum of 2 days of iv 
therapy), see Section 7.6.5. 
• Discontinue test article – this decision will prompt the EOT evaluation (even if the subject 
does not complete the minimum of 7 days of dosing) 
 
At all times during the study the decision to continue iv, switch to po, or discontinue test article 
is made based on the patient’s response including the attainment of clinical stability and the 
clinical judgment of the investigator. Each daily decision is to be recorded on source documents 
and the information to be transferred to eCRFs by blinded study site personnel. 
7.6.4 
Investigator’s Decision to Continue or Discontinue Treatment 
At all times during the study the decision to continue iv, switch to po, or discontinue test article 
is made based on the patient response including the attainment of clinical stability and the 
clinical judgment of the investigator.  
 
The investigator may use microbiological results (e.g., culture and susceptibility results) from the 
local microbiology laboratory to help guide therapy; however, investigator decisions to continue 
or discontinue test article should be based on clinical response rather than susceptibility 
results.  For example, if a respiratory pathogen is detected after randomization that is not 
susceptible to omadacycline and/or moxifloxacin and the subject is stable or clinically 
improving, blinded study treatment may continue unless the investigator perceives an undue risk 
to the subject. 
 
Similarly, if a viral respiratory pathogen is detected after randomization (including but not 
limited to SARS-CoV-2), study drug may be continued if the investigator continues to suspect 
co-infecting bacterial pathogen(s) and the subject is stable or clinically improving , and 
concomitant treatment for the viral pathogen may be administered as appropriate.  Questions 
about individual cases should be discussed with the Medical Monitor prior to discontinuing study 
drug or administering additional antimicrobial agents, and decisions should be recorded in source 
documents.   
 
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7.6.5 
Investigator’s Decision to Switch from iv to po Treatment 
Initially, all randomized subjects will receive at least 2 days of iv antibacterial therapy. 
Beginning on the Day 3 visit, the subject may be eligible to switch from iv to po therapy. The 
decision to switch to po treatment will be made by the investigator; the subject should be 
considered clinically stable and meet all criteria for transition to a po regimen. Specifically, the 
subject must meet the following requirements, and this should be noted in source documents and 
recorded on the eCRF: 
• Temperature ≤ 37.8°C (100°F) 
• Heart rate ≤ 100 beats/minute 
• RR ≤ 24 breaths/minute 
• SBP ≥ 90 mm Hg  
• Oxygen saturation ≥ 90% as measured by pulse oximetry or PaO2 ≥ 60 mm Hg by ABG 
• Normal (“absence of confusion”) or return to baseline mental status 
• Ability to maintain po intake. 
 
The first po dose should be administered in the morning, 12 to 24 hours after the last dose of iv 
test article. Switch to po will not be permitted until after the subject has completed at least the 2 
days of iv treatment. The date and time the investigator confirmed the criteria for the subject’s 
eligibility for po treatment were met and made the decision to switch to po treatment will be 
recorded on source documents and the information transferred to eCRFs by study site personnel. 
7.6.6 
Oral Treatment Phase 
 
Treatment regimens for po dosing are shown in Table 2 below. When switching from iv to po 
test article, the recommended interval between doses will be maintained. The first po dose, for 
both omadacycline and moxifloxacin treatment arms, should be given in the morning 12 to 24 
hours after the last dose of iv test article. 
The po treatment phase will employ a double-blind, double-dummy design. To maintain 
investigator and subject blinding, subjects in both arms will receive 2 tablets and 1 over-
encapsulated tablet in the morning, as shown in Table 2 below. All doses of oral test article 
should be taken with water. 
All oral doses should be taken in a fasted state. Fasting is defined as no food, antacids or 
multivitamins containing multivalent cations (eg, aluminum, magnesium, calcium, bismuth, iron, 
or zinc) or drink except water for at least 4 hours before dosing. After dosing, no food is 
permitted for 2 hours as well as no dairy products, antacids or multivitamins containing 
multivalent cations (eg, aluminum, magnesium, calcium, bismuth, iron, or zinc) for 4 hours. 
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Table 2. 
Treatment Regimens for Oral Test Article 
Time of Dosing 
Omadacycline Arm 
Moxifloxacin Arm 
Dosing Conditiona,b 
Morning 
(upon 
awakening) 
a 
Two 150 mg omadacycline 
tablets and 1 
over-encapsulated placebo 
tablet 
One 400 mg 
over-encapsulated 
moxifloxacin tablet and 2 
placebo tablets 
Fasting overnight (no 
food or drink except 
water) before dosing; 
after dosing, no food for 
2 hours, no dairy 
products for 4 hours 
po = per oral. 
a 
All doses of po test article should be taken with water. 
b 
All subjects will be instructed to avoid taking antacids and multivitamins while taking po test article. 
 
7.6.6.1 
Management While on Oral Test Article 
When subjects are switched to po therapy, subjects will be given instructions on how to 
administer the po therapy, a subject diary to record dates and times of po treatment, and a day 
supply of po test article. Study personnel will review the dosing diary and tablet count with the 
subject when the po therapy is first dispensed to the subject and at subsequent visits until the 
subject has completed therapy. Study personnel will review and record which medication is 
taken in the eCRF. 
While the subject is receiving po therapy, the investigator will assess the subject and choose one 
of the following outcomes based on the overall clinical response of the subject: 
• Continue po test article 
• Discontinue test article – this decision will prompt the EOT evaluation (even if the subject 
does not complete the minimum days of dosing) 
 
At all times during the study the decision to continue or discontinue test article is made based on 
the clinical judgment of the investigator. Each daily decision is to be recorded on source 
documents and the information transferred to eCRFs by blinded study site personnel. 
7.7 
Dose Adjustments and Interruptions of Test Article 
No dose adjustments or planned interruptions of test article will be permitted during this study. 
7.8 
Method of Assigning Patients to Treatment Groups 
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 after confirming that the subject fulfills all 
the inclusion criteria and has 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 PORT Risk Class (III or IV) and receipt of an 
allowed antibacterial (see Appendix 4) in the 72 hours prior to study treatment as defined in the 
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IxRS specifications and Statistical Analysis Plan (SAP). Subjects randomized into the study will 
be assigned the treatment corresponding to the next available number from 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.  Randomization of subjects who have received an allowed antibacterial therapy in 
the 72 hours prior to study treatment will be capped at 25% of the subjects randomized. 
7.8.1 
Subject Numbering 
Upon signing the informed consent, the subject will be assigned a unique subject number. 
Subjects who have been pre-screened, but who do not sign an ICF will not be assigned a subject 
number. A subject who discontinues participation or is withdrawn before receiving a treatment 
assignment, and who is re-screened at a later time will be assigned a new subject number and 
recorded as re-screened. Re-screening is at the discretion of the investigator and in consultation 
with the medical monitor. 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. 
7.9 
Dispensing Test Article 
Each study site will be supplied by the sponsor with the investigational product and comparator. 
The IxRS will instruct the pharmacist or designee as to the appropriate therapy, omadacycline or 
comparator, to be administered. The unblinded site pharmacist or designee will prepare the test 
article as instructed. The unblinded pharmacist or designee will provide the blinded nurse 
administering the infusion with the appropriate solutions for each subject covered to conceal the 
identity of the test article using materials provided by the sponsor and labeled with blinded 
administration instructions. The po test article will be supplied to the sites in kits that contain 
bottles of active omadacycline tablets or matched placebo tablets, and bottles of active over-
encapsulated moxifloxacin tablets or matched over-encapsulated placebo tablets. Oral test article 
supplies are completely blinded. Therefore, oral test article supplies can be transferred from the 
unblinded study personnel to blinded study personnel for storage, dispensation, and 
reconciliation. The study coordinator/staff will instruct the subject on the use of po test article. 
The procedures are detailed in the Pharmacy Manual. 
7.10 Blinding 
The investigator and sponsor will be blinded to treatment arm assignments in both the iv and po 
phases of 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). 
Because the color of the iv test article infusions and placebo infusions differ, all infusion bags 
and iv tubing will be covered with materials provided by the sponsor so that subjects and blinded 
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study personnel will not know the identity of the test article being administered. The infusion 
regimen will follow a blinded design with subjects in each study arm receiving the same infusion 
volumes with the same administration instructions. Blinded study personnel will administer the 
infusions and collect, review and enter data regarding the iv infusions (eg, start and stop times) 
into an eCRF. If gravity administration is not the standard of care, then an infusion pump may be 
used. If an infusion pump is used, then an unblinded administrator will be required. Personnel 
identified as unblinded administrators will not participate in any study procedures other than iv 
administration of test article and the collection, review and entry of iv related data (eg, start and 
stop times) into an eCRF. 
During the po phase, a double-blind, double-dummy design will be used to ensure the blind is 
maintained. Subjects in the omadacycline arm will receive active omadacycline tablets and 
matched comparator over-encapsulated placebo tablets. Subjects on the moxifloxacin arm will 
receive omadacycline placebo tablets and active over-encapsulated moxifloxacin tablets. 
The unblinded source documentation binder containing all descriptions of pharmacy preparations 
and infusions or distributions of test article and any unblinded subject randomization data should 
be stored separately, and under lock and key, separate from the documents containing blinded 
information. 
Data that could potentially lead to unblinding will not be accessible to anyone other than the 
following site personnel: 
• unblinded study pharmacist or designee 
• unblinded study monitor 
• unblinded administrator(s) 
Unblinding by site personnel is only to occur in the case of subject emergencies (see Section 
7.11, below) and at the conclusion of the study. 
7.11 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 
sponsor or sponsor’s designated Medical Monitor or designee to confirm the need to unblind, 
prior to unblinding (see Section 2 for contact information). 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. 
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It is the investigator’s responsibility to ensure that there is a procedure in place at their site 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. 
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. 
7.12 Prior & Concomitant Therapy 
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 
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 10). In addition, for antibacterial agents administered, the dose, unit, 
frequency and route must be entered in the eCRF. 
 
7.13 Prohibited Therapy 
All investigational medications or devices used during the 30 days prior to Screening are 
prohibited. 
All of the following therapies are excluded starting from the time of consent through EOT visit: 
• More than 1 dose of a potentially therapeutic antibacterial agents (with potential activity 
against pathogens responsible for CABP) are prohibited for 72 hours prior to randomization 
through EOT, with the exception of cases where a subject is deemed a clinical failure during 
the course of the study and requires treatment with an additional antibacterial agent 
• Subjects will be instructed to avoid taking antacids and multivitamins containing multivalent 
cations (eg, aluminum, magnesium, calcium, bismuth, iron, or zinc) for 4 hours before and 
within 4 hours after oral doses 
 
7.13.1 
Concomitant Medications That May Interact With Moxifloxacin 
Use of proarrhythmic or QT prolonging medications is prohibited through the EOT. After EOT 
through Final Follow-up, the investigator should use clinical judgement regarding the use of such 
medications, given the half-life of moxifloxacin. For other warnings, precautions, and drug 
interactions for moxifloxacin please see the most current version of the moxifloxacin full 
prescribing information provided under separate cover. 
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7.14 Permitted Treatments 
All other treatments not specified as prohibited are permitted during the study. Subjects requiring 
additional or alternative antibacterial therapy for their CABP 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. 
7.15 Treatment Compliance 
Intravenous and oral administration will be managed by study personnel. 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. 
7.16 Packaging and Labeling 
The investigational test article, omadacycline and moxifloxacin will be packaged by the sponsor 
and supplied to the investigator. Please refer to the Pharmacy Manual for additional information. 
7.17 Storage and Accountability 
Test article must be received at the study site by a designated person, acknowledged in the IxRS, 
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. Intravenous drug 
accountability will be performed by unblinded personnel. Oral drug accountability can be 
performed by blinded or unblinded personnel. 
7.18 Investigational Product Retention at Study Site 
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 as permitted by local site 
operating procedures, or return all unused test articles, packaging, and drug labels. 
Destruction/return of all test article will be documented and maintained in the site files. 
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8 STUDY PROCEDURES 
Written, signed, and dated informed consent will be obtained before any study-related 
procedures have been performed. Upon signing the informed consent, the subject will then be 
assigned a study subject number. Adverse events 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. 
8.1 
Informed Consent 
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 
8.2 
Subject Demographics/Other Baseline Characteristics 
Subject demographic and baseline characteristic data to be collected on all subjects include: date 
of birth (per local regulations), gender, and race/ethnicity. 
8.3 
Medical History 
The investigator will perform a comprehensive history at the Screening visit. Significant medical 
history (at any time) and any medical history within the past 6 months including ongoing 
medical conditions at the time of signing of the ICF will be recorded. In addition, subject’s 
history of prior CABP will be captured and the following: 
• Predisposing factors that may affect lung function (eg, prior lung infection, mild to moderate 
COPD, symptomatic asthma with wheezing, history of smoking, chronic cough with and 
without sputum production, etc). 
• Cardiovascular disease and risk factors 
• History of pneumococcal vaccination (eg, Pneumovax, Prevnar 13). 
• All systemic antimicrobials from onset of the infection will be recorded under concomitant 
medications. 
Where possible, diagnoses are to be recorded. Any event or change in the subject’s condition 
or health status occurring after signing the ICF will be reported as an AE. 
 
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8.4 
Physical Examination 
At Screening, a full physical examination will include the examination of general appearance, 
skin, neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph 
nodes, extremities, and vascular and neurological systems. Beyond the Screening visit, 
abbreviated physical examinations may be performed (see Appendix 1). 
Information for all physical examinations must be included in the source documentation at the 
study site.  Significant and relevant findings that are present prior to the signing of the ICF must 
be included in the subject’s eCRF. Relevant findings that are present prior to the signing of the 
ICF must be included in the relevant medical history/current medical conditions screen on the 
subject’s eCRF. New clinically significant findings made after the signing of the ICF which meet 
the definition of an AE must be recorded as an AE in the subject’s eCRF. 
8.5 
Vital Signs 
Vital signs including BP, heart rate, respiratory rate, pulse oximetry and body temperature will 
be measured at the timepoints as specified in Appendix 1. Additionally, BP and heart rate should 
be measured within 30 minutes before, and approximately 1 hour (± 15 minutes) after the 
completion of the infusions on Day 1 and Day 2. 
The subject’s BP and heart rate should be captured after at least 5 minutes (+ 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 BP will be measured using an automated calibrated device, with an 
appropriately sized cuff. 
Heart rate will be measured using an automated calibrated device, when available. If not 
available, heart rate will be measured manually. 
Temperature will be obtained using an electronic (rapid reading) device whenever possible and 
the same device should be used for all study assessements. 
8.6 
Electrocardiogram 
A standard 12-lead ECG should be obtained using site equipment. The ECG will be obtained 
after the subject has been in a semi-recumbent position for approximately 10 minutes at the 
following times: 
• Screening-any time during the visit 
• EOT-any time during the visit 
• In any case in which a subject develops an AE of non-pleuritic cardiac chest pain, 
palpitations, tachyarrhythmia, or as otherwise clinically indicated 
• Additional ECGs can be performed as needed at the discretion of the investigator. 
 
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Reading and interpretation of the ECG will be performed locally and reviewed by the 
investigator for interpretation, and hard copies of the reports retained in the files. 
8.7 
Height and Weight 
Height and body weight will be collected and recorded in the eCRF. 
8.8 
Assessment of CABP Symptom Severity 
The investigator will specifically assess the presence and severity level of the subject’s 
symptoms of cough, sputum production, pleuritic chest pain and dyspnea on a 4-point scale 
(absent, mild, moderate, or severe) based upon the Community-Acquired Bacterial Pneumonia 
Subject Symptom Severity Guidance Framework for Investigator Assessment (see Appendix 3) 
and enter the symptom severity level into the eCRF. Subjects must have at least 3 of these 4 
symptoms of CABP to be eligible for randomization in the study. 
8.9 
Radiologic Evaluation of Pneumonia 
A CXR or CT scan will be obtained for all subjects at Screening (within 48 hours prior to the 
first dose of test article, see Inclusion Criteria 7). These studies may be obtained as part of 
routine, non-study evaluation of a subject presenting with signs and symptoms of CABP and 
therefore may be performed in some circumstances before informed consent is obtained for 
participation in this study. If a CXR or CT scan is obtained during the course of therapy or 
during the period up to the Final Follow-up assessment, the results of the study will be collected. 
Radiologic evaluation(s) will be performed locally and interpreted by appropriately qualified 
personnel who are certified or licensed to interpret chest radiographs according to applicable 
regional requirements, reviewed by the investigator or qualified personnel and the conclusions of 
this review will be the basis for subject inclusion. The review report should be included in the 
source documents. 
8.10 PORT Risk Class 
All subjects who are being screened for the study will have their PORT Risk Class assessed at 
the Screening evaluation only (see Appendix 5). As part of the Inclusion Criteria to this study, all 
subjects must have disease characterized as PORT Risk Class of III or IV at randomization and 
randomization will be stratified by PORT Risk Class to ensure balance between treatment arms. 
8.11 SF-36v2® Health Survey 
At the Screening and Final Follow-up visits, the subject will complete a SF-36v2® Health Survey 
(Medical Outcomes Trust, Optum™).  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. 
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8.12 Clinical Laboratory Tests 
Clinical safety laboratory tests to be performed include hematology, prothrombin time 
(international normalized ratio), serum chemistry, and pregnancy tests (urine or serum). 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 
eligibility, it is expected that local laboratory testing will be used in circumstances where this 
testing is needed..  
8.12.1 
 Central Laboratory Parameters 
Clinical laboratory tests will include the following: 
Clinical Laboratory Tests (Central) 
Hematology: 
• 
Hematocrit (Hct) 
• 
Hemoglobin (Hgb) 
• 
Mean corpuscular hemoglobin (MCH) 
• 
Mean corpuscular hemoglobin 
concentration (MCHC) 
• 
Mean corpuscular volume (MCV) 
• 
Platelet count 
• 
Red blood cell (RBC) count 
• 
White blood cell (WBC) count with 
differential 
Coagulation: 
• 
Prothrombin time international normalized 
ration (INR) 
Pregnancy (all female subjects): 
• 
Serum β-human chorionic gonadotropin 
(β-HCG) 
Serum Chemistry: 
• 
Alkaline phosphatase (ALP) 
• 
Alanine aminotransferase (ALT) 
• 
Aspartate aminotransferase (AST) 
• 
Blood urea nitrogen (BUN) 
• 
Calcium (Ca) 
• 
Carbon dioxide (CO2) 
• 
Chloride (Cl) 
• 
Creatinine 
• 
Creatine phosphokinase (CK) 
• 
Gamma-glutamyl transpeptidase (GGT) 
• 
Lipase 
• 
Magnesium 
• 
Phosphorus (P) 
• 
Potassium (K) 
• 
Sodium (Na) 
• 
Total bilirubin 
 
In addition, blood samples will be collected and sent to the Central Laboratory for serologic 
microbiology testing (Section 8.12.2.2). 
8.12.2 
Local Laboratory Parameters 
8.12.2.1 
Pregnancy Assessments 
All subjects will have a local urine or serum pregnancy test at the site at the Screening. 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 during Screening, the subject is not to 
be randomized. A serum sample for serum β-human chorionic gonadotropin (β-hCG) testing will 
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be collected at the Screening visit and sent to the Central Laboratory for confirmation of the local 
urine or serum pregnancy test results as well as at EOT and PTE. If a positive β-hCG result is 
reported by the Central Laboratory after a subject is enrolled, test article administration should 
be discontinued (see Section 8.22). 
8.12.2.2 
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. If 
bacteria are isolated from baseline blood cultures, repeat blood cultures must be collected on the 
day that the positive blood culture is detected. If subsequent blood cultures are also positive, 
repeat the blood cultures as necessary until negative blood cultures are obtained. Blood culture 
isolates should be sent to the Central Laboratory. 
8.12.2.3 
Sputum and Urine Samples 
Samples of sputum and urine will be collected and sent to the local laboratory for microbiology 
testing (Section 8.14.1). 
8.12.2.4 
SARS-CoV-2 Sample 
In addition to any local SOC assessment of SARS-CoV-2, molecular testing for SARS-CoV-2 
will be performed at the local laboratory (or a regional reference laboratory) using an upper 
respiratory sample (e.g. nasopharyngeal swab or saliva) collected at Screening. Test results from 
this sample are not required before a subject is randomized. However, test results will be 
documented in the database. If a positive test result is obtained after randomization, the 
investigator will determine whether a subject should continue study treatment (see Section 
7.6.4). Repeat testing may be completed as clinically indicated and should be recorded. Please 
see laboratory manual for additional testing information. 
8.12.3 
Blood Volume 
The total volume of blood collected from each subject will be approximately 4 to 15 mL per 
visit, or approximately 51 mL (approximately 3.5 tablespoons) over the course of the study. In 
addition, a blood culture will be collected at Screening and repeated if positive. The preferred 
volume for each blood culture bottle is 10 mL. However, since these are analyzed locally, site 
staff should refer to their individual laboratory or manufacturers’ recommendation. 
8.13 Efficacy Assessments 
8.13.1 
Investigator’s Assessment of Clinical Response 
In order to satisfy different health authority requirements, the primary variables assessing 
efficacy will be tested with 2 response endpoints. 
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8.13.1.1 
Evaluation of the Infection Under Study at the Early Clinical Response 
Assessment 
The formal determination of the response to therapy at the ECR assessment (72 to 120 hours 
after administration of the first dose of test article) will be done programmatically using the 
investigator’s assessment of the subject’s symptoms associated with CABP entered into the 
eCRF. The investigator is not responsible for categorizing subjects as Clinical Success, Failure, 
or Indeterminate at the ECR assessment. The severity of the subject CABP symptoms of cough, 
sputum production, pleuritic chest pain and dyspnea will be evaluated on a 4-point scale (absent, 
mild, moderate, or severe) based upon the Community-Acquired Bacterial Pneumonia Subject 
Symptom Severity Guidance Framework for Investigator Assessment (see Appendix 3). A 
CABP subject symptom severity assessment should be completed at every scheduled evaluation 
with the exception of the Final Follow-up assessment (see Section 8.8 and Appendix 1). For 
subjects that have been switched to po test article and discharged from the hospital prior to Study 
Day 4, only 1 visit is required between Study Days 4 to 6 (see Appendix 1 for ECR study 
procedures). Subjects who remain hospitalized during the ECR phase should have the study 
procedures performed each day (see Appendix 1). 
Clinical Success: at the ECR assessment will be defined as survival with improvement of at least 
1 level (ie, severe to moderate, moderate to mild, mild to absent) compared to Screening in 2 of 
the 4 CABP symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) with no 
worsening by at least 1 level in the other inclusion CABP symptoms. In order for the subject to 
be considered a Clinical Success, the subject may not meet any criteria for Clinical Failure or 
Indeterminate ECR. 
Clinical Failure: defined as meeting any of the following criteria: 
• There is no improvement by at least 1 level (ie, severe to moderate, moderate to mild, mild to 
absent) compared to Screening in 2 CABP symptoms. 
• Any of the 4 CABP symptoms is worse (by at least 1 level) compared to Screening. 
• The subject requires alternative (rescue) antibacterial treatment for CABP prior to the ECR 
assessment related to either (a) progression or development of new symptoms attributable to 
CABP or (b) development of infectious complications of CABP (eg, empyema, lung 
abscess). 
• The subject is receiving antibacterial therapy that may be effective for the infection under 
study for a different infection from the one under study. 
• Discontinued study therapy due to an AE and received alternative antibacterial treatment for 
CABP prior to the ECR assessment. 
• Death prior to the ECR assessment. 
 
