Conditions: Community Acquired Bacterial Pneumonia
Keywords: Pneumonia
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 860
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the safety and efficacy of delafloxacin compared to moxifloxacin in the treatment of adult patients with community-acquired pneumonia.

Detailed description:
The purpose of this study is to determine if delafloxacin, an investigational drug, is safe and effective in the treatment of community-acquired bacterial pneumonia compared with moxifloxacin, or linezolid in the case of confirmed MRSA.

Arms:
arm 1: IV delafloxacin with potential to switch to oral delafloxacin arm 2: IV moxifloxacin with potential to switch to oral moxifloxacin, and potential to switch moxifloxacin to IV linezolid for confirmed MRSA

Interventions: intervention 1: Delafloxacin intervention 2: Moxifloxacin intervention 3: Linezolid
Intervention descriptions: intervention 1: Antibacterial agent, 300 mg IV, Q12H for at least 6 doses with potential to switch to 450 mg oral tablet, Q12H for up to 20 doses total intervention 2: Antibacterial Agent, 400 mg IV, Q24H for at least 3 doses with potential to switch to 400 mg oral over-encapsulated tablet, Q24H for up to 10 doses total intervention 3: Antibacterial Agent, at local investigator discretion, subjects in the moxifloxacin arm with confirmed MRSA can switch to linezolid 600 mg IV Q12H for all remaining doses

Protocol document:
Prot_000.pdf: 
CLINICAL STUDY PROTOCOL 
IND 76,096  
IND 62,772 
A PHASE 3, MULTICENTER, RANDOMIZED, DOUBLE-BLIND, COMPARATOR-
CONTROLLED STUDY TO EVALUATE THE SAFETY AND EFFICACY OF 
INTRAVENOUS TO ORAL DELAFLOXACIN IN ADULT SUBJECTS WITH 
COMMUNITY-ACQUIRED BACTERIAL PNEUMONIA 
ML-3341-306 
Sponsor: 
Melinta Therapeutics, Inc. 
300 George Street, Suite 301 
New Haven, CT 06511 
Sponsor Contact: 
Laura Lawrence 
Director of Clinical Operations 
Telephone: 312-724-9400 
Email: clinicaltrials@melinta.com 
Medical Monitor: 
Sue Cammarata, MD 
Chief Medical Officer 
Telephone: 312-724-9400 
Version of Protocol: 
Amendment 3 
Date of Protocol: 
04 December 2017 
Previous Date and Version 
03 September 2015, Original 
15 December 2015, Amendment 1 
29 March 2016, Amendment 2 
EudraCT Number: 
2015-003026-14 
CONFIDENTIAL 
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 Melinta Therapeutics, Inc. 
The study will be conducted according to the International Conference on Harmonisation 
harmonised tripartite guideline E6(R2): Good Clinical Practice, FDA and EU clinical trial 
guidelines. (Sites in regions which have not yet implemented the E6(R2) addendum are 
subjecting themselves to it voluntarily.) 
NCT02679573


Melinta Therapeutics, Inc. 
Delafloxacin 
Protocol ML-3341-306 
Version Date: 04 December 2017 
Page 2 
Table of Contents 
Table of Contents ...................................................................................................................... 2 
List of Tables ............................................................................................................................. 7 
List of Figures ........................................................................................................................... 7 
Protocol Approval ..................................................................................................................... 8 
Study Acknowledgement .......................................................................................................... 9 
Protocol Synopsis.................................................................................................................... 10 
List of Abbreviations............................................................................................................... 24 
1. Introduction ....................................................................................................................... 27
1.1 
Microbiology ............................................................................................................27 
1.1.1 Mechanism of Action Pharmacology ............................................................27 
1.1.2 In Vitro Studies .............................................................................................28 
1.1.3 In Vivo Studies ..............................................................................................28 
1.2 
Pharmacokinetics, Safety, and Efficacy of Delafloxacin ..........................................29 
1.2.1 Pharmacokinetics, Safety, and Tolerability of IV and Oral Delafloxacin .....29 
1.2.2 Phase 2 Study for Community-Acquired Pneumonia: Study M01-344 .......30 
1.2.3 Treatment of Acute Bacterial Skin and Skin Structure Infections: 
Study RX-3341-302 ......................................................................................31 
1.3 
Dose Selection of Delafloxacin for This Study ........................................................32 
1.4 
Comparator Selections for This Study ......................................................................33 
2. Study Objectives ............................................................................................................... 34
2.1 
Primary Objective .....................................................................................................34 
2.2 
Secondary Objective(s) .............................................................................................34 
3. Investigational Plan ........................................................................................................... 36
3.1 
Study Design .............................................................................................................36 
3.2 
Selection of Study Sample ........................................................................................39 
3.2.1 Inclusion Criteria ..........................................................................................39 
3.2.2 Exclusion Criteria .........................................................................................41 
3.3 
Patient Withdrawal from Treatment or Study ...........................................................43 
3.3.1 Reasons for Withdrawal ................................................................................43 
3.3.2 Handling of Withdrawals ..............................................................................44 
3.3.3 Replacements ................................................................................................45 


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3.4 
Study Procedures ......................................................................................................45 
3.4.1 Study Visits ...................................................................................................45 
3.4.1.1 
Screening.....................................................................................45 
3.4.1.2 
Day 1 ...........................................................................................46 
3.4.1.3 
Daily While on IV Therapy.........................................................47 
3.4.1.4 
Early Clinical Response at 96 Hours (± 24 hours) .....................48 
3.4.1.5 
Day 5 (+ 1 Day) ..........................................................................48 
3.4.1.6 
Day 7 (+ 1 Day) ..........................................................................49 
3.4.1.7 
End of IV Treatment ...................................................................50 
3.4.1.8 
End of Treatment (EOT) or Early Termination ...........................50 
3.4.1.8.1 Criteria for Determining Treatment Duration ...................... 50 
3.4.1.8.2 End of Treatment or Early Termination Procedures ............ 50 
3.4.1.9 
Reminder Contact (3-9 Days After Last Dose) ...........................51 
3.4.1.10 
Test of Cure (TOC Visit, 5-10 Days After Last Dose of 
Study Drug) .................................................................................51 
3.4.1.11 
Follow-up Visit (FU, Day 28 ± 2 Days)......................................52 
3.4.1.12 
Early Withdrawal Procedures .....................................................52 
3.4.2 Efficacy Assessments ....................................................................................53 
3.4.2.1 
Clinical Evaluation......................................................................53 
3.4.3 Study Assessments ........................................................................................53 
3.4.3.1 
Chest Radiography ......................................................................53 
3.4.3.2 
Microbiological Assessments......................................................54 
3.4.3.2.1 Respiratory Culture .............................................................. 55 
3.4.3.2.2 Blood Culture ....................................................................... 56 
3.4.3.2.3 Urine Antigen Testing .......................................................... 56 
3.4.3.2.4 Nasopharyngeal and Oropharyngeal Testing ....................... 56 
3.4.3.2.5 Serology ............................................................................... 56 
3.4.3.3 
Demographic Data/Medical History ...........................................56 
3.4.3.4 
Prior Medications ........................................................................56 
3.4.3.5 
Clinical Laboratory Tests ............................................................57 
3.4.3.6 
Pharmacokinetic Blood Sample Collections ...............................57 
3.4.3.7 
Vital Sign Measurements ............................................................58 
3.4.3.8 
Physical Examination..................................................................58 
3.4.3.9 
Electrocardiogram .......................................................................58 
3.4.3.10 
Health-Related Quality-of-Life Assessment ...............................59 
3.4.3.11 
Concomitant Medications ...........................................................59 
3.4.3.12 
Post-Treatment Medications .......................................................60 


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3.4.4 Safety Assessments .......................................................................................60 
3.4.4.1 
Adverse Event Definitions ..........................................................60 
3.4.4.2 
Eliciting and Documenting Adverse Events ...............................61 
3.4.4.3 
Reporting Adverse Events...........................................................62 
3.4.4.4 
Assessment of Severity ...............................................................63 
3.4.4.5 
Assessment of Causality .............................................................63 
3.4.4.6 
Reporting Serious Adverse Events ..............................................64 
3.4.4.7 
Follow-up of Subjects Reporting Serious Adverse Events .........65 
3.4.4.8 
Safety Monitoring Committee ....................................................65 
3.4.4.9 
Pregnancy ....................................................................................65 
3.4.4.10 
Criteria for Stopping Study .........................................................65 
3.5 
Overdose Management .............................................................................................66 
3.6 
Study Treatments ......................................................................................................66 
3.6.1 Method of Assigning Subjects to Treatment Groups ....................................66 
3.6.2 Treatments Administered ..............................................................................66 
3.6.3 Description of Investigational Product .........................................................67 
3.6.4 Management of Clinical Supplies .................................................................68 
3.6.4.1 
Study Drug Packaging and Storage ............................................68 
3.6.4.2 
Test Article Accountability .........................................................68 
3.6.4.3 
Blinding.......................................................................................69 
3.6.5 Breaking the Blind ........................................................................................70 
3.6.6 Treatment Compliance ..................................................................................71 
3.6.7 Allowed Concomitant Treatment ..................................................................71 
3.6.8 Prohibited Medications and Restrictions ......................................................71 
3.7 
Statistical Analysis Plans ..........................................................................................72 
3.7.1 Endpoints ......................................................................................................72 
3.7.1.1 
Primary Efficacy Endpoint .........................................................73 
3.7.1.2 
Secondary Efficacy Endpoints ....................................................73 
3.7.1.3 
Exploratory Endpoints ................................................................74 
3.7.1.4 
Health-Related Quality-of-Life Endpoints .................................74 
3.7.1.5 
Pharmacokinetic Endpoints ........................................................74 
3.7.2 Endpoint Definitions .....................................................................................74 
3.7.2.1 
Early Clinical Response ..............................................................74 
3.7.2.2 
Clinical Outcome at EOT and TOC ............................................75 
3.7.2.3 
Microbiologic Response .............................................................75 
3.7.3 Safety Endpoints ...........................................................................................76 


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3.7.4 Sample Size Calculations ..............................................................................77 
3.7.5 Analysis Populations .....................................................................................77 
3.8 
Statistical Analysis ....................................................................................................79 
3.8.1 Demographics and Other Baseline Characteristics .......................................79 
3.8.2 Subject Disposition .......................................................................................79 
3.8.3 Primary Efficacy Analysis ............................................................................80 
3.8.4 Sensitivity Analysis of the Primary Endpoint for each Region 
(FDA and EMA) ...........................................................................................81 
3.8.5 Subgroup Analyses of the Primary Endpoint for each Region 
(FDA and EMA) ...........................................................................................81 
3.8.6 Secondary Efficacy Analyses ........................................................................82 
3.8.6.1 
Early Clinical Response with the Addition of Improvement in 
Vital Signs and No Worsening of the 4 Symptoms Required 
as Response .................................................................................82 
3.8.6.2 
Clinical Outcome at EOT and TOC ............................................82 
3.8.6.3 
Early Clinical Response for Subjects in the MITT, ModITT 
and ModCE Populations .............................................................83 
3.8.6.4 
Microbiologic Response .............................................................83 
3.8.6.5 
All-Cause Mortality ....................................................................83 
3.8.7 Exploratory Analyses ....................................................................................83 
3.8.8 Health-Related Quality-of-Life Analyses .....................................................84 
3.8.9 Interim Analysis ............................................................................................84 
3.8.10 Safety Analyses .............................................................................................84 
3.8.11 Adverse Events .............................................................................................84 
3.8.12 Vital Sign Measurements and Body Temperature .........................................85 
3.8.13 Clinical Laboratory Test Results ...................................................................85 
3.8.14 Physical Examination Findings.....................................................................85 
3.8.15 Concomitant Medications .............................................................................86 
3.8.16 Pharmacokinetic Analyses ............................................................................86 
3.8.17 Missing Data .................................................................................................86 
4. Investigator’s Obligations ................................................................................................. 87 
4.1 
Confidentiality ..........................................................................................................87 
4.2 
Ethics Committee/Institutional Review ....................................................................87 
4.3 
Subject Consent ........................................................................................................88 
4.4 
Study Reporting Requirements .................................................................................88 
4.5 
Financial Disclosure and Obligations .......................................................................88 
4.6 
Investigator Documentation ......................................................................................89 


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4.7 
Study Conduct...........................................................................................................90 
4.8 
Data Collection .........................................................................................................90 
4.8.1 Case Report Forms and Source Documents..................................................90 
4.9 
Adherence to Protocol ..............................................................................................90 
4.10 Reporting Adverse Events ........................................................................................90 
4.11 Investigator’s Final Report .......................................................................................90 
4.12 Records Retention .....................................................................................................91 
4.13 Publications ...............................................................................................................91 
5. Study Management ........................................................................................................... 92 
5.1 
External Data Monitoring Groups ............................................................................92 
5.2 
Monitoring ................................................................................................................92 
5.2.1 Monitoring of the Study ................................................................................92 
5.2.2 Inspection of Records ...................................................................................92 
5.3 
Management of Protocol Amendments and Deviations ...........................................92 
5.3.1 Modification of the Protocol .........................................................................92 
5.3.2 Protocol Deviations .......................................................................................93 
5.4 
Study Termination .....................................................................................................93 
5.5 
Final Report ..............................................................................................................93 
6. References ......................................................................................................................... 95 
7. Appendices ........................................................................................................................ 97 
7.1 
Appendix: Schedule of Events ..................................................................................98 
7.2 
Appendix: PSI/PORT Score: Pneumonia Severity Index for CAP .........................101 
7.3 
Appendix: CURB-65 ..............................................................................................103 
7.4 
Appendix: Child-Pugh Classification of Severity of Liver Disease .......................104 
7.5 
Appendix: Cockcroft-Gault Formula ......................................................................105 
7.6 
Appendix: SF-12v2® Health Survey .......................................................................106 
7.7 
Appendix: Quality-of-Life Questions .....................................................................109 
7.8 
Appendix: Definitions of Symptom Intensity ......................................................... 110 
7.9 
Appendix: Protocol Amendment 1 ......................................................................... 111 
7.9.1 Overview of Changes .................................................................................. 111 
7.9.2 Changes to the Protocol Text ...................................................................... 111 


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7.10 Appendix: Protocol Amendment 2 .........................................................................126 
7.10.1 Overview of Changes ..................................................................................126 
7.10.2 Changes to the Protocol Text ......................................................................127 
7.11 Appendix: Protocol Amendment 3 .........................................................................133 
7.11.1 Overview of Changes ..................................................................................133 
7.11.2 Changes to the Protocol Text ......................................................................134 
List of Tables 
Table 1-1 
Proportion of Patients Achieving Endpoints (Study M01-344) ...................... 30 
Table 1-2 
Target Pathogen Eradication Rates at the TOC Visit (Study M01-344) ......... 30 
Table 1-3 
Proportion of Patients Achieving Endpoints (Study RX-3341-302)............... 31 
Table 3-1 
Treatment Regimens ....................................................................................... 70 
List of Figures 
Figure 3-1 
Schematic of Study Design ............................................................................. 38 


Melinta Therapeutics, Inc. 
Protocol ML-3341-306 
Protocol Approval 
Delafloxacin 
Version Date: 04 December 2017 
Study Title 
A Phase 3, Multicenter, Randomized, Double-Blind, Comparator-
Controlled Study to Evaluate the Safety and Efficacy of Intravenous to 
Oral Delafloxacin in Adult Subjects with Community-Acquired 
Bacterial Pneumonia 
Protocol Number ML-3341-306 
Protocol Date: 
04 December 2017 
Protocol accepted and approved by: 
Sue Cammarata, MD 
Chief Medical Officer 
Melinta Therapeutics, Inc. 
300 TriState International, Suite 272 
Lincolnshire, IL 60069, USA 
Signature 
Oil)~\[ 
Date 
Page8 


Melinta Therapeutics, Inc. 
Delafloxacin 
Protocol ML-3341-306 
Version Date: 04 December 2017 
Page 9 
Study Acknowledgement 
I confirm that I have read protocol ML-3341-306, entitled “A Phase 3, Multicenter, 
Randomized, Double-Blind, Comparator-Controlled Study to Evaluate the Safety and 
Efficacy of Intravenous to Oral Delafloxacin in Adult Subjects with Community-Acquired 
Bacterial Pneumonia.” I understand the study protocol and will conduct the study according 
to the procedures therein and according to the principles of good clinical practice. 
Principal Investigator: 
 
 
 
 
 
Signature 
 
Date 
 
 
 
Print Name 
 
 
 


Melinta Therapeutics, Inc. 
Delafloxacin 
Protocol ML-3341-306 
Version Date: 04 December 2017 
Page 10 
Protocol Synopsis 
Title: 
A Phase 3, Multicenter, Randomized, Double-Blind, Comparator-
Controlled Study to Evaluate the Safety and Efficacy of 
Intravenous to Oral Delafloxacin in Adult Subjects with 
Community-Acquired Bacterial Pneumonia 
Sponsor: 
Melinta Therapeutics, Inc. 
300 George Street, Suite 301 
New Haven, CT  06511 
Study Phase: 
3 
Study Sites: 
Approximately 150 global study sites 
Objectives: 
FOR FDA 
Primary Objective:  
• To assess the clinical efficacy of intravenous (IV) to oral 
delafloxacin in adult subjects with community-acquired 
bacterial pneumonia (CABP) based on Early Clinical Response 
(ECR) defined as improvement at 96 hours (± 24 hours) after 
the first dose of study drug compared to IV to oral 
moxifloxacin in the Intent-to-Treat (ITT) population. 
Secondary Objective(s):  
• To assess the clinical efficacy of IV to oral delafloxacin in 
adult subjects with CABP based on Clinical Outcome at the 
Test of Cure (TOC) visit, 5 to 10 days after the last dose of 
study drug, compared to IV to oral comparator study drug arm 
in the CE and ITT populations. 
• To assess the clinical efficacy of IV to oral delafloxacin in 
adult subjects with CABP based on ECR compared to IV to 
oral moxifloxacin in the microbiologic ITT (MITT) 
population. 
• To assess the microbiologic response to delafloxacin in 
respiratory pathogens. 
• To assess the safety and tolerability of IV to oral delafloxacin 
in adult subjects with CABP. 
• To assess the all-cause mortality in adult subjects with CABP 
on Day 28.  
• To assess delafloxacin pharmacokinetics (PK) in adult subjects 
with CABP. 
FOR EMA 
Primary Objective:  
• To assess the clinical efficacy of IV to oral delafloxacin in 


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adult subjects with CABP at 5 to 10 days after the last dose of 
study drug (TOC) compared to IV to oral comparator study 
drug arm in the Modified ITT (ModITT) and Modified CE 
(ModCE) populations.  
Secondary Objective(s): 
• To assess the clinical efficacy of IV to oral delafloxacin in 
adult subjects with CABP based on ECR defined as 
improvement at 96 hours (± 24 hours) after the first dose of 
study drug compared to IV to oral moxifloxacin in the ModITT 
and ModCE populations. 
• To assess the clinical efficacy of IV to oral delafloxacin in 
adult subjects with CABP at the TOC visit compared to IV to 
oral moxifloxacin in the Modified MITT (ModMITT) and 
Modified ME (ModME) populations. 
• To assess the microbiologic response to delafloxacin in 
respiratory pathogens in the ModMITT and ModME 
populations. 
• To assess the safety and tolerability of IV to oral delafloxacin 
in adult subjects with CABP in safety population. 
• To assess the all-cause mortality in adult subjects with CABP 
on Day 28 in ModITT. 
• To assess delafloxacin PK in adult subjects with CABP in PK 
population. 
Study Population: 
Adult male and female subjects 18 years of age or older with 
clinical and radiographic evidence of CABP and a Pneumonia 
Patient Outcomes Research Team (PORT) risk class of II, III, IV, 
or V (Pneumonia Severity Index [PSI] score > 50).  
Inclusion Criteria: 
1. Male and female subjects 18 years of age or older. 
• Patients from a nursing home setting may be enrolled if 
they are normally ambulatory and are not on enteral 
feeding 
2. Evidence of acute onset of CABP.  
Subjects must have at least 2 of the following clinical signs and 
symptoms (new or worsening): 
• Cough 
• Production of purulent sputum consistent with a bacterial 
infection 
• Difficulty breathing (dyspnea) 
• Chest pain due to pneumonia 
AND 


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Subjects must also have at least 2 of the following findings: 
• Fever (oral temperature > 38°C or equivalent) within 
24 hours prior to randomization 
• Hypothermia (oral temperature < 35°C or equivalent) 
within 24 hours prior to randomization  
• Tachycardia (> 100 beats per minute) 
• Tachypnea (elevated respiratory rate > 18 breaths per 
minute) 
AND 
Subjects must also have at least 1 of the following findings:  
• Hypoxemia (oxygen saturation < 90% or PaO2 
< 60 mmHg) on room air or with subject’s baseline 
(pre-CABP under study) supplemental oxygen flow rate 
• Clinical evidence of pulmonary consolidation and/or 
presence of pulmonary rales 
• An elevated white blood cell count (WBC) > 10,000/mm3 
or 15% immature neutrophils (bands), regardless of total 
peripheral WBC count or leukopenia with WBC 
< 4500/mm3 
3. Presence of lobar, multilobar, or patchy parenchymal 
infiltrate(s) consistent with acute bacterial pneumonia on a 
pulmonary imaging study (e.g., chest radiograph [CXR] 
[posteroanterior and lateral preferred; single view acceptable if 
conclusive] or computed tomography [CT] of thorax), as per 
local standard of care, within 48 hours before the first dose of 
study drug.  
4. PORT risk class of II, III, IV, or V (PSI score greater than 50). 
Subjects may be initially pre-screened based on meeting 
CURB-65 score of 2 to 4. PORT risk class II will be limited to 
no more than 25% of randomized subjects.  
5. In the opinion of the investigator, the subject must be a suitable 
candidate for possible IV to oral switch antibiotic therapy and 
must also be able to swallow large tablets/capsules intact 
without crushing. 
6. Females of childbearing potential (including females less than 
2 years post-menopausal) must have a negative pregnancy test 
prior to enrollment. Sexually active women and men with 
partners of childbearing potential must agree to use an 
acceptable form of contraception, as determined by the 
investigator (e.g., abstinence, oral contraceptives, double 
barrier methods, hormonal injectable, transdermal, or 
implanted contraceptives, tubal ligation, or vasectomy) during 
participation in the study and through the Follow-up Visit 
(Day 28). Female partners of male subjects should also use an 


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additional reliable method of contraception, such as spermicide 
with male or female condoms, cervical sponge, intrauterine 
device, cervical cap or diaphragm, or oral, implantable, 
transdermal, or injectable contraceptives during study and 
through the Follow-up Visit (Day 28). 
7. In the opinion of the investigator, the subject must be able and 
willing to comply with protocol requirements. 
8. A written, voluntarily signed informed consent must be 
obtained from the subject or, where allowed by local 
regulations, legally authorized representative, in accordance 
with local regulations, before the initiation of any study-related 
procedures. The subject or legally authorized representative 
must be able to read and/or understand the informed consent 
form as required by the legal jurisdiction and the institutional 
review board/independent ethics committee where the subject 
is treated. 
Exclusion Criteria: 
1. Medical history of significant hypersensitivity or allergic 
reaction to antibiotics of the quinolone or oxazolidinone class 
or study drug excipients in the judgment of the investigator.  
2. Women who are pregnant or lactating. 
3. Any infection expected to require other systemic antibacterial 
agents in addition to study drug. 
4. Receipt of systemic antibiotic therapy in the 7 days before 
enrollment unless one or more of the following are 
documented: 
• The subject received at least 48 hours of antibiotic therapy 
for CABP and the clinic notes document treatment failure 
(i.e., not by patient history or pulmonary imaging alone) 
with new or worsening symptoms while on pre-study 
therapy, or identification of a respiratory pathogen that is 
resistant to a pre-study antibiotic which would be 
susceptible to study drug (delafloxacin or moxifloxacin) in 
subjects with new or worsening signs and symptoms of 
CABP.  
• The subject received 1 dose of a single, potentially 
effective, short-acting antimicrobial drug or a short-acting 
antimicrobial drug regimen for treatment of the CABP 
under study within 24 hours of enrollment. (Note: 1 dose of 
a regimen is defined as the standard therapy for CABP at 
the study site.) Subjects who received prior antimicrobial 
drug under this criterion will be limited to no more than 
25% of total randomized subjects. 
5. Respiratory infection confirmed or suspected to be secondary 
to hospital-acquired or ventilator-associated pneumonia or that 
requires treatment in an intensive care setting (because they are 


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hemodynamically unstable, and/or likely to need mechanical 
ventilation) at the time of informed consent. 
6. Intubated at the time of informed consent or clinical 
presentation with pneumonia that would require invasive 
mechanical ventilation. 
7. Current or suspected diagnosis of: 
• Viral pneumonia, fungal pneumonia, including 
Pneumocystis jiroveci pneumonia 
• Aspiration pneumonia 
• Other noninfectious causes of pulmonary infiltrates (e.g., 
pulmonary embolism, hypersensitivity pneumonia, 
congestive heart failure) 
• Primary or metastatic lung cancer 
• Cystic fibrosis 
• Active or suspected tuberculosis 
• Empyema (not including sterile parapneumonic effusions) 
8. Known anatomical or pathological bronchial obstruction, or a 
history of bronchiectasis, or documented Global initiative for 
chronic Obstructive Lung Disease (GOLD) Stage 4 chronic 
obstructive pulmonary disease, or a history of post obstructive 
pneumonia. 
9. Severely compromised immune system, e.g.: 
• Known absolute neutropenia (absolute neutrophil count 
< 500 cells/µL) 
• Known human immunodeficiency virus infection (HIV) 
with a CD4 count < 350 cells/µL within the last 4 months 
• Cancer chemotherapy or radiation in the last 3 months 
• Hematological malignancy 
• Bone marrow transplantation 
• Chronic steroid use (> 20 mg prednisone per day or 
equivalent) prior to enrollment 
10. Known history of Child-Pugh Class B or C liver disease and/or 
presence or possible signs of significant hepatic disease, or 
alanine aminotransferase (ALT) > 3× the upper limit of normal 
(ULN). 
11. Severe renal disease, or creatinine clearance (CrCl) 
≤ 29 mL/min using Cockcroft-Gault formula, or need for 
hemodialysis or peritoneal dialysis. 
12. Uncorrected hypokalemia, or known uncorrected 
hypomagnesemia, at the time of enrollment. If treatment 
normalizes the serum potassium or magnesium, confirmed by 
retest during the screening period, the patient may then be 
enrolled. 