Indeterminate: the clinical response to test article could not be adequately inferred due to: 
• Subject was not seen for the evaluation because they withdrew consent or were lost to 
follow-up. 
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• Other specified reason. 
 
8.13.1.2 
Investigator’s Assessment of Clinical Response at EOT 
End of treatment assessments should be performed 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 prior to completion of the planned antibiotic therapy, the EOT visit 
should be conducted. 
The investigator will determine which of the following clinical outcomes the subject meets based 
on the criteria below (must select 1 outcome): 
Clinical Success: 
• The subject is alive and the infection is sufficiently resolved such that further antibacterial 
therapy is not needed. 
o These subjects may have some residual findings related to infection (ie, cough) requiring 
ancillary (ie, non-antibiotic) treatment (eg, expectorant). 
• In order for the subject to be considered a Clinical Success at EOT, the subject may not meet 
any criteria for Clinical Failure or Indeterminate at EOT. 
 
Clinical Failure: 
• The subject requires alternative antibacterial treatment for CABP prior to EOT related to 
either: 
a. progression or development of new symptoms of CABP or, 
b. development of infectious complications of CABP (eg, empyema, lung abscess) or, 
c. subject developed an AE that required discontinuation of study therapy.  
• Other reasons for Clinical Failure are: 
d. Subject is receiving antibacterial therapy that may be effective for the infection under 
study for a different infection from the one under study. 
e. Death prior to EOT visit.  
 
Indeterminate: 
• The Clinical Response to test article could not be adequately inferred due to: 
a. Subjects were not seen for EOT evaluation because they withdrew consent or were lost to 
follow-up. 
b. Other specified reason. 
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8.13.1.3 
Investigator’s Assessment of Clinical Response at PTE 
The PTE assessment is to be performed 5 to 10 days after the subject’s last day of therapy. The 
investigator will determine which of the following clinical outcomes the subject meets based on 
the criteria below (must select 1 outcome): 
Clinical Success: 
• Survival after completion of a test article regimen without receiving any systemic 
antibacterial therapy other than test article; 
• Resolution of signs and symptoms of the infection present at Screening with no new 
symptoms or complications attributable to CABP; and 
• No need for further antibacterial therapy. 
 
Clinical Failure: 
• The subject requires alternative antibacterial treatment for CABP prior to PTE related to 
either: 
a. Progression or development of new symptoms of CABP or 
b. Development of infectious complications of CABP (eg, empyema, lung abscess). 
 
• Other reasons for Clinical Failure are: 
c. The subject is receiving antibiotics that may be effective for the infection under study for 
a different infection from the one under study. 
d. Death prior to PTE. 
 
Indeterminate: 
• The clinical response to test article could not be adequately inferred due to: 
a. Subjects were not seen for PTE evaluation because they withdrew consent or were lost to 
follow-up. 
b. Other specified reason. 
 
8.13.2 
Clinical Stability 
The formal determination of the subject’s Clinical Stability will be done programmatically using 
the investigator’s assessment of the subject’s vital signs entered into the eCRF. The investigator 
is not responsible for categorizing the subject’s Clinical Stability. Clinical Stability will be 
assessed daily and analyzed by day, ECR window, EOT, and PTE. 
Patients will be considered clinically stable if they achieved all of the following criteria: 
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• Temperature ≤ 37.8°C (100°F); 
• Heart Rate ≤ 100 beats/minute; 
• RR ≤ 24 breaths/minute; 
• SBP ≥ 90 mmHg; and 
• Arterial Oxygen Saturation ≥ 90% or PaO2 ≥ 60 mmHg on room air. 
 
8.14 Microbiologic Response 
8.14.1 
Respiratory Culture and Gram Stain 
At the Screening visit collection of an adequate quality expectorated or induced sputum or other 
respiratory specimen reflecting fluid from the lower respiratory tract (eg, respiratory fluid 
obtained by bronchoalveolar lavage or bronchoscopy; pleural fluid obtained by thoracentesis; or 
expectorated or induced sputum meeting adequacy criteria) should be attempted from all subjects 
and submitted to the local microbiology laboratory for Gram stain and culture (see Appendix 1). 
The date, time and type of specimen submitted will be recorded on source documents at the local 
laboratory. These specimens may be obtained as part of routine, non-study evaluation of a 
subject being evaluated for CABP and therefore could be obtained prior to obtaining informed 
consent. 
An adequate quality sputum specimen will be defined as having the following 2 findings as 
reported by the local laboratory: 
1. < 10 Squamous epithelial cells/low power field (LPF) (ie, 100×) 
2. > 25 Polymorphonuclear cells/LPF (ie, 100×) 
Adequate quality sputum specimens and other Screening respiratory specimens for culture 
should be obtained prior to first dose of test article. In the event that a sputum specimen is 
determined to be inadequate or cannot be obtained prior to the first dose of test article, collection 
of a specimen should be attempted within 24 hours after the first dose of test article. As the 
infection responds to therapy, obtaining repeated specimens for culture or examination may not 
be clinically appropriate and/or there may be no material for culture. At the EOT and/or PTE 
visit, respiratory specimen cultures and Gram stains should be obtained only for subjects who are 
Clinical Failures and require alternative antibacterial treatment for CABP. 
All respiratory and blood specimens submitted to the local laboratory are to be processed for a 
Gram stain of the specimen and for aerobic culture. Laboratory reports on Gram stains should 
include a semi-quantitative description of the number of polymorphonuclear leukocytes per LPF 
(ie, 100×) and a description of bacteria seen. For Gram stains of respiratory specimens, a semi-
quantitative description of the number of squamous epithelial cells per LPF (ie, 100×) should 
also be included. Culture results are to include identification of all pathogens to the level of 
genus and species. Susceptibility testing for moxifloxacin (or other fluoroquinolones) 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. 
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All isolates identified by the local laboratory from expectorated or induced sputum specimens 
meeting the 2 criteria that define the specimen as being of adequate quality and/or that are 
isolated from respiratory specimens or blood and are potential pathogens as defined in the 
Local/Regional Clinical Microbiology Laboratory Manual, will be submitted to the Central 
Laboratory for verification of genus and species and for standardized minimum inhibitory 
concentration (MIC) testing performed for omadacycline, moxifloxacin 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. 
Details concerning Gram stains and cultures will be provided in the Local/Regional Clinical 
Microbiology Laboratory Manual. 
8.14.2 
Urine for Legionella pneumophila and Streptococcus pneumoniae Antigen 
Screening 
At the Screening visit, urine will be collected to test for the presence of Legionella pneumophila, 
and Streptococcus pneumoniae antigens. Testing will be performed at the local laboratory using 
kits supplied by the sponsor and the results will be recorded on the eCRF. 
8.14.3 
Serology for Legionella pneumophila, Mycoplasma pneumoniae, and 
Chlamydophila pneumoniae Titers 
At the Screening visit, and at the PTE visit, blood samples will be collected to conduct serology 
for Legionella pneumophila, Mycoplasma pneumoniae and Chlamydophila pneumoniae by the 
Central Laboratory. 
8.15 Pharmacokinetic Assessments 
Instructions will be provided to sites with detailed information on sample collection, handling, 
and shipment requirements. All samples will be given a unique identifier. The exact clock time 
of dosing, date and time of last food intake, as well as actual sample collection date and time will 
be entered on the eCRF. 
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8.16 Adverse Events 
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. 
8.17 Serious Adverse Events 
A serious adverse event (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 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 that, had it occurred in a more severe 
form, might have caused death, but as it actually occurred, did not create an immediate risk of 
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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. 
8.18 Other Reportable Information 
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. 
8.19 Overdose 
Any administration of omadacycline of greater than 600 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 2.8 g 
of moxifloxacin in a single administration 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 
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by contacting the IxRS. Interactive Response System will also provide a confirmation report of 
the drug assignment to site personnel. The site personnel will retain this confirmation report. In 
the case of a potential overdose, the subject should maintain a high level of fluid intake to 
promote urinary excretion (as recommended in the moxifloxacin USPI). 
The physician managing the overdose may order any test he/she thinks is necessary to manage 
the subject properly. 
8.20 Medication Errors 
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 e-mailing the Clinical Test 
Article Error Incident Report Form as indicated in the Emergency Contacts (see Section 2.1). 
8.21 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 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. 
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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. 
8.21.1 
Serious Adverse Event Reporting 
All SAEs and follow-up information must be reported within 1 business day or 24 hours as 
required by local regulations by emailing a completed SAE Report to the email address below. 
Serious Adverse Event (SAE) contact information 
E-Mail: 
8.21.2 
Assessment of Relatedness 
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 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. 
Adverse events and SAEs also will be assessed for their potential relationship to the protocol. A 
protocol-related AE 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. 
8.21.3 
Assessment of Severity 
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. 
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• 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. 
8.21.4 
Laboratory Findings 
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. 
8.21.5 
Worsening or Progression of Disease Under Study 
Worsening or progression of the qualifying CABP 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 considers to be distinct from the 
qualifying CABP should be reported as AEs in all cases, whether non-serious or serious. 
8.22 Pregnancies 
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. 
8.23 Concomitant Medication Assessments 
The investigator should instruct the subject to notify the study site about any new medications 
they take after the start of the test article. 
All prescription medications, over-the-counter (OTC) drugs, and recreational drugs taken within 
the timeframe defined in the entry criteria prior to the start of the study and during the study, 
must be recorded on the Concomitant Medications/Non-Drug Therapies page of the eCRF.  
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8.24 Subject Discontinuation or Withdrawal 
Reasons why a subject may discontinue or be withdrawn from the study include, but are not 
limited to, AE, lost to follow up, withdrawal by subject, physician decision, death, and other 
(specify reason eg, subject non-compliance or 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 should not be considered withdrawn from the study 
(unless the subject withdraws informed consent). The date and primary reason for 
discontinuation of study treatment should be recorded. Subjects who discontinue study treatment 
prematurely should complete the EOT visit, PTE visit and Final Follow-up Assessment, if 
possible (see Schedule of Events - Appendix 1). The site should also collect subject safety 
information through the Final Follow-up assessment. 
Site personnel must also contact the IxRS to register the subject’s discontinuation from test 
article. 
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). 
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9 STUDY ACTIVITIES 
9.1 
Screening Phase 
The Screening visit should be completed within a 24-hour period prior to randomization. The 
Screening procedures will be used to establish subject eligibility and baseline characteristics for 
each subject. Following the signing of an ICF, the site staff will collect/perform the assessments 
detailed in Appendix 1. 
9.2 
Double-blind Treatment Phase 
The double-blind treatment period is 7 to 10 days in duration. Additionally, subjects with 
bacteremia confirmed from local blood culture drawn at Screening can receive up to 14 days of 
treatment. Subjects who meet all of the inclusion criteria and none of the exclusion criteria may 
be randomized. 
Visits will occur on Day 1, 2, 3, 4 to 6 (ECR), and Day 7/EOT. Visits will occur on Days 8 to 10 
only if the EOT visit does not coincide with day of last dose OR treatment extends beyond 
7 days. Subjects with bacteremia identified at Screening may have visits up to Day 14. 
For subjects that have been switched to po treatment and were discharged from the hospital prior 
to the Day 4 visit, only 1 visit is required between Study Days 4 to 6. Subjects who remain 
hospitalized during the ECR phase should have the study procedures performed each day (see 
Appendix 1). Beginning on Day 7, subjects are eligible to have their test article discontinued at 
the discretion of the investigator (see Section 7.6.4). If the investigator determines that the 
subject does not need further antibacterial therapy on Day 7, the EOT evaluation may be 
performed the day of or within 2 days of the last dose of test article. If the subject is hospitalized 
in the period between the last day of study drug treatment and the EOT evaluation, the study 
procedures should be performed as outlined in Appendix 1. If the subject is outpatient during this 
period, the study procedures do not need to be performed until the EOT visit. have their test 
article discontinued at the discretion of the investigator (see Section 7.6.4). If the investigator 
determines that the subject does not need further antibacterial therapy on Day 7, the EOT 
evaluation may be performed the day of or within 2 days of the last dose of test article. If the 
subject is hospitalized in the period between the last day of study drug treatment and the EOT 
evaluation, the study procedures should be performed as outlined in Appendix 1. If the subject is 
outpatient during this period, the study procedures do not need to be performed until the EOT 
visit. 
9.3 
EOT Visit Procedures 
The EOT evaluation should be conducted on the day of or within the 2 days following the last 
dose of test article. If the subject voluntarily withdraws or is discontinued from their dosing 
regimen, the visit procedures should be performed on that day. 
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9.4 
Follow-up Phase 
9.4.1 
Post-therapy Evaluation Visit Procedures 
The PTE visit should be conducted 5 to 10 days after the last dose. This evaluation should also 
be conducted for any prematurely withdrawn subject. 
9.4.2 
Final Follow-up 
The Final Follow-up assessment should be conducted within 30 to 37 days following the 
subject’s first dose of test article. This evaluation should also be conducted for any prematurely 
withdrawn subject, with the exception of subjects who withdraw consent. The Final Follow-up 
assessment may be conducted via telephone contact or by another interactive technology for 
subjects who are a Clinical Success 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. 
10 STUDY SUSPENSION, TERMINATION, AND COMPLETION 
10.1 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 performed up through the final 
follow-up assessment (Final Follow-up). The study will be completed when the last subject has 
either discontinued or completed the Final Follow-up assessment. 
No long-term follow-up of subjects is planned, with the exception of pregnancies, as described in 
Section 8.22 , and SAEs described in Section 8.21. 
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, but not yet randomized will 
be allowed to continue Screening procedures. 
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. 
10.2 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 8.24 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 IRBs 
and/or Ethics Committees (ECs) of the early termination of the study. 
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If the investigator suspends or prematurely terminates their participation in 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 8.24 for prematurely withdrawn subjects. The investigator will also return all test 
articles, containers, and other study materials to the sponsor. 
11 QUALITY CONTROL AND ASSURANCE 
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. 
12 PLANNED STATISTICAL METHODS 
12.1 General Considerations 
All analyses of data for this study will comply with International Council on Harmonisation 
(ICH) 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®). 
The SAP incorporating the sections below, along with mock tables, figures, and listings (TFL) 
shells, will be prepared, 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. Analyses of PK endpoints will be 
described in a separate analysis plan. 
Descriptive statistics, including the numbers and percentages for categorical variables, and the 
numbers, means, standard deviation, medians, minimums, and maximums for continuous 
variables will be provided. Exploratory analyses may also be performed. Listings of individual 
subject’s data will be produced. 
All eCRFs must be completed, entered, and source data verified; all safety and microbiology 
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. 
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12.2 Determination of Sample Size 
Table 3 provides a summary of clinical success rates in the CABP-1200 study at ECR and PTE 
in the PORT III and IV subjects. 
 
Table 3. 
Clinical Success Rates in CABP-1200 at ECR and PTE in PORT III and IV 
Subjects 
Outcome 
Omadacycline 
n/N1 (%) 
 
Moxifloxacin  
n/N1 (%) 
ECR Success  - ITT 
270/329 (82.1) 
228/332 (84.3) 
PTE Success – ITT 
291/329 (88.4) 
282/331 (85.2) 
PTE Success – CE 
273/295 (92.5) 
268/296 (90.5) 
CABP = community-acquired bacterial pneumonia, ECR = Early Clinical Response, PTE = post-therapy 
evaluation, ITT = Intent to treat, CE = Clinically evaluable. 
 
The primary efficacy outcome for the FDA is ECR at 72-120 hours following the first dose of 
test article in the ITT population.  An NI margin of 10% will be used for the analysis in the ITT 
population. The NI margin was based on an analysis of historical data regarding the treatment 
effect of antibiotics in pneumonia.  Based on data from study CABP-1200, it is reasonable to 
assume the rate of ECR success will be approximately 80% in both treatment groups.  With a NI 
margin of 10%, 1-sided alpha level of 0.025 and about 90% power and using the sample size 
determination method of Farrington and Manning, a total of 670 subjects are required. 
For the Investigator's Assessment of Clinical Response at PTE endpoint (EMA co-primary 
endpoint) with 670 subjects in the ITT population, assuming an outcome rate of 85% in both 
treatment groups, NI margin of 10% and 1-sided alpha level of 0.025, there is 94.7% power to 
show NI.  Assuming the evaluability rate for the CE population is 80%, an outcome rate of 80% 
in both treatment groups, NI margin of 10% and 1-sided alpha level of 0.025, there is 94.9% 
power to show NI in the CE population. 
Thus, 670 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 4. 
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Table 4. 
Sample Size and Power Calculations 
 
Primary Outcome FDA 
(Early Clinical Response) 
Primary Outcome EMA (Investigator’s 
Assessment of Clinical Response at PTE) 
Population 
ITT 
ITT 
CE 
NI Margin 
10% 
10% 
10% 
Evaluability Rate 
N/A 
N/A 
80% 
Outcome Rate 
80% 
85% 
89% 
N 
670 
670 
536 
Power 
89.6% 
94.7% 
94.9% 
CE = clinically evaluable; ITT = intent-to-treat;  N = number; N/A = not applicable; NI = 
non-inferiority; PTE = post-therapy evaluation. 
 
Assuming the microbiological evaluability rate is 30%, a total of 201 subjects are expected to be 
in the microbiological intent-to-treat (micro-ITT) population. 
12.3 Analysis Populations 
The following subject analysis populations have been defined for the various analyses of efficacy 
and safety: 
• The ITT population will consist of all randomized subjects. 
• The micro-ITT population will consist of subjects in the ITT population who have at least 1 
causative pathogen identified at Screening from culture of a respiratory specimen (eg, 
respiratory fluid obtained by bronchoalveolar lavage or bronchoscopy; pleural fluid obtained 
by thoracentesis; or expectorated or induced sputum meeting adequacy criteria), culture of 
blood, or from a culture-independent method (eg, positive urinary antigen test for 
Streptococcus pneumoniae or Legionella pneumophila, or positive serology for Legionella 
pneumophila, Mycoplasma pneumoniae or Chlamidophila pneumoniae). 
• The CE population will consist of all ITT subjects who received test article, have a qualifying 
CABP, an assessment of outcome, and meet all other evaluability criteria detailed in the SAP. 
• The microbiologically evaluable (ME) population will include subjects in the CE population 
who have at least 1 causative pathogen identified at Screening. 
• The Safety population will consist of all randomized subjects who receive test article. 
 
12.4 Demographics and Other Baseline Characteristics 
Descriptive statistics, by treatment arm, will be provided for the following:  
• Subject disposition: 
o completed test article 
o discontinued test article by reason for discontinuation 
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o completed study 
o discontinued study by reason for discontinuation 
• Protocol deviations 
• CABP background information 
o subject demographics: age (years), gender, race, height (cm), weight (kg), Body Mass 
Index (BMI) (kg/m2) 
• PORT Risk Class  
• Medical histories and continuing medical conditions  
Baseline 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). 
12.5 Treatments (Test Article, Rescue Medication, Other Concomitant Therapies, 
Compliance) 
The number of iv infusions will be summarized.  Number of days on iv before switch to po will 
be summarized.  For the po medication, actual 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.   
12.6 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. 
12.6.1 
Early Clinical Response Efficacy Variable 
The Early Clinical Response can be Clinical Success, Clinical Failure or Indeterminate (defined 
in Section 8.13.1.1).   
An Indeterminate Response is included in the denominator for the calculation of the percentage 
of subjects with a Clinical Success in the ITT population and thus, is essentially considered as a 
Clinical Failure for the purpose of the primary analysis for the FDA. 
12.6.2 
Investigator’s Assessment of Clinical Response at PTE Efficacy Variable 
The investigator will make an assessment of Clinical Response at the EOT and PTE Visits.  The 
primary outcome for the EMA, Investigator’s Assessment of Clinical Response at the PTE visit, 
is derived from the assessments at EOT and PTE visits in that a subject with a clinical response 
of failure at EOT is considered to have a clinical response of failure at PTE (ie, the clinical 
failure is carried forward) and a subject with an indeterminate response at EOT is considered to 
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have an indeterminate response at PTE, unless the outcome is a clinical failure at PTE.    
Investigator's Assessment of Clinical Response has  outcomes of Clinical Success, Clinical 
Failure or Indeterminate (defined in Section 8.13.1.3) in the ITT population and Clinical Success 
and Clinical Failure in the CE population.  An Indeterminate Response is included in the 
denominator for the calculation of the percentage of subjects with a Clinical Success in the ITT 
population and thus, is essentially considered a Clinical Failure for the purpose of the primary 
analysis for the EMA. 
12.6.3 
Statistical Model, Hypothesis, and Method of Analysis 
To demonstrate that the efficacy of omadacycline is non-inferior to moxifloxacin in the treatment 
of adults with CABP, the following hypothesis will be evaluated by analysis of the Clinical 
Success rates. 
The null hypothesis and alternate hypothesis for the ECR endpoint will be assessed in the ITT 
population as follows: 
Ho: θT – θC ≤ -∆  
Hai: θT – θC > -∆ 
Where the Clinical Success rate for the omadacycline regimen is θT and for 
moxifloxacin 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 ECR (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 moxifloxacin response proportion) will be used to test for the NI of the 
omadacycline arm compared to the moxifloxacin arm in the ITT population.  The 95% CI will be 
calculated using the unstratified method proposed by Miettinen and Nurminen.8  Omadacycline 
will be considered non-inferior to moxifloxacin 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 ITT 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 moxifloxacin response proportion) will be used to test for the NI of the omadacycline arm 
compared to the moxifloxacin arm.  The 95% CI will be calculated using the stratified (for the 
randomization stratification factors) method proposed by Miettinen and Nurminen.8  
Omadacycline will be considered non-inferior to moxifloxacin 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 of showing NI for an 
ineffective drug based on PTE efficacy is 2.5%, regardless of the result for the ECRendpoint and 
vice versa.  In addition, no alpha adjustment is needed for the co-primary efficacy endpoints for 
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the EMA (ITT and CE populations) since NI must be shown in both populations to conclude NI.  
Hence there will be no adjustment for multiple endpoints. 
12.6.4 
Additional Analyses of Primary Efficacy Outcomes 
Additional and sensitivity analyses of the primary efficacy outcomes (ECR and Investigator’s 
Assessment of Clinical Response at PTE) will be performed.  Analyses for the FDA primary 
outcome will be described here and in more detail in the SAP.  Analyses for the EMA primary 
outcome will be described in the SAP. 
If the null hypothesis of inferiority is rejected for the ECR in the ITT population and the 
observed success response proportion for omadacycline is larger than the observed proportion for 
moxifloxacin, a formal statistical analysis of superiority will be conducted.  If the lower limit of 
the 2-sided CI for the treatment difference is greater than 0%, omadacycline will be considered 
superior to moxifloxacin. 
The primary efficacy outcome will be assessed separately across the stratification factors of 
PORT Risk Class and receipt of allowed antibacterial therapy in the 72 hours prior to study 
treatment.  For each PORT Risk Class stratum and each prior antibacterial therapy stratum, a 
2-sided 95% CI for the observed difference in ECRsuccess rates will be calculated for the ITT 
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. 
12.7 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 ITT 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.8  
For Investigator’s Assessment of Clinical Response at PTE in the ITT and CE populations (FDA 
secondary outcome) the 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 
ECRwill be presented for the microITT 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 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.8 
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The number and percentage of subjects with an ECR of success and an Investigator’s 
Assessment of Clinical Response at PTE of Clinical Success by pathogen will be provided in the 
microITT and ME populations. 
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. 
12.8 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 a Clinical Success, Clinical Failure and 
Indeterminate by the Investigator’s Assessment at EOT in the ITT and CE populations (by 
definition, subjects with an Indeterminate response are excluded from the CE 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.8 
The number and percentage of subjects with stabilization of vital signs and clinical 
signs/laboratory findings associated with CABP at 72-120 hours post first dose of test article will 
be presented by treatment group in the ITT population.  These include body temperature (no 
fever or hypothermia), SBP (> 90 mm Hg), heart rate (< 90 bpm), RR (< 20 breaths/minute), 
PaO2 (≥ 60 mm Hg by ABG or oxygen saturation ≥ 90% by pulse oximetry), physical exam 
findings (no findings of pulmonary consolidation), WBC count (< 12,000 cells/mm3 or 
≥ 4,000 cells/mm3) or immature neutrophils (< 15%). 
A summary (number and percentage of subjects) of the assessment of clinical signs and 
symptoms of CABP at each time point throughout the study will be presented by treatment group 
in the ITT population.  The number and percentage of subjects with resolution of signs and 
symptoms present at Screening (back to pre-CABP status) will also be provided by study visit.  
The number and percentage of subjects with no worsening of clinical symptoms of CABP and 
with the absence of new symptoms of CABP will also be provided by treatment group in the ITT 
population. 
The per-subject and per-pathogen microbiologic outcomes will be provided for the microITT 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. 
At Screening and Final Follow-up visits, the subject will complete a SF-36v2® Health Survey 
(Medical Outcomes Trust, Optum™).  The SF-36v2® Health Survey has 8 subscales: physical 
functioning, bodily pain, role limitations due to physical health problems, role limitations due to 
personal or emotional problems, emotional well-being, social functioning, energy/fatigue and 
general health perceptions.  It also has a single item that provides an indication of perceived 
change in health. Physical and mental health composite scores (PCS and MCS) are computed 
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and range from 0 (lowest level of health measured by the scales) to 100 (highest level of health).  
Descriptive statistics for the total score, PCS and MCS will be provided at Screening, the Final 
Follow-up Visit and the change from baseline by treatment group in the Safety Analysis Set. 
12.9 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. 
12.9.1 
Adverse Events 
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, TEAEs 
leading to dose interruption of test article, and TEAEs of special interest. 
12.9.2 
Vital Signs 
The following variables will be analyzed descriptively: 
• Vital signs (systolic and diastolic BP, pulse rate, body temperature, RR) including change 
from Screening by visit 
• Clinically notable vital signs (meeting predefined criteria as specified in the SAP) by visit 
 
Subjects with notable vital signs data will be listed. 
12.9.3 
Electrocardiograms 
Electrocardiogram data (RR interval, PR interval, QRS interval, Corrected QT interval [QTc], 
QTc Bazzett’s Correction Formula [QTcB], and QTc Fridericia’s Correction Formula [QTcF]) 
will be summarized descriptively at each scheduled evaluation and for the overall worst post-
Screening value.  Changes from Screening at each visit will also be provided.  An outlier 
analysis will be conducted based on the worst post-Screening value. 
12.9.4 
Laboratory Tests 
The following variables will be analyzed descriptively: 
• Laboratory variables by visit 
• Change from Screening of laboratory variable by visit 
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• 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. 
12.10 Resource Utilization 
Data for resource utilization will be collected through the Final Follow up assessment and will 
include: 
• number of days in hospital from the time of initiation of therapy, initiation of second therapy, 
as well as from the first day in hospital to date of discharge for all subjects and by country 
(due to the varying clinical practices per country)  
• number of hospital re-admissions 
• duration (days) and number of doses on iv therapy (test article) 
• duration (days) and number of outpatient iv doses (test article) 
• duration (days) and number of doses on po therapy (test article) 
• number of ER/ED and physician visits 
 
Descriptive statistics for the resource utilization parameters will be provided by treatment group 
for the purpose of health economic evaluation. 
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12.12 Pharmacogenetics/Pharmacogenomics 
Pharmacogenetics/pharmacogenomics studies are not planned as part of this protocol. 
12.13 Biomarkers 
Not applicable. 
12.14 Pharmacokinetics/Pharmacodynamics 
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. 
12.15 Interim Analysis 
No interim analyses of efficacy are planned.  However, a DMC will review safety data (eg, AEs 
and SAEs, laboratory data, ECG, and vital signs assessments) while the study is ongoing (see 
Section 12.17). 
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12.16 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 outcome measure of ECR, if any data field needed 
to determine the response is missing the subject will be assigned an Indeterminate response.  
Subjects with an Indeterminate response are included in the denominator, and thus, are 
considered Clinical Failures.  A sensitivity analysis of the primary outcome of ECR will be 
conducted in which subjects with an Indeterminate response are considered Clinical Successes.   
For the EMA primary outcome measure of Investigator’s Assessment of Clinical Response at 
PTE in the ITT population (secondary outcomes for FDA), 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 6 provides a summary of the handling of 
missing/indeterminate outcomes for the Investigator’s Assessment of Clinical Response at PTE. 
Table 6 
Investigator’s Assessment of Clinical Response at PTE Determination Given 
Missing Data 
EOT Visit 
PTE Visit 
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 
For the analysis in the ITT analysis set of Investigator’s Assessment of Clinical Response at PTE, Indeterminate 
outcomes 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. 
EOT = end of treatment; ITT = intent-to-treat; PTE = post-therapy evaluation. 
 
12.17 Data Monitoring Committee 
A data monitoring committee (DMC) will provide ongoing monitoring of safety data. The 
charter for the DMC will clearly outline membership, all roles, responsibilities, and decision- 
making criteria. This will include a detailed description of the manner in which security and 
blinding of the data for the study management team will be maintained, in addition to the 
procedures that ensure the independence and objectivity of the DMC’s activities. As the DMC 
will be reviewing data for this study, it may require reports indicating treatment assignment to 
assist in clinical interpretation of its findings. Therefore, the DMC charter will provide a detailed 
explanation of the processes by which the DMC will obtain the information necessary for its 
operation that will not prejudice or create any potential source of bias in the conduct of the study. 
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12.18 Clinical Events Committee 
A clinical events committee (CEC) will adjudicate all deaths to ensure that they have been 
reported and assessed for relatedness uniformly using the same definition by experts who are 
blinded to the treatment status.  The charter for the CEC will outline membership, roles, 
responsibilities, and standardized definitions. This will include a detailed description of the way 
security and blinding of the data will be maintained. 
13 ADMINISTRATIVE CONSIDERATIONS 
13.1 Investigators and Study Administrative Structure 
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 solution including but not 
limited to storage for all study-related documents. Regulatory agencies will be notified with the 
appropriate documentation. 
An updated Form FDA 1572 will be filed with the sponsor for any changes in the study 
personnel reported in the current Form FDA 1572. 
13.2 Institutional Review Board or Independent Ethics Committee Approval 
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. 
13.3 Ethical Conduct of the Study 
This clinical study was designed and shall be implemented and reported in accordance with the 
ICH Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local 
regulations (including European Directive 2001/20/EC, US 21 Code of Federal Regulations 
[CFR], and Japanese Ministry of Health, Labor, and Welfare), and with the ethical principles laid 
down in the Declaration of Helsinki. 
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13.4 Patient Information and Consent 
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. 
 
13.5 Direct Access, Data Handling, and Record Keeping 
13.5.1 
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 FDA 1572 will be filed with the sponsor for any changes in the study 
personnel reported in the current Form FDA 1572. 
13.5.2 
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. 
13.6 Protocol Adherence 
13.6.1 
Violations/Deviations 
Investigators will agree to apply due diligence to avoid protocol deviations. Under no 
circumstances should the investigator contact the sponsor or its agents to request approval of a 
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prospective 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). 
13.6.2 
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. 
13.7 Subject Injury 
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. 
13.8 Pre-study Documentation 
The investigator must provide the sponsor with the following documents before enrolling any 
subjects: 
• Completed and signed Form FDA 1572 or equivalent. 
• 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 FDA 
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. 
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• 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. 
 
13.9 Retention of Data 
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. 
13.10 Publication and Disclosure Policy 
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 
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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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14 REFERENCE LIST 
1 
Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, et al. 
Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines 
on the Management of Community-Acquired Pneumonia in Adults. Clin Infect Dis. 2007; 
44:S27-S72. 
2 
Niederman MS, McCombs JS, Unger AN, Kumar A, Popovian R. The cost of treating 
community-acquired pneumonia. Clin Ther. 1998; 20(4):820-37. 
3 
Spellberg et al. The Epidemic of Antibiotic-Resistant Infections: A Call to Action for the 
Medical Community from the Infectious Diseases Society of America. CID.  2008; 46:155-
64. 
4 
Paterson DL. "Collateral damage" from cephalosporin or quinolone antibiotic therapy. Clin 
Infect Dis. 2004; 38 Suppl 4:S341-5. 
5 
NUZYRA® (omadacycline) USPI. 
6 
FDA. Guidance for Industry, Community-Acquired Bacterial Pneumonia: Developing 
Drugs for Treatment. 2014 CDER. 
7 
EMA. 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. 
2013. EMA/CHMP/351889/2013. 
8 
Miettinen O, Nurminen M. Comparative analysis of two rates. Statistics in Medicine.  
1985; 4:213-26. 
9 
FDA. Guidance for Industry, Population Pharmacokinetics. 1999 CDER. 
10     Fine MJ, et al.  A Prediction Rule to Identify Low-Risk Patients with Community-Acquired 
Pneumonia.  New England Journal of Medicine.  1997; 336(4): 243-250 
 
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Schedule of Events 
 
Study Phase 
Screeningb 
iv 
Treatment 
iv or po Treatment 
EOT and Follow-upf 
Study Daya 
-1 
1 
2 
3 
4 
inpatient 
only 
5 
6 
inpatient 
only 
7 d 
8 
9 
10 
11 
12 
13 
EOTe 
PTE 
FFUf 
inpatient 
only 
inpatient only 
 
ECR visit 
must occur 72 
to 120 hours 
after first dose 
c 
 
Perform only if study treatment is 
continuing and this is not the EOT 
visit. Treatment past 10 days is 
allowed for subjects with bacteremia at 
Screening. 
5 to 10 
days after 
last day 
of   
therapy 
30 to 
37 days 
after 
Day 1 
Screening and eligibility procedures 
Signed informed consentg 
X 
Medical history, current medical 
conditions, demography 
X 
Assessment of CABP symptom 
severityh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chest X-ray or CT scani 
X 
PORT risk class, ABG (or pulse 
oximetry)j 
X 
Sample collection for local SARS- 
CoV-2 molecular testing 
X 
Blood and urine samples for local lab 
hematology/chemistry/pregnancyk 
X 
SF-36v2® Health Survey 
X 
 
X 
Review of Inclusion/Exclusion criteria 
X 
Randomization (if Eligible) 
X 
Clinical Procedures and Test Article Administration 
Test article administration and 
accountabilityl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examinationm 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsn 
X 
Xo 
Xo 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECGw 
X 
X 
Blood for central lab tests: 
hematology/chemistry/pregnancy 
Xp 
X 
Xp 
Xp 
AEs, SAEs, and mortalityq 
X 
X  
X 
Prior & concomitant medicationsr 
X 
X  
X 
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Plasma samples (in heparin) for PK 
analysess 
X 
X 
Study Phase 
Screeningb 
iv 
Treatment 
iv or po Treatment 
EOT and Follow-upf 
Study Daya 
-1 
1 
2 
3 
4 
inpatient 
only 
5 
6 
inpatient 
only 
7 d 
8 
9 
10 11 
12 
13 
EOTe 
PTE 
FFUf 
inpatient only
inpatient only 
Assessment for po switch or need for 
continued therapyt 
X ---------------------------------------------------------------------- X 
Investigator’s Assessment of Clinical 
Response 
X 
X 
 
Assessment of Resource Utilization 
X  
X 
Microbiological Procedures 
Blood cultureu 
X 
As Clinically Indicated 
Respiratory culture & Gram stainv 
X 
X 
X 
Urine for Local lab Legionella 
pneumophila and Streptococcus 
pneumoniae antigen test 
X 
Blood for Central lab Legionella 
pneumophila, Mycoplasma 
pneumoniae & Chlamydophila 
pneumoniae serology 
X 
X 
ABG = arterial blood gas, AE = adverse event, BP = blood pressure, β-hCG = beta-human Chorionic Gonadotropin, CABP = community-acquired bacterial 
pneumonia, CT = computed tomography, CXR = chest X-ray, ECG = electrocardiogram, ECR = Early Clinical Response, eCRF = electronic case report form, EOT 
= end of treatment, FFU = final follow-up, ICF = informed consent form, iv = intravenous, IxRS = interactive voice/web response system, 
PK = pharmacokinetics, po = per oral, PORT = Pneumonia Patient Outcomes Research Team, PTE = post-therapy evaluation, RR = respiratory rate, SAE = serious 
adverse event. 
a Study Day 1 is the first day of test article administration. Subsequent study days may be consecutive calendar days. 
b Following the signing of an ICF, all Screening evaluations (except radiographic confirmation of pneumonia and blood cultures in some cases), should be completed 
within the 24 hours prior to randomization. The radiographic confirmation of pneumonia should be completed within the 48 hours prior to the first dose of test 
article.  The blood cultures should be collected within 24 hours prior to the first dose of test article. 
c The ECR visit must be conducted within 72 to 120 hours after the first dose of test article; the study day for this visit could be on Days 4, 5, or 6, depending on 
the time of the first dose of test article. Subjects who remain hospitalized (inpatients) during study treatment will have daily assessments. For subjects who 
are not hospitalized, only 1 visit is required between Study Days 4 to 6. 
d If the investigator determines that no additional treatment is required beyond Day 7, the Day 7 visit can be considered the EOT visit and a separate EOT visit is 
not required. 
e To be conducted on the day of, or within 2 days following the last dose of test article. Should also be conducted for any prematurely withdrawn subject on the 
day of, or within 2 days following the last dose of test article. 
f 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 ongoing AEs, clinically significant laboratory findings or ECG abnormalities noted at or after the PTE visit. Otherwise, the visit must 
be conducted in person.  Home nursing can be considered for EOT, PTE, and in person FFU visits, if deemed necessary and approved by Sponsor. 
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g Written and signed ICF must be obtained before any study assessment is performed. 
h The investigator should assess the severity of the subject’s CABP symptoms of cough, sputum production, pleuritic chest pain, and dyspnea based upon 
the Community-Acquired Bacterial Pneumonia Subject Symptom Severity Guidance Framework for Investigator Assessment (Appendix 3). 
i Subjects must have a confirming CXR or CT scan consistent with acute bacterial pneumonia within the 48 hours prior to the first dose of test article. 
j Only subjects with a PORT Risk Class of III or IV are eligible for enrollment. 
k Local laboratory hematology and chemistry evaluations required for assessing subject eligibility.. 
l Subjects should receive their first dose of test article within 4 hours after randomization. The total duration of test article therapy (iv plus po) for all subjects 
will be 7-10 days (up to 14 days for subjects with bacteremia identified at Screening). The pharmacist or designee will be unblinded to prepare 
appropriate iv doses of the IxRS identified test article. An unblinded field monitor will perform drug accountability and review the pharmacist’s records. 
Oral test article may be dispensed and reconciled by blinded or unblinded personnel. All oral doses should be taken in a fasted state (no food, antacids or 
multivitamins containing multivalent cations [eg, aluminum, magnesium, calcium, bismuth, iron, or zinc] or drink except water for at least 4 hours 
before dosing). After dosing, no food is permitted for 2 hours as well as no dairy products, antacids, or multivitamins containing multivalent cations (eg, 
aluminum, magnesium, calcium, bismuth, iron, or zinc) for 4 hours. Subjects discharged with po test article will be asked to return all unused test article 
and packaging at each visit. At the EOT visit subjects discharged with po test article will return any remaining unused po test article and site staff will 
perform accountability. 
m A full physical examination will be completed at Screening. Thereafter, abbreviated physical examinations may be performed at the indicated timepoints. 
       Additional physical examinations may be performed as clinically indicated. 
n Vital signs include body temperature, BP, pulse oximetry, heart rate, and RR. 
o Blood pressure and heart rate should be measured within 30 minutes before, and approximately 1 hour (± 15 minutes) after the completion of the infusions 
on Day 1 and Day 2. 
p Blood will be collected from all female subjects for a serum β-hCG pregnancy test at the Central Laboratory at the Screening, EOT and PTE visits. 
q AEs and SAEs will be recorded from the time of signing of the ICF to the Final Follow-up assessment. 
r Medications administered within the 7 days prior to the date of signing the ICF or during the Screening phase will be recorded in the eCRF, as will all 
medications and significant non-drug therapies administered after the first dose of test article. 
s PK sample collection to occur on Day 1 (2 to 3 hours after the start of Dose 1) and at the ECR visit (Days 4 to 6; at any time during the visit). 
t At any time after the second day of iv treatment (Day 2), the subject may be switched to po medication based upon determination of clinical stability. Refer 
to Section 7.6.5 for required criteria to switch to po treatment. The first po dose should be administered in the morning, 12-24 hours after the last iv dose. 
Test article administration and total duration of study treatment are outlined in footnote l. 
u If bacteria are isolated from baseline blood cultures, repeat blood cultures must be collected on the day that the positive blood culture is detected. If subsequent 
blood cultures are also positive, repeat the blood cultures as necessary until negative blood cultures are obtained. 
v Culture and Gram stain from an adequate quality sputum specimen or other respiratory specimen. At the EOT and/or PTE visit, respiratory specimen cultures 
and Gram stains should be obtained only for subjects who are Clinical Failures and require alternative antibacterial treatment for CABP. 
w Additional ECGs can be performed as clinically indicated, at the discretion of the investigator. 
 