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13. Ongoing treatment for seizures or untreated history of seizures. 
14. History of peripheral neuropathy. 
15. History of tendon damage/disorders due to quinolone therapy. 
16. Known history of myasthenia gravis. 
17. History of post-antibiotic colitis within the last 3 months. 
18. Ventricular arrhythmia and /or ongoing proarrhythmic 
conditions such as clinically significant bradycardia, acute 
myocardial ischemia. 
19. History of prolonged QT syndrome, or mean QTcF (QT 
interval corrected with the Fridericia formula) greater than 
450 msec for males and 470 msec for females on screening 
summary electrocardiogram (ECG). 
20. Concomitant use of drugs known to prolong the QT interval, 
including class IA (such as quinidine, procainamide, 
disopyramide) or Class III (such as amiodarone, sotalol 
bretylium, ibutilide) antiarrhythmics. 
21. Concomitant use of monoamine oxidases (MAO) A or B 
inhibitor agents and adrenergic and serotonergic agents within 
2 weeks of screening. 
22. Patients with known uncontrolled hypertension, 
pheochromocytoma, carcinoid thyrotoxicosis; and rare 
hereditary problems of galactose intolerance, the Lapp lactase 
deficiency or glucose-galactose malabsorption. 
23. Life expectancy of < 3 months. 
24. Immediate life-threatening disease. 
25. Any underlying disease (e.g., severe cardiac disease, 
malignancy, or psychiatric disorder) that, in the opinion of the 
investigator, may interfere with the subject’s ability to 
participate in the study. 
26. Previous participation in any study of delafloxacin. 
27. Receipt of an investigational drug within 30 days of 
randomization. 
28. Subject should not participate in the study, in the opinion of 
the investigator. 
Laboratory tests with exclusionary results judged by the 
investigator as not compatible with the subject’s clinical status 
may be repeated once for eligibility purposes. 
Study Design: 
This is a Phase 3, randomized, double-blind, comparator 
controlled, multicenter, global study. Subjects who consent to the 
study will have screening procedures performed. Subjects will be 
evaluated for baseline characteristics that include chest 
radiography within 48 hours before the first dose of study drug, 
and medical history, physical examination, clinical laboratory 
evaluation and blood cultures within 24 hours before the first dose 


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of study drug. Subjects may be initially pre-screened based on 
meeting CURB-65 score of 2 to 4, but will be eligible for 
enrollment only if classified as PORT Risk Class II, III, IV, or V. 
A pretreatment respiratory specimen will be collected for Gram 
stain and culture and susceptibility testing, if positive. Blood 
samples for procalcitonin and serology will be obtained at Day 1, 
as well as nasopharyngeal and oropharyngeal swabs for culture 
and/or polymerase chain reaction (PCR) testing, and urine samples 
for antigen testing. Subjects may be enrolled and may start study 
drug before results of the baseline pathogen identification are 
known.  
Subjects who meet the entry criteria will be randomly assigned in a 
1:1 ratio to receive delafloxacin or moxifloxacin. Randomization 
will be stratified by PORT Class, medical history of chronic 
obstructive pulmonary disease (COPD)/asthma, and prior single-
dose/regimen systemic antimicrobial use. Enrollment will be 
limited to no more than 25% PORT Class II and no more than 25% 
of subjects who received 1 dose of a single, potentially effective, 
short-acting antimicrobial drug or drug regimen for treatment of 
the CABP under study within 24 hours of enrollment.  
Subjects will be randomized to receive either IV delafloxacin 
300 mg every 12 hours (BID) with an option to switch to oral 
delafloxacin 450 mg BID, or IV moxifloxacin 400 mg every 
24 hours (QD) with an option to switch to oral moxifloxacin 
400 mg QD for the remaining doses. Subjects randomized to 
receive IV moxifloxacin 400 mg QD will receive alternating IV 
placebo QD to preserve the double blind nature of the study, such 
that all randomized subjects will receive an IV infusion on a BID 
basis.  
The investigator may elect to switch subjects from 
moxifloxacin/moxifloxacin placebo to linezolid (600 mg IV 
BID)/linezolid placebo if methicillin-resistant Staphylococcus 
aureus (MRSA) is confirmed (up to 10 days total moxifloxacin 
and linezolid duration of therapy). In this case of confirmed 
MRSA, subjects randomized to delafloxacin will continue to 
receive delafloxacin BID, discontinue moxifloxacin placebo QD, 
and start linezolid placebo BID.  
Subjects who meet suggested criteria can switch to oral treatment 
after a minimum of 6 IV delafloxacin/delafloxacin placebo doses, 
regardless of the treatment arm, to complete treatment. The total 
duration of treatment (IV and oral) is 5 days up to 10 days if 
clinically indicated (minimum 10 doses and up to 20 
delafloxacin/delafloxacin placebo doses). 
Key visits will be ECR at 96 hours (± 24 hours) after the start of 
the first dose of study drug, End of Treatment (EOT), and TOC, 
5-10 days after last dose. A Follow-up (FU) Visit or phone contact 


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will also be conducted at Day 28.  
Efficacy Assessments: 
Efficacy will be evaluated through assessment of clinical signs and 
symptoms of pneumonia and microbiological culture and 
susceptibility testing of bacterial isolates. Other measures of 
clinical efficacy as detailed in the protocol will be assessed at 
baseline and at multiple time points during the study. 
Health-Related 
Quality-of-Life 
Assessments: 
Health-related quality of life will be assessed through 
administration of the SF-12v2® Health Survey (acute) 
multipurpose short-form survey and quality-of-life questions.  
Pharmacokinetic 
Assessments: 
Serial blood samples for PK analysis will be obtained at select 
investigative sites on Day 3 (± 1 day) of treatment within the 
30 minutes before study drug administration and at 1.5 and 3 hours 
after the start of the infusion. All time points will have a 
± 10-minute window. Subjects should have received a minimum of 
3 consecutive doses of study drug prior to the start of PK blood 
collection. Subjects do not need to be fasted before dosing or 
during PK sample collections.  
Safety Assessments: 
Safety will be assessed by monitoring of AEs (including serious 
AEs [SAEs]), vital sign measurements and body temperature, 
clinical laboratory tests, (including pregnancy testing), physical 
examination findings, electrocardiograms (ECGs) if clinically 
warranted, and concomitant medications.  
Study Drug, Dosage, 
and Route of 
Administration: 
Delafloxacin 300 mg will be administered as a 1-hour IV infusion 
every 12 hours (± 2 hours) for a minimum of 6 doses with an 
option to switch to delafloxacin 450 mg tablet administered orally 
every 12 hours (± 2 hours) for the remaining doses.  
Comparator Study 
Drug, Dosage, and 
Route of 
Administration: 
Moxifloxacin 400 mg will be administered as a 1-hour IV infusion 
every 24 (± 2 hours) hours for a minimum of 3 active doses with 
an option to switch to moxifloxacin 400 mg (over-encapsulated 
tablet) administered orally every 24 hours (± 2 hours) for the 
remaining doses.  
Comparator Study 
Drug, Dosage, or 
Route of 
Administration:  
At local investigator discretion, subjects in the moxifloxacin arm 
with confirmed MRSA, in place of remaining moxifloxacin doses, 
can receive linezolid 600 mg administered as a 1-hour IV infusion 
every 12 hours (± 2 hours) for the remaining doses. 
Placebo Study Drug , 
Dosage, and Route of 
Administration:  
Each site will document a blinding plan prior to study start. All 
blinded IV dosing will be maintained with a 12-hour schedule. IV 
bags will be blinded.  
Subjects in the moxifloxacin arm, when on IV therapy, will 
receive once-daily active therapy via alternating doses of IV 
moxifloxacin and IV placebo every 12 (± 2) hours.  
Subjects in the delafloxacin arm, when on oral therapy, will 
receive oral placebo moxifloxacin QD or IV placebo linezolid BID 


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to maintain blinding.  
Subjects in the moxifloxacin/linezolid arm, when on oral therapy 
or when meeting criteria for oral therapy, will receive placebo 
delafloxacin oral formulation to maintain blinding. 
Sample Size: 
FOR FDA PRIMARY ENDPOINT: At least 860 adult male and 
female subjects (430 subjects per treatment group) will be 
randomized. Used on a normal approximation approach (Miettinen 
and Nurminen’s Likelihood Score Test), 860 subjects in ITT 
population will provide a 90% power to assess noninferiority of 
delafloxacin vs. moxifloxacin based on the following assumptions: 
(1) a rate of Early Clinical Response for the moxifloxacin therapy 
and delafloxacin of 77% and 74%, respectively; (2) 1-sided type I 
error (α) of 0.025; (3) a noninferiority margin of 12.5%. 
FOR EMA PRIMARY ENDPOINT: At least 860 adult male and 
female subjects (430 subjects per treatment group) will be 
randomized. Used on a normal approximation approach (Miettinen 
and Nurminen’s Likelihood Score Test), and assuming 
approximately 12% of patients will be in PORT Class II, and 80% 
of patients will be clinically evaluable, 755 subjects in the ModITT 
population and 604 subjects in the ModCE population will 
provide, respectively, a power of 91% and 83% to assess 
noninferiority of delafloxacin vs. moxifloxacin based on the 
following assumptions: (1) a rate of Clinical Outcome at the TOC 
visit for moxifloxacin and delafloxacin of 88% and 86%, 
respectively; (2)  1-sided type I error (α) of 0.025; (3) a 
noninferiority margin of 10%. 
Statistical Methods: 
Continuous characteristics including baseline values will be 
summarized by treatment group using means, standard deviations, 
minimum, maximum, and median values. Categorical variables 
will be summarized by treatment group using frequency 
distributions. For the baseline characteristics, data will be 
presented overall as well. The differences in proportions for the 
responders from the 2 treatment groups will be tested for 
noninferiority using confidence intervals (CIs) generated by the 
Miettinen-Nurminen method, without stratification. Continuous 
secondary efficacy measures will be analyzed using an analysis of 
covariance (ANCOVA) model with treatment as the main effect 
and adjusted for PORT Class, medical history of COPD/asthma, 
and prior antimicrobial therapy, and the baseline measure as the 
covariate. All statistical analyses, unless otherwise specified, will 
be based on 2-sided 95% CIs around the difference in treatment 
outcomes. 
Efficacy Endpoints: 
FOR FDA 
In order to control Type 1 error rate of 5%, a gate-keeping 
statistical method of a fixed sequence procedure will be used to 


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test for the secondary efficacy endpoints once the primary efficacy 
endpoint is claimed to be successful. If the noninferiority of 
delafloxacin is declared in the primary analysis, the secondary 
endpoints will be tested for superiority in a sequential 
(hierarchical) fashion using a fixed sequential procedure. The 
difference (delafloxacin – moxifloxacin) and CIs for all secondary 
endpoints will be reported. The primary and secondary efficacy 
endpoints are presented in the following text.  
Primary Efficacy Endpoint: The ECR defined as improvement at 
96 hours (± 24 hours) after first dose of study drug in at least 2 of 
the following symptoms: chest pain, frequency or severity of 
cough, amount and quality of productive sputum, and difficulty 
breathing, and no worsening in the other symptoms in the ITT 
population.  
Secondary Efficacy Endpoint(s): 
• ECR with the addition of improvement in vital signs and no 
worsening of the 4 symptoms required as Response in the ITT 
population 
• Clinical Outcome at TOC (Clinically Evaluable [CE] and ITT 
populations) 
• Clinical outcome at EOT  
• ECR in the MITT population 
• Microbiologic response (ME and MITT) 
• All-cause mortality (ITT) 
FOR EMA 
All the primary and secondary endpoints will be analyzed for 
noninferiority with the possibility to switch to superiority.  
Primary Efficacy Endpoint: The Clinical Outcome responder 
rate at 5 to 10 days after the last dose of study drug (TOC) defined 
as resolution or near resolution of the symptoms of CABP present 
at study entry, and no use of additional antimicrobial therapy for 
the current infection, and no new symptoms associated with the 
current CABP infection (success) in the ModITT and ModCE 
populations. 
Secondary Efficacy Endpoint(s): 
• ECR defined as improvement at 96 hours (± 24 hours) after 
first dose of study drug in at least 2 of the following 
symptoms: chest pain, frequency or severity of cough, amount 
and quality of productive sputum and difficulty breathing and 
no worsening of any of the other symptoms in the ModITT and 
ModCE populations 
• ECR with the addition of improvement in vital signs and no 
worsening of the 4 symptoms required as Response in the 


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ModITT and ModCE populations 
• Clinical Outcome at EOT (ModITT and ModCE) 
• Clinical Outcome at TOC in the ModMITT and ModME 
populations 
• Microbiologic response (ModMITT and ModME) 
• All-cause mortality (ModITT) 
Health-Related 
Quality-of-Life 
Endpoints: 
Health-related quality-of-life and Health Economics Outcomes 
Research (HEOR) endpoints include: 
• Compare SF-12v2® from baseline to EOT to TOC 
• Compare subject’s ability to work and earn income from 
baseline to EOT and TOC 
• Compare time to oral switch 
• Compare time to hospital discharge 
Pharmacokinetic 
Endpoints: 
The time course of delafloxacin plasma concentrations will be 
assessed. 
Safety Endpoints: 
• AEs, including SAEs 
• Vital sign measurements and body temperature 
• Clinical laboratory test results 
• Physical examination findings 
• Concomitant medications 
• ECGs (obtained after baseline only if clinically indicated) 
Analysis Populations: 
The following analysis populations will be analyzed: 
Safety: All randomized subjects who receive at least 1 dose of 
study drug, analyzed according to the treatment they received. 
Intent-to-Treat (ITT): All randomized subjects analyzed 
according to the treatment arm to which they were randomized. 
Modified ITT (ModITT): All randomized subjects who received 
at least one dose of study medication, classified as PORT Class III-
V, analyzed according to the treatment arm to which they were 
randomized. 
Microbiological ITT (MITT): All subjects in the ITT population 
who had a baseline bacterial pathogen identified on culture of a 
respiratory or blood specimen, or a nonculture method of detection 
of bacterial pathogens (i.e., urinary antigen test, PCR, and 
serologic testing) that is known to cause CABP against which the 
study drug has antibacterial activity. 
Modified MITT (ModMITT): All subjects in the MITT 
population classified as PORT Class III-V. 
Clinically Evaluable (CE): All subjects in the ITT population 


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who met the following criteria: 
• Evidence of acute onset of community-acquired bacterial 
pneumonia (CABP). 
• Received the correct study drug based on the randomization 
assignment. 
• Received 80% of the expected doses of study drug in the 
treatment period (e.g., at least 11 doses of delafloxacin for a 7-
day treatment period). 
• Did not receive any concomitant, systemic antibacterial 
therapy except for lack of efficacy. 
• Had no protocol deviations that would affect assessment of 
efficacy. 
Modified CE (ModCE): All subjects in the CE population 
classified as PORT Class III-V. 
Microbiologically Evaluable (ME): All subjects in the MITT 
population who also met the criteria for the CE population. 
Modified ME (ModME): All subjects in the ME population 
classified as PORT Class III-V. 
Pharmacokinetic (PK): All subjects who receive at least 
3 consecutive IV doses of study drug prior to the start of the blood 
sample collections on Day 3 (± 1 Day), and have at least one 
delafloxacin plasma concentration data available. The PK 
population will be used for PK analyses. 
Criteria for 
Evaluation - 
Definitions: 
For Early Clinical Response: 
Responders: Improvement at 96 hours (± 24 hours) after first dose 
of study drug in at least 2 of the following symptoms: pleuritic 
chest pain, frequency or severity of cough, amount and quality of 
productive sputum, and dyspnea (difficulty breathing), and no 
worsening of the other symptoms.  
Non-responders: Improvement is not achieved at 96 hours 
(± 24 hours) after first dose of study drug in at least 2 of the 
following symptoms: pleuritic chest pain, frequency or severity of 
cough, amount and quality of productive sputum, and dyspnea 
(difficulty breathing); or there is use of additional non-study 
antimicrobial therapy for treatment of the current CABP infection 
due to lack of efficacy; or the subject died from the current CABP 
infection. Indeterminate/missing assessments will be mapped to 
Non-responders in the statistical analysis of the ITT population.  
Symptoms for the Early Clinical Response will be evaluated on a 
4-point scale (absent, mild, moderate, severe) with improvement 
defined as at least a 1-point improvement (decrease) from baseline 
to the assessment at 96 hours (±24 hours) after the first dose of 
study drug (e.g., from severe to moderate, from moderate to mild, 


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or from mild to absent).  
For Clinical Outcome at EOT and TOC: 
Success: Resolution or near resolution of the symptoms of CABP 
present at study entry, and no use of additional antimicrobial 
therapy for the current infection, and no new symptoms associated 
with the current CABP infection. 
Failure: Symptoms of CABP present at study entry have not 
resolved, or new symptoms of CABP have developed, or the 
subject died from pneumonia, or use of additional non-study 
antimicrobial therapy for treatment of the current CABP infection 
due to lack of efficacy. Subjects must receive at least 4 doses of 
study drug by the end of Day 3 to be called a Failure. 
Indeterminate/Missing: A response cannot be determined 
because an efficacy assessment was not completed at the visit, or 
subject did not complete the planned course of study therapy for 
reasons other than lack of efficacy. Indeterminate/missing 
responses will be considered failures for purposes of the primary 
ITT/ModITT analyses and will be excluded from the CE and ME 
populations. 
For Microbiologic Response 
Eradication: The respiratory and/or blood specimen at the TOC 
Visit shows all causative pathogen(s) at enrollment eradicated and 
no use of additional antimicrobial therapy for the current infection. 
Presumed Eradication: No respiratory and/or blood specimen 
was available at TOC with a clinical assessment of Success.  
Persistence: The respiratory and/or blood specimen at the TOC 
visit shows appearance of causative pathogen(s) present at 
enrollment. 
Presumed Persistence: No respiratory and/or blood specimen was 
available for a case classified as clinical failure.  
Superinfection: A culture taken during treatment shows 
appearance of a new pathogen causing respiratory infection 
associated with clinical failure. 
Colonization/Contamination: A culture taken post-baseline 
through the TOC visit shows appearance of a new pathogen(s), 
with a clinical assessment of Success and no use of additional 
antimicrobial therapy for the current infection. 
Microbiologic 
Measures: 
The following pathogens are examples of primary pathogens that 
will be used to determine the microbiological responses in the 
study: the typical bacterial pathogens include but may not be 
limited to Streptococcus pneumoniae, Haemophilus influenzae, 
S. aureus, Klebsiella pneumoniae, and Moraxella catarrhalis, and 
the atypical bacterial pathogens Chlamydophila pneumoniae, 
Mycoplasma pneumoniae, and Legionella pneumophila. The 
causative pathogen will be identified by isolation from a baseline 


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culture specimen (either a respiratory specimen or blood), by 
urinary antigen, by serology, and/or by PCR. 
Date of Final 
Protocol: 
04 December 2017 


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List of Abbreviations  
Abbreviation 
Definition 
ABG 
Arterial blood gas 
ABSSI 
Acute bacterial skin and skin structure infection 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AUC0-24 
Area under the concentration versus time curve from time 0 to 24 hours 
AUC0-t 
Area under the concentration versus time curve from time 0 to the time 
of the last quantifiable concentration 
AUCinf 
Area under the concentration versus time curve from time 0 
extrapolated to infinity 
BAL 
Bronchoalveolar lavage 
BCRP 
Breast cancer–resistant protein 
BID 
Bis in die (twice daily) 
BMI 
Body mass index 
CABP 
Community-acquired bacterial pneumonia 
CAP 
Community-acquired pneumonia 
CE 
Clinically evaluable 
CFR 
Code of Federal Regulations 
cfu 
Colony-forming units 
CI 
Confidence interval 
CLSI 
Clinical Laboratory Standards Institute 
Cmax 
Maximum concentration 
COPD 
Chronic obstructive pulmonary disease 
CrCl 
Creatinine clearance 
CRO 
Contract research organization 
CT 
Computerized tomography 
CURB-65 
Confusion, urea, respiratory rate, blood pressure, age 65 or older 
CV 
Coefficient of variation 
CXR 
Chest radiograph 
CYP 
Cytochrome 
D5W 
Dextrose 5% in water 
DNA 
Deoxyribonucleic acid 
ECG 
Electrocardiogram 
ECR 
Early clinical response 


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Abbreviation 
Definition 
eCRF 
Electronic case report form 
EDTA 
Ethylenediaminetetraacetic acid 
EMA 
European Medicines Agency 
EOT 
End of Treatment 
ESRD 
Erythrocyte sedimentation rate 
EUCAST 
European Committee on Antimicrobial Susceptibility Testing 
FDA 
Food and Drug Administration 
GOLD 
Global initiative for chronic Obstructive Lung Disease 
HIV 
Human immunodeficiency virus 
HEOR 
Health economics outcomes research 
HRQoL 
Health-related quality of life 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent ethics committee 
IRB 
Institutional review board 
ITT 
Intent-to-treat  
IV 
Intravenous 
IXRS 
Interactive voice and web response system 
LOE 
Lack of efficacy 
MAOI 
Monoamine oxidase inhibitor 
MCS 
Mental component summary 
ME 
Microbiologically evaluable 
MIC 
Minimum inhibitory concentration 
MIC50 
Minimum inhibitory concentration required to inhibit the growth of 
50% of organisms 
MIC90 
Minimum inhibitory concentration required to inhibit the growth of 
90% of organisms 
MITT 
Microbiological intent-to-treat 
ModCE 
Modified clinically evaluable 
ModITT 
Modified intent-to-treat 
ModME 
Modified microbiologically evaluable 
ModMITT 
Modified microbiological intent-to-treat 
MRSA 
Methicillin-resistant Staphylococcus aureus 
MSSA 
Methicillin-susceptible Staphylococcus aureus 
MTD 
Maximum tolerated dose 
PA 
Posteroanterior 