 
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Equations and Conversion Factors 
1. Cockcroft-Gault equation to calculate creatinine clearance (CrCl) (relevant to 
Exclusion Criterion number 9): 
 
(140-age [yrs]) * weight (kg) * (Z) 
Z = 1.0, if Male 
Z = 0.85, if Female 
Cr (mg/dL) * 72 
2. Corticosteroid conversions (relevant to Exclusion Criterion number 11): 
 
 
The following have equivalent glucocorticoid activitya 
Hydrocortisone 
160 mg 
Prednisone 
40 mg 
Prednisolone 
40 mg 
Methylprednisolone 
32 mg 
Triamcinolone 
32 mg 
Dexamethasone 
6 mg 
a 
Axelrod L. Glucocorticoid therapy. In: Jameson JL & De Groot LJ, eds. Endocrinology. 6th ed. 
 
Philadelphia, PA:  Saunders; 2010:1840. 
 
 
 
 
 
 
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Community-acquired Bacterial Pneumonia Subject Symptom 
Severity Guidance Framework for Investigator Assessment 
COUGH? 
Absent 
Mild 
Moderate 
Severe 
No cough or 
resolution (to pre- 
CABP Baseline) 
Cough present but it 
does not interfere 
with subject’s usual 
daily activities 
Cough present, 
frequent and it does 
interfere with some 
of the subject’s 
usual daily activities 
Cough is present 
throughout the day 
and night; it limits 
most of the subjects’ 
usual daily activities 
and sleep patterns 
PLEURITIC CHEST 
PAIN? 
Absent 
Mild 
Moderate 
Severe 
Chest pain present 
Chest pain is present 
with normal breaths 
and it does interfere 
with the subject’s 
usual daily activities 
Chest pain is present 
No chest pain or 
occasionally with 
at rest and/or with 
resolution of chest deep breathing but it 
shallow breathing; it 
pain related to 
does not interfere 
limits most of the 
CABP 
with subject’s usual 
subject’s usual daily 
daily activities 
activities 
SHORTNESS OF 
BREATH? 
Absent 
Mild 
Moderate 
Severe 
Shortness of breath 
Shortness of breath 
with usual activities 
and it does interfere 
with the subject’s 
usual daily activities 
Shortness of breath 
No shortness of 
with strenuous 
with minimal 
breath or 
activities only but it 
exertion or at rest; it 
resolution (to pre- 
does not interfere 
limits most of the 
CABP Baseline) 
with subject’s usual 
subject’s usual daily 
daily activities 
activities 
PHLEGM/SPUTUM 
PRODUCTION? 
Absent 
Mild 
Moderate 
Severe 
No coughing up of 
phlegm/sputum or 
resolution (to pre- 
CABP Baseline) 
Subject coughs up a 
small amount of 
phlegm/sputum 
Subject coughs up a 
moderate amount of 
phlegm/sputum 
Subject coughs up a 
large amount of 
phlegm/sputum 
CABP = community-acquired bacterial pneumonia 
 
 
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Allowed and Disallowed Prior Antibiotics 
Allowed Antibiotics 
(1 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 more than 1 dose 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 (capped at 25% of randomized subjects). For the purposes of this protocol, short-acting is 
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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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PORT Risk Class Calculation 
Adapted from Fine et al 1997*. 
PORT Risk Class Calculation Worksheet 
Subject Characteristic 
Point Assignment 
Number of Points 
Added (+0, +10, +20, 
etc.) 
DEMOGRAPHICS 
Male 
Age (years) 
Number of Years: 
 
Female 
Age (years) -10 
Number of Years – 10: 
 
Nursing home resident1 
 
+10 
Exclusionary per this 
protocol 
 
Sum of numbers in DEMOGRAPHICS: 
 
 
 
 
COEXISTING ILLNESSES 
Neoplastic disease2  
Potentially exclusionary per this protocol 
+30 
 
Liver disease3  
Potentially exclusionary per this protocol 
+20 
 
Congestive heart failure4 
Potentially exclusionary per this protocol 
+10 
 
Cerebrovascular disease5 
 
+10 
 
Renal disease6 
Potentially exclusionary per this protocol 
+10 
 
 
Sum of numbers in COEXISTING ILLNESSES: 
 
 
 
 
PHYSICAL EXAMINATION FINDINGS 
Altered mental status7 
 
+20 
 
Respiratory rate ≥30/minute 
+20 
 
 
Systolic blood pressure <90 mm Hg 
+20 
 
 
Temperature <35oC (95oF) or ≥40oC 
(104oF) 
+15 
 
 
Pulse ≥125/minute 
+10 
 
 
 
Sum of numbers in PHYSICAL EXAMINATION FINDINGS: 
 
 
 
 
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LABORATORY AND RADIOGRAPHIC FINDINGS 
Arterial pH <7.358 
+30  
 
 
Blood urea nitrogen ≥30 mg/dL (11 
mmol/L)6  
+20 
 
 
Sodium <130 mmol/L 
+20 
 
 
Glucose ≥250 mg/dL (14 mmol/L)  
+10 
 
 
Hematocrit <30% 
+10 
 
 
Partial pressure of arterial oxygen <60 mm 
Hg or oxygen saturation <90% (by pulse 
oximetry)  
+10 
 
 
Pleural effusion 
+10 
 
 
 
Sum of numbers in LABORATORY AND RADIOGRAPHIC 
FINDINGS: 
 
 
 
 
PORT Score 
Sum of numbers in 
shaded boxes above: 
 
 
 
 
PORT Risk Class 
PORT Score 
I (ineligible for study) 
0-50 
II (ineligible for study) 
51-70 
III 
71-90 
IV 
91-130 
V (ineligible for study) 
≥131 
 
Before you proceed with signing this form, please use medical records and check yourself with online 
PORT risk class calculator:  
https://qxmd.com/calculate/calculator_248/pneumonia-severity-index-port-score 
 
Name:  
Signature:  
Date: 
 
Time: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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1. A nursing home is defined as any residence that provides 24-hour medical 
supervision.  Subjects who reside in a long-term care or subacute/intermediate 
healthcare facility (eg, nursing home) are excluded from the study and should 
not be enrolled per Exclusion Criterion number 5. 
2. Neoplastic disease is defined as any cancer, except basal or squamous cell 
cancer of the skin that was active at the time of presentation or diagnosed 
within one year of presentation.  Subjects with neoplastic lung disease are 
excluded from the study and should not be enrolled per Exclusion Criterion 
number 15; and subjects who received cancer chemotherapy, radiotherapy, or 
potent, non-corticosteroid immunosuppressant drugs within the past 3 months 
should not be enrolled per Exclusion Criterion number 11. 
3. Liver disease is defined as a clinical or histologic diagnosis of cirrhosis or 
another form of chronic liver disease, such as chronic active hepatitis.  Subjects 
with cirrhosis that would preclude use of systemic fluoroquinolone antibiotic 
should not be enrolled per Exclusion Criterion number 8. 
4. Congestive heart failure is defined as systolic or diastolic ventricular 
dysfunction documented by history, physical examination, and chest 
radiograph, echocardiogram, multiple gated acquisition scan, or left 
ventriculogram.  Subjects with unstable cardiac disease (including acute 
congestive heart failure) within the 3 months prior to Screening should not be 
enrolled per Exclusion Criterion number 6.  
5. Cerebrovascular disease is defined as a clinical diagnosis of stroke or transient 
ischemic attack or stroke documented by magnetic resonance imaging or CT.   
6. Renal disease is defined as a history of chronic renal disease or abnormal blood 
urea nitrogen and creatinine concentrations documented in the medical record.  
Subjects with history or evidence of severe renal disease or who have a 
calculated creatinine clearance (CrCl) of < 30 mL/minute, or who require any 
form of dialysis should not be enrolled per Exclusion Criterion number 9. 
7. Altered mental status is defined as disorientation with respect to person, place, 
or time that is not known to be chronic, stupor, or coma.   
8.  In cases where the arterial blood gas (ABG) test is not collected as part of 
hospital routine, no points should be added during PORT score calculation. If 
ABG test results are available, please ensure that arterial pH value is taken into 
account for PORT risk class calculation. 
 
 
 
 
 
 
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Sponsor Signature 
 
Study Title: 
A Phase 3b Randomized, Double-Blind, Multi-Center Study to 
Compare the Safety and Efficacy of IV/PO Omadacycline to IV/PO 
Moxifloxacin for Treating Adult Subjects with Community- Acquired 
Bacterial Pneumonia (CABP) 
Study Number: PTK0796-CABP-19302 
Final Date: 
19- November-2020 
 
 
This clinical study protocol was subject to critical review and has been approved by the 
sponsor.  The following personnel contributed to writing and/or approving this protocol: 
 
Signed:  
Date: 
 
 
 MD 
VP, Medical and Scientific Strategy 
 
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 Investigator’s Signature 
 
 
 
Study Title: 
A Phase 3b Randomized, Double-Blind, Multi-Center Study to 
Compare the Safety and Efficacy of IV/PO Omadacycline to 
IV/PO Moxifloxacin for Treating Adult Subjects with 
Community-Acquired Bacterial Pneumonia (CABP) 
Study Number: 
PTK0796-CABP-19302 
Final Date: 
19-November-2020 
 
 
I have read the protocol described above. I agree to comply with all applicable 
regulations and to conduct the study as described in the protocol. 
 
 
 
 
Signed:  
Date: 
 
 
Investigator Name:  
 
 
Investigator Title:  
 
  
Investigator Affiliation:  
  
Investigator Address:  
   
Investigator Phone Number:  
 
  
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SAP_001.pdf: 
Omadacycline 
Paratek Pharma, LLC 
Clinical Study Report:  PTK0796-CABP-19302 
 
 
 
Confidential and Proprietary  
 
16.1.9 Statistical Analysis Plan and Associated Document 
 
 
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Statistical Analysis Plan:  PTK0796-CABP-19302  
Study Title: 
A Phase 3b Randomized, Double-Blind, Multi-
Center Study to Compare the Safety and 
Efficacy of Omadacycline IV/PO to 
Moxifloxacin IV/PO for Treating Adult 
Subjects with Community-Acquired Bacterial 
Pneumonia (CABP) 
Study Number: 
PTK0796-CABP-19302 
Study Phase:  
3b 
Sponsor: 
Paratek Pharmaceuticals, Inc. 
75 Park Plaza, 4th Floor  
Boston, MA 02116  
 
1000 First Ave  
Suite 200  
King of Prussia, PA 19406  
Tel:  +1 617-275-0040 
Version: 
5.0 (Final) 
Date: 
28-MAY-2024 
 
 
 
 
 
 
 
 
 
Confidentiality Statement 
This document contains confidential and proprietary information, and is not to 
be distributed to any third party. 
 
 
 
 
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APPROVALS  
Authors: 
 
 Clinical Operations 
 
 Clinical Microbiology 
 
 Biostatistics 
 
 
Vice President of Clinical & Medical 
Operations: 
Signature / Date: 
 
 
 
 
 
Medical Monitor: 
 
 
Signature / Date: 
 
 
 
Executive Director of Microbiology 
and Nonclinical Development: 
Signature / Date: 
 
 
 
 
 
 
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1 
TABLE OF CONTENTS 
APPROVALS ............................................................................................................................2 
1 
TABLE OF CONTENTS ...................................................................................................3 
LIST OF TABLES .....................................................................................................................5 
LIST OF APPENDICES ............................................................................................................5 
2 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS ....................................6 
3 
INTRODUCTION .............................................................................................................8 
4 
TRIAL OBJECTIVES .......................................................................................................9 
4.1 
Primary Objectives...................................................................................................9 
4.2 
Secondary Objectives...............................................................................................9 
5 
STUDY DESIGN CONSIDERATIONS .........................................................................10 
5.1 
Study Design ..........................................................................................................10 
5.1.1 
Sample Size ..................................................................................................11 
5.1.2 
Randomization and Masking .......................................................................12 
5.2 
Efficacy Measures ..................................................................................................12 
5.2.1 
Primary Efficacy Outcome ..........................................................................12 
5.2.1.1 
Estimand Framework .........................................................................14 
5.2.2 
Secondary Efficacy Outcomes .....................................................................15 
5.2.2.1 
Investigators Assessment of Clinical Response .................................15 
5.2.2.2 
Estimand Framework for Investigators Assessment of Clinical 
Response ............................................................................................17 
5.2.2.3 
Microbiologic Outcomes ...................................................................18 
5.3 
Safety Measures .....................................................................................................21 
5.4 
Pharmacokinetic Parameters ..................................................................................21 
6 
ANALYSIS POPULATIONS .........................................................................................22 
6.1 
Analysis Populations ..............................................................................................22 
6.1.1 
Intent-to-Treat (ITT) Population ..................................................................22 
6.1.2 
Safety Population .........................................................................................22 
6.1.3 
Microbiological Intent-to-Treat (microITT) Population ..............................22 
6.1.4 
Clinically Evaluable (CE) Populations ........................................................25 
6.1.4.1 
Diagnosis of CABP ............................................................................25 
6.1.4.2 
Prior Antibiotic Therapy ....................................................................26 
6.1.4.3 
Concomitant Antibiotic Therapy .......................................................27 
6.1.4.4 
Test Article Therapy ..........................................................................27 
6.1.4.5 
Clinical Outcome Assessment ...........................................................28 
6.1.4.6 
Baseline Medical Events ....................................................................28 
6.1.5 
Microbiologically Evaluable (ME) Populations ..........................................29 
6.2 
Evaluability Review Team .....................................................................................29 
6.2.1 
Membership and Responsibilities ................................................................29 
6.2.2 
Process for Determining Inclusion in Populations.......................................29 
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6.3 
Subgroups ..............................................................................................................30 
7 
OVERALL STATISTICAL CONSIDERATIONS .........................................................31 
7.1 
General Conventions ..............................................................................................31 
7.2 
Baseline Definition ................................................................................................31 
7.3 
Handling of Missing Data ......................................................................................32 
7.4 
Interim Analysis .....................................................................................................33 
7.5 
Pooling Strategy for Study Sites ............................................................................33 
7.6 
Visit Windows/Unscheduled Visits .......................................................................33 
8 
STATISTICAL ANALYSIS METHODS .......................................................................35 
8.1 
Subject Disposition ................................................................................................35 
8.2 
Demographics and Baseline Characteristics ..........................................................35 
8.2.1 
Microbiology................................................................................................37 
8.3 
Treatment Compliance and Exposure ....................................................................39 
9 
EFFICACY PARAMETERS ...........................................................................................40 
9.1 
Primary Analysis ....................................................................................................40 
9.2 
Sensitivity and Additional Analyses of the Primary Efficacy Outcome ................41 
9.3 
Secondary Analysis ................................................................................................42 
9.4 
Additional Analyses ...............................................................................................43 
9.5 
Interim Analysis .....................................................................................................45 
9.6 
Subgroup Analyses ................................................................................................45 
10 SAFETY AND TOLERABILITY ...................................................................................46 
10.1 
Adverse Events ......................................................................................................46 
10.2 
Vital Signs ..............................................................................................................47 
10.3 
Electrocardiogram ..................................................................................................47 
10.4 
Laboratory Values ..................................................................................................48 
10.5 
Physical Examinations ...........................................................................................50 
11 RESOURCE UTILIZATION ANALYSES ....................................................................51 
12 OTHER RELEVANT DATA ANALYSES/SUMMARIES ...........................................52 
12.1 
Protocol Deviations ................................................................................................52 
12.2 
Prior and Concomitant Medications ......................................................................52 
13 REFERENCES ................................................................................................................53 
14 APPENDICES .................................................................................................................54 
 
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LIST OF TABLES  
Table 3. 
Community-Acquired Bacterial Pneumonia Subject Symptom Severity 
Guidance Framework for Investigator Assessment .........................................13 
Table 4. 
Investigator's Assessment of Clinical Response ..............................................17 
Table 5. 
Per-Pathogen Microbiological Response Definitions at the EOT and PTE 
Visits ................................................................................................................18 
Table 6. 
Per-Pathogen Microbiologic Response ............................................................19 
Table 7. 
Microbiological Response Definitions:  Superinfection or New Infection .....20 
Table 8. 
Scheduled Study Visits ....................................................................................34 
Table 9. 
Criteria for Treatment Emergent Clinically Notable Vital Signs ....................47 
Table 10. 
Laboratory Parameters and Organ Class..........................................................48 
 
LIST OF APPENDICES  
Appendix 1 
Schedule of Assessments and Procedures........................................................55 
Appendix 2 
Summary of Efficacy Analyses .......................................................................58 
Appendix 3 
Adverse Event and Prior/Concomitant Medication Date Imputations ............59 
Appendix 4 
Directionality of Worst Laboratory Parameters ...............................................60 
Appendix 5 
Modified Division of Microbiology and Infectious Diseases Adult 
Toxicity Table ..................................................................................................61 
 
 
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2 
LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS  
ACM 
all-cause mortality 
AE 
adverse event 
BMI 
body mass index 
CABP 
community-acquired bacterial pneumonia 
CE 
clinically evaluable 
CN 
clinically notable 
CT 
computed tomography 
CXR 
chest X-ray 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
ECR 
Early Clinical Response 
EMA 
European Medicines Agency 
EOT 
End of Treatment 
FDA 
Food and Drug Administration 
IND 
Investigational New Drug  
IV 
Intravenous 
IxRS 
Interactive Response System 
lpf 
Low Power Field 
ME 
microbiologically evaluable 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
MIC 
minimum inhibitory concentration 
MRSA 
Methicillin-Resistant Staphylococcus aureus 
NI 
non-inferiority 
PORT 
Pneumonia Outcomes Research Team 
PK 
Pharmacokinetic 
PO 
Orally 
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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 
SAS  
Statistical Analysis Software 
spp 
species (plural) 
SIRS 
Systemic Inflammatory Response Syndrome 
TEAE 
treatment emergent adverse event 
UAT  
urinary antigen test 
ULN 
upper limit of normal 
US 
United States 
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3 
INTRODUCTION  
This document presents the Statistical Analysis Plan (SAP) for the protocol 
PTK0796-CABP-19302, “A Phase 3b Randomized, Double-Blind, Multi-Center Study to 
Compare the Safety and Efficacy of Omadacycline IV/PO to Moxifloxacin IV/PO for 
Treating Adult Subjects with Community-Acquired Bacterial Pneumonia (CABP) Version 
5.0 Dated 19-November-2020.”  The statistical plan described is an a priori plan and no 
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-CABP-19302.   
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 5 to 10 days after the last dose 
of test article) as the primary endpoint, the FDA guidelines require using an earlier primary 
endpoint ( 72-120 hours after the first dose of test article) based on improvement in 
pneumonia symptoms.   
 
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4 
TRIAL OBJECTIVES  
4.1 
Primary Objectives  
The primary objective of this study is: 
 To demonstrate that iv to po omadacycline is non-inferior to iv to po moxifloxacin in the 
treatment of adults with PORT Risk Class III and IV CABP. 
4.2 
Secondary Objectives  
The secondary objectives are as follows: 
• To evaluate the safety of omadacycline in the treatment of adult subjects with CABP in 
the Safety population. 
• To evaluate the Clinical Response (Early Clinical Response [ECR] and investigator 
assessment of response) according to the identified causative pathogen. 
• To evaluate the pharmacokinetics (PK) of omadacycline in adult subjects with CABP. 
 
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5 
STUDY DESIGN CONSIDERATIONS  
5.1 
Study Design  
This is a randomized (1:1), active comparator controlled, double-blind, Phase 3 study 
comparing omadacycline and moxifloxacin in the treatment of adults with CABP (PORT 
Risk Class III and IV). Both iv and po phases of the study will be double-blind. 
Approximately 670 subjects will be enrolled at approximately 75 sites globally. 
Subjects will participate in the study for up to 37 days. Following a Screening period of up to 
24 hours, eligible subjects will be randomized to receive treatment. Subjects will be stratified 
by PORT Risk Class (III or IV) at Screening. 
Eligible subjects with a PORT Risk Class III or IV will be randomized to receive 7 to 10 
days of iv treatment with the option to switch to po treatment beginning on Day 3. Subjects 
with bacteremia identified at Screening can receive up to 14 days of treatment. 
Switch to po will NOT be permitted until after the subject has completed at least 2 days of iv 
treatment. The decision to switch to po treatment will be made by the investigator; the 
subject should be considered clinically stable and meet all criteria for transition to a po 
regimen. Specifically, the subject must meet the following requirements, and this should be 
noted in source documents and recorded on the electronic case report form (eCRF): 
 Temperature ≤ 37.8°C (100°F) 
 Heart rate ≤ 100 beats/minute 
 Respiratory rate (RR) ≤ 24 breaths/minute 
 Systolic blood pressure (SBP) ≥ 90 mm Hg 
 Oxygen saturation ≥ 90% as measured by pulse oximetry or partial pressure of arterial 
oxygen (PaO2) ≥ 60 mm Hg by arterial blood gas (ABG) 
 Normal (“absence of confusion”) or return to baseline mental status 
 Ability to maintain po intake. 
Eligible subjects will be randomized to one of the following treatment groups: 
Study Day 
Study Day 
Study Days 
Group 
Test Article 
1 
2 
3 to 10a 
1 
Omadacycline 
200 mg iv QD or 
100 mg iv BID 
100 mg iv 
100 mg iv or 300 mg po 
2 
Moxifloxacin 
400 mg iv 
400 mg iv 
400 mg iv or 
400 mg po 
BID = twice a day dosing, iv = intravenous, po = per oral, PORT = pneumonia patient outcomes research 
team, QD = once a day dosing. 
a 
The total duration of treatment for subjects is 7-10 days, with up to 14 days of treatment for subjects 
with bacteremia. 
 
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Subjects will return to the study site for a Post Therapy Evaluation (PTE) 5 to 10 days after 
the last dose of test article. A Final Follow-up visit (Final Follow-up) will be conducted 
within 30 to 37 days following 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 Success in the opinion of the investigator at end of 
treatment (EOT) and PTE and had no adverse events (AEs) or clinically significant 
laboratory or electrocardiogram (ECG) abnormalities noted at or after the PTE visit. 
Otherwise, this assessment is to be performed with an in-person study visit. 
 
A detailed Schedule of Study Procedures is provided in Appendix 1.  
5.1.1 
Sample Size  
Table 1 provides a summary of clinical success rates in the omadacycline CABP-1200 
study at ECR and PTE in the PORT Risk Class III and IV subjects. 
 
Table 1. 
Clinical Success Rates in CABP-1200 at ECR and PTE in PORT III and IV 
Subjects 
Outcome 
Omadacycline 
n/N1 (%) 
 
Moxifloxacin
n/N1 (%) 
ECR Success  - ITT 
270/329 (82.1) 
279/331 (84.3) 
PTE Success - ITT 
291/329 (88.4) 
282/331 (85.2) 
PTE Success - CE 
273/295 (92.5) 
268/296 (90.5) 
CABP = community-acquired bacterial pneumonia, ECR = Early Clinical Response, PTE = post-therapy 
evaluation, ITT = Intent to treat, CE = Clinically evaluable. 
 
The primary efficacy outcome for the FDA is ECR at 72-120 hours following the first dose 
of test article in the ITT population.  An NI margin of 10% will be used for the analysis in 
the ITT population. The NI margin was based on an analysis of historical data regarding 
the treatment effect of antibiotics in pneumonia.  Based on data from study CABP-1200, it 
is reasonable to assume the rate of ECR success will be approximately 80% in both 
treatment groups.  With a NI margin of 10%, 1-sided alpha level of 0.025 and 90% power, 
and using the sample size determination method of Farrington and Manning, a total of 670 
subjects are required. 
 
For the Investigator's Assessment of Clinical Response at PTE endpoint (EMA co-primary 
endpoint) with 670 subjects in the ITT population, assuming an outcome rate of 85% in 
both treatment groups, NI margin of 10% and 1-sided alpha level of 0.025, there is 94.7% 
power to show NI.  Assuming the evaluability rate for the CE population is 80%, an 
outcome rate of 89% in both treatment groups, NI margin of 10% and 1-sided alpha level 
of 0.025, there is 94.9% power to show NI in the CE population. 
 
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Thus, 670 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 2. 
 
Table 2  Sample Size and Power Calculations 
 
Primary Outcome FDA 
(Early Clinical Response) 
Primary Outcome EMA (Investigator’s 
Assessment of Clinical Response at PTE) 
Population 
ITT 
ITT 
CE 
NI Margin 
10% 
10% 
10% 
Evaluability Rate 
N/A 
N/A 
80% 
Outcome Rate 
80% 
85% 
89% 
N 
670 
670 
536 
Power 
89.6% 
94.7% 
94.9% 
CE = clinically evaluable; ITT = intent-to-treat;  N = number; N/A = not applicable; NI = 
non-inferiority; PTE = post-therapy evaluation. 
 
Assuming the microbiological evaluability rate is 30%, a total of 201 subjects are 
expected to be in the microbiological intent-to-treat (micro-ITT) population. 
 
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 2 treatment arms omadacycline or moxifloxacin (in a 1:1 ratio).  The 
site delegate will contact the IxRS (via web) after confirming that the subject fulfills all the 
inclusion criteria and has 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 PORT Risk Class (III and IV) and receipt 
of an allowed antibacterial therapy in the 72 hours prior to study treatment (yes and 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 (ie, completes a randomization transaction), regardless of whether the subject 
actually receives any medication.  Randomization of subjects who have received an allowed 
antibacterial therapy in the 72 hours prior to study treatment will be capped at 25% of the 
total number of subjects randomized.   
5.2 
Efficacy Measures  
5.2.1 
Primary Efficacy Outcome  
The primary efficacy outcome is the determination of the response to therapy at the Early 
Clinical Response (ECR) assessment (72 to 120 hours after administration of the first dose of 
test article) and will be determined programmatically using the investigator’s assessment of 
the subject’s symptoms associated with CABP entered into the electronic case report form 
(eCRF).  The severity of the subject's CABP symptoms of cough, sputum production, 
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pleuritic chest pain, and dyspnea will be evaluated on a 4-point scale (absent, mild, moderate, 
or severe) based upon the Community-Acquired Bacterial Pneumonia Subject Symptom 
Severity Guidance Framework for Investigator Assessment in Table 3. 
Table 3. 
Community-Acquired Bacterial Pneumonia Subject Symptom Severity 
Guidance Framework for Investigator Assessment  
COUGH? 
Absent 
Mild 
Moderate 
Severe 
No cough or 
resolution (to 
pre-CABP 
Baseline) 
Cough present but 
it does not interfere 
with subject’s usual 
daily activities 
Cough present, 
frequent and it does 
interfere with some 
of the subject’s 
usual daily 
activities 
Cough is present 
throughout the day 
and night; it limits 
most of the 
subjects’ usual 
daily activities and 
sleep patterns 
PLEURITIC 
CHEST PAIN? 
Absent 
Mild 
Moderate 
Severe 
No chest pain or 
resolution of chest 
pain related to 
CABP 
Chest pain present 
occasionally with 
deep breathing but 
it does not interfere 
with subject’s usual 
daily activities 
Chest pain is 
present with normal 
breaths and it does 
interfere with the 
subject’s usual 
daily activities 
Chest pain is 
present at rest 
and/or with shallow 
breathing; it limits 
most of the 
subject’s usual 
daily activities 
SHORTNESS OF 
BREATH? 
Absent 
Mild 
Moderate 
Severe 
No shortness of 
breath or resolution 
(to pre-CABP 
Baseline) 
Shortness of breath 
with strenuous 
activities only but it 
does not interfere 
with subject’s usual 
daily activities 
Shortness of breath 
with usual activities 
and it does interfere 
with the subject’s 
usual daily 
activities  
Shortness of breath 
with minimal 
exertion or at rest; 
it limits most of the 
subject’s usual 
daily activities 
PHLEGM/ 
SPUTUM 
PRODUCTION? 
Absent 
Mild 
Moderate 
Severe 
No coughing up of 
phlegm/sputum or 
resolution (to pre-
CABP Baseline) 
Subject coughs up 
a small amount of 
phlegm/sputum 
Subject coughs up 
a moderate amount 
of phlegm/sputum 
Subject coughs up 
a large amount of 
phlegm/sputum 
 
The categories of Early Clinical Response are defined as follows: 
Clinical Success:  at the ECR assessment will be defined as survival with improvement of at 
least 1 level (ie, severe to moderate, moderate to mild, mild to absent) compared to baseline 
(Screening) in at least 2 CABP symptoms (cough, sputum production, pleuritic chest pain, 
and dyspnea) with no worsening by at least 1 level in the other CABP symptoms.  In order 
for the subject to be considered a Clinical Success, the subject may not meet any criteria for 
Clinical Failure or Indeterminate ECR.   
Clinical Failure:  meeting any of the following criteria: 
• There is no improvement by at least 1 level (ie, severe to moderate, moderate to mild, 
mild to absent) compared to baseline (Screening) in 2 CABP symptoms.  
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• Any of the 4 CABP symptoms is worse (by at least 1 level) compared to baseline 
(Screening).  
• The subject requires alternative (rescue) antibacterial treatment for CABP prior to the 
ECR assessment related to either (a) progression or development of new symptoms 
attributable to CABP; (b) development of infectious complications of CABP (eg, 
empyema, lung abscess) or (c) discontinuation of study therapy due to an AE. 
• The subject is receiving antibacterial therapy that may be effective for the infection under 
study for a different infection from the one under study. 
• Death prior to the ECR assessment. 
 
Indeterminate:  the clinical response to test article could not be adequately inferred due to: 
• Subject was not seen for the evaluation because s/he withdrew consent, or were lost to 
follow-up 
• Other specified reason. 
 
Assuming none of the above definitions of failure is met, the following cases will be 
considered an indeterminate response: Subjects with missing data such that an ECR 
Response cannot be determined; subjects who did not have at least 2 symptoms of CABP at 
baseline; subjects with an ECR assessment outside of the 72–120-time window. Since 
subjects with an indeterminate response are included in the denominator of the calculation of 
Clinical Success, these subjects are essentially Clinical Failures.  For the ITT population, the 
proportion of ITT subjects with a 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 
 
 
5.2.1.1 
Estimand Framework  
An addendum to ICH E9 introduces the concept of an estimand which translates the trial 
objective into a precise definition of the treatment effect that is to be estimated.  The 
description of the estimand includes 4 attributes: the population, the variable (or endpoint) to 
be obtained for each subject, the specification of how to account for intercurrent events (ICE) 
and the population-level summary for the variable.  These attributes are described below: 
 
Early Clinical Response 
Population 
ITT Population 
Variable/Endpoint 
Programmatic determination of early clinical success 
Handling of intercurrent 
events 
Composite estimand as the following ICE's are 
incorporated into the variable/endpoint: 
 Receipt of alternative (rescue) therapy (failure) 
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 Receipt of antibiotic that may be effective for 
CABP for a different infection (failure) 
 Death (failure) 
 
Population-level summary 
Difference between treatment groups in percentage of 
subjects with an early clinical sucess 
 
5.2.2 
Secondary Efficacy Outcomes  
5.2.2.1 
Investigators 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 clinical response at PTE 
based on the investigator assessments at the EOT and PTE Visits in the ITT and CE-PTE 
populations as defined in Table . 
EOT Visit  
At the EOT Visit (on the calendar 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:   
 The subject is alive and the infection is sufficiently resolved such that further 
antibacterial therapy is not needed.   
o These subjects may have some residual findings related to infection (ie, 
cough) requiring ancillary (ie, non-antibiotic) treatment (eg, expectorant). 
 In order for the subject to be considered a Clinical Success at EOT, the subject may 
not meet any criteria for Clinical Failure or Indeterminate at EOT.   
Clinical Failure:   
 The subject requires alternative antibacterial treatment for CABP prior to EOT related 
to either  
o progression or development of new symptoms to CABP, or 
o  development of infectious complications of CABP (eg, empyema, lung 
abscess), or  
o subject developed an AE that required discontinuation of study therapy prior 
to the EOT.  
 Other reasons for clinical failure are: 
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• Subject is receiving antibacterial therapy that may be effective for the infection under 
study for a different infection from the one under study. 
• Death prior to EOT. 
 
Indeterminate:   
 The clinical response to test article could not be adequately inferred due to: 
o Subjects were not seen for EOT evaluation because they withdrew consent, were 
lost to follow-up, other reason (specify). 
o Other specified reason. 
 
PTE Visit  
At the PTE Visit (5 to 10 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:   
 Survival after completion of a test article regimen without receiving any systemic 
antibacterial therapy other than test article; 
 Resolution of signs and symptoms of the infection present at Screening with no new 
symptoms or complications attributable to CABP; and  
 No need for further antibacterial therapy.   
Clinical Failure:  
 The subject requires alternative antibacterial treatment for CABP prior to PTE 
related to either: 
o progression or development of new symptoms of CABP, or  
o development of infectious complications of CABP (eg, empyema, lung abscess). 
Other reasons for clinical failure are: 
• The subject is receiving antibiotics that may be effective for the infection under study 
for a different infection from the one under study. 
• Death prior to PTE. 
 
Indeterminate:   
• The clinical response to test article could not be adequately inferred due to: 
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o Subjects were not seen for PTE evaluation because they withdrew consent, were lost 
to follow-up, other (specify). 
o Other specified reason. 
 
The efficacy outcome of Clinical Response at PTE is determined as follows from the 
investigator's assessments at the EOT and PTE Visits: 
Table 4. 
Investigator's Assessment of Clinical Response 
EOT Visit 
PTE Visit 
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 
Abbreviations:  EOT = end of treatment; PTE = post-therapy evaluation. 
 
For the ITT population, the proportion of ITT subjects with a Clinical Success is defined 
using the following formula (where the denominator adds to the total number of subjects in 
the ITT 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) 
 
5.2.2.2 
Estimand Framework for Investigators Assessment of Clinical Response  
The four attributes of estimand are described below: 
 
Investigators Assessment of Clinical Response 
Population 
ITT and CE-PTE Populations 
Variable/Endpoint 
Investigator Assessment of Clinical Success 
Handling of intercurrent 
events 
Composite estimand as the following ICE's are 
incorporated into the variable/endpoint: 
 Receipt of alternative (rescue) therapy (failure) 
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 Receipt of antibiotic that may be effective for 
CABP for a different infection (failure) 
 Death (failure) 
 
Population-level summary 
Difference between treatment groups in percentage of 
subjects with an investigators assessment clinical 
sucess 
 
 
 
 
5.2.2.3 
Microbiologic Outcomes  
Microbiological response definitions for the evaluations performed at the EOT and PTE 
Visits and analyzed in the microITT and microbiologically evaluable (ME) populations are 
presented in the table below.  Post-baseline microbiological samples will be collected only as 
clinically indicated.  Atypical pathogens identified only by acute and convalescent serology 
or baseline urinary antigen tests (UAT), and Streptococcus pneumoniae identified only by 
baseline UAT can only have a presumed or indeterminate microbiologic response. 
If a subject has the same pathogen (ie, same genus and species) identified from both a 
respiratory and blood specimen, a microbiological response is determined for each of the 
pathogens.  The microbiologic response for the respiratory 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.  For the pathogen specific microbiologic response, the worst outcome for 
the pathogen should be summarized.  If Streptococcus pneumoniae is identified from both a 
UAT and a culture, the culture should be used to determine microbiological response. 
Table 5. 
Per-Pathogen Microbiological Response Definitions at the EOT and PTE 
Visits 
Term 
Definition 
Eradication 
The baseline pathogen based on culture was absent from repeat 
culture(s) of the same sample type (blood or respiratory specimen).  
Presumed Eradication 
No post-baseline source specimen to culture in a subject assessed 
with a clinical success by the Investigator 
Persistence 
The baseline pathogen based on culture was present in repeat 
culture(s) of the same sample type (blood or respiratory specimen). 
Presumed Persistence 
No post-baseline 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 
Abbreviations:  EOT = end of treatment; PTE = post-therapy evaluation. 
 
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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 and from pathogen determination provided by the Sponsor for 
each baseline isolate.   
Overall microbiological response at PTE is determined as follows from the microbiological 
responses at the EOT and PTE Visits: 
Table 6. 
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 
Abbreviations:  EOT = end of treatment; PTE = post-therapy evaluation. 
Note:  Favorable is defined as eradication or presumed eradication.  Unfavorable is defined as persistence or 
presumed persistence.   
 
Per-subject responses will be based on per-pathogen responses.  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 multiple sample types (blood, respiratory, 
urine), 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 in the same manner as the per-pathogen 
microbiologic response in Table 6.  For subjects with a per-subject favorable response at the 
EOT Visit, the overall microbiologic response at PTE of eradication, presumed eradication, 
persistence, and presumed persistence are based on the response at the PTE Visit.  For 
subjects with a per-subject unfavorable response at the EOT Visit, the overall microbiologic 
response at PTE of persistence and presumed persistence are based on the response at the 
EOT Visit except for when the response at the PTE Visit is unfavorable.  In this case, the 
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overall microbiologic response at PTE of persistence and presumed persistence are based on 
the response at the PTE Visit.  For subjects with a per-subject indeterminate response at the 
EOT Visit and unfavorable at the PTE Visit, the overall microbiologic response at PTE of 
persistence and presumed persistence are based on the response at the PTE Visit.   
For the microITT 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 microITT 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 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 populations, 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) 
 
Microbiological response definitions of superinfection and new infection are presented in 
Table 7 below:  
Table 7. 
Microbiological Response Definitions:  Superinfection or New Infection 
Term 
Definition 
Superinfection 
Isolation of a non-baseline pathogen from blood or respiratory 
cultures while the subject is on test article and the subject shows 
progression or development of new symptoms of CABP or 
development of infectious complications of CABP (ie, the subject is 
deemed a clinical failure by the investigator at the EOT Visit) 
New infection 
Isolation of a non-baseline pathogen from a post-treatment culture of 
a blood or respiratory specimen and the subject shows progression or 
development of new symptoms of CABP or development of 
infectious complications of CABP (ie, the subject is deemed a 
clinical failure by the investigator at the PTE Visit) 
Abbreviations:  CABP = community-acquired bacterial pneumonia. 
 