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Abbreviation 
Definition 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamics 
PD50 
Dose of vaccine required to protect 50% 
PK 
Pharmacokinetic 
PORT 
Pneumonia Patient Outcomes Research Team 
P-gp 
P-glycoprotein 
PSB 
Protected specimen brush 
PSC 
Physical component summary 
PSI 
Pneumonia severity index 
QD 
Quaque die (once daily) 
QoL 
Quality of life 
QSSP 
Quinolone-susceptible Streptococcus pneumoniae 
RBC 
Red blood cell 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SCr 
Serum creatinine 
SD 
Standard deviation 
SF 
Short form 
SmPC 
Summary of Product Characteristics 
TEAE 
Treatment-emergent adverse event 
TOC 
Test of Cure 
ULN 
Upper limit of normal 
 


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1. Introduction 
Delafloxacin is an investigational broad spectrum fluoroquinolone antibiotic. Throughout the 
world, the incidence of antimicrobial resistance has increased for bacterial infections in 
hospital and community settings. Delafloxacin is active against an array of bacteria, 
including Gram-positive organisms (methicillin-susceptible Staphylococcus aureus [MSSA], 
methicillin-resistant S. aureus [MRSA], Streptococcus pyogenes, enterococci), Gram-
negative organisms (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), 
atypical organisms and anaerobes (Bacteroides fragilis and Clostridium spp.). Delafloxacin 
provides antimicrobial coverage of prevalent MRSA and methicillin-resistant coagulase-
negative staphylococci. Delafloxacin is more active than levofloxacin against most Gram-
positive pathogens, and notably has been shown to have a minimum inhibitory concentration 
required to inhibit the growth of 90% of organisms (MIC90) of at least 32-fold more active 
than levofloxacin against MRSA isolates. Delafloxacin has good activity against Gram-
negative organisms that are susceptible to levofloxacin, including species responsible for 
surgical site infections, community and nosocomial respiratory tract infections, urinary tract 
infections, bloodstream infections, skin and skin structure infections, and anaerobic 
infections. 
Delafloxacin is being developed as a sterile 300-mg lyophilized formulation for intravenous 
(IV) administration as well as an oral 450-mg tablet formulation.  
Delafloxacin has been generally well tolerated, with mild to moderate gastrointestinal 
adverse events (AEs) being most common. Refer to the Investigator’s Brochure 
(Melinta 2016) for a more complete discussion of these studies, the safety and tolerability 
profile to date, and for detailed information presented in the section.  
1.1 
Microbiology 
1.1.1 
Mechanism of Action Pharmacology 
Fluoroquinolones act on DNA gyrase and topoisomerase IV, the 2 bacterial type-II 
topoisomerases involved in maintaining appropriate DNA supercoiling and chromosome 
segregation, respectively. Data suggest that delafloxacin is dual-targeting by inhibiting both 
DNA gyrase and topoisomerase IV in both Gram-positive and Gram-negative bacteria to a 
similar extent, unlike most other fluoroquinolones. Delafloxacin has slightly increased 
inhibitory activity against Gram-positive DNA gyrase and nearly equivalent activity against 
Gram-negative DNA gyrase compared to its activity against topoisomerase IV in enzymatic 
assays.  


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1.1.2 
In Vitro Studies 
Comparative Antibacterial Activity 
In a recent survey of 2014 US and European isolates, delafloxacin’s MIC50 and MIC90 were 
0.008 µg/mL and 0.015 µg/mL, respectively for Streptococcus pneumoniae. Delafloxacin 
was 128 times more active than levofloxacin in this study. Against levofloxacin-resistant 
S. pneumoniae, delafloxacin had MIC50 and MIC90 of 0.12 µg/mL and 0.5 µg/mL, 
respectively. Delafloxacin is highly active against Moraxella catarrhalis; and delafloxacin 
has MIC50 and MIC90 of ≤ 0.001 µg/mL and 0.004 µg/mL, respectively, against Haemophilus 
influenzae. MIC90s of 0.12 µg/mL and 0.5 µg/mL have been reported for delafloxacin against 
MSSA and MRSA, respectively. 
Time-Kill Analysis 
The rate of bacterial killing was determined for S. pneumoniae 2486; delafloxacin was 
bactericidal at as low as 4 times the MIC against S. pneumoniae 2486. Delafloxacin 
demonstrated bactericidal activity against a quinolone-resistant isolate of S. aureus at 4 and 
8 times the MIC, similar to ciprofloxacin and moxifloxacin.  
1.1.3 
In Vivo Studies 
Delafloxacin was evaluated for in vivo activity against clinical isolates of S. pneumoniae, 
including strains bearing macrolide- and penicillin-resistance mechanisms, and H. influenzae 
in a series of rat lung-infection studies. Against quinolone-susceptible S. pneumoniae (QSSP) 
6303, oral delafloxacin was 3-fold more efficacious than trovafloxacin and 10-fold more 
efficacious than levofloxacin. Against S. pneumoniae 5649, a multidrug-resistant strain, 
delafloxacin demonstrated a dose required to protect 50% (ED50) of < 5.0 mg/kg/day, 
whereas levofloxacin and trovafloxacin resulted in ED50s of 12.9 and 10.2 mg/kg/day, 
respectively. Against H. influenzae, all compounds were highly efficacious in this rat lung-
infection model, with delafloxacin, levofloxacin, and trovafloxacin demonstrating ED50s of 
2.1, 6.9, and 5.9 mg/kg/day, respectively.  
Evaluation of Delafloxacin in the Mouse Lung-Infection Model 
Delafloxacin was evaluated for its ability to both reduce lung bacterial burdens and protect 
mice from lethal infection by S. pneumoniae D39. The untreated control group had an 
increase in lung bacterial burden of 1.63 log10 colony-forming units (cfu) from the start of 
therapy to the end of the study at 40 hours, whereas delafloxacin dosed at 50, 25, 10, 5, and 
1 mg/kg/dose was efficacious, demonstrating reductions in lung bacterial burdens of 4.70, 
4.76 (limit of detection), 3.33, 3.11, and 0.12 log10 cfu, respectively, compared to untreated 
controls at the start of therapy. Seven-day survival was also monitored; for delafloxacin 


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dosed at 50, 25, 10, 5, and 1 mg/kg/dose, 100, 60, 0, 0, and 0% survival was observed, 
respectively. 
1.2 
Pharmacokinetics, Safety, and Efficacy of Delafloxacin 
1.2.1 
Pharmacokinetics, Safety, and Tolerability of IV and Oral Delafloxacin 
Single doses ranging from 50 to 1200 mg were assessed for safety, tolerability, and 
pharmacokinetics (PK) in 5 Phase 1 studies with 4 different IV formulations. In the 
RX-3341-108 study (Rib-X 2011), a maximum tolerated dose (MTD) for single IV 
administration was 900 mg given over 1 hour. Delafloxacin was given to subjects in daily 
doses ranging from 50 to 1600 mg as either single dose or multiple oral doses for up to 
5 consecutive days in 8 Phase 1 studies. The aggregate data suggested a dose relationship for 
the frequency and severity of diarrhea. The primary dose-limiting AEs were gastrointestinal 
in nature. 
Delafloxacin is rapidly absorbed orally, reaching peak concentrations in 0.8 hour. The 
absolute bioavailability of delafloxacin after oral administration is 58.8%. After IV and oral 
administration, delafloxacin has a mean half-life of 10.9 and 14.1 hours, respectively. There 
is minimal accumulation (Rac = 1.09) of delafloxacin upon twice-daily IV (300 mg) or 
twice-daily oral (450 mg) administration. Delafloxacin is renally excreted primarily as the 
parent compound, metabolism by glucuronidation represents ≤ 20% of an administered dose. 
The 450-mg commercial tablet and 300-mg IV Captisol® lyophilized formulations are 
bioequivalent with regard to total exposure (AUC). The administration of delafloxacin with 
food delays absorption and reduces maximum concentration (Cmax), but does not alter total 
absorption (AUC). Plasma protein binding is approximately 84%. 
Delafloxacin does not inhibit cytochrome P450 enzymes or transporters to any significant 
degree. In vitro, delafloxacin has been shown to be a mild inducer of CYP3A4. Hence, 
clinically significant drug-drug interactions due to inhibition of CYP-mediated 
biotransformation of co- administered drugs by delafloxacin are unlikely in humans. 
Delafloxacin is a substrate of breast cancer–resistant protein (BCRP) and a possible substrate 
of P-glycoprotein (P-gp). Delafloxacin is well absorbed (BA = 58.8%), so any interaction 
with inhibitors of BCRP or P-gp at the enterocyte is not expected to increase peak exposures 
beyond those exposures already shown to be tolerable at doses higher than a 450-mg oral 
dose. 
The pharmacokinetics of delafloxacin has been studied in subjects with mild, moderate, and 
severe renal disease, including subjects with end-stage renal disease (ESRD) on dialysis. 
Patients with severe renal impairment should receive delafloxacin 200 mg IV BID. Dosing 
recommendations are not available for patients with ESRD with or without dialysis. 


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Two dedicated QT studies have been conducted with the oral and IV formulations with no 
evidence of delafloxacin impact on QT interval. The effect of delafloxacin on cardiac 
repolarization using the QTcF interval showed no signal. A phototoxicity study has been 
performed with oral delafloxacin with no evidence of phototoxic effects.  
1.2.2 
Phase 2 Study for Community-Acquired Pneumonia: Study M01-344 
Study M01-344, a double-blind, randomized, parallel-group, Phase 2 study, was conducted to 
determine the safety and efficacy of a 7-day oral course of delafloxacin in subjects with 
community-acquired pneumonia (Abbott 2003). Three hundred and nine subjects were 
randomized to 1 of 3 dosing groups: 100, 200, or 400 mg delafloxacin once daily for 7 days. 
The Test of Cure (TOC) was on study Day 16-21. The primary endpoint of this trial was the 
investigators’ assessment of clinical response rate at the TOC time point in the Clinically 
Evaluable (CE) group. All doses tested showed similar excellent response rates in all of the 
analysis groups. All pathogens in this study had a delafloxacin MIC ≤ 0.015 µg/mL. 
Table 1-1 
Proportion of Patients Achieving Endpoints (Study M01-344) 
Outcome at Test of Cure 
Proportion of Patients With: 
Delafloxacin 
100 mg 
Delafloxacin 
200 mg 
Delafloxacin 
400 mg 
Investigator Assessment of Clinical Response (CE) 
90% (83/92) 
95% (79/83) 
93% (90/97) 
Investigator Assessment of Clinical Response (ITT) 
80% (83/104) 
87% (79/91) 
87% (90/104) 
Microbiologic response (ME) 
90% (54/60) 
96% (48/50) 
94% (47/50) 
 
Among subjects who were microbiologically evaluable, at TOC, 91% of pathogens in the 
100-mg group, 95% of pathogens in the 200-mg group, and 97% of pathogens in the 400-mg 
group were eradicated. Eradication rates are shown in the table below. All pathogens had a 
delafloxacin MIC of 0.015 µg/mL or lower. 
Table 1-2 
Target Pathogen Eradication Rates at the TOC Visit (Study M01-344) 
Pathogen 
Delafloxacin  
100 mg QD 
Delafloxacin  
200 mg QD 
Delafloxacin  
400 mg QD 
Streptococcus pneumoniae 
14/16 (88%) 
12/14 (86%) 
16/16 (100%) 
Moraxella catarrhalis 
6/6 (100%) 
4/4 (100%) 
0/0 
Haemophilus influenzae 
14/15 (93%) 
13/13 (100%) 
15/16 (94%) 
H. parainfluenzae 
18/20 (90%) 
14/15 (93%) 
15/15 (100%) 
Staphylococcus aureus 
8/8 (100%) 
7/7 (100%) 
2/2 (100%) 
Legionella pneumophila 
0/0 
1/1 (100%) 
1/1 (100%) 
Mycoplasma pneumoniae 
7/8 (88%) 
6/6 (100%) 
8/8 (100%) 
Chlamydophila pneumoniae 
3/4(75%) 
3/3 (100%) 
1/2 (50%) 
 
The common AEs in this trial were nausea, diarrhea, and headache. No subjects died during 
the study.  


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1.2.3 
Treatment of Acute Bacterial Skin and Skin Structure Infections: 
Study RX-3341-302 
Study RX-3341-302 was a randomized, double-blind, Phase 3 study comparing the efficacy 
of IV delafloxacin 300 mg to IV vancomycin (15 mg/kg) with aztreonam (1-2 g) for the 
treatment of ABSSSI including infections caused by MRSA (Rib-X 2015). All patients were 
randomized and dosed twice daily for 5-14 days in a double-blind fashion. The study 
enrolled 660 patients at 34 sites in the United States and Europe.  
The primary outcome measure for the FDA was a comparison of the proportion of patients 
who achieved an objective response at 48 to 72 hours following initiation of treatment, based 
on at least 20% decrease in lesion size. The trial protocol also had secondary and exploratory 
endpoints including a secondary outcome measure of noninferiority of the proportion of 
patients with a clinical response at the follow-up visit based on the investigator’s assessment 
of cure (total resolution of all signs and symptoms); “improved” outcome was grouped with 
failure in the primary analysis. 
Delafloxacin achieved its primary FDA efficacy endpoint of noninferiority for objective 
response at 48 to 72 hours after initiation of therapy as determined by at least 20% decrease 
in lesion size in the Intent-to-Treat (ITT) population. Delafloxacin also met the primary 
endpoint for the European Medicine Agency (EMA), the investigator assessment of cure 
defined as complete resolution of signs and symptoms at the Follow-up visit. Delafloxacin’s 
outcome was sustained with clinical outcomes comparable to vancomycin at the Late Follow-
up visit. Delafloxacin also demonstrated clinical activity against MRSA with comparable 
eradication rates to vancomycin in patients with MRSA infections in the microbiologically 
evaluable (ME) population. 
Table 1-3 
Proportion of Patients Achieving Endpoints (Study RX-3341-302) 
Key Endpoints 
Delafloxacin 
Vancomycin 
(+aztreonam) 
Difference  
(V-D) (95% CI) 
Objective response at 48-72 hours (ITT)  
(FDA primary) 
259/331 (78.2%) 
266/329 (80.9%) 
2.60 (-3.57,8.78) 
Investigator assessment of cure at 
Follow-up visit (ITT) (EMA Primary) 
172/331 (52.0%) 
166/329 (50.5%) 
-1.51 (-9.11, 6.11) 
Investigator assessment of cure at 
Late Follow up (ITT) (Secondary) 
233/331 (70.4%) 
219/329 (66.6%) 
-3.83 (-10.89, 3.27) 
Microbiological response of eradicated at  
the Follow-up Visit in patients (ME) with  
MRSA infections (ME) (Secondary) 
58/58 (100%) 
65/66 (98.5%) 
-1.52 (-8.14, 4.79) 
Abbreviations: BID = 2 times a day; BMI = body mass index; CI = confidence interval; EMA = European 
Medicine Agency; FDA = US Food and Drug Administration; ITT = intent-to-treat population; 
IV = intravenous; ME = microbiologically evaluable population; MRSA = methicillin-resistant 
Staphylococcus aureus; V-D = difference between vancomycin and delafloxacin. 
 


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Safety data from this trial shows that delafloxacin is well tolerated and has a favorable safety 
profile compared to vancomycin. The most common AEs related to delafloxacin treatment, 
reported in at least 2% of patients, were nausea, vomiting, diarrhea, and headache, which are 
events typically reported for other antibiotics. There were more reports of diarrhea for 
delafloxacin compared to vancomycin (8.3% vs 3.1%, respectively). None of these events 
caused patients to stop delafloxacin treatment, and there were no reports of Clostridium 
difficile diarrhea. There were fewer reports of pruritus (0.9% vs 4.6% respectively) and 
infusion site extravasation (8.6% vs 13.5% respectively) for delafloxacin compared to 
vancomycin.  
1.3 
Dose Selection of Delafloxacin for This Study 
Delafloxacin will be administered as 300 mg IV every 12 hours with an option to switch to 
450 mg orally every 12 hours in this study. This dosage regimen is currently being used in 
the ABSSSI program and was selected based on MIC90 data against MRSA, Phase 1 PK data, 
PK/pharmacodynamics (PD) data in murine models of thigh infection, clinical PK/PD 
modeling, and previous clinical experience. The IV dose of 300 mg, as demonstrated by 
animal PK/PD and human clinical trial ABSSSI data, is expected to provide an adequate free-
drug AUC0-24: MIC ratio to cover primary pathogens implicated in ABSSSI. 
In treatment of patients with community-acquired bacterial pneumonia (CABP), the same 
dosage regimen is planned based on MIC90 data against S. pneumoniae and other respiratory 
pathogens, in vivo models of infection, Phase 1 PK data, PK/PD data in murine models of 
thigh infection as well as preliminary PK/PD data in murine model of lung infection, and 
previous clinical experience. The following information, provided in more detail in the 
Investigator’s Brochure (Melinta 2016), is supportive of this dosing regimen: 
• Based on MIC50 and MIC90, delafloxacin was several-fold more potent than levofloxacin 
against evaluated Gram-positive organisms. In a recent study against bacterial isolates 
associated with respiratory infections collected from the US, delafloxacin was determined 
to be the most active agent against S. pneumoniae, H. influenzae, and M. catarrhalis, with 
MIC90 values that were 64 to 128 times lower than levofloxacin against S. pneumoniae 
and 8 times lower against H. influenzae and M. catarrhalis. In that same study, 
delafloxacin was found to be active against subsets of S. pneumoniae that were penicillin-
resistant, ceftriaxone non-susceptible, and levofloxacin-resistant.  
• Delafloxacin is active in animal models against key respiratory pathogens, primarily 
S. pneumoniae, including data from a mouse protection model, mouse lung infection 
model, rat lung infection model, rat neutropenic thigh model, mouse neutropenic thigh 


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model, and mouse neutropenic lung model. In these models, delafloxacin is multi-fold 
more active than other quinolones tested.  
• In human subjects, delafloxacin 300 mg IV BID delivers a total AUC0-24 of 
approximately 50 µg•h/mL. Based on preliminary PK/PD assessments of the free 
AUC0-24/MIC ratio which predicts response in animal models, the 300 mg IV/450 mg oral 
twice-daily dose is predicted to provide adequate coverage for most MIC values observed 
in CABP. 
• Delafloxacin has shown evidence of efficacy in a completed phase 2 community-acquired 
pneumonia (CAP) trial (M01-344 [Abbott 2003]). In addition, a phase 2 trial in acute 
bacterial exacerbation of chronic bronchitis (M01-298 [Abbott 2003]) and 2 phase 2 
ABSSSI trials (studies RX-3341-201 [Rib-X 2009] and RX-3341-202 [Rib-X 2014]) 
provide evidence of efficacy of delafloxacin in these indications. 
• Delafloxacin has shown evidence of efficacy in a completed Phase 3 ABSSSI trial 
(RX-3341-302 [Melinta 2015]) using the intended 300 mg IV BID dose. 
• Delafloxacin has been well tolerated at the 300 mg IV BID dose used in 2 phase 2 
ABSSSI trials (studies RX-3341-201 [Rib-X 2009] and -202 [Rib-X 2014]) and 
1 Phase 3 ABSSSI trial (study RX-3341-302). 
1.4 
Comparator Selections for This Study 
Moxifloxacin is the comparator for this study. Moxifloxacin 400 mg IV or oral once daily is 
the recommended dosage in treatment of patients with CABP. As a fluoroquinolone used in 
CABP, moxifloxacin has the antibacterial coverage to treat the range of Gram-positive and 
Gram-negative pathogens seen in CABP such as S. pneumoniae and H. influenzae as well as 
atypical pathogens. In vitro, moxifloxacin is active against both extracellular and intracellular 
community acquired-MRSA (CA-MRSA) if the MIC is low (does not exceed 0.125 mg/L) 
(Lemaire 2011). 
At the investigator’s discretion in patients with confirmed infection due to MRSA, linezolid 
may be substituted for moxifloxacin. Linezolid is approved for treatment of CABP at dose of 
600 mg BID. Linezolid is one of the currently recommended treatments for patients with 
confirmed MRSA infections (Mandell 2007). 
The treatment duration in this study is 5 to 10 days. Treatment guidelines recommend at least 
5 days of therapy, noting that in clinical trials, 5 days appears to be the minimal overall 
duration of therapy documented to be effective in usual forms of CAP (Mandell 2007).  


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2. Study Objectives 
2.1 
Primary Objective 
The primary objective is: 
FDA 
EMA 
To assess the clinical efficacy of IV to oral 
delafloxacin in adult subjects with CABP 
based on Early Clinical Response (ECR) 
defined as improvement at 96 hours 
(± 24 hours) after the first dose of study drug 
compared to IV to oral moxifloxacin in the 
ITT population. 
To assess the clinical efficacy of IV to oral 
delafloxacin in adult subjects with CABP at 
5 to 10 days after the last dose of study drug 
(TOC) compared to IV to oral comparator 
study drug arm in the Modified ITT 
(ModITT) and Modified CE (ModCE) 
populations. 
 
2.2 
Secondary Objective(s) 
The secondary objectives are: 
FDA 
EMA 
To assess the clinical efficacy of IV to oral 
delafloxacin in adult subjects with CABP 
based on clinical outcome at the TOC visit, 
5 to 10 days after the last dose of study drug 
compared to IV to oral comparator study 
drug arm in the CE and ITT populations. 
To assess the clinical efficacy of IV to oral 
delafloxacin in adult subjects with CABP 
based on ECR defined as improvement at 
96 hours (± 24 hours) after the first dose of 
study drug compared to IV to oral 
moxifloxacin in the ModITT and ModCE 
populations. 
To assess the clinical efficacy of IV to oral 
delafloxacin in adult subjects with CABP 
based on ECR compared to IV to oral 
moxifloxacin in the Microbiological ITT 
(MITT) population 
To assess the clinical efficacy of IV to oral 
delafloxacin in adult subjects with CABP at 
the TOC visit compared to IV to oral 
moxifloxacin in the Modified MITT 
(ModMITT) and Modified ME (ModME) 
populations. 
To assess the microbiologic response to 
delafloxacin in respiratory pathogens. 
To assess the microbiologic response to 
delafloxacin in respiratory pathogens in the 
ModMITT and ModME populations. 


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FDA 
EMA 
To assess the safety and tolerability of IV to 
oral delafloxacin in adult subjects with 
CABP  
To assess the safety and tolerability of IV to 
oral delafloxacin in adult subjects with 
CABP in safety population. 
To assess the all-cause mortality in adult 
subjects with CABP on Day 28 
To assess the all-cause mortality in adult 
subjects with CABP on Day 28 in ModITT. 
To assess delafloxacin PK in adult subjects 
with CABP 
To assess delafloxacin PK in adult subjects 
with CABP in PK population. 
 


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3. Investigational Plan 
3.1 
Study Design 
This is a Phase 3, randomized, double-blind, comparator-controlled, multicenter, global study. 
Subjects who consent to the study will have screening procedures performed. Subjects will 
be evaluated for baseline characteristics that include chest radiography within 48 hours 
before the first dose of study drug, and medical history, physical examination, clinical 
laboratory evaluation, and blood cultures within 24 hours before the first dose of study drug. 
Subjects may be initially pre-screened based on meeting CURB-65 score of 2 to 4, but will 
be eligible for enrollment only if classified as Pneumonia Patient Outcomes Research Team 
(PORT) Risk Class II, III, IV or V. A pretreatment respiratory specimen will be collected for 
Gram stain and culture, and susceptibility testing, if positive. Blood samples for procalcitonin 
and serology will be obtained at Day 1, as well as nasopharyngeal and oropharyngeal swabs 
for culture and/or polymerase chain reaction (PCR) testing, and urine samples for antigen 
testing. Subjects may be enrolled and may start study drug before results of the baseline 
pathogen identification are known.  
Subjects who meet the entry criteria will be randomly assigned in a 1:1 ratio to receive 
delafloxacin or moxifloxacin. Randomization will be stratified by PORT Class, medical 
history of COPD/asthma, and prior single-dose/regimen systemic antimicrobial use. 
Enrollment will be limited to no more than 25% PORT Class II and no more than 25% of 
subjects who received 1 dose of a single, potentially effective, short-acting antimicrobial 
drug or drug regimen for treatment of the CABP under study within 24 hours of enrollment. 
Subjects will be randomized to receive either IV delafloxacin 300 mg every 12 hours (BID) 
with an option to switch to oral delafloxacin 450 mg BID, or IV moxifloxacin 400 mg every 
24 hours (QD) with an option to switch to oral moxifloxacin 400 mg QD for the remaining 
doses. Subjects randomized to receive IV moxifloxacin 400 mg QD will receive alternating 
IV placebo QD to preserve the double blind nature of the study, such that all randomized 
subjects will receive an IV infusion on a BID basis.  
The investigator may elect to switch subjects from moxifloxacin/moxifloxacin placebo to 
linezolid (600 mg IV BID)/ linezolid placebo if MRSA is confirmed (up to 10 days total 
moxifloxacin and linezolid duration of therapy). In this case of confirmed MRSA, subjects 
randomized to delafloxacin will continue to receive delafloxacin BID, discontinue 
moxifloxacin placebo QD, and start linezolid placebo BID.  
Subjects who meet suggested criteria can switch to oral treatment after a minimum of 6 IV 
delafloxacin/delafloxacin placebo doses, regardless of the treatment arm, to complete 
treatment. The total duration of treatment (IV and oral) is 5 days up to 10 days if clinically 


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indicated (minimum 10 doses and up to 20 delafloxacin/delafloxacin placebo doses). Key 
visits will be ECR at 96 hours (± 24 hours) after the start of the first dose of study drug, End 
of Treatment (EOT), and Test of Cure (TOC), 5-10 days after last dose. A Follow-up (FU) 
Visit or phone contact will also be conducted at Day 28. A schematic of the study design is 
provided in Figure 3-1. 
 


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Figure 3-1 
Schematic of Study Design 
 
SCREENING 
 
TREATMENT PERIOD 
 
FOLLOW-UP PERIOD 
 
 
 
 
 
 
Screening and Enrollment 
Days –1 to 1 
 
Days 1 to 7 (up to 10 
days)  
 
End of 
Treatment 
(EOT) 
 
Test Of Cure  
(TOC) 
5 to 10 days after 
last dose 
 
Follow-
up  
(FU) 
Day 28 
(±2 days) 
 
 
 
 
 
 
 
Obtain informed consent 
 
 
Blinded Study Drug 
Administration: 
One IV dose every 12 
hours (± 2 hours) for a 
total of 10 up to 20 doses* 
(IV alone or IV and oral) 
 
 
 
 
 
 
 
 
 
 
 
 
Screening procedures 
 
 
 
 
 
 
 
 
 
Early Clinical Response at 
96 hours (± 24 hours) after 
first dose of study drug 
 
 
Investigator Assessment of Clinical 
Outcome  
 
Capture 
post- 
study 
SAEs 
 
 
Enrollment and random assignment to 
treatment arm (1:1 ratio) via IXRS 
 
 
  
 
 
 
Blinded delafloxacin 
 
Blinded moxifloxacin 
Day 5 and Day 7 
Assess the need to 
continue dosing up to 10 
days (20 doses)* 
 
 
 
Delafloxacin 300 mg 
IV BID option to 
switch to delafloxacin 
450 mg oral BID 
 
 
Moxifloxacin 400 mg IV 
administered QD option 
to switch to moxifloxacin 
400 mg oral QD  
 
Optional switch to 
linezolid 600 mg IV 
BID if MRSA is 
confirmed 
 
 
 
 
 
 
* delafloxacin/delafloxacin placebo doses 
Abbreviations: EOT = End of Treatment; TOC = Test of Cure; FU = Follow-up; IXRS = interactive voice and web response system; IV = intravenous; 
BID = every 12 hours; QD = every 24 hours; MRSA = methicillin-resistance Staphylococcus aureus
Reminder Contact 
3–9 days after  
last dose 


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3.2 
Selection of Study Sample 
At least 860 male and female subjects, 18 years of age or older, with clinical and 
radiographic evidence of CABP and a pneumonia Patient Outcomes Research Team (PORT) 
Risk Class of II, III, IV, or V (pneumonia severity index score [PSI] greater than 50) will be 
enrolled in the study. 
3.2.1 
Inclusion Criteria 
To be enrolled in this study, subjects must meet the following criteria at Screening: 
1. Male and female subjects 18 years of age or older. 
• Patients from a nursing home setting may be enrolled if they are normally 
ambulatory and are not on enteral feeding. 
2. Evidence of acute onset of CABP.  
Subjects must have at least 2 of the following clinical signs and symptoms (new or 
worsening): 
• Cough 
• Production of purulent sputum consistent with a bacterial infection 
• Difficulty breathing (dyspnea) 
• Chest pain due to pneumonia 
AND 
Subjects must also have at least 2 of the following findings: 
• Fever (oral temperature > 38°C or equivalent ) within 24 hours prior to 
randomization 
• Hypothermia (oral temperature < 35°C or equivalent) within 24 hours prior to 
randomization 
• Tachycardia (> 100 beats per minute) 
• Tachypnea (elevated respiratory rate > 18 breaths per minute) 
AND 
Subjects must also have at least 1 of the following findings: 
• Hypoxemia (oxygen saturation < 90% or PaO2 < 60 mmHg) on room air or with 
subject’s baseline (pre-CABP under study) supplemental oxygen flow rate 


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• Clinical evidence of pulmonary consolidation and/or presence of pulmonary rales 
• An elevated white blood cell count (WBC) > 10,000/mm3 or 15% immature 
neutrophils (bands), regardless of total peripheral WBC count or leukopenia with 
WBC < 4500/mm3 
3. Presence of lobar, multilobar, or patchy parenchymal infiltrate(s) consistent with 
acute bacterial pneumonia on a pulmonary imaging study (e.g., chest radiograph 
[CXR] [posteroanterior and lateral preferred; single view acceptable if conclusive] or 
computed tomography [CT] of thorax), as per local standard of care, within 48 hours 
before the first dose of study drug.  
4. PORT Risk Class of II, III, IV, or V (PSI Score greater than 50) (Fine 1997) 
(Appendix 7.2). Subjects may be initially pre-screened based on meeting CURB-65 
Score (Appendix 7.3) of 2 to 4. PORT Risk Class II will be limited to no more than 
25% of randomized subjects.  
5. In the opinion of the investigator, the subject must be a suitable candidate for possible 
IV to oral switch antibiotic therapy and must also be able to swallow large 
tablets/capsules intact without crushing. 
6. Females of childbearing potential (including females less than 2 years post-
menopausal) must have a negative pregnancy test prior to enrollment. Sexually active 
women and men with partners of childbearing potential must agree to use an 
acceptable form of contraception, as determined by the investigator (e.g., abstinence, 
oral contraceptives, double-barrier methods, hormonal injectable, transdermal, or 
implanted contraceptives, tubal ligation, or vasectomy) during participation in the 
study through the Follow-up Visit (Day 28). Female partners of male subjects should 
also use an additional reliable method of contraception, such as spermicide with male 
or female condoms, cervical sponge, intrauterine device, cervical cap or diaphragm, 
or oral, implantable, transdermal, or injectable contraceptives during study and 
through the Follow-up Visit (Day 28). 
7. In the opinion of the investigator, the subject must be able and willing to comply with 
protocol requirements. 
8. A written, voluntarily signed informed consent must be obtained from the subject or, 
where allowed by local regulations, legally authorized representative, in accordance 
with local regulations, before the initiation of any study-related procedures. The 
subject or legally authorized representative must be able to read and/or understand the 
informed consent form as required by the legal jurisdiction and the institutional 
review board/independent ethics committee where the subject is treated. 


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3.2.2 
Exclusion Criteria 
Potential subjects who meet any of the following criteria at Screening will be excluded from 
the study: 
1. Medical history of significant hypersensitivity or allergic reaction to antibiotics of the 
quinolone or oxazolidinone class or study drug excipients in the judgment of the 
investigator. 
2. Women who are pregnant or lactating. 
3. Any infection expected to require other systemic antibacterial agents in addition to 
study drug. 
4. Receipt of systemic antibiotic therapy in the 7 days before enrollment unless one or 
more of the following are documented: 
• The subject received at least 48 hours of antibiotic therapy for CABP and the 
clinic notes document treatment failure (i.e., not by patient history or pulmonary 
imaging alone) with new or worsening symptoms while on pre-study therapy, or 
identification of a respiratory pathogen that is resistant to a pre-study antibiotic 
which would be susceptible to study drug (delafloxacin or moxifloxacin) in 
subjects with new or worsening signs and symptoms of CABP. 
• The subject received 1 dose of a single, potentially effective, short-acting 
antimicrobial drug or a short-acting antimicrobial drug regimen for treatment of 
the CABP under study within 24 hours of enrollment. (Note: 1 dose of a regimen 
is defined as the standard therapy for CABP at the study site.) Subjects who 
received prior antimicrobial drug under this criterion will be limited to no more 
than 25% of total randomized subjects. 
5. Respiratory infection confirmed or suspected to be secondary to hospital-acquired or 
ventilator-associated pneumonia or that requires treatment in an intensive care setting 
(because they are hemodynamically unstable, and/or likely to need mechanical 
ventilation) at the time of informed consent. 
6. Intubated at the time of informed consent or clinical presentation with pneumonia that 
would require invasive mechanical ventilation. 
7. Current or suspected diagnosis of: 
• Viral pneumonia, fungal pneumonia, including Pneumocystis jiroveci pneumonia 
• Aspiration pneumonia 


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• Other noninfectious causes of pulmonary infiltrates (e.g., pulmonary embolism, 
hypersensitivity pneumonia, congestive heart failure) 
• Primary or metastatic lung cancer 
• Cystic fibrosis 
• Active or suspected tuberculosis 
• Empyema (not including sterile parapneumonic effusions) 
8. Known anatomical or pathological bronchial obstruction, or a history of 
bronchiectasis, or documented Global initiative for chronic Obstructive Lung Disease 
(GOLD) Stage 4 chronic obstructive pulmonary disease, or a history of post 
obstructive pneumonia. 
9. Severely compromised immune system, e.g.:  
• Known absolute neutropenia (absolute neutrophil count < 500 cells/µL) 
• Known human immunodeficiency virus infection (HIV) with a CD4 count 
< 350 cells/µL within the last 4 months 
• Cancer chemotherapy or radiation in the last 3 months 
• Hematological malignancy 
• Bone marrow transplantation 
• Chronic steroid use (> 20 mg prednisone per day or equivalent) prior to 
enrollment 
10. Known history of Child-Pugh Class B or C liver disease (Appendix 7.4) and/or 
presence or possible signs of significant hepatic disease, or alanine aminotransferase 
(ALT) > 3× the upper limit of normal (ULN). 
11. Severe renal disease, or creatinine clearance (CrCl) ≤ 29 mL/min using Cockcroft-
Gault formula (Appendix 7.5), or need for hemodialysis or peritoneal dialysis. 
12. Uncorrected hypokalemia, or known uncorrected hypomagnesemia, at the time of 
enrollment. If treatment normalizes the serum potassium or magnesium, confirmed by 
retest during the screening period, the patient may then be enrolled. 
13. Ongoing treatment for seizures or untreated history of seizures. 
14. History of peripheral neuropathy. 
15. History of tendon damage/disorders due to quinolone therapy. 


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16. Known history of myasthenia gravis. 
17. History of post-antibiotic colitis within the last 3 months. 
18. Ventricular arrhythmia and/or ongoing proarrhythmic conditions such as clinically 
significant bradycardia, acute myocardial ischemia. 
19. History of prolonged QT syndrome, or mean QTcF (QT interval corrected with the 
Fridericia formula) greater than 450 msec for males and 470 msec for females on 
screening summary electrocardiogram (ECG). 
20. Concomitant use of drugs known to prolong the QT interval, including class IA (such 
as quinidine, procainamide, disopyramide) or Class III (such as amiodarone, sotalol, 
bretylium, ibutilide) antiarrhythmics. 
21. Concomitant use of monoamine oxidases (MAO) A or B inhibitor agents and 
adrenergic and serotonergic agents within 2 weeks of screening. 
22. Patients with known uncontrolled hypertension, pheochromocytoma, carcinoid 
thyrotoxicosis; and rare hereditary problems of galactose intolerance, the Lapp lactase 
deficiency or glucose-galactose malabsorption. 
23. Life expectancy of < 3 months. 
24. Immediate life-threatening disease. 
25. Any underlying disease (e.g., severe cardiac disease, malignancy, or psychiatric 
disorder) that, in the opinion of the investigator, may interfere with the subject’s 
ability to participate in the study. 
26. Previous participation in any study of delafloxacin. 
27. Receipt of an investigational drug within 30 days of randomization. 
28. Subject should not participate in the study, in the opinion of the investigator. 
Laboratory tests with exclusionary results judged by the investigator as not compatible with 
the subject’s clinical status may be repeated once for eligibility purposes. 
3.3 
Patient Withdrawal from Treatment or Study 
3.3.1 
Reasons for Withdrawal 
Subjects will be informed that they are free to withdraw from the study drug treatment or 
study at any time and for any reason. Any subject may withdraw his or her consent at any 
time. 


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Subjects will be discontinued from the study drug if any of the following occur: 
• The subject requires other systemic antibacterial agents to treat the primary CABP in 
addition to study drug.  
• In the opinion of the investigator, it is not in the best interest of the subject to continue. 
• There is a change in compliance with an inclusion or exclusion criterion that is clinically 
relevant and affects subject safety. 
• The subject takes a concomitant medication that might affect patient safety or study 
assessments/objectives. 
• The subject experiences (a) serious or intolerable AE(s). 
• The subject has ALT or AST of > 5× ULN or total bilirubin > 3× ULN. 
Upon occurrence of a serious or intolerable AE, the principal investigator will confer with the 
Medical Monitor. If a subject is discontinued from the study drug because of an AE, the event 
will be followed to a satisfactory resolution or until the principal investigator deems the event 
to be chronic or the subject to be stable.  
3.3.2 
Handling of Withdrawals 
Subjects who discontinue study drug and receive a non-study antibiotic for CABP will have 
EOT visit procedures performed with clinical assessment, but will not return for further 
on-site visits. Additional specimens for microbiological cultures and CXR should be 
collected before initiation of any rescue therapy and/or if the subject is a clinical failure, if 
possible. These subjects should be contacted by phone for the FU visit. 
Subjects who discontinue study drug and do not receive additional non-study antibiotic for 
CABP will have EOT visit procedures performed and should return to the site for the TOC 
and FU visits.  
Should a subject’s study participation be discontinued after receiving study drug, efforts must 
be made to perform all required EOT procedures with corresponding data recorded in the 
electronic case report form (eCRF). Subjects who prematurely discontinue study treatment 
should be encouraged to return to the study site for these safety evaluations. 
Every attempt will be made to contact all subjects who received at least 1 dose of study drug 
to collect all-cause mortality data on Day 28 (FU visit). Subjects who withdraw consent will 
not be contacted after withdrawal. 
Subjects who fail to return for a study visit will be contacted directly by the study site 
personnel. A minimum of 2 documented phone calls should be made over the course of at 


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least 2 weeks. If the study site personnel receive no response, and if the local government or 
regulatory agency permits, they should send a certified letter requesting that the subject 
contact the study site regarding his or her status in the study. If a subject does not return for 
the final visit, and the appropriate permission has been obtained, the investigator may obtain 
a verbal report on the subject’s health status from the subject’s local health care provider. 
It is vital to obtain follow-up data on any subject withdrawn because of an AE or SAE. In 
every case, efforts must be made to undertake protocol-specified safety and follow-up 
procedures. 
3.3.3 
Replacements 
Subjects who prematurely discontinue after randomization will not be replaced. 
3.4 
Study Procedures 
Before performing any study procedures, all potential subjects will sign an informed consent 
form (ICF). Subjects will have the opportunity to have any questions answered before 
signing the ICF. The investigator or subinvestigator must address all questions raised by the 
subject. The investigator or subinvestigator will also sign the ICF. 
3.4.1 
Study Visits 
Subjects enrolled in the study will have signs and symptoms consistent with CABP which are 
moderate to severe enough to warrant initial IV therapy. Subjects may be treated as 
hospitalized inpatients or outpatients in accordance with local treatment guidelines for 
moderate to severe CABP, provided that all study-drug infusions are administered by study-
site personnel or hospital staff who have been trained on protocol specifics and the Sponsor-
approved study drug-blinding plan. Hospital discharge will be at the discretion of the 
investigator. The date of hospital discharge will be recorded in the eCRF. 
3.4.1.1 
Screening  
Screening procedures will occur in the 24 hours prior to the first dose of study drug. The 
following will be performed after the subject or, where allowed by local regulations, their 
legally authorized representative provides informed consent: 
• Access interactive voice and web response system (IXRS) to register screening. 
• Record demographic data and medical, pulmonary, surgical, alcohol, and smoking history. 
• Record medications taken once or more in the 14 days before Screening, including 
nonprescription medications and dietary supplements. In addition, prior antibacterial 
treatments up to 30 days before first dose of study drug will be collected. 


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• Assess clinical signs/symptoms of CABP. 
• Record vital signs, body temperature and pulse oximetry (or arterial blood gases [ABGs], 
if clinically warranted). 
• Perform 12-lead electrocardiogram (ECG). 
• Conduct complete physical examination with height and weight. 
• Obtain posteroanterior (PA) and lateral CXR. A CT scan of the thorax is an acceptable 
alternative, if available per local standard of care. The CXR or CT scan obtained per local 
standard of care will not be repeated if obtained within 48 hours before the first dose of 
study drug.  
• Perform urine or serum pregnancy test for women of childbearing potential. 
• Obtain blood samples for hematology, serum chemistry, and coagulation profile and 
urine sample for urinalysis. The results of any of these tests obtained within 24 hours 
before enrollment may be used for screening purposes and to verify entry criteria by the 
local laboratory; however, blood and urine samples must be obtained at Screening (prior 
to the first dose of study drug) and sent to the central laboratory for analysis to serve as 
baseline values.  
• Obtain 2 sets of blood specimens for culture from 2 separate venipuncture sites. 
• Collect deep cough sputum specimen for Gram stain and culture, if possible. Additionally, 
other respiratory sources are acceptable if available (refer to Section 3.4.3.2.1). 
• Obtain blood samples for hepatitis serology. 
• Determine PORT Risk Class and CURB-65 score. 
• Collect and assess any AEs that have occurred since informed consent was signed. 
• Verify entry criteria. 
• Access the IXRS to randomize (or screen fail) subject. 
3.4.1.2 
Day 1 
Treatment may begin immediately after enrolling the subject via the IXRS. Subjects must 
begin study drug within 24 hours after the start of Screening procedures. If the first dose is 
administered the same day as Screening, then assessments that are required on Day 1, but 
already completed for Screening, will not be repeated unless otherwise specified below 
(assessments should be recorded in the Screening eCRF and NOT duplicated in the Day 1 


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eCRF). If not already performed on that day as part of the Screening visit, the following 
procedures will be performed on Day 1: 
• Record concomitant medications (update from screening, if applicable). 
• Assess clinical signs/symptoms of CABP. 
• Administer SF-12v2® Health Survey and Quality-of-Life (QoL) assessment questions. 
• Record vital signs, body temperature, and pulse oximetry around the time of the first dose. 
• Collect deep cough sputum specimen for Gram stain and culture prior to dosing if not 
collected or determined to be not acceptable at Screening (if possible). Additionally, 
other respiratory sources are acceptable if available (refer to Section 3.4.3.2.1). 
• Obtain urine sample for urinary antigen tests for S. pneumoniae and Legionella 
pneumophila. 
• Obtain blood samples for procalcitonin and Chlamydia pneumoniae, M. pneumoniae and 
L. pneumophila serology.  
• Obtain nasopharyngeal and oropharyngeal swabs prior to dosing. 
• Administer first dose of study drug. 
• Assess for AEs. 
• Administer second dose of study drug after 12 hours (± 2 hours). If the first dose is 
started late in the day because of screening and eligibility verifications, a 1-time 
adjustment is allowed for a more customary dosing schedule that is within ± 4 hours of 
the normally scheduled second dose. The every-12-hour (± 2 hour) dosing schedule is set 
after the first dose (or dose adjustment).  
3.4.1.3 
Daily While on IV Therapy 
The following procedures will be performed daily only while on IV therapy: 
• Assess clinical signs and symptoms of CABP. 
• Record vital signs, body temperature, and pulse oximetry at a consistent time each day. 
• Collect blood cultures if clinically indicated.  
• Record concomitant medications. 
• Assess for AEs. 
• Administer study drug every 12 hours (± 2 hours).  


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• For sites participating in PK assessments, blood samples for PK analysis will be obtained 
on Day 3 (± 1 day) of treatment within the 30 minutes before study drug administration, 
and at 1.5 and 3 hours after the start of the infusion. All time points have a ± 10-minute 
window. Subjects should have received a minimum of 3 consecutive doses of study drug 
prior to the start of PK blood sample collections. Subjects do not need to be fasted before 
dosing or during PK sample collections. Refer to Section 3.4.3.6 Pharmacokinetic Blood 
Sample Collections for details.  
3.4.1.4 
Early Clinical Response at 96 Hours (± 24 hours) 
The following procedures will be performed on all subjects at 96 hours (± 24 hours) after the 
start of the first dose of study drug. Procedures already completed as specified in 
Sections 3.4.1.3 or 3.4.1.5 do not need to be repeated unless they occurred prior to the ECR 
96 hour (± 24 hours) window. If not already performed within the ECR window, the 
following procedures will be performed: 
• Assess clinical signs and symptoms of CABP. 
• Perform targeted physical examination. 
• Record vital signs, body temperature, and pulse oximetry. 
• Collect blood cultures if clinically indicated.  
• Obtain hematology and serum chemistry.  
• Record concomitant medications. 
• Assess for AEs. 
• Administer study drug every 12 hours (± 2 hours). 
• Subjects who continue oral treatment as an outpatient will be dispensed/administered 
study drug and instructed to return to the clinic on Day 5 (if applicable) with their study 
drug container(s). 
3.4.1.5 
Day 5 (+ 1 Day) 
The assessments that are required on Day 5, but already completed as specified in 
Section 3.4.1.3 or 3.4.1.4 do not need to be repeated. If not already performed on that day, 
the following procedures will be performed:  
• Assess clinical signs and symptoms of CABP. 
• Record vital signs and body temperature for all subjects, and pulse oximetry if clinically 
indicated and/or for subjects on supplemental oxygen. 