For subjects with multiple microbiological samples taken either while the subject is on test 
article (for determination of superinfection) or post-treatment (for determination of new 
infection) all cultures will be used in the analysis. 
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5.3 
Safety Measures  
The safety parameters include AEs, clinical laboratory evaluations, vital signs, and 
electrocardiogram (ECG) findings.  AEs will be coded using the Medical Dictionary of 
Regulatory Activities (MedDRA, Version to be delineated in the CSR)  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 
ANALYSIS 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 (ie, completes a randomization transaction).  
6.1.2 
Safety Population  
The Safety population will consist of all randomized subjects who receive test article (either 
active or placebo).  All safety analyses will be conducted in this population.   
6.1.3 
Microbiological Intent-to-Treat (microITT) Population  
The microITT population will consist of all subjects in the ITT population who have at least 
one causative bacterial pathogen identified from a culture of a respiratory specimen (eg, 
respiratory fluid obtained by bronchoalveolar lavage [BAL] or bronchoscopy; pleural fluid 
obtained by thoracentesis; or expectorated or induced sputum meeting adequacy criteria as 
defined by the Gram stain results), culture of blood or from a culture-independent method 
(eg, positive urinary antigen test for Streptococcus pneumoniae or Legionella pneumophila, 
or positive serology for Legionella pneumophila, Mycoplasma pneumoniae, or 
Chlamydophila pneumoniae) at baseline. 
Pathogen determination of typical bacteria 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. 
In general, baseline is defined as the 24-hour period prior to the administration of the first 
dose of test article.  However, if the subject is unable to produce a sputum sample at baseline 
or the sputum sample is not adequate based on the Gram stain criteria, a specimen obtained 
within 24 hours after the first dose of test article may be considered a baseline sample.  If the 
sputum sample collected in the 24-hour period prior to the administration of the first dose of 
test article is not adequate based on the Gram stain criteria and the sputum sample obtained 
within 24 hours after the first dose of test article is not adequate based on the Gram stain 
criteria, only the sputum sample collected in the 24-hour period prior to administration of the 
first dose of test article will be considered baseline.  UAT samples up through 24 hours after 
the first dose of test article may be considered the baseline sample, if a previous sample was 
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not taken or was found to be negative.  Blood samples up through 24 hours after the first 
dose of test article may be considered the baseline sample, if a previous sample was not taken 
or was found not to have a pathogen. 
The following isolates will always be considered a pathogen:  
Streptococcus pneumoniae 
• Positive BAL, bronchoscopy, pleural fluid, or blood culture; or  
• Positive sputum culture in the presence of an adequate Gram stain defined as having 
> 25 polymorphonuclear neutrophils (PMNs)/Low Power Field (LPF) and 
< 10 Squamous Epithelial Cells (SECs)/LPF; or 
• Positive urinary antigen test 
 
Haemophilus influenzae  
• Positive BAL, bronchoscopy, pleural fluid, or blood culture; or  
• Positive sputum culture in the presence of an adequate Gram stain (> 25 PMNs/LPF and 
< 10 SECs/LPF) 
 
Staphylococcus aureus 
• Positive BAL, bronchoscopy, pleural fluid, or blood culture 
• Positive sputum culture in the presence of an adequate Gram stain (> 25 PMNs/LPF and 
< 10 SECs/LPF) 
 
Moraxella catarrhalis 
• Positive BAL, bronchoscopy, pleural fluid, or blood culture; or  
• Positive sputum culture in the presence of an adequate Gram stain (>25 PMNs/LPF and 
< 10 SECs/LPF) 
 
Legionella pneumophila 
• Positive BAL, bronchoscopy, pleural fluid, or blood culture; or 
• Positive sputum culture, regardless of Gram stain findings; or 
• Positive or borderline acute (baseline) or positive or borderline convalescent (PTE) IgM 
(Euroimmun IgM ELISA IgM ≥0.80 ratio).  
• Negative acute (baseline) and positive or borderline convalescent (PTE) IgG (Euroimmun 
IgG ELISA IgG ≥16 RE/mL). 
 
• A positive urine antigen test 
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Mycoplasma pneumoniae 
• Positive or borderline acute (Baseline) or positive or borderline convalescent (PTE) IgM 
(Euroimmun IgM ELISA IgM ≥0.80 ratio). 
• Negative acute (Baseline) and positive or borderline convalescent (PTE) IgG 
(Euroimmun IgG ELISA IgG ≥16 RE/mL).  
 
Chlamydophila pneumoniae 
• Positive or borderline acute (Baseline) or positive or borderline convalescent (PTE) IgM 
(Euroimmun IgM ELISA IgM ≥0.80 ratio) 
• Negative acute (Baseline) and positive or borderline convalescent (PTE) IgG 
(Euroimmun IgG ELISA IgG ≥16 RE/mL) 
 
The following isolates are considered as contaminants from respiratory specimens rather than 
pathogens of CABP:  Candida spp. and other fungi, Enterococcus spp., viridans streptococci, 
coagulase-negative staphylococci, Micrococcus spp., Neisseria spp. other than N. 
meningitidis, Corynebacterium spp. and other coryneforms, Lactobacillus spp., Vibrio spp., 
Capnocytophaga spp., Cardiobacterium spp., Flavobacterium spp, Staphylococcus 
lugdunensis, Staphylococcus capitis, Staphylococcus caprae , Staphylococcus chine, 
Staphylococcus condiment, Staphylococcus epidermidis, Staphylococcus haemolyticus, 
Staphylococcus hominis, Staphylococcus saprophyticus, Staphylococcus sciuri, 
Staphylococcus simulans, Streptococcus epidermidis, Streptococcus viridans, Staphylococcus 
warneri, Staphylococcus xylosus 
 
Other isolates identified from culture of blood and respiratory specimens will be reviewed in 
a blinded manner by the Sponsor on a case-by-case basis for determination of whether the 
organism is a pathogen for CABP.   
Staphylococcus aureus will be considered a distinct pathogen with methicillin-resistant 
Staphylococcus aureus (MRSA) and methicillin-susceptible Staphylococcus aureus 
considered distinct pathogens.  Likewise, Streptococcus pneumoniae will be a distinct 
pathogen with penicillin-nonsusceptible Streptococcus pneumoniae, penicillin-susceptible 
Streptococcus pneumoniae, macrolide-resistant Streptococcus pneumoniae, quinolone-
resistant Streptococcus pneumoniae, and multiple drug resistant Streptococcus pneumoniae 
each considered distinct pathogens.  A pathogen will be considered multiple drug resistant if 
susceptibility testing shows resistance to one drug in 3 or more of the classes of antibiotics 
provided below except in the case of MRSA where penicillin and cephalosporin are due to a 
single mechanism in which case 2 non-β-lactam resistances in addition to oxacillin, will be 
considered multi-drug resistant.  Streptococcus spp. and Staphylococcus spp., isolates 
resistant to macrolides but susceptible to lincosamides and D-test positive (> 4/0.5 ug/ml) 
will be considered resistant to both macrolides and lincosamides.  Susceptibility will be 
based on the most current CLSI guidelines for each antibiotic or if unavailable, on FDA 
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labeled susceptibility criteria.  Antibiotics that define resistance for the class are listed as 
follows: 
• Penicillins – penicillin  
• Fluoroquinolones – moxifloxacin  
• Cephalosporins – ceftriaxone  
• Lincosamides – clindamycin 
• Macrolides – azithromycin or erythromycin  
• Tetracyclines – tetracycline or doxycycline 
• Folate Pathway Inhibitors – Trimethoprim/sulfamethoxazole  
• Glycopeptides – vancomycin 
• Oxazolidinone – linezolid 
 
If there are multiple specimens (of the same testing modality) from the same time-point 
where the same pathogen is isolated, only the pathogen with the highest MIC to the test 
article received will be used.  If the pathogens have the same MIC to the test article received, 
the pathogen with the lowest accession number will be used.  The Gram stain associated with 
the selected pathogen will be utilized for analysis. 
If the same pathogen is identified from the blood and respiratory sample, for tables providing 
MIC or disk diffusion data, the pathogen with the highest MIC to the test article received will 
be used. 
6.1.4 
Clinically Evaluable (CE) Populations  
Two CE populations will be defined:  the CE-EOT and the CE-PTE.  Subjects will be 
included in or excluded from the CE analysis sets based on the criteria listed below.   
6.1.4.1 
Diagnosis of CABP  
To be included in the CE-EOT and CE-PTE populations, subjects must meet the following 
protocol defined inclusion criteria that describe the CABP: 
Inclusion Criterion 3:  Has at least 3 of the following symptoms: 
• Cough  
• Production of purulent sputum 
• Dyspnea (shortness of breath) 
• Pleuritic chest pain.   
 
Inclusion Criterion 4:  Has at least 2 of the following abnormal vital signs: 
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• Fever or hypothermia documented by the investigator (po or rectal temperature > 38.0oC 
[100.4oF] or < 36.0oC [95.5oF]) 
• Hypotension with systolic blood pressure (SBP) < 90 mmHg 
• Heart rate > 90 bpm 
• Respiratory rate (RR) > 20 breaths/minute. 
 
Inclusion Criterion 5:  Has at least 1 clinical sign or laboratory finding associated with 
CABP: 
• Hypoxemia Partial pressure of arterial oxygen (PaO2) < 60 mmHg by arterial blood gas 
(ABG)  
• Physical examination findings of pulmonary consolidation (dullness on percussion, 
bronchial breath sounds, egophony, rales, rhonchi, or decreased breath sounds) 
• An elevated total white blood cell (WBC) count (> 12,000 cells/mm3) or leucopenia 
(WBC < 4,000 cells/mm3) or elevated immature neutrophils (> 15% band forms 
regardless of total peripheral WBC count). 
 
Inclusion Criterion 6: Has disease categorized as being PORT III or IV at Screening  
Inclusion Criterion 7: Radiographically-confirmed pneumonia, ie, new or progressive 
pulmonary infiltrate(s) on chest X-ray (CXR) or chest computed tomography (CT) scan 
consistent with acute bacterial pneumonia within 48 hours prior to the first dose of test 
article. 
The Sponsor Medical Monitor will also review those subjects with a concomitant illness 
identified after baseline that could have presented at baseline as pneumonia, including 
COVID-19.  If it is determined that the subject does not have pneumonia but had another 
condition such as lung cancer or COVID-19 at baseline, the subject will not be evaluable for 
the CE populations. Any subject who is confirmed or suspected to have severe acute 
respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on local standard-of-care 
assessments during the post-randomization period may be excluded from the CE populations 
based on Sponsor review. 
6.1.4.2 
Prior Antibiotic Therapy  
Subjects will be excluded from the CE populations if they meet the prior antibiotic exclusion 
criteria: 
Exclusion Criterion 1:  Has received 1 or more dose(s) of a potentially effective systemic 
antibacterial treatment within the 72 hours prior to the first dose of test article (a subject will 
be considered to have received a potentially effective systemic antibacterial treatment if the 
pathogen identified as causing infection is shown to be susceptible to the antibacterial given 
or, in the circumstance where a pathogen is not identified, if the antibacterial agent is 
approved for treatment of pneumonia or is known to have activity against any of the leading 
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causes of CABP [eg, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella 
catarrhalis, Staphylococcus aureus, Legionella pneumophila]).  EXCEPTION:  Subjects (not 
exceeding 25% of the total study population) may be eligible despite prior antibacterial 
therapy if they have been treated with a single dose of a short-acting antibacterial (ie, an 
antibacterial whose standard dosing regimen is more frequent than once per day, see 
Appendix 4 of the protocol).   
6.1.4.3 
Concomitant Antibiotic Therapy  
Subjects who receive any systemic concomitant antibiotic therapy from the time of the first 
dose of test article through the time of the last dose of test article at EOT and through the 
PTE Visit with a spectrum of activity against the known or potential infecting pathogen(s) 
responsible for the CABP 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 CABP due to insufficient therapeutic effect of the test article (ie, for progression or 
development of new symptoms of CABP or development of infectious complications of 
CABP). 
Subjects who receive a systemic concomitant antibiotic that is not effective against the 
baseline pathogen, or if no pathogen is isolated, and the antibiotic does not have activity 
against CABP pathogens, will be included in the CE-EOT and CE-PTE populations.   
6.1.4.4 
Test Article Therapy  
Subjects must meet all of the following to be included in the CE populations: 
• Received at least 1 dose of active 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 (AE) occurred which required 
emergency unblinding.   
• Evaluable failure:  The subject received the first 2 doses (if receiving 200 mg iv QD on 
Day 1) or 3 doses (if receiving 100 mg iv on Day 1) of active test article (omadacycline 
group) or first 2 doses of active test article (moxifloxacin 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 the first 3 doses (if receiving 200 mg iv QD on 
Day 1) or 4 doses (if receiving 100 mg iv on Day 1) of active test article (omadacycline 
group) or the first 3 doses of active test article (moxifloxacin 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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6.1.4.5 
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 5 to 10 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 or the patient died after EOT and before PTE.   
 
6.1.4.6 
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 2:  Is known or suspected to have CABP caused by a pathogen that may 
be resistant to either test article (eg, , Pseudomonas aeruginosa, Proteus spp., Morganella 
morganii, Providencia spp. Pneumocystis jiroveci, obligate anaerobes, mycobacteria, fungal 
pathogens). 
Exclusion Criterion 3:  Suspected or confirmed empyema (a parapneumonic pleural effusion 
is not an exclusion criteria) or lung abscess. 
Exclusion Criterion 5:  Subjects who reside in a long-term care or subacute/intermediate 
healthcare facility (eg, nursing home) or a subject admitted with pneumonia following a 
recent hospitalization (overnight admission within 90 days prior to current admission. 
Exclusion Criterion 12: Requires acute pharmacologic intervention to stabilize blood 
pressure (BP) and/or adequate tissue perfusion, OR meets septic shock criteria (meets ALL 
of the following):  
 Meets at least 2 criteria for sepsis as defined by the quick Sequential Organ 
Failure Assessment (qSOFA) score: (a) Altered mental status with Glasgow 
Coma Scale (GCS) < 15, (b) RR ≥ 22 breaths per minute, and (c) SBP ≤ 100 
mmHg 
 Despite adequate fluid resuscitation, persistent hypotension requiring vasopressors 
to maintain mean arterial pressure (MAP) ≥ 65 mmHg. 
 Serum lactate ≥ 2 mmol/L (serum lactate measurement is not required at 
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Screening if any of the above septic shock criteria are not met) 
 
Exclusion Criterion 13: PORT Risk Class I, II and V patients. 
1. Exclusion Criterion 14; Requires or expected to require Intensive Care Unit (ICU) 
admittance or invasive or non-invasive ventilation. 
 
Exclusion Criterion 15:   Known or suspected primary or metastatic neoplastic 
lung disease, aspiration pneumonia, active tuberculosis, cystic fibrosis, 
bronchiectasis, bronchial obstruction (eg, post-obstructive pneumonia), chronic 
neurological disorder preventing clearance of pulmonary secretions, or severe 
chronic obstructive pulmonary disease (COPD) (severe COPD is defined as 
known forced expiratory volume in 1 second [FEV1] < 50% of predicted in a 
patient with FEV1/forced vital capacity [FVC] < 70%; note that spirometry or 
pulmonary function testing is not required during Screening). 
 
6.1.5 
Microbiologically Evaluable (ME) Populations  
The ME-EOT and ME-PTE populations will consist of all subjects in both the microITT 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 Document.   
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 
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 microITT 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 Gram stain results, and local and central 
laboratory genus and species identification.  Inclusion into the ME populations will be 
determined programmatically.   
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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. 
6.3 
Subgroups  
Analyses will be conducted (as described in Section 9) for subgroups defined by the 
randomization stratification factors:  PORT Risk Class (III and IV) and receipt of an allowed 
antibacterial therapy in the 72 hours prior to study treatment (yes vs no).  Analyses of ECR 
(in the ITT population) and clinical response at the PTE visit (in the ITT and CE-PTE 
populations) will also be conducted in the following subgroups:  bacteremic subjects, defined 
as subjects with a positive blood culture at baseline (microITT population), by CURB-65 
Score, and subjects meeting the systemic inflammatory response syndrome (SIRS) criteria at 
baseline.  CURB-65 Score is derived from the eCRF data and ranges from 0-5 where 1 point 
is given for each of the following at baseline:  confusion, blood urea nitrogen > 19 mg/dL 
(urea > 6.8 mmol/L), respiratory rate ≥ 30 breaths/min, systolic blood pressure < 90 mmHg 
or diastolic blood pressure ≤ 60 mmHg, and age ≥ 65 years.  Confusion is defined as altered 
mental status as recorded on the PORT Risk Class Determination eCRF.  SIRS is defined as 
having 2 or more of the following criteria:  temperature < 36°C or > 38°C (oral or oral 
equivalent), heart rate > 90 bpm, respiratory rate > 20 breaths/min, 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 
OVERALL STATISTICAL CONSIDERATIONS  
7.1 
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.   
 
7.2 
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 (the 24-hour period 
prior to the administration of the first dose of test article) or if the subject is unable to 
produce a sputum sample at baseline or the sputum sample does not have an adequate Gram 
stain, a specimen obtained within 24 hours after the first dose of test article may be used as 
baseline.  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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7.3 
Handling of Missing Data  
Missing data will be handled as outlined below:  
• All missing and partial dates for AEs 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 assessments of CABP symptoms will be queried for a value.  If 
minutes are not available, the time will be recorded to the closest hour.   
• 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 AEs cannot be missing.  Missing data will be 
queried for a value.   
• If the time of administration of the first dose of test article is missing, it will be set to 1 
minute after midnight (00:01) 
 
For clinical and microbiological response, missing data will be handled as follows: 
• For the primary outcome measure (ECR at 72 to 120 hours after administration of the 
first dose of test article): 
o The subject will be considered to have missing data if an assessment of all of the 
CABP symptoms (cough, sputum production, pleuritic chest pain, and dyspnea) is not 
made from 72 to 120 hours after the administration of the first dose of test article, 
unless the subject is considered a Clinical Failure for another reason.  Subjects who 
do not have at least 2 symptoms of CABP at baseline will also be considered to have 
missing data unless the subject is considered a Clinical Failure for another reason.  
Subjects with missing data will be defined as an Indeterminate response which is 
essentially a Clinical Failure for the primary analysis in the ITT population.   
 
• 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 Table 4.  By definition, subjects with an Indeterminate 
response are included in the denominator for analyses in the ITT and microITT 
populations, and thus, are considered Clinical Failures.  Subjects with an 
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Indeterminate response are excluded from the CE-EOT, CE-PTE, ME-EOT and 
ME-PTE populations.   
• For microbiologic response: 
o If no post-baseline 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).   
 