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• Collect blood cultures if clinically indicated.  
• Record concomitant medications. 
• Assess for AEs. 
• Administer study drug every 12 hours (± 2 hours). 
• Perform study drug accountability on returned oral drug (outpatient subjects). 
• Study drug may be stopped at the discretion of the investigator after completing a 
minimum of 10 delafloxacin/delafloxacin placebo doses. Determination of appropriate 
treatment duration is described in Section 3.4.1.8.1.  
• Access the IXRS to register completion or continued treatment. 
• Subjects who continue oral treatment as an outpatient will be dispensed/administered 
study drug and instructed to return to the clinic on Day 7 with their study drug 
container(s).  
3.4.1.6 
Day 7 (+ 1 Day) 
The assessments that are required on Day 7 but already completed as specified in 
Section 3.4.1.3 do not need to be repeated. If not already performed on that day, the 
following procedures will be performed:  
• Perform study drug accountability on returned oral drug (outpatient subjects).  
• Assess clinical signs and symptoms of CABP.  
• Record vital signs and body temperature for all subjects, and pulse oximetry if clinically 
indicated and/or for subjects on supplemental oxygen. 
• Collect blood cultures if clinically indicated.  
• Record concomitant medications. 
• Assess for AEs. 
• Study drug may be stopped at the discretion of the investigator. Subjects may be 
evaluated and study drug may be administered/dispensed as described above until the 
subject completes the investigator’s planned course of therapy, up to a maximum 10 days 
of treatment (20 doses delafloxacin/delafloxacin placebo). Criteria for determination of 
appropriate treatment duration are described in Section 3.4.1.8.1.  
• Access the IXRS to register completion or continued treatment.  


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• Subjects who continue on treatment will be dispensed/administered sufficient quantity of 
study drug to complete treatment and will be instructed to return to the clinic (outpatient 
subjects) for the EOT visit with their study drug container(s).  
3.4.1.7 
End of IV Treatment 
After a minimum of 6 delafloxacin/delafloxacin placebo doses, subjects can switch to oral 
treatment if, in the past 24 hours, the subject meets the following suggested criteria for 
switch to oral treatment:  
• Is able to ingest intact large tablets/capsules, 
• Has a normally functioning gastrointestinal tract, and  
• Is clinically stable and has improved stability of vital sign indices, such as, no worsening 
from entry vital signs. 
Register the IV to oral switch in the IXRS. For subjects completing treatment as an 
outpatient, dispense oral study drug. Outpatient subjects will be instructed to return to the 
clinic on Day 5 (+ 1 day), Day 7 (+ 1 day) as applicable, and at EOT with their study drug 
container(s). Refer to Section 3.6.6. 
3.4.1.8 
End of Treatment (EOT) or Early Termination 
3.4.1.8.1 Criteria for Determining Treatment Duration 
After completing 5 days of treatment (minimum of 10 doses of delafloxacin/delafloxacin 
placebo), the investigator will assess the subject for clinical response to treatment to 
determine adequate treatment duration. The following suggested criteria can be used to assess 
clinical response; however, the duration of therapy should be individualized based upon the 
subject’s clinical response to treatment and comorbidities up to a maximum treatment of 
10 days (20 delafloxacin/delafloxacin placebo doses). 
• Afebrile for 48 to 72 hours,  
• Breathing without supplemental oxygen (unless required for preexisting disease), 
AND 
• Have no more than 1 clinical instability factor (defined as heart rate > 100 beats per 
minute, respiratory rate > 24 breaths per minute, and systolic blood pressure ≤ 90 mmHg) 
(Mandell 2007). 
3.4.1.8.2 End of Treatment or Early Termination Procedures 
Subjects who prematurely discontinue study drug or are completing treatment will have EOT 
procedures performed that same day or up to 24 hours (+ 4 hours) after the last dose of study 


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drug. Assessments already completed on the same day as the last dose of study drug can 
serve as EOT procedures, and do not need to be repeated. Assessments should be recorded in 
the EOT eCRF and not duplicated in other eCRF visits. Laboratory tests completed for a 
routine visit will not be repeated at EOT, if collected within 24 hours of the EOT visit.  
• Assess clinical signs and symptoms of CABP. 
• Investigator assessment of clinical response. 
• ONLY FOR LACK OF EFFICACY, collect deep cough sputum specimen for Gram 
stain and culture, if possible. Additionally, other respiratory sources are acceptable if 
available (refer to Section 3.4.3.2.1). 
• ONLY FOR LACK OF EFFICACY, obtain a repeat CXR.  
• Administer SF-12v2® Health Survey and QoL questions. 
• Targeted physical examination. 
• Record vital signs and body temperature for all subjects, and pulse oximetry for subjects 
on supplemental oxygen. 
• Collect blood cultures if clinically indicated.  
• Perform urine or serum pregnancy test for women of childbearing potential. 
• Obtain hematology and serum chemistry.  
• Record concomitant medications. 
• Assess for AEs. 
• Perform study drug accountability on returned drug (outpatient subjects).  
• Contact the IXRS to register treatment completion status.  
3.4.1.9 
Reminder Contact (3-9 Days After Last Dose) 
Subjects will receive a telephone call or contact via other interactive method, e.g., text or 
email as allowed by local regulations, to remind the subject about the upcoming TOC Visit.  
3.4.1.10 
Test of Cure (TOC Visit, 5-10 Days After Last Dose of Study Drug) 
The following procedures will be performed 5 to 10 days after the last dose of study drug: 
• Assess clinical signs and symptoms of CABP.  
• Investigator assessment of clinical response. 
• Administer SF-12v2® Health Survey and QoL questions. 


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• Targeted physical examination. 
• Record vital signs and body temperature on all subjects, and pulse oximetry for subjects 
on supplemental oxygen. 
• Collect deep cough sputum specimen for culture, if possible. Additionally, other 
respiratory sources are acceptable if available (refer to Section 3.4.3.2.1). 
• ONLY FOR LACK OF EFFICACY, obtain a repeat CXR. 
• Perform urine or serum pregnancy test for women of childbearing potential. 
• Obtain hematology and serum chemistry.  
• Obtain blood samples for C. pneumoniae, M. pneumoniae and L. pneumophila serology 
and procalcitonin.  
• Record post-treatment medications. 
• Assess for AEs. 
3.4.1.11 
Follow-up Visit (FU, Day 28 ± 2 Days) 
All efforts will be made to have subjects return to the clinic for a FU visit. Telephone contact 
is permissible for subjects unable, unwilling or not required (see Section 3.3.2) to return to 
the clinic. The following procedures will be performed at the FU Visit on Day 28 (± 2 days).  
• Urine or serum pregnancy test in female subjects of childbearing potential (for subjects 
who return to the clinic). 
• Obtain blood sample for C. pneumoniae, M. pneumoniae and L. pneumophila serology 
(for subjects who return to the clinic). 
• Assess for AEs and record AEs in the subject’s source (only SAEs will be collected in the 
eCRF) for all-cause mortality assessment. 
• Record post-treatment medications in the subject’s source, particularly any antibiotics 
taken after EOT. 
• Administer SF-12v2® Health Survey and QoL questions (may be completed by interview 
for subjects contacted by phone).  
3.4.1.12 
Early Withdrawal Procedures 
If a subject withdraws from study participation early, EOT procedures will be performed at 
the time of early withdrawal. Refer to Section 3.3 for further instructions on early withdrawal. 


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3.4.2 
Efficacy Assessments 
Efficacy will be evaluated through assessment of clinical signs and symptoms of pneumonia 
and microbiological culture and susceptibility testing of bacterial isolates. Other measures of 
clinical efficacy as detailed in the protocol will be assessed at baseline and at multiple time 
points during the study.  
3.4.2.1 
Clinical Evaluation 
The following signs and symptoms of CABP will be assessed and evaluated: 
• Pleuritic chest pain  
• Frequency or severity of cough  
• Dyspnea  
• Sputum production (if present, change in character and quantity from baseline and 
purulence) 
Symptom severity will be evaluated by the investigator on a 4-point scale (absent, mild, 
moderate, severe, see Section 7.8 for definitions) with improvement defined as at least a 
1-point improvement (decrease) from baseline to the assessment at 96 hours (± 24 hours) 
after first dose of study drug (e.g., from severe to moderate, from moderate to mild, or from 
mild to absent). See Appendix 7.8 for definitions of symptom intensity.  
In addition, at EOT and TOC, the investigator will assess the subject’s Clinical Outcome 
based on criteria in Section 3.7.2.2. Subjects’ outcomes will be assessed as Success, Failure, 
or Indeterminate/Missing. Subjects must receive at least 4 doses of study drug through study 
Day 3 before the investigator can consider the subject to be a clinical failure.  
3.4.3 
Study Assessments 
The following assessments will be performed to collect data needed for this research study. It 
is expected that the investigator and hospital staff will follow the usual standard of patient 
care and that local/regional laboratory results will be used to manage patient care.  
3.4.3.1 
Chest Radiography 
A chest radiograph (chest x-ray; posteroanterior and lateral preferred; single view acceptable 
if conclusive) must be obtained prior to randomization with initial interpretation and included 
in the source documents. Computed tomography of the thorax may be used as an alternative, 
if available as per local standard of care. The presence of lobar, multilobar, or patchy 
parenchymal infiltrate(s) consistent with acute bacterial pneumonia on a pulmonary imaging 
study is required for study entry. Chest radiography should be performed before 


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randomization and repeated at EOT or TOC only for lack of efficacy. Chest radiography 
obtained per local standard of care will not be repeated if obtained within 48 hours before the 
first dose of study drug. Findings will be recorded in the eCRF. Radiologic films must have a 
formal interpretation available in the source documents. Source, i.e., radiologist report and 
imaging, will be maintained by the site.  
3.4.3.2 
Microbiological Assessments 
The following pathogens are examples of primary pathogens that will be used to determine 
the microbiological responses in the study: the typical bacterial pathogens include but may 
not be limited to S. pneumoniae, H. influenzae, S. aureus, K. pneumoniae, and Moraxella 
catarrhalis, and the atypical bacterial pathogens C. pneumoniae, M. pneumoniae, and 
L. pneumophila. The causative pathogen will be identified by isolation from a baseline 
culture specimen (either a respiratory specimen or blood), by urinary antigen, by serology, 
and/or by PCR.  
Residual respiratory samples, nasopharyngeal swabs, and oropharyngeal swabs will be sent 
to specialty laboratories for possible culture, PCR, serotyping, and/or susceptibility testing 
(S. pneumoniae, L. pneumophila, M. pneumoniae). Respiratory and blood specimens will be 
sent to local/regional/specialty laboratories for culture, microorganism identification, and 
antibiotic sensitivity testing and will be processed according to standard recognized methods 
(Garcia 2010, Murray 2007). Sites will use local/regional culture results for patient 
management.  
Two Gram stain slides of the sputum specimen will be prepared by the local/regional 
laboratories. One slide will be stained and read locally. Both slides, read and unread, will be 
sent to the central laboratory to confirm results. An additional Gram stain slide may be 
retained by the local microbiology laboratory, if required by local regulations. Culture will be 
performed at local or regional laboratories, as applicable. Rapid MRSA identification 
methods are acceptable to use if S. aureus is identified by the local/regional laboratory. 
Isolates that are not considered contaminants will be forwarded to the central microbiology 
laboratory for confirmation of identity and antimicrobial susceptibility testing and any further 
molecular or phenotypic characterization (e.g., PCR for Panton-Valentine leukocidin and 
mecA genes, pulsed-field gel electrophoresis). Specific handling and shipping instructions 
that will maintain viability of all organisms will be provided in the laboratory manual. A 
duplicate sample of the isolate(s) (from all sources) submitted to the central microbiology 
laboratory will be maintained (in a frozen state) by the local laboratory or sent to the central 
laboratory until the conclusion of the study. Directions for collection, processing and 
handling of specimens are included in the laboratory manual.  


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Pathogens will be specifically identified to the genus and species levels. In vitro 
susceptibility of target pathogens to delafloxacin and moxifloxacin will be determined at the 
central laboratory according to Clinical Laboratory Standards Institute (CLSI) and European 
Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines for broth and agar 
dilution and disk diffusion. Susceptibility to additional antibiotics will also be evaluated.  
In all cases, the investigator should make decisions about subject withdrawal or continuation 
based on his or her best clinical judgment, and not based solely upon culture/susceptibility 
results.  
3.4.3.2.1 Respiratory Culture 
The collection of an adequate sputum sample for Gram stain, culture, and susceptibility 
testing, as applicable, will be attempted in all subjects at baseline. Other sources of 
respiratory specimens such as those obtained from bronchoalveolar lavage (BAL), protected 
specimen brush (PSB), transtracheal aspirate, and pleural fluid, if available, are acceptable to 
submit for culture. All respiratory specimens will be sent to the local/regional laboratory for 
gram stain, culture and susceptibility testing, as applicable. 
All sputum and transtracheal aspirate samples will be evaluated to determine quality. A Gram 
stain will be performed immediately after the sample is delivered to the microbiology 
laboratory. A microscopic examination of the slide will be performed. A “good” sputum 
sample is one with polymorphonuclear leukocytes but few (or no) squamous epithelial cells 
on Gram stain. All efforts will be made to obtain a sputum or transtracheal aspirate specimen 
that yields an acceptable Gram-stain, defined as < 10 squamous epithelial cells and/or 
> 25 polymorphonuclear cells per low-power field.  
All respiratory specimens will be sent for culture and susceptibility testing. In addition, any 
residual respiratory sample will be frozen and sent to the central laboratory for culture, 
L. pneumophila identification, antibiotic susceptibility testing, and serotyping at a specialty 
microbiology laboratory. The respiratory culture, if positive, will be used to identify isolates 
for submission to the central microbiology laboratory and to freeze for back-up storage. 
Collection of a repeat respiratory specimen for culture should be attempted at EOT only for 
lack of efficacy, prior to any rescue therapy, at TOC if possible, or if clinically indicated.  
The method used to obtain the respiratory culture will be documented in the subject’s source 
record and in the eCRF. Specimens will be collected and shipped using acceptable materials, 
timelines and shipping conditions to ensure specimen integrity and viability. Instructions for 
the processing of respiratory samples for Gram stain and culture are provided in the 
laboratory manual.  


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3.4.3.2.2 Blood Culture 
Two sets (aerobic and anaerobic) of blood specimens for culture will be obtained at baseline 
from anatomically different locations. Additional blood samples will be collected for culture 
at subsequent visits only if a previous culture was positive, or if clinically indicated. If 
positive, blood cultures will be repeated until they are negative. Culture will be performed at 
a local or regional laboratory, as applicable. The blood culture, if positive, will be used to 
identify isolates for submission to the central microbiology laboratory and to freeze for back-
up storage.  
3.4.3.2.3 Urine Antigen Testing 
Urine samples will be obtained for L. pneumophila and S. pneumoniae urine antigen testing 
at baseline and forwarded to the central laboratory.  
3.4.3.2.4 Nasopharyngeal and Oropharyngeal Testing 
A nasopharyngeal swab will be obtained at baseline and forwarded to the central laboratory 
for S. pneumoniae PCR analysis and/or S. pneumoniae culture, serotyping and antibiotic 
susceptibility testing at a specialty microbiology laboratory. Two oropharyngeal swabs will 
be obtained at baseline and forwarded to the central laboratory for M. pneumoniae culture 
and/or PCR analysis, antibiotic susceptibility testing at a specialty microbiology laboratory.  
3.4.3.2.5 Serology 
Serum serology samples will be tested for identification of atypical pathogens 
C. pneumoniae, M. pneumoniae and L. pneumophila at baseline, TOC, and FU.  
3.4.3.3 
Demographic Data/Medical History 
Demographic data and a complete medical, pulmonary, and surgical history including past 
and current alcohol use/abuse and smoking history will be collected at Screening. The 
medical history should include clinically significant medical, pulmonary or surgical history 
ongoing at baseline or with onset in the previous 2 years, as well as hospitalizations of more 
than 2 days within the last 90 days. Data related to the current infection under study should 
be recorded not in the medical history but on the CABP signs and symptoms form of the 
eCRF. 
3.4.3.4 
Prior Medications 
All medications taken once or more in the 14 days before Screening, including 
nonprescription medications and dietary supplements, will be recorded. Prior antibacterial 
treatments up to 30 days before the first dose of study drug will also be collected. 
Medications started after the first study dose (i.e., concomitant medications) will be collected 
as described in Sections 3.4.3.11 and 3.4.3.12. 


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3.4.3.5 
Clinical Laboratory Tests 
Clinical laboratory testing will be performed according to the Schedule of Events 
(Appendix 7.1). Local results of pregnancy test, serum chemistry and coagulation profile, 
hematology, and urinalysis tests obtained within 24 hours before enrollment may be used for 
screening purposes and to verify entry criteria. However, blood and urine samples will be 
collected at Screening and on Day 1 prior to the first dose of study drug and will be sent to 
the central laboratory to serve as baseline values. Directions for collection, processing, and 
handling of specimens are included in the laboratory manual. 
Tests to be performed are as follows: 
Serum Chemistry: A serum chemistry panel will be taken to include sodium, potassium, 
chloride, bicarbonate, magnesium, calcium, phosphorus, blood urea nitrogen, creatinine, 
creatine phosphokinase, albumin, glucose, total protein, alkaline phosphatase, alanine 
aminotransferase, aspartate aminotransferase, uric acid, and total bilirubin. Creatinine 
clearance (CrCl) will be calculated with every chemistry panel. Serum chemistry samples 
will be analyzed by a central laboratory.  
Other Chemistry: Procalcitonin will be analyzed by a central laboratory.  
Hepatitis Serology: Hepatitis B virus surface antigen and hepatitis C virus antibody will be 
tested at Screening and will not be exclusionary. If Hepatitis B or C is discovered based on 
this testing, this should be recorded as Medical History and not an adverse event. Hepatitis 
serology will be analyzed by a central laboratory.  
Hematology: A hematology panel will be taken to include complete blood count with 
hematocrit, hemoglobin, platelet count, red blood cell count (RBC), RBC morphology and 
mean corpuscular volume, and white blood cell count with differential. Prothrombin time and 
international normalized ratio will also be measured at Screening. Hematology samples will 
be analyzed by a central laboratory. 
Urinalysis: A urine panel will be taken at screening to include pH, specific gravity, 
leukocytes, nitrite, leukocyte esterase, protein, urobilinogen, bilirubin, blood, glucose, and a 
microscopic examination. The urine samples will be analyzed by a central laboratory.  
Pregnancy Test: A urine or serum pregnancy test will be performed in women of 
childbearing potential. Pregnancy testing will be performed by a local laboratory.  
3.4.3.6 
Pharmacokinetic Blood Sample Collections 
Serial blood samples for PK analysis will be obtained at select investigative sites on Day 3 
(± 1 day) of treatment within the 30 minutes before study drug administration and at 1.5 and 


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3 hours after the start of the infusion. All time points will have a ± 10-minute window. 
Subjects should have received a minimum of 3 consecutive doses of study drug prior to the 
start of PK blood collection. Subjects do not need to be fasted before dosing or during PK 
sample collections. Samples will be processed according to the laboratory manual and sent to 
the central laboratory for analysis.  
All plasma samples will be assayed using a validated liquid chromatography coupled with 
tandem mass spectrometry assay for delafloxacin. 
3.4.3.7 
Vital Sign Measurements 
Vital signs including body temperature, heart rate, respiratory rate, systolic and diastolic 
blood pressure, and pulse oximetry will be obtained according to the Schedule of Events 
(Appendix 7.1). Arterial blood gases can be obtained at Screening if clinically warranted. 
Daily supplemental oxygen will be recorded. Blood pressure and pulse rate will be measured 
after subjects have been in a sitting position for at least 5 minutes. Respirations will be 
counted and documented in breaths per minute. Body temperature can be measured via 
different methods including oral, rectal, tympanic, and axillary. Vital signs should be 
measured at a consistent time each day while on IV therapy. Subjects who require pressor 
support should have regular blood pressure monitoring as per local standard of care. 
3.4.3.8 
Physical Examination 
A complete physical examination, including height and weight, will be performed at 
Screening. 
Targeted physical examinations will be performed during the study to assess changes from 
baseline parameters, AEs, and other relevant safety information. 
3.4.3.9 
Electrocardiogram 
A 12-lead ECG will be performed at Screening, and if clinically indicated by the investigator 
after Screening. A single ECG will be recorded after the subject has been in a supine position 
and at rest for at least 3 minutes. The ECG tracings should be collected and retained with the 
source documents for study monitoring. The investigator or designee will be responsible for 
reviewing the 12-lead ECG to assess whether the results are within the reference limits and to 
determine the clinical significance of the results. These assessments will be recorded in the 
eCRF. 


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3.4.3.10 
Health-Related Quality-of-Life Assessment  
SF-12v2® Health Survey 
The SF-12v2® Health Survey (acute) is a multipurpose short form survey with 12 questions. 
This validated tool includes questions which were combined, scored, and weighted to create 
2 scales that provide glimpses into mental and physical functioning and overall health-related 
quality of life. The “Acute” requires the patient’s recall of the patient’s status in the week 
prior to questioning. The SF-12v2® is a generic measure and does not target a specific age or 
disease group. 
The SF-12v2® measures 8 attributes of functional health status: physical functioning, role 
limitations resulting from physical health problems, bodily pain, general health, vitality 
(energy and fatigue), social functioning, role limitations resulting from emotional problems, 
and mental health (psychological distress and psychological well-being). In addition, the 
SF-12v2® assesses overall physical and mental function using summary scales, Physical 
Component Summary Score (PCS-12), and Mental Component Summary Score (MCS-12), 
which are scored through comparison with population norms estimated from responses to the 
1990 National Survey of Functional Health Status. This survey will be completed at baseline, 
EOT, TOC, and FU based on availability of the validated survey in local language.  
Changes, i.e., worsening, will not be documented as AEs unless reported during the 
non-directed questioning for AEs (see Section 3.4.4.2). The SF-12v2® Health Survey is 
provided in Appendix 7.6.  
Quality-of-Life Questions 
Quality-of-life questions will be asked/administered to determine the effect of the subject’s 
CABP under study on his/her usual daily activities of doing their job and earning income. 
The questions require the subject to recall their status in the 24 hours prior to questioning. 
Changes, i.e., worsening will not be documented as AEs unless reported during the 
non-directed questioning for AEs (see Section 3.4.4.2). The QoL assessment questions are 
provided in Appendix 7.7.  
3.4.3.11 
Concomitant Medications 
All concomitant medications will be recorded in the source and eCRF from the time the 
subject signs informed consent through the EOT. Nonprescription medications, medications 
given as part of any surgical procedure, and dietary supplements will be included. 
Concomitant medications that are allowed or prohibited during the study are described in 
Sections 3.6.7 and 3.6.8. 


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If an allergic reaction occurs, the investigator should discontinue treatment (if ongoing) and 
follow the usual standard of care. The reaction will be recorded as an AE, and all medications 
given will be recorded as concomitant medications. 
3.4.3.12 
Post-Treatment Medications 
All medications, including nonprescription medications and dietary supplements, taken once 
or more from the EOT Visit through the FU Visit will be recorded in the subject source. The 
post-treatment medications recorded in the eCRF will be limited. Enter any antibiotics taken 
after EOT in the eCRF for all subjects. All other medications will only be entered in the 
eCRF through the TOC Visit, and only medications associated with an SAE from the TOC 
Visit through the FU Visit will be recorded in the eCRF. For subjects not required to have or 
missing the TOC Visit, post-treatment medications other than antibiotics will only be 
recorded in the eCRF if associated with an SAE through the Follow-up Visit. 
3.4.4 
Safety Assessments 
Safety will be assessed by monitoring of AEs (including serious AEs [SAEs]), vital sign 
measurements and body temperature, clinical laboratory tests (including pregnancy testing), 
physical examination findings, electrocardiograms (ECGs) if clinically warranted, and 
concomitant medications.  
3.4.4.1 
Adverse Event Definitions 
The investigator is responsible for reporting all AEs that are observed or reported during the 
study, regardless of their relationship to study drug or their clinical significance. 
A pretreatment event is defined as any untoward medical occurrence in a clinical 
investigation subject who has signed informed consent to participate in a study but prior to 
administration of double-blind study medication; it does not necessarily have to have a causal 
relationship with study participation. 
An AE is defined as any untoward medical occurrence associated with the use of a drug in a 
subject enrolled into this study regardless of its causal relationship to study treatment. 
Subjects or, where allowed by local regulations, their legally authorized representatives will 
be instructed to contact the principal investigator or subinvestigator at any time after signing 
the informed consent if any symptoms develop. 
A treatment-emergent adverse event (TEAE) is defined as any event not present before 
exposure to study drug or any event already present that worsens in either intensity or 
frequency after exposure to study drug. 
A treatment-related AE is defined as any event with suspected causality to study drug. 