7.4 
Interim Analysis  
An interim analysis to assess efficacy is not planned.  However, a Data and Safety 
Monitoring Committee (DSMC) will review safety data (eg, AEs and serious adverse events 
[SAEs], laboratory data, ECG and vital signs assessments) by unblinded (treatment A and 
treatment B) treatment assignment at regular time points while the study is ongoing.  
However the DSMC can convene unscheduled meetings as necessary.  A detailed DSMC 
charter outlines the responsibilities of the DSMC, format and frequency of the meetings, 
methods of providing data to and from the DSMC, statistical issues, documentation of the 
meeting outcomes, and communication pathways.   
7.5 
Pooling Strategy for Study Sites  
Data will be pooled across sites and geographic regions..  Due to the large number of sites 
and the small number of subjects per site, no analyses by site will be conducted 
7.6 
Visit Windows/Unscheduled Visits  
For the primary efficacy outcome, if more than one complete assessment of the symptoms of 
CABP is done in the ECR assessment  window of 72 to 120 hours after administration of the 
first dose of test article, 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 ITT and microITT analyses.  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 8).  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 
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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, 5 to 10 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.   
Table 8. 
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 
Day 1-Day 10 
 Visits occur on Days 1,2,3,4 to 6 (ECR). Visits will occur 
on Days 8 to 10 if treatment extends beyond  7 days.  
Subjects with bacteremia identified at Screening may have 
visits up to Day 14.  For subjects that have been switched to 
po treatment and were discharged from the hospital prior to 
Day 4, only 1 visit is required between Study Days 4 to 6. 
EOT 
 
Within 2 days following the last dose of test article 
PTE 
 
5-10 days after the subject's last day of therapy 
Final Follow-up 
Day 30-37 
30-37 days after the start of the first infusion 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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8 
STATISTICAL ANALYSIS METHODS  
8.1 
Subject Disposition  
The number of Screen Failures and reason for screen failure will be presented. A listing, 
grouped by randomization stratum (PORT Risk Class and receipt of prior antibiotics), will be 
provided that indicates the subject's date and time of randomization, randomized treatment 
assignment, and randomization number. 
The number of subjects included in each of the analysis populations (ie, ITT, Safety, 
microITT,  CE-EOT, CE-PTE, ME-EOT, and ME-PTE) will be summarized by treatment 
group and country.  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 1 dose of test article and returning for all of the EOT, 
PTE, and Follow-up Visits), not completing the study, missing each of the EOT and PTE 
Visits, and prematurely discontinuing from test article (including due to COVID-19) will be 
presented for each treatment group and overall for the ITT, microITT, 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 
(including due to COVID-19), as recorded on the eCRF will be summarized (number and 
percentage) by treatment group for the ITT, microITT, and CE-PTE populations.  
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, as well as 
the visit(s) missed and the reason for missing the visit(s), will be provided.   
8.2 
Demographics and Baseline Characteristics  
Except where indicated, demographic data and baseline characteristics will be presented by 
treatment group for the ITT, Safety, microITT, and CE-PTE populations.  A table will 
present the subject demographics (eg, gender, age, ethnicity, and race) and baseline 
characteristics (height, weight, body mass index (BMI), and creatinine clearance categorized 
as severe renal impairment [< 30 mL/min], moderate renal impairment [30-50 mL/min], mild 
renal impairment [> 50-80 mL/min], and normal renal function [> 80 mL/min]) collected 
before the start of test article.  .  Age will be summarized as a continuous variable and in the 
categories, 18-45 years, > 45-65 years and > 65 years.  The number and percentage of 
subjects > 75 years of age will also be provided.  Creatinine clearance will be calculated from 
the local laboratory data since these data were used for determination of the inclusion and 
exclusion criteria and will be determined from the Cockcroft-Gault equation: 
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(140-age[yrs])*weight [kg]* (Z) 
Z = 1.0, if Male 
Z = 0.85, if Female 
 
 
 
 
Serum Creatinine (mg/dL) x 72 
Differences between treatment groups will be analyzed using Fisher’s exact test for 
dichotomous variables (gender and ethnicity), Chi-squared test for categorical variables (age 
category and race) and the Wilcoxon Rank Sum test for continuous variables (age, height, 
weight, and BMI).   
A table will provide the frequency counts and percentages by treatment group for subjects 
who received prior antibiotics (as randomized), PORT Risk Class (from the eCRF and as 
randomized), CURB-65 Score, subjects meeting the modified American Thoracic Society 
(ATS) severity criteria, and subjects meeting the SIRS criteria for the ITT, microITT and 
CE-PTE populations.  PORT score will also be summarized as a continuous variable.  
CURB-65 score is derived from the eCRF data and ranges from 0-5 where 1 point is given 
for each of the following at baseline:  confusion, blood urea nitrogen > 19 mg/dL 
(urea > 6.8 mmol/L), respiratory rate ≥ 30 breaths/min, systolic blood pressure < 90 mmHg 
or diastolic blood pressure ≤ 60 mmHg, and age ≥ 65 years.  Confusion is defined as altered 
mental status as recorded on the PORT Risk Class Determination eCRF.  Modified ATS 
severity and SIRS criteria are derived from the eCRF data.  Modified ATS severity criteria is 
defined as presence of ≥ 3 of the following 9 criteria at baseline:  respiratory rate 
≥ 30 breaths/min, O2 saturation < 90% or PaO2 < 60 mmHg, blood urea nitrogen ≥ 20 mg/dL, 
WBC < 4000 cells/mm3, confusion, multilobar infiltrates, platelets < 100,000 cells/mm3, 
temperature < 36C, and systolic blood pressure < 90 mmHg.  SIRS criteria is defined as 
having 2 or more of the following 4 symptoms at baseline:  temperature < 36C or > 38C 
(oral or oral equivalent), heart rate > 90 bpm, respiratory rate > 20 breaths/min, 
WBC < 4000 cells/mm3 or WBC > 12,000 cells/mm3, or bands > 10%.  Differences between 
treatment groups will be tested using Fisher’s exact test for categorical variables and the 
Wilcoxon rank sum test for continuous variables. 
By-subject listings of the modified ATS severity criteria and SIRS criteria will be provided.  
A listing of subjects with discrepancies between the PORT Risk Class to which they were 
randomized and their true PORT Risk class as captured in the clinical database will also be 
provided. 
Baseline assessments of clinical symptoms, clinical signs, abnormal vital signs, and abnormal 
laboratory signs of CABP will be presented for the ITT, Safety, microITT, and CE-PTE 
populations.  The number and percentage of subjects with each of the CABP symptoms 
(cough, pleuritic chest pain, dyspnea, and phlegm/sputum production) by severity (absent, 
mild, moderate, severe) will be presented by treatment group.  The number and percentage of 
subjects with the presence by severity (ie, absent, mild, moderate, severe) of the following 
clinical signs will be provided by treatment group:  rales, rhonchi, dullness on percussion, 
bronchial breath sounds, wheezing, decreased breath sounds, and egophony.  The number 
and percentage of subjects with fever (defined as body temperature  38C [100.4F] oral or 
rectal), hypothermia (defined as body temperature < 36C [95.5F] oral or rectal), 
hypotension with systolic blood pressure < 90 mmHg, heart rate > 90 bpm, respiratory 
rate > 20 breaths/min, hypoxemia (defined as PaO2 < 60 mmHg by arterial blood gas or 
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oxygen saturation < 90% by pulse oximetry), elevated total WBC count 
(> 12,000 cells/mm3), leucopenia (WBC < 4,000 cells/mm3), elevated immature neutrophils 
(> 15% band forms regardless of total peripheral WBC count) and any of elevated total WBC 
count, leucopenia or elevated immature neutrophils will be summarized by treatment group.  
Differences between treatment groups will be tested for statistical significance using Fisher's 
exact test.  
Risk factors for CABP will be presented by treatment group for the ITT, Safety, microITT, 
and CE-PTE populations.  Risk factors include smoking (current, past, and descriptive 
statistics of the number of years since quitting for those subjects who were previous 
smokers), receipt of pneumococcal vaccine, prior lung infection, whether the subject had 
mild to moderate COPD, symptomatic asthma with wheezing, and chronic cough with or 
without sputum production.  Differences between treatment groups will be tested for 
statistical significance using Fisher's exact test for categorical variables and the Wilcoxon 
rank sum test for continuous variables.  Other medical and surgical history will be 
summarized based on MedDRA system organ class by treatment group for the ITT and 
Safety populations.   
Readings of baseline chest radiographs, including the type of assessment (CXR or CT scan), 
presence of pleural effusion, whether the pleural effusion is unilateral or bilateral, whether 
the pulmonary infiltrate was uni- or multi-lobar and the location of the pulmonary infiltrate 
(combining left upper lobe and lingula) will be summarized by treatment group for all 
subjects in the ITT, Safety, microITT, and CE-PTE populations.  Differences between 
treatment groups will be tested for statistical significance using Fisher's exact test. 
8.2.1 
Microbiology  
Findings from the local laboratory assessment of the Gram-stained respiratory specimens 
(SECs [< 10, 10-25, > 25], PMNs [< 10, 10-24, ≥ 25], combinations of the bacteria found 
[monomicrobial Gram negative only, polymicrobial Gram negative only, monomicrobial 
gram positive only, polymicrobial Gram positive only, any Gram negative and Gram 
positive, and other] and whether or not a culture was performed) will be tabulated by 
treatment group for all subjects in the ITT, microITT, and ME-PTE populations.  
If a subject has more than one baseline respiratory specimen, the best will be summarized.  
The best respiratory specimens include deep respiratory samples (eg, bronchoalveolar lavage 
[BAL], bronchoscopy) or pleural fluid cultures.  Sputum adequacy criteria do not apply to 
these types of specimens. 
If no deep respiratory or pleural fluid specimens are available, expectorated sputum will be 
assessed using Gram stain criteria.  Best sputum samples are defined based on the PMNs and 
SECs as follows (ranked best to worst): 
1.       > 25 PMNs and < 10 SECs 
2.       10-25 PMNs and < 10 SECs 
3.       < 10 PMNs and < 10 SECs 
4.       >25 PMNs and 10-25 SECs 
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5.       10-25 PMNs and 10-25 SECs 
6.       < 10 PMNs and 10-25 SECs 
7.       > 25 PMNs and > 25 SECs 
8.       10-25 PMNs and > 25 SECs 
9.       < 10 PMNs and > 25 SECs 
The number and percentage of subjects with a qualifying Gram-stain (ie, ≥ 25 PMNs and 
< 10 SECs) will also be presented. 
The pathogenic organisms identified from the baseline blood culture, culture of the 
respiratory specimen, UAT, and serology will be presented by genus and species and by 
testing modality (ie, culture, UAT, serology) for Streptococcus pneumoniae and Legionella 
pneumophila, for the microITT,  ME-EOT, and ME-PTE populations.  The same pathogen 
identified from multiple testing modalities will be counted only once in the summary at the 
genus and species level.  The pathogenic organisms identified from the baseline blood 
culture, culture of the respiratory specimen, UAT, and serology will also be presented by 
country in the microITT population.  The number and percentage of subjects with CABP 
caused by monomicrobial and polymicrobial Gram-positive or Gram-negative pathogens, 
only atypical pathogens (ie, Legionella pneumophila, Mycoplasma pneumoniae, or 
Chlamydophila pneumoniae), a mixture of both Gram-positive and Gram-negative 
pathogens, a mixture of Gram-positive and atypical pathogen, or a mixture of Gram-negative 
and atypical pathogens will be summarized by treatment group overall (microITT and ME-
PTE populations) and by PORT Risk Class and country for the microITT and ME-PTE 
populations.   
The number and percentage of subjects with a positive blood culture by pathogenic organism 
will be provided for the microITT 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.  The percentage of 
subjects with a positive blood culture by pathogenic organism will be provided for the 
microITT population by geographic region. 
A listing will be provided that includes all baseline and post-baseline isolates obtained from 
the blood, respiratory specimen, UAT, and serology and will indicate the type of specimen, 
testing modality, and pathogenic organism.   
Several tables providing the minimum inhibitory concentration (MIC) data for the pathogens 
identified from the baseline blood and respiratory cultures will be provided for the microITT 
and ME populations:  
• The MIC distribution to omadacycline and moxifloxacin, 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.  
 Susceptibility (susceptible, intermediate or resistant) to the test article received will 
be summarized by pathogen. 
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8.3 
Treatment Compliance and Exposure  
Exposure summary by treatment group will be presented for the Safety, microITT, and 
CE-PTE populations.  The distribution of subjects by the total number of days on therapy (0, 
1-3, 4-6, 7-10, 11-14, and > 14 days), the number of days on iv infusion (0, 1-2, 3-6, 7-10, 
11-14, and > 14 days), the number of days of oral test article (0, 1-4, 5-7, 8-11, and 
> 11 days) and the number of days of oral switch (1-2, 3-5, 6-7, >8) will be presented.  A 
summary of the number of days of iv therapy prior to oral switch defined as 24-hour periods 
(ie, time to oral switch), the day of oral switch, and the criteria for iv to oral switch will be 
presented by treatment group.  For the Safety population, the summary of test article 
exposure will be based on the actual treatment received whereas for all other analysis sets, 
the summary will be based on the randomized treatment.  
Treatment compliance is defined as the number of iv doses (including partial doses, active 
and placebo) and oral doses actually received divided by the number of doses expected 
(× 100) over the time period defined by the first infusion date and the last dose date.  
Descriptive statistics for treatment compliance and the number and percentage of subjects at 
least 80% compliant will be presented by treatment group for the ITT, Safety, and CE-PTE 
populations.   
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9 
EFFICACY PARAMETERS  
For all efficacy analyses, subjects will be analyzed in the group to which they were 
randomized.  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 
PORT Risk Class 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. 
Subjects who miss the efficacy assessment due to COVID-19 will have an indeterminate 
response and the number and percentage of subjects with an indeterminate response due to 
COVID-19 will be summarized. Depending on the number of subjects in the study diagnosed 
with COVID-19, primary efficacy outcome may be analyzed in patients with and without 
COVID-19 and additional sensitivity analyses may be included to treat indeterminates in 
various ways. 
 
9.1 
Primary Analysis  
The primary efficacy analyses will be based on the ITT 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 a Clinical Success at 
the ECR Assessment (72 to 120 hours after the first infusion of test article).   
The number and percentage of subjects in each treatment group defined as an ECR 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 success rate in the omadacycline treatment group, p2 is the 
primary efficacy success rate in the moxifloxacin 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 moxifloxacin treatment group) will be calculated 
for the ITT population.  If the lower limit of the 95% CI for the difference in the ITT 
population exceeds –10%, then the null hypothesis will be rejected and the non-inferiority of 
omadacycline to moxifloxacin will be declared.   
The 2-sided 95% CI for non-inferiority testing based on the difference of ECR Clinical 
Success rates at the ECR assessment (72 to 120 hours after the first infusion of test article), 
will be computed using the method proposed without stratification by Miettinen and 
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Nurminen (1985).  For notation purposes, assume 1 represents the omadacycline group 
(Group 1) and 2 represents the moxifloxacin 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
(





 
 
where 
2

is the cut point of size  from the chi-square distribution (
2

=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 
1n = 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 Manning (1990).   
The reasons for Clinical Failure and reasons for Indeterminate response will be summarized 
by treatment group.   
9.2 
Sensitivity and Additional Analyses of the Primary Efficacy Outcome  
If the null hypothesis of inferiority is rejected for ECR in the ITT population and the 
observed Clinical Success proportion for omadacycline is larger than the observed proportion 
for moxifloxacin, a formal statistical analysis of superiority will be conducted.  If the lower 
limit of the 95% 2-sided CI for the treatment difference is greater than 0.00, omadacycline 
will be considered superior to moxifloxacin. 
Sensitivity analyses of the primary outcome include:  
• Determination of the 95% CI adjusted for PORT Risk Class (III and IV) and prior use of 
antibiotics (yes and no). 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, the receipt of prior 
antibiotics (yes vs no) will be combined.  The 95% CI interval will be computed using 
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the stratified methodology of Miettinen and Nurminen (1985).  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 having an ECR assessment or have missing data, as a Clinical 
Success (these subjects are considered Indeterminates and analyzed as Clinical Failures 
in the primary analysis). 
 
9.3 
Secondary Analysis  
The number and percentage of subjects in each treatment group with a Clinical Success, 
Clinical Failure, and Indeterminate for the assessment of Clinical Response at the PTE Visit 
(based on the investigator’s assessment) will be reported for the ITT, CE-PTE, and ME-PTE 
populations (by definition CE-PTE and ME-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 (1985) without 
stratification.  The 95% CIs are for descriptive purposes only and no conclusion of NI will be 
made.  The reasons for Clinical Failure and Indeterminate will be summarized by treatment 
group.   
The number and percentage of subjects in each treatment group in each response category for 
ECR will be presented for the microITT populations.  The number and percentage of subjects 
who are classified as a Clinical Success and Clinical Failure based on the 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% CIs without stratification will be constructed 
for the observed difference in the Clinical Success rates in the microITT, and ME-PTE 
populations using the method of Miettinen and Nurminen (1985). 
Early Clinical Response and the 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.  The number and percentage of subjects in each 
treatment group with a Clinical Success (based on ECR and investigator's assessment of 
response) will be tabulated per pathogen for the microITT, and ME-PTE (for Investigators 
assessment only).  
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 (ie, included in the numerator and denominator of the calculation) 
but will be presented separately on the summary table.  An additional analysis in the ITT 
population of ACM will be completed that includes only those subjects whose status is 
known at 15 and 30 days after the first dose of study drug.  
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9.4 
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 a Clinical Success, Clinical Failure, and 
Indeterminate by the Investigator’s Assessment at EOT in the ITT and CE-EOT populations 
(by definition subjects with an Indeterminate response are excluded from the CE-EOT 
population) will be calculated.  The number and percentage of subjects in each response 
category for the assessment of Clinical response at PTE (based on the investigator's 
assessment) in the microITT population will also be provided.  Two-sided unadjusted 95% 
CIs will be constructed for the observed difference in the Clinical Success rate using the 
method of Miettinen and Nurminen (1985). 
The number and percentage of subjects with stabilization of all vital signs associated with 
CABP at 72 to 120 hours post first dose of test article will be presented by treatment group in 
the ITT population as will the number and percentage of subjects with stabilization of each 
vital sign.  These include temperature (no fever or hypothermia), SBP (> 90 mmHg), heart 
rate (< 90 bpm), RR (< 20 breaths/minutes), and PaO2 (> 60 mmHg by pulse oximetry or 
ABG).  WBC count (< 12,000 cells/mm3 or ≥ 4,000 cells/mm3) and immature neutrophils 
(< 15%). 
A summary (number and percentage of subjects) of the assessment of clinical symptoms of 
CABP at each time point throughout the study will be presented by treatment group in the 
ITT population.  Clinical symptoms of CABP (cough, pleuritic chest pain, dyspnea, and 
phlegm/sputum production) will be summarized as shift tables of score (absent, mild, 
moderate, and severe) as compared with baseline.  Percentages for clinical symptoms will be 
based on the number of subjects with a baseline and post-baseline evaluation at the time 
point of the specific clinical symptom.  The number and percentage of subjects with 
resolution of all symptoms present at baseline (back to pre-CABP status) will also be 
provided by study visit in the ITT population.  The number and percentage of subjects with 
no worsening of clinical symptoms of CABP and with the absence of new symptoms of 
CABP will also be provided by treatment group and study visit in the ITT population. 
The number and percentage of subjects with an ECR Clinical Success (microITT population) 
with an assessment of Clinical Success (based on the investigator's assessment) at the EOT 
Visit (microITT and ME-EOT populations), and with an assessment of Clinical Success at 
the PTE Visit (based on investigator's assessment, for the microITT and ME-PTE 
populations), will be tabulated by baseline MIC to omadacycline and moxifloxacin by 
pathogen (for those pathogens occurring at least 5 times in one of the treatment groups) and 
treatment group. 
At Screening and Final Follow-up visits, the subject will complete a SF-36v2® Health Survey 
(Medical Outcomes Trust, Optum™).  The SF-36v2® Health Survey has 8 subscales: physical 
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functioning, bodily pain, role limitations due to physical health problems, role limitations due 
to personal or emotional problems, emotional well-being, social functioning, energy/fatigue 
and general health perceptions.  It also has a single item that provides an indication of 
perceived change in health. Physical and mental health composite scores (PCS and MCS) are 
computed and range from 0 (lowest level of health measured by the scales) to 100 (highest 
level of health).  Descriptive statistics for the subscales, PCS and MCS will be provided at 
Screening, the Final Follow-up Visit and the change from baseline by treatment group in the 
ITT Analysis Sets. 
Microbiological Outcomes  
The per-subject microbiological response at the EOT and PTE Visits in the microITT, 
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 populations) 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 
moxifloxacin groups using the method of Miettinen and Nurminen (1985).   
Per-subject microbiological response at the PTE Visit in the microITT and ME-PTE 
populations will also be provided for infections caused by monomicrobial and polymicrobial 
Gram-positive or Gram-negative pathogens, only atypical pathogens, a mixture of both 
Gram-positive and Gram-negative pathogens, a mixture of Gram-positive and atypical 
pathogens, or a mixture of Gram-negative and atypical pathogens. 
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.  The number and percentage of 
subjects in each treatment group with a microbiologically favorable outcome will be 
tabulated for the microITT, 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 microITT 
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 >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 microITT 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, 
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including the type of specimen, pathogen, and MIC values.  Additional exploratory 
microbiological analyses may be conducted.   
Health Surveyl Outcomes 
At Screening and Final Follow-up visits, the subject will complete a SF-36v2® Health Survey 
(Medical Outcomes Trust, Optum™).  The SF-36v2® Health Survey has 8 subscales: physical 
functioning, bodily pain, role limitations due to physical health problems, role limitations due 
to personal or emotional problems, emotional well-being, social functioning, energy/fatigue 
and general health perceptions.  It also has a single item that provides an indication of 
perceived change in health. Physical and mental health composite scores (PCS and MCS) are 
computed and range from 0 (lowest level of health measured by the scales) to 100 (highest 
level of health).   
The eight SF-36 subscales, PCS, and MCS will be derived in accordance with established 
norm-based standards for the survey using the software provided by the Medical Outcomes 
Trust, Optum™.  Descriptive statistics for the eight subscales, PCS and MCS will be provided 
at Screening, the Final Follow-up Visit and the change from baseline by treatment group in 
the ITT Population. 
The change from baseline for each of the eight subscale, PCS, and MCS scores will be 
analyzed using an analysis of covariance model with treatment group as a fixed effect and 
baseline scaled score as a covariate. Least-squares mean differences, corresponding 95% 
confidence intervals, and P-values were obtained using this model.  
9.5 
Interim Analysis  
No interim analysis of efficacy is planned.   
9.6 
Subgroup Analyses  
The primary analysis (ECR) results will be assessed separately across PORT Risk Class and 
use of prior antibiotics by treatment group for both the as randomized strata and the actual 
strata as indicated on the eCRF.  For each PORT Risk Class stratum– and prior antibiotic 
stratum, a 2-sided 95% CI for the observed difference in the Early Clinical Success rates will 
be calculated for the ITT population.   
Results of the 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 PORT Risk Class and 
use of prior antibiotics by treatment group for both the as randomized strata and the actual 
strata as indicated on the eCRF.  Separately for each PORT Risk Class stratum and use of 
prior antibiotics stratum, 2-sided 95% CIs for the observed difference in clinical response in 
the ITT and CE-PTE populations will be calculated.     
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10 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 moxifloxacin, the subject will 
be analyzed in the omadacycline arm regardless of the amount of omadacycline received or 
the randomized treatment assignment.  Safety parameters include AEs, vital signs, 
electrocardiogram (ECG) parameters, and clinical laboratory parameters.  
10.1 Adverse Events  
Verbatim descriptions of AEs will be coded using MedDRA (Version to be delineated in the 
CSR).  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 infusion of active test article.  If time of the AE 
is missing and it occurred on the same date as the first infusion 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 
study drug discontinuation.  The number and percentage of subjects reporting a TEAEs 
representing administration/infusion site reaction (based on the appropriate MedDRA higher 
level term) will be tabulated by treatment group, preferred term and severity (mild, moderate, 
and severe).  The incidence of serious TEAEs, TEAEs leading to premature discontinuation 
of test article, and TEAEs leading to a dose interruption 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, and separately for the time period subjects are on iv and po test article will be 
summarized by system organ class and preferred term. 
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In addition, all AEs (including non-TEAEs), serious TEAEs, TEAEs leading to 
discontinuation of test article, and TEAEs leading to dose interruption 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 flag, severity, relationship to 
test article, relationship to study protocol, action taken with test article, non-test article action 
taken and outcome.   
10.2 Vital Signs  
Blood pressure (systolic and diastolic), respiratory rate, temperature, and pulse/heart rate will 
be summarized using descriptive statistics at the following time points:  Day 1 to Day 14,, 
ECR Visit, EOT Visit, PTE Visit, and highest and lowest post-baseline value.  Heart rate and 
blood pressure will also be summarized for the following additional time points: 30 minutes 
before and approximately 1 hour after the completion of the infusions on Day 1 and Day 2.  
Descriptive statistics of the change from baseline to each post-baseline time point and the 
highest and lowest post-baseline value 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. 
Post-baseline vital signs will be defined as clinically notable (CN) if they meet the criterion 
value or both the criterion value and the change from baseline criterion listed in Table 9.  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 9. 
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 
Temperature (oC) 
Low (CL) 
<36.0 
NA 
High (CH) 
>38.0 
NA 
 