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An SAE is defined as any event that: 
• Results in death, 
• Is immediately life threatening, 
• Requires in-subject hospitalization or prolongation of existing hospitalization, 
• Results in persistent or significant disability/incapacity or substantial disruption of the 
ability to conduct normal life functions, or 
• Is a congenital anomaly/birth defect. 
• Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered an SAE when, based upon appropriate medical 
judgment, they may jeopardize the subject and may require medical or surgical 
intervention to prevent one of the outcomes listed in this definition. 
• Examples of such medical events include allergic bronchospasm requiring intensive 
treatment in an emergency room or at home, blood dyscrasias, convulsions that do not 
result in in-subject hospitalization, or the development of drug dependency or drug abuse. 
• Pretreatment events that fulfill 1 or more of the serious criteria above are also to be 
considered SAEs and should be reported and followed up in the same manner. 
3.4.4.2 
Eliciting and Documenting Adverse Events 
All AEs that occur from the time the subject or authorized representative signs the ICF 
through the FU Visit must be reported in detail in the subject source and followed to 
satisfactory resolution or until the principal investigator or subinvestigator deems the event to 
be chronic or the subject to be stable. The description of the AE will include the onset date, 
duration, date of resolution, severity (refer to Section 3.4.4.4), seriousness, etiology, and the 
likelihood of relationship of the AE to study treatment. 
Collection of pretreatment events will commence from the time the subject signs the 
informed consent to participate in the study and continues until the subject is first 
administered double-blind study medication. For subjects who discontinue study 
participation prior to double-blind study medication administration, pretreatment events are 
collected until the subject discontinues. Collection of TEAEs will commence from the time 
that the subject is first administered double-blind study drug through the FU Visit.  
Assessment of relationship to study drug will only be captured after the subject is first 
administered study drug. 


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At every study visit, subjects will be asked a non-directed question to elicit any medically 
related changes in their well-being. They will also be asked if they have been hospitalized, 
had any accidents, used any new medications, or changed concomitant medication regimens 
(both prescription and over-the-counter medications). Patient-reported outcome instruments 
such as SF-12v2® Health Survey and QoL questions will not be used directly as a source of 
potential AE information. 
In addition to subject observations, AEs will be documented from any data collected in the 
eCRF or other source documents (e.g., laboratory values, physical examination findings, 
ECG changes) that are relevant to subject safety. An allergic reaction to study drug must be 
reported as an AE. 
3.4.4.3 
Reporting Adverse Events 
All AEs reported or observed during the study will be recorded in the AE eCRF from the 
time that the subject is first administered double-blind study drug through the EOT or TOC 
Visit, whichever is later. All SAEs will be recorded in the eCRF from the time the subject or 
authorized representative signs the ICF through the FU Visit.  
Information to be collected includes drug treatment, dosage, type of event, time of onset, 
investigator-specified assessment of severity and relationship to study drug, time of 
resolution of the event, seriousness, any required treatment or evaluations, and outcome. 
Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, 
reactions to concurrent medications, or progression of disease states must also be reported. 
All AEs will be followed to adequate resolution. The Medical Dictionary for Regulatory 
Activities will be used to code all AEs. 
Preexisting conditions: 
Preexisting conditions (present before the start of the AE collection period) are considered 
concurrent medical conditions and should not be recorded as AEs. However, if the subject 
experiences a worsening or complication of such a concurrent condition, the worsening or 
complication should be recorded as an AE. Investigators should ensure that the AE term 
recorded captures the change in the condition (e.g., “worsening of [condition]”). 
Insufficient clinical response (lack of efficacy): 
Insufficient clinical response, efficacy, or pharmacological action should NOT be recorded as 
an AE. The principal investigator must make the distinction between exacerbation of 
preexisting illness and lack of therapeutic efficacy. Progression of the current CABP due to 
lack of efficacy of the study drug will be recorded on the Clinical Response eCRF. 


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Abnormal laboratory values or test results constitute AEs only if they induce clinical signs or 
symptoms, are considered clinically significant, require therapy or further diagnosis beyond 
repeat testing for confirmation alone. 
3.4.4.4 
Assessment of Severity 
The severity, or intensity, of an AE refers to the extent to which an AE affects the subject’s 
daily activities. The intensity of the AE will be rated as mild, moderate, or severe using the 
following criteria: 
Mild: 
These events 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 
functioning. 
Severe: 
These events interrupt a subject’s usual daily activity and may require systemic 
drug therapy or other treatment. 
 
Changes in the severity of an AE should be documented to allow an assessment of the 
duration of the event at each level of intensity to be performed. Adverse events characterized 
as intermittent require documentation of onset and duration of each episode. 
3.4.4.5 
Assessment of Causality 
The investigator’s assessment of an AE’s relationship to study drug is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the 
study. If there is any doubt as to whether a clinical observation is an AE, the event should be 
reported. 
The relationship or association of the test article in causing or contributing to the AE will be 
characterized using the following classification and criteria: 
Unrelated: 
This relationship suggests that there is no association between the study drug 
and the reported event. 
Possible: 
This relationship suggests that treatment with the study drug caused or 
contributed to the AE, i.e., the event follows a reasonable temporal sequence 
from the time of drug administration and/or follows a known response pattern 
to the study drug, but could also have been produced by other factors. 


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Probable: 
This relationship suggests that a reasonable temporal sequence of the event 
with study drug administration exists and, based upon the known 
pharmacological action of the drug, known or previously reported adverse 
reactions to the drug or class of drugs, or judgment based on the investigator’s 
clinical experience, the association of the event with the study drug seems 
likely. 
Definite: 
This relationship suggests that a definite causal relationship exists between drug 
administration and the AE, and other conditions (concurrent illness, 
progression/expression of disease state, or concurrent medication reaction) do 
not appear to explain the event. 
 
3.4.4.6 
Reporting Serious Adverse Events 
Any AE considered serious by the principal investigator or subinvestigator or which meets 
the above seriousness criteria which occurs after the signing of the informed consent through 
the FU Visit (as described in Section 3.4.4.1) must be reported to the Medical Monitor or 
designee immediately or within 24 hours from the time study-site personnel first learn about 
the event. A copy of the initial SAE report must be submitted to the CRO Pharmacovigilance 
Department within 24 hours. The SAE report should provide as much of the required 
information as is available at the time. The following minimum information is required for 
reporting an SAE: subject identification, reporting source, causality, and an event outcome. 
Supplemental information may be transmitted using a follow-up report and should not delay 
the initial report. The study sponsor or its designee may contact the investigational site to 
solicit additional information or to follow up on the event. All sites will be supplied with 
SAE Reporting Instructions as part of the Onsite Study File; all necessary contact 
information including SAE reporting lines/faxes for communication of safety data will be 
provided in the Onsite Study File Contact Sheet.  
Withdrawal from the study and all therapeutic measures will be performed at the discretion 
of the principal investigator or subinvestigator. 
The sponsor or designee will be responsible for reporting all applicable SAEs to regulatory 
authorities, investigators, and IRBs or IECs, as applicable, in accordance with national 
regulations in the countries where the study is conducted. The sponsor or designee will 
prepare an expedited report for all SAEs that are unexpected and potentially related to the 
study medication, and copies will be distributed according to all applicable laws and 
regulations in countries with active investigators. The investigational site will also forward a 
copy of all expedited reports to their IRB or IEC, as applicable. Copies of SAE 


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correspondence with all principal investigator or subinvestigators, governing authorities, 
IECs, and the sponsor must be submitted to CRO for filing. 
3.4.4.7 
Follow-up of Subjects Reporting Serious Adverse Events 
A subject experiencing 1 or more SAEs will receive treatment and follow-up evaluations by 
the principal investigator or subinvestigator or will be referred to another appropriate 
physician for treatment and follow-up. All SAEs will be followed until satisfactory resolution 
or until the principal investigator or subinvestigator deems the event to be chronic or the 
subject to be stable. The timelines and procedure for follow-up reports are the same as those 
for the initial report. 
3.4.4.8 
Safety Monitoring Committee 
The sponsor may utilize an independent safety monitoring committee during the study. In 
that event, the membership, activities, and responsibilities of the safety monitoring 
committee will be described in detail in a separate charter document established for this study.  
3.4.4.9 
Pregnancy 
Women with known or suspected pregnancy are excluded from the study. In the event a 
subject becomes pregnant during treatment, the subject will be requested to discontinue study 
drug immediately and will complete EOT Visit procedures as specified in Section 3.3.2. The 
investigator must inform the subject of her right to receive treatment information. If 
pregnancy is discovered after administration of study drug, the investigator must report 
information using the Pregnancy Report Form to the Pharmacovigilance Department staff. 
All subject pregnancies will be followed up to final outcome, using the pregnancy follow-up 
form. The outcome, including any premature termination, must be reported to the CRO. The 
pregnancy is not considered an AE; however, pregnancy complications, including 
miscarriage or spontaneous abortion, are considered AEs. Any untoward outcome for the 
mother or infant is considered an SAE.  
3.4.4.10 
Criteria for Stopping Study 
The study may be terminated by the sponsor if new data becomes available which raises 
concern about the safety of the study drug, so that continuation might cause unacceptable 
risks to participants. 
In addition, the Sponsor reserves the right to discontinue the study prior to inclusion of the 
intended number of subjects, but intends only to exercise this right for valid scientific or 
administrative reasons.  


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After such a decision, the Investigator must promptly contact all subjects, assure appropriate 
therapy and follow-up for the subjects and provide written notification to the IRB/IEC.  
3.5 
Overdose Management 
Single oral doses of delafloxacin as high as 1600 mg and multiple doses of 1200 mg have 
been administered to subjects in Phase 1 trials. Single IV doses as high as 1200 mg have been 
administered to subjects in Phase 1 trials. In study RX-3341-302, 3 patients received 600 mg 
IV BID for up to 13 days due to pharmacy error (Rib-X 2015). There were no drug-related 
AEs reported. The most common AEs associated with the high doses of delafloxacin were 
gastrointestinal effects (diarrhea, abdominal pain/discomfort, nausea, vomiting) and 
headache. General supportive care is suggested for intentional or unintentional overdosage of 
delafloxacin.  
Refer to the moxifloxacin and or linezolid Summary of Product Characteristics (SmPC) or 
prescribing information for treatment for intentional or unintentional overdose. 
3.6 
Study Treatments 
3.6.1 
Method of Assigning Subjects to Treatment Groups 
Each subject will be randomly assigned in a 1:1 ratio to the delafloxacin or moxifloxacin 
treatment group. 
The investigator or designee will enter the enrollment information in the IXRS. The 
unblinded pharmacist or unblinded designee will obtain the treatment assignment from the 
IXRS as described in the IXRS manual. A statistician who is not otherwise involved in the 
conduct of the study will create the randomization code. Randomization will be stratified by 
PORT Risk Class, medical history of COPD/asthma, and by prior single-dose/regimen 
antibiotic use.  
Subjects in PORT Risk Class II will be limited to no more than 25% of total randomized 
subjects, and prior single-dose/regimen antibiotic use limited to no more than 25% of total 
randomized subjects.  
3.6.2 
Treatments Administered 
An unblinded pharmacist or an unblinded designee will prepare the study drug infusions.  
• Delafloxacin 300 mg will be administered as a 1-hour IV infusion every 12 hours 
(± 2 hours) for a minimum of 6 doses with an option to switch to delafloxacin 450 mg 
tablet administered orally every 12 hours (± 2 hours) for the remaining doses. 


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• Moxifloxacin 400 mg will be administered as a 1-hour IV infusion every 24 hours 
(± 2 hours) for a minimum of 3 active doses with an option to switch to moxifloxacin 
400 mg (over-encapsulated tablet) administered orally every 24 hours (± 2 hours) for the 
remaining doses.  
• At local investigator discretion, subjects in the moxifloxacin arm with confirmed MRSA, 
in place of remaining moxifloxacin doses, can receive linezolid 600 mg administered as a 
1-hour IV infusion every 12 hours (± 2 hours) for the remaining doses. 
Refer to Section 3.6.4.3 for blinding information. Refer to the pharmacy manual for further 
details regarding dose preparation and administration. 
3.6.3 
Description of Investigational Product 
Delafloxacin 
Delafloxacin for Injection, 300 mg/vial, is a light-yellow to tan-colored lyophilized powder 
provided in a 20 mL clear borosilicate glass vial. Each vial contains the following 
ingredients: 432.9 mg delafloxacin meglumine equivalent of 300 mg free acid, 58.56 mg 
meglumine, 2400 mg sulfobutyl ether sodium beta-cyclodextrin (Captisol®), and 2.6 mg 
ethylene-diamine-tetra-acetate disodium (as EDTA, amount as acid).  
After reconstitution in the vial, the drug concentration is 25 mg/mL in an aqueous solution of 
12.4 mL (0.4 mL as overage). 
Oral delafloxacin is a capsule-shaped tablet in beige color with tan spots (delafloxacin 
particles) and with RX3341 debossed on one side. Each tablet contains the following 
ingredients: 649.35 mg delafloxacin meglumine equivalent of 450-mg free acid; cellulose; 
povidone; crospovidone; sodium bicarbonate; sodium phosphate; citric acid; and magnesium 
stearate. For more information on the description of delafloxacin, refer to the Investigator’s 
Brochure (Melinta 2016).  
Moxifloxacin Hydrochloride 
Moxifloxacin hydrochloride is a synthetic broad spectrum fluoroquinolone antibacterial 
agent for IV and oral use. Moxifloxacin injection for IV use and moxifloxacin as film-coated 
tablets containing moxifloxacin hydrochloride (equivalent to 400 mg moxifloxacin) are 
planned to be used. For the description of the product, refer to its SmPC or prescribing 
information.  
Linezolid 
Linezolid is an oxazolidinone-class antibacterial. Linezolid injection for IV use is planned to 
be used. For the description of the product, refer to its SmPC or prescribing information.  


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3.6.4 
Management of Clinical Supplies 
3.6.4.1 
Study Drug Packaging and Storage 
Delafloxacin for Injection (300 mg/vial) will be provided in a 20-mL clear borosilicate glass 
vial. The contents of the vial will be reconstituted and diluted before administration 
according to the pharmacy manual. Delafloxacin (450 mg) tablets will be supplied in blister 
packaging.  
Do not store delafloxacin in conditions over 30°C. In the US, storage conditions will be 
specified as Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. 
Moxifloxacin (400 mg) for IV use is intended to be provided in glass bottles or infusion bags 
as local availability allows. Moxifloxacin (400 mg) over-encapsulated tablets are intended to 
be supplied in daily dose bottles.  
Moxifloxacin should be stored as per its SmPC or prescribing information.  
Linezolid (600 mg) for IV use is intended to be provided as a ready-to-use sterile isotonic 
solution for IV infusion.  
Linezolid should be stored as per its SmPC or prescribing information.  
Vials, bottles, and blister packs of study drug will be provided to the study sites. Vials, bags, 
and bottles for IV use may be bulk or kitted as availability allows.  
Additional study drug will be supplied as needed based on information provided via the 
IXRS. 
Detailed information on study drug packaging, preparation, storage, and handling may be 
found in the pharmacy manual. 
3.6.4.2 
Test Article Accountability 
The pharmacy and/or clinic will maintain accurate records of receipt of all test articles, 
including dates of receipt. In addition, accurate records will be kept regarding when and how 
much test article is dispensed and used for each subject in the study. Reasons for departure 
from the expected dispensing regimen must also be recorded. At the completion of the study, 
to satisfy regulatory requirements regarding drug accountability, all study drug will be 
reconciled and retained or destroyed according to applicable local regulations. 
All study drug must be kept in a secure location with access restricted to only necessary 
study site personnel and hospital pharmacist. 


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3.6.4.3 
Blinding 
The majority of the involved parties in this study (subjects, investigators, laboratories, CRO, 
and sponsor personnel) will be blinded to the identity of study drug and randomization 
assignments until the study is formally unblinded. Unblinding will occur after all subjects 
have completed the study and after resolution of all data queries. Each site will document a 
blinding plan prior to study start. 
The pharmacist will not be blinded, and will cover the IV infusion bag and tubing so that the 
identification of the study drug solution will not be seen by the blinded study staff or study 
subjects. Certain clinical research staff will not be blinded in order to monitor the pharmacy, 
administer study drug (if applicable), and monitor study administration records and will not 
reveal a subject’s treatment assignment to study staff. The statistician who creates the 
randomization code will not be involved otherwise in the conduct of the study. 
• All IV blinded dosing will be maintained with a 12-hour schedule.  
• IV bags will be blinded. The IV infusion bag and tubing will be masked so that the 
delafloxacin, moxifloxacin, linezolid, and placebo solutions will be indistinguishable. 
Infusion lines from the study drug bag to the subject must be flushed after each 
administration to ensure the subject receives a complete dose. 
• Subjects in the moxifloxacin treatment arm will receive once-daily active IV therapy 
alternating doses of IV moxifloxacin and IV placebo BID.  
• Subjects in the delafloxacin arm, when on oral therapy, will receive oral placebo 
moxifloxacin QD or IV placebo linezolid BID to maintain blinding.  
• Subjects in the moxifloxacin/linezolid arm, when on oral therapy or when meeting 
criteria for oral therapy, will receive placebo delafloxacin oral formulation (tablets 
identical in appearance to the delafloxacin tablets) to maintain blinding. 
Treatment regimens are summarized in Table 3-1. 


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Table 3-1 
Treatment Regimens 
 
Regimens Given 
Subjects Randomized 
to Delafloxacin 
 
Subjects Randomized 
to Moxifloxacin 
WHILE ON 
IV 
THERAPY 
IV regimen given 
with blinding 
covers 
IV active delafloxacin 
twice daily  
 
IV active moxifloxacin 
once daily, alternative 
with IV placebo to 
maintain blind for BID 
dosing 
If linezolid is 
prescribed during 
IV dosing period 
Continue IV active 
delafloxacin twice daily  
 
Discontinue IV 
moxifloxacin/placebo 
and begin IV active 
linezolid twice daily 
 
 
 
 
 
WHILE ON 
ORAL 
THERAPY 
Delafloxacin 
Oral active delafloxacin 
twice daily 
AND 
 
Oral placebo 
delafloxacin twice daily 
AND 
Moxifloxacin 
Oral placebo 
moxifloxacin once daily 
 
Oral active moxifloxacin 
once daily  
If linezolid is 
prescribed for 
MRSA in 
moxifloxacin 
subjects a partial 
switch back to IV 
applies 
Oral placebo 
moxifloxacin will be 
discontinued (oral 
delafloxacin continues) 
and subjects randomized 
to delafloxacin will 
receive IV placebo 
linezolid twice daily 
 
Oral active moxifloxacin 
will be discontinued and 
subjects randomized to 
moxifloxacin will 
receive IV active 
linezolid twice daily  
 
3.6.5 
Breaking the Blind 
A double-blind design is used to maintain blinding for all personnel involved with the 
evaluation of subject efficacy and safety during the study. The blind should only be broken in 
an emergency when it is essential for the Investigator to know which treatment an individual 
subject has received in order to provide appropriate care. In an emergency situation, the 
Investigator will be able to obtain the unblinded treatment assignment through the password-
protected IXRS or the unblinded pharmacist. Instructions for obtaining the unblinded 


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treatment assignment will be provided to the site. The Investigator should discuss the subject 
with the Medical Monitor in an emergency situation if possible. If it was not possible to 
discuss the situation with the Medical Monitor prior to breaking the blind, this 
communication must occur as soon as possible after the blind was broken. In all cases where 
the blind is broken through the IXRS, a notification from the IXRS will be sent to the 
Medical Monitor. The date, time, and reason the blind is broken must be recorded in the 
subject source documents and recorded on the eCRF. 
Every attempt will be made to maintain the blind throughout the study. 
3.6.6 
Treatment Compliance 
Compliance will be evaluated through review of study drug dispensing and administration 
records. For outpatient dosing, subjects will be required to bring study drug containers (used 
and unused) to each site visit, and a pill count will be conducted to assess compliance. All 
subjects will be instructed about the dosing requirements during the study. Noncompliance 
will be documented and the subject reinstructed as appropriate. The authorized study 
personnel conducting the education/reeducation must document the process in the subject 
source record.  
3.6.7 
Allowed Concomitant Treatment 
All concomitant medications will be recorded in the eCRF. 
As with other quinolones, concurrent administration of oral delafloxacin and moxifloxacin 
with magnesium, aluminum, or calcium antacids as well as metal cations such as iron, and 
multivitamins preparations with zinc or didanosine chewable/buffered tablets should be 
avoided. The study drug may be taken 4 hours before or 8 hours after taking these food 
supplements or medicinal products.  
Systemic steroid use during the treatment period is allowed for a short duration (e.g., steroid 
burst). Inhaled steroids are allowed without any restriction. 
Any concomitant medication deemed necessary for the welfare of the subject during the 
study may be given at the discretion of the investigator. However, it is the responsibility of 
the principal investigator to ensure that details regarding the medication are recorded in full 
in the source and on the eCRF. 
3.6.8 
Prohibited Medications and Restrictions 
Concurrent systemic antimicrobial treatments are prohibited. Any subject who requires 
additional (i.e., nonstudy) antibiotics for any of the following reasons will be considered a 
treatment failure: lack of efficacy after at least 4 doses of study drug by the end of Day 3, 


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antibiotic therapy required for more than 20 delafloxacin/delafloxacin placebo doses. Study 
drug should be stopped for all treatment failures, and the subject should complete end of 
treatment procedures.  
Subjects may not take other investigational products during the study.  
Refer to the moxifloxacin and or linezolid SmPC or prescribing information for additional 
prohibited medications and restrictions, including, but not limited to contraindications for the 
concomitant use of monoamine oxidases (MAO) A or B inhibitor agents and adrenergic and 
serotonergic agents with linezolid. 
3.7 
Statistical Analysis Plans 
Continuous characteristics including baseline values will be summarized by treatment group 
using means, standard deviations, minimum, maximum, and median values. Categorical 
variables will be summarized by treatment group using frequency distributions. For the 
baseline characteristics, data will be presented overall as well. The differences in proportions 
for the responders from the 2 treatment groups will be tested for noninferiority using CIs 
generated by the Miettinen-Nurminen method, without stratification. Continuous secondary 
efficacy measures will be analyzed using an analysis of covariance (ANCOVA) model with 
treatment as the main effect and adjusted for PORT Class, medical history of COPD/asthma 
and prior antimicrobial therapy, and the baseline measure as the covariate. All statistical 
analyses, unless otherwise specified, will be based on 2-sided 95% CIs around the difference 
in treatment outcomes. 
3.7.1 
Endpoints 
For FDA, in order to control Type 1 error rate of 5%, a gate-keeping statistical method of a 
fixed sequence procedure will be used to test for the secondary efficacy endpoints once the 
primary efficacy endpoint is claimed to be successful. If the noninferiority of delafloxacin is 
declared in the primary analysis, in order to control type 1 error, the secondary endpoints will 
be tested for superiority in a sequential (hierarchical) fashion using a fixed sequential 
procedure.  
For EMA, all the primary and secondary endpoints will be analyzed for noninferiority with 
the possibility to switch to superiority.  
The difference (delafloxacin – moxifloxacin) and CIs for all secondary endpoints will be 
reported. The primary and secondary efficacy endpoints are presented in the following text.  


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3.7.1.1 
Primary Efficacy Endpoint 
The primary efficacy endpoint is: 
FDA 
EMA 
The ECR defined as improvement at 
96 hours (± 24 hours) after first dose of 
study drug in at least 2 of the following 
symptoms: chest pain, frequency or 
severity of cough, amount and quality 
of productive sputum, and difficulty 
breathing, and no worsening in the 
other symptoms in the ITT population. 
The Clinical Outcome responder rate at 5 to 
10 days after the last dose of study drug (TOC) 
defined as resolution or near resolution of the 
symptoms of CABP present at study entry, and no 
use of additional antimicrobial therapy for the 
current infection, and no new symptoms 
associated with the current CABP infection 
(success) in the ModITT and ModCE populations. 
 
3.7.1.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are: 
FDA 
EMA 
ECR with the addition of improvement 
in vital signs and no worsening of the 
4 symptoms required as Response in the 
ITT population 
ECR defined as improvement at 96 hours 
(± 24 hours) after first dose of study drug in at 
least 2 of the following symptoms: chest pain, 
frequency or severity of cough, amount and 
quality of productive sputum and difficulty 
breathing and no worsening of any of the other 
symptoms in the ModITT and ModCE 
populations 
Clinical Outcome at TOC  
(CE and ITT populations) 
ECR with the addition of improvement in vital 
signs and no worsening of the 4 symptoms 
required as Response in the ModITT and ModCE 
populations 
Clinical Outcome at EOT 
Clinical Outcome at EOT (ModITT and ModCE) 
ECR in the MITT population 
Clinical Outcome at TOC in the ModMITT and 
ModME populations 
Microbiologic Response  
(ME and MITT) 
Microbiologic response (ModMITT and ModME) 
All-cause mortality (ITT) 
All-cause mortality (ModITT) 


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3.7.1.3 
Exploratory Endpoints 
Exploratory endpoints include: 
• Shift of outcomes from the ECR to the Clinical Outcome at EOT 
• Shift of outcomes from the ECR to the Clinical Outcome at TOC 
• Shift of outcomes from the Clinical Outcome at EOT to the Clinical Outcome at TOC 
• Change in individual signs and symptoms 
3.7.1.4 
Health-Related Quality-of-Life Endpoints 
Health-related QoL (HRQoL) and Health Economic Outcomes Research (HEOR) endpoints 
include: 
• Compare SF-12v2® from baseline to EOT to TOC 
• Compare subject’s ability to work and earn income from baseline to EOT and TOC 
• Compare time to oral switch 
• Compare time to hospital discharge 
3.7.1.5 
Pharmacokinetic Endpoints 
The time course of delafloxacin plasma concentrations will be assessed.  
3.7.2 
Endpoint Definitions 
3.7.2.1 
Early Clinical Response 
Symptoms for the Early Clinical Response will be evaluated by the investigator on a four-
point scale (absent, mild, moderate, severe, see Section 7.8 for definitions) with improvement 
defined as at least a 1-point improvement (decrease) from baseline to the assessment at 
96 hours (± 24 hours) after first dose of study drug (e.g., from severe to moderate, from 
moderate to mild, or from mild to absent). 
Responders: Improvement at 96 hours (± 24 hours) after first dose of study drug in at least 2 
of the following symptoms: pleuritic chest pain, frequency or severity of cough, amount and 
quality of productive sputum, and dyspnea (difficulty breathing), and no worsening of the 
other symptoms.  
Non-responders: Improvement is not achieved at 96 hours (± 24 hours) after first dose of 
study drug in at least 2 of the following symptoms: pleuritic chest pain, frequency or severity 
of cough, amount and quality of productive sputum, and dyspnea (difficulty breathing); or 


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there is use of additional non-study antimicrobial therapy for treatment of the current CABP 
infection due to lack of efficacy; or the subject died from the current CABP infection. 
Indeterminate/missing assessments will be mapped to Non-responders in the statistical 
analysis of the ITT Population.  
3.7.2.2 
Clinical Outcome at EOT and TOC 
The principal investigator will define the Clinical Outcome based on the assessment of the 
subject’s signs and symptoms of infection at the EOT and TOC. The investigator’s 
assessment of clinical response will be categorized as Success, Failure, or 
Indeterminate/missing. 
Success: Resolution or near resolution of the symptoms of CABP present at study entry, and 
no use of additional antimicrobial therapy for the current infection, and no new symptoms 
associated with the current CABP infection. 
Failure: Symptoms of CABP present at study entry have not resolved, or new symptoms of 
CABP have developed, or the subject died from pneumonia, or use of additional non-study 
antimicrobial therapy for treatment of the current CABP infection due to lack of efficacy. 
Failure outcome due to Lack of Efficacy (LOE) will be carried forward to later time points if 
the subject discontinues the trial for LOE. Subjects must receive at least 4 doses of study 
drug by the end of Day 3 to be called a Failure.  
Indeterminate/Missing: A response cannot be determined because an efficacy assessment 
was not completed at the visit, or subject did not complete the planned course of study 
therapy for reasons other than lack of efficacy. Indeterminate/missing responses will be 
considered failures for purposes of the primary ITT/ModITT analyses and will be excluded 
from the CE and ME analysis populations. 
3.7.2.3 
Microbiologic Response 
Microbiological response for subjects in the MITT and ME set will be based on results of the 
baseline and follow-up cultures and susceptibility testing or serology. When follow-up 
culture results are missing, the clinical response assigned by the investigator will be 
considered. Microbiological response will be generated at the TOC assessment at both the 
subject and the pathogen levels. The following microbiological responses will be considered: 
Eradication: The respiratory and/or blood specimen at the TOC Visit shows all causative 
pathogen(s) present at enrollment eradicated and no use of additional antimicrobial therapy 
for the current infection. 
Presumed Eradication: No respiratory and/or blood specimen was available at TOC with a 
clinical assessment of Success.  


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Persistence: The respiratory and/or blood specimen at the TOC Visit shows appearance of 
causative pathogen(s) present at enrollment. 
Presumed Persistence: No respiratory and/or blood specimen was available for a case 
classified as clinical failure.  
Superinfection: A culture taken during treatment shows appearance of a new pathogen 
causing respiratory infection associated with clinical failure. 
Colonization/Contamination: A culture taken post-baseline through the TOC visit shows 
appearance of a new pathogen(s), with a clinical assessment of Success and no use of 
additional antimicrobial therapy for the current infection. 
3.7.3 
Safety Endpoints 
Safety endpoints are as follows: 
• AEs, including SAEs 
• Vital sign measurements and body temperature 
• Clinical laboratory test results 
• Physical examination findings 
• Concomitant medications 
• ECGs (obtained after baseline only if clinically indicated) 


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3.7.4 
Sample Size Calculations 
FDA 
EMA 
At least 860 adult male and female 
subjects (430 subjects per treatment 
group) will be randomized. Used on a 
normal approximation approach 
(Miettinen and Nurminen’s Likelihood 
Score Test), 860 subjects in the ITT 
population will provide a 90% power 
to assess noninferiority of delafloxacin 
vs. moxifloxacin based on the 
following assumptions: (1) a rate of 
Early Clinical Response for 
moxifloxacin therapy and delafloxacin 
of 77% and 74%, respectively; 
(2) 1-sided type I error (α) of 0.025; 
(3) a noninferiority margin of 12.5%. 
At least 860 adult male and female subjects 
(430 subjects per treatment group) will be 
randomized. Used on a normal approximation 
approach (Miettinen and Nurminen’s Likelihood 
Score Test), and assuming approximately 12% of 
patients will be in PORT Class II, and 80% of 
patients will be clinically evaluable, 755 subjects in 
the ModITT population and 604 subjects in the 
ModCE population will provide, respectively, a 
power of 91% and 83% to assess noninferiority of 
delafloxacin vs. moxifloxacin based on the 
following assumptions: (1) a rate of Clinical 
Outcome at the TOC visit for moxifloxacin and 
delafloxacin of 88% and 86%, respectively; 
(2) 1-sided type I error (α) of 0.025; (3) a 
noninferiority margin of 10%. 
 
As Early Clinical Response is a new endpoint, as new information arises (without unblinding 
the study) that informs sample size, this information may be used to reassess sample size. If 
ever utilized, any potential sample size recalculation would be based on pooled information 
across the 2 treatment arms. 
3.7.5 
Analysis Populations 
Data analysis will be based on different analysis populations according to the purpose of the 
analysis (e.g., safety or efficacy). Within the efficacy analysis, different combinations of 
analysis sets will be used for the clinical response and the microbiologic response. The 
analysis for clinical response will be generally presented using the ITT, MITT, CE, and ME 
populations for FDA and the ModITT, ModMITT, ModCE and ModME populations for 
EMA. The analysis for microbiologic response will be presented using the MITT and ME 
populations for FDA and the ModMITT and the ModME populations for EMA. 
The number of subjects in each analysis population and the reasons for exclusion from a 
given analysis population will be summarized by treatment group. The following analysis 
populations will be considered in this study: 


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Safety Population 
The Safety Population will include all randomized subjects who receive at least 1 dose of 
study drug, analyzed according to the treatment they received.  
Intent-to-Treat (ITT) Population 
All randomized subjects analyzed according to the treatment arm to which they were 
randomized.  
Modified ITT (ModITT) Population 
All randomized subjects who received at least one dose of study medication, classified as 
PORT Class III-V, analyzed according to the treatment arm to which they were randomized. 
Microbiological ITT (MITT) Population 
All subjects in the ITT population who had a baseline bacterial pathogen identified on culture 
of a respiratory or blood specimen, or a nonculture method of detection of bacterial 
pathogens (i.e., urinary antigen test, PCR and serologic testing) that is known to cause CABP 
against which the study drug has antibacterial activity. 
Modified MITT (ModMITT) Population 
All subjects in the MITT population classified as PORT Class III-V. 
Clinically Evaluable (CE) Population 
All subjects in the ITT population who met the following criteria: 
• Evidence of acute onset of community-acquired bacterial pneumonia (CABP). 
• Received the correct study drug based on the randomization assignment. 
• Received 80% of the expected doses of study drug in the treatment period (e.g., at least 
11 doses of delafloxacin for a 7-day treatment period.  
• Did not receive any concomitant, systemic antibacterial therapy except for LOE.  
• Had no protocol deviations that would affect assessment of efficacy. 
A CE analysis population will be identified for the Early Clinical Response time point as well 
as the EOT and TOC time points. 
Modified CE (ModCE) Population 
All subjects in the CE population classified as PORT Class III-V. 


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Microbiologically Evaluable (ME) Population 
All subjects in the MITT population who also met the criteria for the CE population. A ME 
analysis population will be identified for the Early Clinical Response time point as well as 
the EOT and TOC time points. 
Modified ME (ModME) Population 
All subjects in the ME population classified as PORT Class III-V. 
Pharmacokinetic (PK) Population 
All subjects who receive at least 3 consecutive IV doses of study drug prior to the start of the 
blood sample collections on Day 3 (± 1 Day) and have at least one delafloxacin plasma 
concentration data available. The PK population will be used for PK analyses. 
3.8 
Statistical Analysis 
3.8.1 
Demographics and Other Baseline Characteristics 
Demographics and other baseline characteristics including gender, age, race, ethnicity, height, 
weight, BMI and the data for PORT Class and CURB-65 score will be summarized for the 
ITT, Safety, ModITT, MITT, ModMITT, CE, ModCE, ME and ModME populations to 
assess the comparability of the treatment groups. 
Medical history data including pulmonary and hospitalization history will be summarized for 
the ITT and ModITT populations using the number of observations and percentage of 
subjects reporting each category. Baseline radiograph findings and signs and symptoms 
required for study entry will be summarized for the ITT and ModITT populations using the 
number of observations and percentage of subjects reporting each category. 
3.8.2 
Subject Disposition 
The numbers of subjects who are randomized and complete the study will be tabulated. 
Subjects who fail to complete the study will be tabulated and categorized by reason for 
termination (lost to follow-up, AE, etc). In addition, the following will be tabulated by 
treatment group, as applicable: the number of subjects dosed with study drug, the number of 
subjects randomly assigned to each treatment, and the numbers of subjects in each analysis 
population. 


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3.8.3 
Primary Efficacy Analysis 
The primary efficacy endpoint is: 
FDA 
EMA 
The ECR defined as improvement at 96 hours 
(± 24 hours) in at least 2 of the following 
symptoms: chest pain, frequency or severity 
of cough, amount and quality of productive 
sputum, and difficulty breathing, and no 
worsening of the other symptoms in the ITT 
population. 
Each treatment group’s response rate will be 
defined as: (# Responders) / (# Responders 
+ Non-responders). 
The treatment difference (delafloxacin – 
moxifloxacin) in the rates of this endpoint will 
be presented, and the Miettinen-Nurminen 
test, without stratification, will be used for the 
2-sided 95% confidence interval (CI) on the 
difference in response rate. This analysis will 
be performed using the ITT population. 
The lower bound of this CI will demonstrate 
the maximum extent to which the response 
rate for moxifloxacin may exceed that for 
delafloxacin. If the lower bound is greater 
than -12.5%, it will be concluded that 
delafloxacin is noninferior to moxifloxacin for 
treating patients with CABP. In addition, 
superiority will be claimed if the lower bound 
of the 95% CI exceeds 0. 
An indeterminate/missing response will be 
classified as Non-responders for purposes of 
the primary analysis. 
The Clinical Outcome at TOC. 
For the assessment of Clinical Outcome at 
TOC, each treatment group’s Clinical 
Outcome rate will be defined as: 
(# Success) / (# Success + Failure). 
The treatment difference (delafloxacin – 
moxifloxacin) in the rates of this endpoint 
will be presented, and the Miettinen-
Nurminen test, without stratification, will be 
used for the 2-sided 95% CI on the 
difference in response rate. This analysis 
will be performed using the ModCE and 
ModITT analysis populations, and the result 
at TOC will be tested for noninferiority with 
the possibility to switch to superiority. 
The lower bound of this CI for 
delafloxacin – moxifloxacin will 
demonstrate the maximum extent to which 
the response rate for moxifloxacin may 
exceed that for delafloxacin. If the lower 
bound is greater than 10%, it will be 
concluded that delafloxacin is noninferior to 
moxifloxacin for treating patients with 
CABP. In addition, superiority will be 
claimed if the lower bound of the 95% CI 
exceeds 0.  
A missing response will be classified as 
failure for purposes of the primary ModITT 
analysis. 
 


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3.8.4 
Sensitivity Analysis of the Primary Endpoint for each Region 
(FDA and EMA) 
The following sensitivity analyses for the primary endpoint will be performed:  
• The primary analysis stratified by baseline PORT classification, medical history of 
COPD and asthma, and prior systemic antimicrobial use using the same Miettinen-
Nurminen test.  
• The primary analysis performed on the MITT/ModMITT, CE and ME/ModME analysis 
populations as per the corresponding region.  
• For EMA region, in order to control the possible age influence on the clinical evaluation, 
the primary endpoint will be tested including the age class, defined as Age < 65 and 
Age ≥ 65, as an additional factor in the model. 
• The primary analysis performed for additional analysis populations to be specified in the 
SAP. 
3.8.5 
Subgroup Analyses of the Primary Endpoint for each Region 
(FDA and EMA) 
An exploration of homogeneity of efficacy across subgroups will be undertaken by 
constructing a 2-sided 95% CI similar to the primary efficacy analysis using nonstratified 
Miettinen-Nurminen methodology, within the subgroups identified below. In the event that 
there are large imbalances between treatment groups between these subgroups, further 
exploration will be undertaken as an adjusted analysis of the primary outcome. 
• Demographic subgroups: age categories (age < 65, ≥ 65, ≥ 75), gender, BMI categories 
(BMI < 30 and ≥ 30), baseline PORT Risk Class, baseline CURB-65 Score, ethnicity, 
region, and race categories. 
• Prior antibiotics for subjects classified as a Failure at study entry and single dose prior 
antibiotic (Yes/No). 
• Presence or absence of: baseline bacteremia, multilobar pneumonia, diabetes, history of 
COPD/asthma, history of hepatitis, renal impairment/disease, baseline S. pneumoniae 
infection, baseline Gram stain adequacy. 
These subgroup analyses will be performed using the ITT/ModITT population for the 
primary efficacy endpoint. 


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3.8.6 
Secondary Efficacy Analyses 
For each of the FDA submissions, in order to control Type 1 error rate of 5%, a gate-keeping 
statistical method of a fixed-sequence procedure will be used to test for the secondary 
efficacy endpoints once the primary efficacy endpoint is claimed to be successful. If the 
noninferiority of delafloxacin is declared in the primary analysis, the secondary endpoints 
will be tested for superiority in a sequential (hierarchical) fashion using a fixed sequential 
procedure, in the order given in Section 3.7.1.2. Unless specified otherwise in the endpoint 
definition, the testing will be performed in the ITT analysis population.  
For EMA, all the primary and secondary endpoints will be tested for noninferiority with the 
possibility to switch to superiority.  
Each test, both for FDA and EMA, will be performed using the type 1 error rate of 0.05. 
The secondary endpoints with proportion will be tested, both for FDA and EMA, using 
Miettinen-Nurminen test for delafloxacin – moxifloxacin, without stratification. Superiority 
for the corresponding study endpoint will be claimed using a 5% significance level.  
3.8.6.1 
Early Clinical Response with the Addition of Improvement in Vital Signs and 
No Worsening of the 4 Symptoms Required as Response 
The treatment difference (delafloxacin – moxifloxacin) of ECR with the addition of 
improvement in vital signs and no worsening of the 4 symptoms required as response will be 
presented, and the Miettinen-Nurminen test, without stratification, will be used for the 
2-sided 95% CI on the difference in ECR with the addition of improvement in vital signs and 
no worsening of the 4 symptoms required as response rate. This analysis will be performed 
using the ITT and ModITT/ModCE population, respectively for FDA and EMA. 
3.8.6.2 
Clinical Outcome at EOT and TOC 
The treatment difference (delafloxacin – moxifloxacin) in the rates of this endpoint will be 
presented, and the Miettinen-Nurminen test, without stratification, will be used for the 
2-sided 95% CI on the difference in response rate. This analysis of clinical outcome at EOT 
and TOC will be performed using the CE and ITT analysis populations for FDA. The ModCE 
and ModITT analysis populations will be used to perform the analysis of clinical outcome at 
EOT for EMA. The ModMITT and ModME analysis populations will be used to perform the 
analysis of the EMA secondary endpoint of clinical outcome at TOC. 
A missing response will be classified as failure for purposes of the primary ITT analysis. For 
the assessment of Clinical Outcome at EOT and TOC, each treatment group’s Clinical 
Outcome rate will be defined as: (# Success) / (# Success + Failure). 


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3.8.6.3 
Early Clinical Response for Subjects in the MITT, ModITT 
and ModCE Populations 
The treatment difference (delafloxacin – moxifloxacin) of ECR for patients in the MITT and 
ModITT/ModCE populations respectively for FDA and EMA will be presented, and the 
Miettinen-Nurminen test, without stratification, will be used for the 2-sided 95% CI on the 
difference in ECR rate.  
3.8.6.4 
Microbiologic Response 
The treatment difference (delafloxacin – moxifloxacin) of microbiologic response rate will be 
presented, and the Miettinen-Nurminen test, without stratification, will be used for the 
2-sided 95% CI on the difference in microbiologic response rate. This analysis will be 
performed using the ME and the MITT populations for FDA, and the ModME and 
ModMITT populations for EMA.  
3.8.6.5 
All-Cause Mortality 
All-cause mortality in adult subjects with CABP on Day 28 will be assessed and compared 
between the two treatment groups. Kaplan-Meier estimates will be used to summarize the 
time to all-cause mortality on Day 28. Patients who have not died by Day 28 will be censored 
at Day 28. The probabilities of all-cause mortality at each day with associated standard error 
and 95% CIs will be presented. The log-rank test will be used to compare the time to 
all-cause mortality between the 2 treatment groups. In addition, the hazard ratio for treatment 
and its 95% CI will be calculated from a Cox proportional hazards model.  
The Cox proportional hazards regression model will be used to evaluate the difference 
between the 2 treatment groups adjusting for the baseline covariates including baseline 
PORT classification, history of COPD/asthma, and prior systemic antimicrobial use. 
Interactions between treatment and each covariate will be evaluated at the 0.10 significance 
level; if not significant, they will be removed from the final model. These analyses will be 
performed for ITT and ModITT populations respectively for FDA and EMA. 
3.8.7 
Exploratory Analyses 
The SAP will describe analyses on additional endpoints not specified as primary or 
secondary endpoints or linked to study objectives. 
Exploratory efficacy analyses will include summaries for the primary and secondary 
endpoints measured at additional study time points and for different analysis population. As 
other exploratory analyses, secondary analyses of secondary endpoints that used nonstratified 
Miettinen-Nurminen CIs will be repeated using the same method but stratified by PORT 
Class/PSI score, medical history of COPD/asthma, and prior systemic antimicrobial use.  


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In addition, the following shift analyses will be performed: 
• Shift of outcomes from the Early Clinical Response to the Clinical Outcome at EOT 
• Shift of outcomes from the Early Clinical Response to the Clinical Outcome at TOC 
• Shift of outcomes from the Clinical Outcome at EOT to the Clinical Outcome at TOC 
• Change in individual signs and symptoms 
3.8.8 
Health-Related Quality-of-Life Analyses 
Within each treatment group, the following health-related quality-of-life scores will be 
compared between baseline score to EOT and baseline score to TOC score using a paired 
t-test. In addition, the change from baseline scores will be compared between the 2 treatment 
groups using an ANCOVA model adjusted by baseline characteristics.  
• SF-12v2® domain scores and the total scores 
• Subject’s ability to work and earn income  
In addition, the following 2 health economic related measurements will be compared using a 
Kaplan-Meier analysis method: 
• Time to oral switch 
• Time to hospital discharge 
3.8.9 
Interim Analysis 
No interim analysis will be performed for this study. 
3.8.10 
Safety Analyses 
All safety endpoints will be summarized for all subjects in the Safety set. 
3.8.11 
Adverse Events 
Adverse events will be summarized by treatment group and overall. Events that occur after a 
subject provides informed consent but before the time of the first dose of study drug will be 
considered “pretreatment AEs.” Treatment-emergent AEs are defined as events that are newly 
occurring or worsening from the time of the first dose of study drug through the FU Visit. 
The total number of subjects experiencing any event will be summarized by body system and 
preferred term. At each level of summarization, a subject will be counted once if the subject 
reports 1 or more events at that level. Separate summaries will be presented for all AEs, 
treatment-related AEs, SAEs, and TEAEs. In the case of duplicate preferred terms for a 


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subject, the most severe case will be reported in the severity table and related will be reported 
if any of the duplicate preferred terms for a subject are assessed as related. 
In the event that only a partial end date (month/year) is available, and the month/year occurs 
before Day 1 of the study, the AE will not be considered treatment-emergent. However, if the 
onset date is a partial date (month/year) and the month/year occurs on or after Day 1 of the 
study, the following cases will be considered: 
• If the month/year of the onset date is later than the month/year of Day 1 of the study, the 
AE will be considered treatment-emergent. 
• If the month/year of the onset date is equal to the month/year of Day 1 of the study, and 
the end date is present, the end date will be used to determine when the AE resolved. If 
the end date is on or after Day 1 of the study, the AE will be considered 
treatment-emergent; otherwise, if the AE stopped before Day 1 of the study, then it will 
not be considered treatment-emergent. 
• If the month/year of the onset date is equal to the month/year of Day 1 of the study, and 
the end date is a partial date, the AE will be considered treatment-emergent. 
3.8.12 
Vital Sign Measurements and Body Temperature 
Vital sign measurements (systolic and diastolic blood pressure [mmHg], heart rate 
[beats/minute], respiration rate [breaths/minute], and body temperature [°C]) will be 
summarized and tabulated. The number of subjects with the reported value, mean, median, 
standard deviation, minimum value, maximum value, and inner quartile percentiles will be 
reported. Change from baseline by visit will also be reported using the number of subjects 
with the reported value, mean, median, standard deviation, minimum value, maximum value, 
and inner quartile percentiles. Subjects with missing data for a given visit will not contribute 
to the tabulations for that visit. 
3.8.13 
Clinical Laboratory Test Results 
Laboratory test results will be summarized by treatment group and visit for absolute value 
and changes from baseline. Tables showing shift from baseline will also be presented. 
3.8.14 
Physical Examination Findings 
Changes from Screening in physical examination results will be listed by subject for all 
subjects in the Safety set. Height and weight will be summarized by reporting the number of 
subjects evaluated, mean, median, standard deviation, minimum value, maximum value, and 
inner quartile percentiles. The number of baseline findings and the percentage of subjects 
with findings will be reported.  