10.3 Electrocardiogram  
Descriptive statistics for ECG parameters (heart rate, RR interval, PR interval, QRS interval, 
QT interval, and QT corrected (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) 
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corrections.  The change from baseline to the minimum and maximum post-baseline values 
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. 
The number and percentage of subjects with any post-baseline   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.  Any post-baseline ECG includes unscheduled ECGs as well as the ECG completed at 
EOT.  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 - ≤ 480 msec, > 480 - ≤ 500 msec, and 
> 500 msec) at EOT and the distribution of change from baseline in QTcF values at EOT 
(0 or less [no increase], 1-29 msec, 30-60 msec, and > 60 msec) will be summarized by 
treatment group.   
10.4 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 below. 
Table 10. 
Laboratory Parameters and Organ Class 
Organ Class 
Laboratory Parameter 
Renal 
Blood urea nitrogen (BUN) 
Renal 
Creatinine 
Liver 
Alkaline phosphatase (ALP) 
Liver 
Alanine aminotransferase (ALT) 
Liver 
Aspartate aminotransferase (AST) 
Liver 
Total bilirubin  
Liver 
Gamma-glutamyl transpeptidase (GGT) 
Electrolytes 
Calcium (Ca) 
Electrolytes 
Carbon dioxide (CO2) 
Electrolytes 
Chloride (Cl) 
Electrolytes 
Magnesium (Mg) 
Electrolytes 
Phosphorus (P) 
Electrolytes 
Potassium (K) 
Electrolytes 
Sodium (Na) 
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Table 10. 
Laboratory Parameters and Organ Class 
Organ Class 
Laboratory Parameter 
Other 
Creatinine phosphokinase (CK) 
Other 
Lipase 
 
Baseline is defined as the central lab value closest to and prior to the first dose of study drug.  
If no central lab value is available prior to the first dose of study drug, the local lab value that 
is closest to and prior to the first dose of study drug 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 
International System units) for chemistry, hematology and coagulation values, and the 
change from baseline will be summarized by treatment group at each time point (ECR Visit, 
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 will be provided which gives all laboratory results for a given 
laboratory test for subjects who have at least one 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 × upper limit of 
normal [ULN], > 5×ULN, and > 10 × ULN), an elevated bilirubin level (> 1.5 × ULN and 
> 2 × ULN) will be presented by study visit.  A listing of subjects who meet the laboratory 
criteria for Hy’s law at the same visit 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 ULN and 2) ALT or AST> 3 × ULN, ALP ≤ 2.0 × ULN, and total bilirubin > 2 × ULN. 
Detailed subject listings of all laboratory data collected during the study (local and central 
laboratory data) 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). 
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10.5 Physical Examinations  
Subject listings of all physical examination results by body system will be provided.  
Physical examination results will be coded using MedDRA (Version to be delineated in the 
CSR) .  Any changes from baseline will be recorded as AEs. 
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11 RESOURCE UTILIZATION ANALYSES  
Descriptive statistics of the following resource utilization parameters will be provided by 
treatment group: 
• Number of days in the hospital from the time of initiation of test article until discharge.   
Subjects who are not admitted to the hospital will be assigned a value of 0 for number of 
days in the hospital.  Analyses will also be completed by country due to varying clinical 
practices per country. 
• Number of days in the hospital from the time of initiation of rescue antibiotic (ie, a 
second antibiotic) therapy until discharge.  Analyses will be completed only for those 
subjects admitted to the hospital and who required a second antibiotic therapy (ie, were 
treatment failures) and separately for all subjects.  For the latter, subjects who are not 
admitted to the hospital or who did not require a second antibiotic therapy will be 
assigned a value of 0 for number of days in the hospital.  Analyses will also be completed 
by country. 
• Number of days in the hospital from the time of admission for CABP until discharge.  
Subjects who are not admitted to the hospital will be assigned a value of 0 for number of 
days in the hospital.  Analyses will also be completed by country. 
• Number of hospital re-admissions after discharge from the hospital for the CABP 
admission through the Final Follow-up Visit will be summarized. 
• Number of emergency room/department and physician visits after discharge from the 
hospital for the CABP admission through the Final Follow-up Visit will be summarized. 
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12 OTHER RELEVANT DATA ANALYSES/SUMMARIES  
12.1 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, noncompliance with dose, and use of prohibited 
medications or treatments, consent-Institutional Review Board 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 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.   
12.2 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 eCRF.  Prior medications will be summarized by 
WHODRUG ( Version to be delineated in the CSR) 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 
infusion 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 infusion of test article, or if their stop date is 
unknown or marked as continuing.   
The number and percentage of subjects who receive the following prior and concomitant 
medications will be summarized by treatment group: 
• Systemic antibacterial medications taken within 72 hours prior to first infusion of test 
article and the reasons for receipt (ITT and CE-PTE populations) 
• Systemic antibacterial medications (excluding test article) taken between first infusion of 
test article and the EOT Visit (CE-EOT population) and the reasons for receipt 
• Systemic antibacterial medications (excluding test article) taken between first infusion of 
test article and the PTE Visit (CE-PTE population) and the reasons for receipt 
• Non-antibacterial medications taken prior to informed consent through the first infusion 
of test article (ITT and Safety populations)  
• Non-antibacterial medications taken from the first infusion of test article through the 
Final Follow-up Visit (ITT and Safety populations) 
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13 REFERENCES  
1. 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. Stat Med. Dec;9(12):1447–54. 
2. Miettinen O, Nurminen M. 1985. Comparative analysis of two rates.  Stat Med. 
4(2):213-26. 
3. 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.  
4. Teflaro. Full Prescribing Information. Revision 12/2013. Forest Pharmaceuticals, Inc. St. 
Louis, MO.  
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14 APPENDICES  
Appendix 1 
Schedule of Assessments and Procedures 
Appendix 2 
Summary of Efficacy Analyses  
Appendix 3 
Adverse Event and Prior/Concomitant Medication Date Imputations 
Appendix 4 
Directionality of Worst Laboratory Parameters 
Appendix 5 
Modified Division of Microbiology and Infectious Diseases Adult Toxicity 
Table 
 
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Appendix 1 
Schedule of Assessments and Procedures 
 
Study Phase 
Screeningb 
iv 
Treatment 
iv or po Treatment 
EOT and Follow-up 
Study Daya 
-1 
1 
2 
3 
4 
inpatient 
only 
5 
6 
inpatient 
only 
7 d 
8 
9 
10 
11 
12 
13 
EOTe 
PTE 
FFUf 
inpatient 
only 
inpatient only 
 
ECR visit 
must occur 72 
to 120 hours 
after first dose 
c 
→ 
Perform only if study treatment is 
continuing and this is not the EOT 
visit. Treatment past 10 days is 
allowed for subjects with bacteremia at 
Screening. 
5 to 10 
days after 
last day 
of   
therapy 
30 to 
37 days 
after 
Day 1 
Screening and eligibility procedures 
Signed informed consentg 
X 
Medical history, current medical 
conditions, demography 
X 
Assessment of CABP symptom 
severityh 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Chest X-ray or CT scani 
X 
PORT risk class, ABG (or pulse 
oximetry)j 
X 
Blood and urine samples for local lab 
hematology/chemistry/pregnancyk 
X 
SF-36v2® Health Survey 
X 
 
X 
Review of Inclusion/Exclusion criteria 
X 
Randomization (if Eligible) 
X 
Clinical Procedures and Test Article Administration 
Test article administration and 
accountabilityl 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Physical examinationm 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signsn 
X 
Xo 
Xo 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
12-lead ECGw 
X 
X 
Blood for central lab tests: 
hematology/chemistry/pregnancy 
Xp 
X 
Xp 
Xp 
AEs, SAEs, and mortalityq 
X 
X  
X 
Prior & concomitant medicationsr 
X 
X  
X 
Plasma samples (in heparin) for PK 
analysess 
X 
X 
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Study Phase 
Screeningb 
iv 
Treatment 
iv or po Treatment 
EOT and Follow-up 
Study Daya 
-1 
1 
2 
3 
4 
inpatient 
only 
5 
6 
inpatient 
only 
7 d 
8 
9 
10 
11 
12 
13 
EOTe 
PTE 
FFUf 
npatient only
inpatient only 
Assessment for po switch or need for 
continued therapyt 
X ---------------------------------------------------------------------- X 
Investigator’s Assessment of Clinical 
Response 
X 
X 
X 
Assessment of Resource Utilization 
X  
X 
Microbiological Procedures 
Blood cultureu 
X 
As Clinically Indicated 
Respiratory culture & Gram stainv 
X 
X 
X 
Urine for Local lab Legionella 
pneumophila and Streptococcus 
pneumoniae antigen test 
X 
Blood for Central lab Legionella 
pneumophila, Mycoplasma 
pneumoniae & Chlamydophila 
pneumoniae serology 
X 
X 
ABG = arterial blood gas, AE = adverse event, BP = blood pressure, β-hCG = beta-human Chorionic Gonadotropin, CABP = community-acquired bacterial 
pneumonia, CT = computed tomography, CXR = chest X-ray, ECG = electrocardiogram, ECR = Early Clinical Response, eCRF = electronic case report form, 
EOT = end of treatment, FFU = final follow-up, ICF = informed consent form, iv = intravenous, IxRS = interactive voice/web response system, 
PK = pharmacokinetics, po = per oral, PORT = Pneumonia Patient Outcomes Research Team, PTE = post-therapy evaluation, RR = respiratory rate, SAE = serious 
adverse event. 
a Study Day 1 is the first day of test article administration. Subsequent study days may be consecutive calendar days. 
b Following the signing of an ICF, all Screening evaluations (except radiographic confirmation of pneumonia), should be completed within the 24 hours prior to 
randomization. The radiographic confirmation of pneumonia should be completed within the 48 hours prior to the first dose of test article. 
c The ECR visit must be conducted within 72 to 120 hours after the first dose of test article; the study day for this visit could be on Days 4, 5, or 6, depending on 
the time of the first dose of test article. Subjects who remain hospitalized (inpatients) during study treatment will have daily assessments. For subjects who 
are not hospitalized, only 1 visit is required between Study Days 4 to 6. 
d If the investigator determines that no additional treatment is required beyond Day 7, the Day 7 visit can be considered the EOT visit and a separate EOT visit is 
not required. 
e To be conducted on the day of, or within 2 days following the last dose of test article. Should also be conducted for any prematurely withdrawn subject on the 
day of, or within 2 days following the last dose of test article. 
f 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 ongoing AEs, clinically significant laboratory findings or ECG abnormalities noted at or after the PTE visit. Otherwise, the visit must 
be conducted in person. 
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g Written and signed ICF must be obtained before any study assessment is performed. 
h The investigator should assess the severity of the subject’s CABP symptoms of cough, sputum production, pleuritic chest pain, and dyspnea based upon 
the Community-Acquired Bacterial Pneumonia Subject Symptom Severity Guidance Framework for Investigator Assessment (Appendix 3 of the 
protocol). 
iSubjects must have a confirming CXR or CT scan consistent with acute bacterial pneumonia within the 48 hours prior to the first dose of test article. 
jOnly subjects with a PORT Risk Class of III or IV are eligible for enrollment. 
k Local laboratory hematology and chemistry evaluations required for assessing subject eligibility, including (at minimum): white blood cell count, serum 
  transaminases and bilirubin levels, and serum or urine pregnancy test (for women only). 
l Subjects should receive their first dose of test article within 4 hours after randomization. The total duration of test article therapy (iv plus po) for all subjects 
 will be 7-10 days (up to 14 days for subjects with bacteremia identified at Screening). The pharmacist or designee will be unblinded to prepare appropriate  
 iv doses of the IxRS identified test article. An unblinded field monitor will perform drug accountability and review the pharmacist’s records. Oral test article  
 may be dispensed and reconciled by blinded or unblinded personnel. All oral doses should be taken in a fasted state (no food, antacids or multivitamins  
 containing multivalent cations [eg, aluminum, magnesium, calcium, bismuth, iron, or zinc] or drink except water for at least 4 hours before dosing). After  
 dosing, no food is permitted for 2 hours as well as no dairy products, antacids, or multivitamins containing multivalent cations (eg, aluminum, magnesium,  
 calcium, bismuth, iron, or zinc) for 4 hours. Subjects discharged with po test article will be asked to return all unused test article and packaging at each visit.At  
  the EOT visit subjects discharged with po test article will return any remaining unused po test article and site staff will perform accountability. 
m A full physical examination will be completed at Screening. Thereafter, abbreviated physical examinations may be performed at the indicated timepoints. 
  Additional physical examinations may be performed as clinically indicated. 
   n Vital signs include body temperature, BP, pulse oximetry, heart rate, and RR. 
o Blood pressure and heart rate should be measured within 30 minutes before, and approximately 1 hour (± 15 minutes) after the completion of the infusions 
 on Day 1 and Day 2. 
p Blood will be collected from all female subjects for a serum β-hCG pregnancy test at the Central Laboratory at the Screening, EOT and PTE visits. 
q AEs and SAEs will be recorded from the time of signing of the ICF to the Final Follow-up assessment. 
r Medications administered within the 7 days prior to the date of signing the ICF or during the Screening phase will be recorded in the eCRF, as will all  
  medications and significant non-drug therapies administered after the first dose of test article. 
s PK sample collection to occur on Day 1 (2 to 3 hours after the start of Dose 1) and at the ECR visit (Days 4 to 6; at any time during the visit). 
t At any time after the second day of iv treatment (Day 2), the subject may be switched to po medication based upon determination of clinical stability. Refer 
  to Section 7.6.5 of the protocol for required criteria to switch to po treatment. The first po dose should be administered in the morning, 12-24 hours after the  
  last iv dose. Test article administration and total duration of study treatment are outlined in footnote l. 
u If bacteria are isolated from baseline blood cultures, repeat blood cultures must be collected on the day that the positive blood culture is detected. If subsequent  
  blood cultures are also positive, repeat the blood cultures as necessary until negative blood cultures are obtained. 
v Culture and Gram stain from an adequate quality sputum specimen or other respiratory specimen. At the EOT and/or PTE visit, respiratory specimen cultures  
  and Gram stains should be obtained only for subjects who are Clinical Failures and require alternative antibacterial treatment for CABP. 
w Additional ECGs can be performed as clinically indicated, at the discretion of the investigator. 
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Appendix 2 
Summary of Efficacy Analyses  
 
72 to 120 hours  
post first dose 
End of Therapy Visit 
(EOT) 
Post Treatment 
Evaluation Visit (PTE) 
ITT 
ECR  
IA 
IA 
MicroITT 
ECR  
ECR (by pathogen) 
ECR (by pathogen and 
MIC) 
Micro (by subject) 
Micro (by pathogen) 
IA 
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) 
 
 
 
 
 
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Confidential and Proprietary 
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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 study drug 
Date of first dose of study drug 
M and/or Y not same as date of first dose of study drug 
First day of month 
D and M 
Y same as Y of first dose of study drug 
Date of first dose of study drug 
Y prior to Y of first dose of study drug but same as Y 
of screening date 
Date of screening date 
D, M, Y 
None - date completely missing 
Date of first dose of study drug 
Stop date 
for AEs 
D 
M and Y same as M and Y of last dose of study drug 
Date of last dose of study drug 
M and/or Y not same as date of last dose of study drug 
Use last day of month 
D and M 
Y same as Y of last dose of study drug 
Date of last dose of study drug 
Y not same as Y of last dose of study drug 
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 study drug, it will be assumed that the 
medication was received prior to the first dose of study drug. 
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 
study drug, it will be assumed that the medication was received prior to the first dose 
of study drug unless the indication notes that the medication was received after the 
first dose of study drug. 
 
Stop date for con 
meds  
Non-
Antibacterial 
If it cannot be determined whether or not the stop date of a medication (nonantibacterial) is 
after the first dose of study drug, it will be assumed that the medication was received 
after the first dose of study drug 
 
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 
study drug, it will be assumed that the medication was received after the first dose of 
study drug unless the indication notes that the medication was received prior to the 
first dose of study drug.  If it cannot be determined whether the antibacterial was 
received prior to the assessment of Early Clinical Response, the EOT and/or the PTE 
Visit, the antibacterial will be assumed to have been received through the PTE Visit. 
 
 
Page 60 of 64


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Appendix 4 
Directionality of Worst Laboratory Parameters 
Laboratory 
Test 
Parameter 
Worst Value 
Hematology 
Hematocrit 
Lowest value 
 
Red blood cell count 
Lowest value 
 
Mean corpuscular hemoglobin 
Lowest value 
 
Mean corpuscular hemoglobin concentration 
Lowest value 
 
Hemoglobin 
Lowest value 
 
Mean corpuscular volume 
Lowest value 
 
White blood cell count 
Lowest value 
 
Platelets 
Eosinophils/Differential                           
Neutrophils  
Lowest value 
Highest Value 
Lowest Value 
Chemistry 
 
 
 
Alkaline phosphatase (ALP) 
Highest value 
 
Alanine aminotransferase (ALT) 
Highest value 
 
Aspartate aminotransferase (AST) 
Highest value 
 
Bicarbonate 
Blood glucose 
Blood urea nitrogen 
Lowest value 
Both highest value and lowest value 
Highest value 
 
Calcium 
Both highest value and lowest value 
 
Chloride 
Both highest value and lowest value 
 
Creatinine 
Highest value 
 
Creatine phosphokinase (CK) 
Highest value 
 
Gamma-glutamyl transpeptidase (GGT) 
Highest value 
 
Lipase 
Highest value 
 
Magnesium 
Both highest value and lowest value 
 
Phosphorus 
Both highest value and lowest value 
 
Potassium 
Both highest value and lowest value 
 
Sodium 
Both highest value and lowest value 
 
Total bilirubin 
Highest value 
Coagulation 
Prothrombin time international normalized 
ratio (INR) 
Highest value 
 
Page 61 of 64


Omadacycline (PTK 0796) 
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Confidential and Proprietary 
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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.  Grades for enzymes were modified as 
indicated in the table below. 
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 
 
 
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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 
 
 
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