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3.8.15 
Concomitant Medications 
Concomitant medications will be categorized and presented using the World Health 
Organization Anatomical Therapeutic Chemical drug classification system. The number and 
percentage of subjects using concomitant medications will be summarized by treatment 
group. 
3.8.16 
Pharmacokinetic Analyses 
Summary statistics will be calculated for the plasma concentration-time data including N, 
mean, standard deviation (SD), coefficient of variation (CV), median, minimum, maximum, 
and geometric mean.  
Plasma concentration data will be subjected to a separate population PK analysis. 
3.8.17 
Missing Data 
The following rules will be used for handling missing data: 
1. Missing data for ECR will be considered Non-responders. 
2. Missing data for Clinical Response based on the investigator assessment of signs and 
symptoms of pneumonia will be considered a Failure in the ITT/ModITT analysis. 
3. For each secondary and exploratory efficacy endpoint, missing data will be imputed 
as the worst possible response. For instance, subjects missing assessment data at 
either the Early Clinical Response time point or the TOC will be considered as 
Failures or Non-responders in the ITT/ModITT analysis.  
4. Missing values for safety data (except for dates) will not be imputed. Missing or 
partial dates will be imputed as described in the statistical analysis plan. 
5. Failure outcome due to LOE will be carried forward to later time points (i.e., TOC) if 
the subject discontinues the trial for LOE. These subjects will be considered evaluable 
if other factors of evaluability are met.  


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4. Investigator’s Obligations 
The following administrative items are meant to guide the principal investigator or 
subinvestigator in the conduct of the study but may be subject to change based on industry 
and government standard operating procedures, working practice documents, or guidelines. 
Changes will be reported to the IRB/IEC but will not result in protocol amendments. 
4.1 
Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain subject confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the written 
permission of the subject (or the subject legal representative), except as necessary for 
monitoring and auditing by the sponsor, its designee, the FDA, the EMA, other applicable 
regulatory authorities, or the IRB/IEC. 
The principal investigator or subinvestigator and all employees and coworkers involved with 
this study may not disclose or use for any purpose other than performance of the study, any 
data, record, or other unpublished, confidential information disclosed to those individuals for 
the purpose of the study. Prior written agreement from the sponsor or its designee must be 
obtained for the disclosure of any said confidential information to other parties. 
4.2 
Ethics Committee/Institutional Review 
Federal or local regulations and the International Conference on Harmonisation (ICH) 
guidelines require that approval be obtained from relevant Regulatory bodies and an IRB/IEC 
before participation of human subjects in research studies. The Ethics Committee, including 
IRBs and IECs, must be constituted according to the applicable state and federal/local 
requirements of each participating region. Before the study onset, the protocol, informed 
consent, and advertisements to be used for subject recruitment and any other written 
information regarding this study to be provided to the subject or the subject’s legal 
representative must be approved by the IRB/IEC. Documentation of all IRB/IEC approvals 
and of the IRB/IEC compliance with ICH E6(R2) will be maintained by the study site and 
will be available for review by the sponsor or its designee. 
All IRB/IEC opinion letters should be signed by the IRB/IEC chairman or designee and must 
identify the IRB/IEC name and address, the clinical protocol by title and/or protocol number, 
and the date approval and/or favorable opinion was granted. 
Sites must adhere to all requirements stipulated by their respective IRB/IEC. This may 
include notification to the IRB/IEC regarding protocol amendments, updates to the informed 
consent form, recruitment materials intended for viewing by subjects, local safety reporting 


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requirements, reports and updates regarding the ongoing review of the study at intervals 
specified by the respective IRB/IEC, and submission of the investigator’s final status report 
to the IRB/IEC. All IRB/IEC opinion letters and relevant documentation for these items must 
be provided to the sponsor or its designee. 
4.3 
Subject Consent 
A written informed consent in compliance with US Title 21 of the Code of Federal 
Regulations (CFR) Part 50, ICH E6(R2), and other applicable regulatory requirements shall 
be obtained from each subject or where allowed by local regulations, legally authorized 
representative before entering the study or performing any unusual or nonroutine procedure 
that involves risk to the subject. An informed consent template may be provided by the 
sponsor to study sites. If any institution-specific modifications to study-related procedures 
are proposed or made by the study site, the consent should be reviewed by the sponsor and/or 
its designee, if appropriate, before IRB/IEC submission. Once reviewed, the consent will be 
submitted to the applicable IRB/IEC for review and approval before the start of the study. If 
the ICF is revised during the course of the study, all active participating subjects or their 
legally authorized representatives must sign the revised form. 
Before recruitment and enrollment, each prospective subject or his/her legally authorized 
representative will be given a full explanation of the study and allowed to read the approved 
ICF. Once the principal investigator or subinvestigator is assured that the subject/legal 
representative understands the implications of participating in the study, the subject/legal 
representative will be asked to give consent to participate in the study by signing the ICF.  
The principal investigator or subinvestigator shall sign the informed consent and provide a 
copy of the signed informed consent to the subject and/or legal representative. The original 
form shall be maintained in the subject medical records at the study site. 
4.4 
Study Reporting Requirements 
By participating in this study, the principal investigator or subinvestigator agrees to submit 
reports of SAEs according to the timeline and method outlined in the protocol. In addition, 
the principal investigator or subinvestigator agrees to submit periodic reports to his/her 
IRB/IEC in accordance with IRB/IEC requirements. The principal investigator or 
subinvestigator also agrees to provide the sponsor with an adequate report shortly after 
completion of the principal investigator’s or subinvestigator’s participation in the study. 
4.5 
Financial Disclosure and Obligations 
The principal investigators or subinvestigators are required to provide financial disclosure 
information to allow the sponsor to submit the complete and accurate certification or 


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disclosure statements required under US 21 CFR 54. In addition, the principal investigator or 
subinvestigators must provide to the sponsor a commitment to update promptly this 
information if any relevant changes occur during the course of the investigation and for 
1 year after the completion of the study. 
Neither the sponsor nor CRO is financially responsible for further testing/treatment of any 
medical condition, which may be detected during the screening process. In addition, in the 
absence of specific arrangements, neither the sponsor nor CRO is financially responsible for 
further treatment of the subject disease. 
4.6 
Investigator Documentation 
Before beginning the study, the principal investigator will be asked to comply with 
ICH E6(R2) 8.2, US. 21 CFR 54, European Commission Directive 2001/20/EC and other 
applicable regulations by providing the following essential documents, including but not 
limited to: 
• An original investigator-signed Investigator Agreement page of the protocol. 
• An IRB/IEC-approved informed consent, samples of study site advertisements for 
recruitment for this study, and any other written information regarding this study that is 
to be provided to the subject or legal representative. 
• IRB/IEC approval. 
• Form FDA 1572 or equivalent, fully executed, and all updates on a new fully executed 
Form FDA 1572 (or equivalent). 
• Curriculum vitae for the principal investigator and each subinvestigator listed on Form 
FDA 1572. Current licensure must be noted on the curriculum vitae. They will be signed 
and dated by the principal investigators and subinvestigators at study start-up, indicating 
that they are accurate and current. 
• Financial disclosure information to allow the sponsor to submit complete and accurate 
certification or disclosure statements required under US. 21 CFR 54. In addition, the 
investigators must provide to the sponsor a commitment to promptly update this 
information if any relevant changes occur during the course of the investigation and for 
1 year after the completion of the study. 
• Laboratory certifications and reference ranges for any local laboratories used by the study 
site, in accordance with US 42 CFR 493 or other applicable requirements. 


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4.7 
Study Conduct 
The principal investigator agrees that the study will be conducted according to the principles 
of ICH E6(R2) and the principles of the World Medical Association Declaration of Helsinki. 
The principal investigator will conduct all aspects of this study in accordance with all 
national, state, and local laws or regulations. 
4.8 
Data Collection 
4.8.1 
Case Report Forms and Source Documents 
As part of the responsibilities assumed by participating in the study, the principal investigator 
or subinvestigator agrees to maintain adequate case histories for the subjects treated as part of 
the research under this protocol. The principal investigator or subinvestigator agrees to 
maintain complete and accurate eCRFs and source documentation as part of the case 
histories. These source documents include laboratory reports and original ECGs, and 
electronic capture will be used to record the study data. The sponsor’s representative will 
supply the eCRF. Refer to the eCRF Completion Guidelines for further details regarding 
requisite study data. 
4.9 
Adherence to Protocol 
The investigator agrees to conduct the study as outlined in this protocol in accordance with 
ICH E6(R2) and all applicable guidelines and regulations. 
4.10 Reporting Adverse Events 
By participating in this study the principal investigator or subinvestigator agrees to submit 
reports of SAEs according to the time line and method outlined in the protocol. In addition, 
the principal investigator or subinvestigator agrees to submit annual reports to his/her 
IRB/IEC as appropriate. The principal investigator or subinvestigator also agrees to provide 
the sponsor with an adequate report shortly after completion of the principal investigator’s or 
subinvestigator’s participation in the study. 
4.11 Investigator’s Final Report 
Upon completion of the study, the investigator, where applicable, should inform the 
institution; the investigator/institution should provide the IRB/IEC with a summary of the 
study’s outcome, and the sponsor and regulatory authority(ies) with any reports required. 


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4.12 Records Retention 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region, or at least 2  years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents 
should be retained for a longer period, however, if required by the applicable regulatory 
requirements or by an agreement with the sponsor. It is the responsibility of the sponsor to 
inform the principal investigator or subinvestigator/institution as to when these documents no 
longer need to be retained. 
4.13 Publications 
After completion of the study, the data may be considered for reporting at a scientific 
meeting or for publication in a scientific journal. In these cases, the sponsor will be 
responsible for these activities and will work with the investigators to determine how the 
manuscript is written and edited, the number and order of authors, the publication to which it 
will be submitted, and other related issues. The sponsor has final approval authority over all 
such issues. 
Data are the property of the sponsor and cannot be published without prior authorization 
from the sponsor, but data and publication thereof will not be unduly withheld. 


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5. Study Management 
5.1 
External Data Monitoring Groups 
An external data monitoring group (data safety monitoring board) may be employed in this 
study. In that event, the membership, activities, and responsibilities of the safety monitoring 
committee will be described in detail in a separate charter document established for this study. 
5.2 
Monitoring 
5.2.1 
Monitoring of the Study 
The clinical monitor, as a representative of the sponsor, has the obligation to follow the study 
closely. The monitor will visit the principal investigator or subinvestigator, other study staff, 
and the study facility at periodic intervals, in addition to maintaining necessary contact 
through telephone, e-mail, and letter. The monitor will maintain current personal knowledge 
of the study through observation, review of study records and source documentation, and 
discussion of the conduct of the study with the principal investigator or subinvestigator and 
staff. The monitor will assure that the hospital or clinic facility pharmacy staff maintains 
appropriate study drug accountability and dose-preparation records. The monitor will confirm 
the study drugs are stored under appropriate conditions. 
All aspects of the study will be carefully monitored by the sponsor or its designee, for 
compliance with applicable government regulation with respect to ICH E6(R2) and current 
standard operating procedures. 
5.2.2 
Inspection of Records 
The principal investigators or subinvestigators and institutions involved in the study will 
permit study-related monitoring, audits, IRB/IEC review, and regulatory inspection(s) by 
providing direct access to all study records. In the event of an audit, the principal investigator 
or subinvestigator agrees to allow the sponsor, representatives of the sponsor, the FDA, or 
other regulatory agency access to all study records. 
The principal investigator or subinvestigator should promptly notify the sponsor and CRO of 
any audits scheduled by any regulatory authorities and promptly forward copies of any audit 
reports received to the sponsor. 
5.3 
Management of Protocol Amendments and Deviations 
5.3.1 
Modification of the Protocol 
Any changes in this research activity, except those necessary to remove an apparent, 
immediate hazard to the subject, must be reviewed and approved by the sponsor or its 


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designee. Amendments to the protocol must be submitted in writing to the principal 
investigator’s or subinvestigator’s IRB/IEC and, if applicable, to the appropriate regulatory 
authorities for approval before subjects can be enrolled into an amended protocol. 
5.3.2 
Protocol Deviations 
The principal investigator, subinvestigator, or designee must document and explain in the 
subject source documentation any deviation from the approved protocol. The principal 
investigator or subinvestigator may implement a deviation from, or a change of, the protocol 
to eliminate an immediate hazard to study subjects without prior IRB/IEC approval. As soon 
as possible after such an occurrence, the implemented deviation or change, the reasons for it, 
and any proposed protocol amendment(s) should be submitted to the IRB/IEC for review and 
approval, to the sponsor for agreement, and to the regulatory authorities, if required. 
A deviation from the protocol is an unintended or unanticipated departure from the 
procedures or processes approved by the sponsor and the IRB/IEC and agreed to by the 
principal investigator or subinvestigator. A significant deviation occurs when there is 
nonadherence to the protocol that results in a significant, additional risk to the subject when 
the subject, principal investigator, or subinvestigator has failed to adhere to significant 
protocol requirements. Significant deviations can include nonadherence to inclusion or 
exclusion criteria, enrollment of the subject without sponsor approval, or when there is 
nonadherence to FDA or other applicable regulations and/or ICH E6(R2) guidelines. 
Protocol deviations will be documented by the clinical monitor throughout the course of 
monitoring visits. The monitor will notify the principal investigators or subinvestigators in 
writing of all deviations. The IRB/IEC should be notified of all protocol deviations in a 
timely manner. 
5.4 
Study Termination 
Although the sponsor has every intention of completing the study, it reserves the right to 
discontinue the study at any time for clinical or administrative reasons or if required by the 
FDA or other review bodies. Both the sponsor and CRO medical monitors will review the 
safety of delafloxacin throughout the study. The study may be halted at any time for safety 
concerns. 
5.5 
Final Report 
Whether the study is completed or prematurely terminated, the sponsor will ensure that the 
clinical study reports are prepared and provided to the regulatory agency(ies) as required by 
the applicable regulatory requirement(s). The sponsor will also ensure that the clinical study 


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reports in marketing applications meet the standards of the ICH Harmonised Tripartite 
Guideline E3: Structure and Content of Clinical Study Reports. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report. The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results. 
Upon completion of the clinical study report, the sponsor will provide the investigator with 
the full summary of the study results. The investigator is encouraged to share the summary 
results with the study subjects, as appropriate. 


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6. References
Abbott Laboratories (Abbott Park, IL). A phase 2b comparative study of the safety and 
efficacy of three oral doses of ABT-492 for the treatment of subjects with community 
acquired pneumonia. 2003 Dec 15. Clinical Study Report R&D/03/393. Protocol M01-344. 
Abbott Laboratories (Abbott Park, IL). A phase 2a comparative study of the safety and 
efficacy of ABT-492 100 mg QD, 200 mg QD, 400 mg QD and levofloxacin 500 mg QD for 
the treatment of subjects with acute bacterial exacerbation of chronic bronchitis. 
2003 Dec 16. Clinical Study Report R&D/03/392. Protocol M01-298. 
Department of Health and Human Services (DHHS), Food and Drug Administration (FDA), 
Center for Drug Evaluation and Research (US). Draft guidance. Community-Acquired 
Bacterial Pneumonia: Developing Drugs for Treatment. January 2014. Available from: 
https://www.fda.gov/downloads/drugs/guidances/ucm123686.pdf. 
European Medicines Agency (EMA). Committee for Human Medicinal Products (CHMP). 
Addendum to the guideline on the evaluation of medicinal products indicated for treatment of 
bacterial infections. London, 24 October 2013. EMA/CHMP/351889/2013. Available from: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/11/WC 
500153953.pdf. 
Fine MJ, Auble TE, Yealy DM, et al. A prediction rule to identify low-risk patients with 
community-acquired pneumonia. N Engl J Med. 1997;336:243-50.  
Garcia LS, editor. Clinical microbiology procedures handbook, 3rd ed. Washington, DC: 
ASM Press; 2010. 
Lemaire S, Kosowska-Shick K, Appelbaum PC, et al. Activity of moxifloxacin against 
intracellular community-acquired methicillin-resistant Staphylococcus aureus: comparison 
with clindamycin, linezolid and co-trimoxazole and attempt at defining an intracellular 
susceptibility breakpoint. J Antimicrob Chemother 2011;66:596-607. 
Mandell LA, Wunderink RG, Anzueto A, 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(suppl 2):S27-72. 
Melinta Therapeutics, Inc. (New Haven, CT). Evaluation of delafloxacin in a murine 
respiratory tract infection model against S. pneumoniae D39. 2015 Apr 28. Melinta Report 
#EF-3341-006. 


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Melinta Therapeutics, Inc. (Melinta) (New Haven, CT). A phase 3, multicenter, randomized, 
double-blind, active-controlled study to evaluate the efficacy and safety of delafloxacin 
compared with vancomycin + aztreonam in patients with acute bacterial skin and skin 
structure infections. 2015 Nov 04. Clinical Study Report. Protocol RX-3341-302. 
Melinta Therapeutics, Inc. (Melinta) (New Haven, CT). A phase 3, multicenter, randomized, 
double-blind, active-controlled study to evaluate the efficacy and safety of IV and oral 
delafloxacin compared with vancomycin + aztreonam in patients with acute bacterial skin 
and skin structure infections. 2017 Jan 06. Clinical Study Report: Amendment No. 1. 
Protocol RX-3341-303. 
Melinta Therapeutics, Inc. (New Haven, CT). Investigator’s Brochure: Edition 21. 
Investigational New Drug: Delafloxacin (RX-3341). Edition Date: 2 December 2016. 
Meulbroek J. Efficacy of ABT-492 against Streptococcus pneumoniae and Haemophilus 
influenzae in the rat pulmonary infection model. 2001 Feb 27. Research and Development 
Report R&D/01/135. 
Murray PR, Baron EJ, Jorgensen JH, et al. Manual of clinical microbiology, 9th ed. 
Washington, DC: ASM Press; 2007. 
Rib-X Pharmaceuticals, Inc. (New Haven, CT). A Phase 1, single-dose, safety, tolerability, 
and pharmacokinetic study of IV and oral formulations, and a maximum tolerated dose study 
of delafloxacin in healthy subjects. 2011 Sep 21. Clinical Study Report. Protocol 
RX-3341-108. 
Rib-X Pharmaceuticals, Inc. (New Haven, CT). A randomized, double-blind, multicenter 
study of the safety and efficacy of RX-3341 compared with tigecycline for the treatment of 
complicated skin and skin structure infections. 2009 Jul 21. Clinical Study Report. Protocol 
RX-3341-201. 
Rib-X Pharmaceuticals, Inc. (New Haven, CT). A phase 2 exploratory study of objective 
endpoints in subjects with acute bacterial skin and skin structure infections treated with 
delafloxacin, vancomycin, or linezolid. 2014 Aug 11. Clinical Study Report. Protocol 
RX-3341-202. 


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7. Appendices 
7.1 
Appendix: Schedule of Events 
7.2 
Appendix: PSI/PORT Score: Pneumonia Severity Index for CAP 
7.3  
Appendix: CURB-65 
7.4 
Appendix: Child-Pugh Classification of Severity of Liver Disease 
7.5 
Appendix: Cockcroft-Gault Formula  
7.6 
Appendix: SF-12v2® Health Survey 
7.7 
Appendix: Quality-of-Life Questions 
7.8 
Appendix: Definitions of Symptom Intensity 
7.9 
Appendix: Protocol Amendment 1 
7.10 
Appendix: Protocol Amendment 2 
7.11 
Appendix: Protocol Amendment 3 
 


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7.1 
Appendix: Schedule of Events 
Assessment or Procedure 
Screeninga 
Treatment Periodb 
End of 
Treatment 
(EOT)/ 
Early Termc 
Reminder 
Contactd 
Test of 
Cure 
(TOC)e 
Follow-
Up 
(FU)f 
Study Day(s) 
–1 to 1 
1a 
Daily 
while 
on IV 
ECR 
96 hrs 
± 24 hrg 
5 
(+ 1 
day) 
7 
(+ 1 
day) 
End 
of IVh 
 
 
5 to 10 
days after 
last dose 
28  
(± 2 
days) 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Demographics, medical, pulmonary,  
surgical, alcohol and smoking history 
X 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
 
X 
 
 
 
Clinical signs/symptoms CABPi 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
Investigator assessment of clinical response 
 
 
 
 
 
 
 
X 
 
X 
 
Assess subject status for switch to oral 
 
 
 
 
 
 
X 
 
 
 
 
Vital signs, body temperature, pulse oximetryj 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
 
12-lead electrocardiogramk 
X 
 
 
 
 
 
 
 
 
 
 
Complete physical examination  
with height and weight 
X 
 
 
 
 
 
 
 
 
 
 
Targeted physical examinationl 
 
 
 
X 
 
 
 
X 
 
X 
 
Chest radiograph or CT scan 
X 
 
 
 
 
 
 
Xm 
 
Xm 
 
Local laboratory tests for eligibilityn 
X 
 
 
 
 
 
 
 
 
 
 
Pregnancy testo 
X 
 
 
 
 
 
 
X 
 
X 
X 
Clinical laboratory tests (serum chemistry, 
coagulationp, hematology, urinalysisp )  
X 
 
 
X 
 
 
 
X 
 
X 
 
Hepatitis serology 
X 
 
 
 
 
 
 
 
 
 
Blood cultureq 
X 
 
 
 
 
 
 
 
 
 
 
Respiratory specimen for Gram stain and culturer 
X 
X 
 
 
 
 
 
Xm 
 
X 
 
Determine PORT Risk Class  
and CURB-65 Score 
X 
 
 
 
 
 
 
 
 
 
 
SF-12v2® Health Survey and QoL Questions 
 
X 
 
 
 
 
 
X 
 
X 
X 
Verify entry criteria 
X 
 
 
 
 
 
 
 
 
 
 
Chlamydia/Legionella/Mycoplasma serology  
 
Xs 
 
 
 
 
 
 
 
X 
X 
Urine antigen testing for  
L. pneumophila/S. pneumoniae 
 
Xs 
 
 
 
 
 
 
 
 
 


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Assessment or Procedure 
Screeninga 
Treatment Periodb 
End of 
Treatment 
(EOT)/ 
Early Termc 
Reminder 
Contactd 
Test of 
Cure 
(TOC)e 
Follow-
Up 
(FU)f 
Study Day(s) 
–1 to 1 
1a 
Daily 
while 
on IV 
ECR 
96 hrs 
± 24 hrg 
5 
(+ 1 
day) 
7 
(+ 1 
day) 
End 
of IVh 
 
 
5 to 10 
days after 
last dose 
28  
(± 2 
days) 
Nasopharyngeal and oropharyngeal swabs 
 
Xs 
 
 
 
 
 
 
 
 
 
Blood sample for procalcitonin  
 
X 
 
 
 
 
 
 
 
X 
 
Study drug administration every 12 ± 2 hours 
 
Xt 
X 
X 
X 
X 
 
 
 
 
 
Dispense oral study drug u 
 
 
 
 
 
 
X 
 
 
 
 
Perform drug accountability on returned drug u 
 
 
 
 
 
 
 
X 
 
 
 
Determine adequate treatment duration  
 
 
 
 
Xv 
Xv 
 
 
 
 
 
PK blood sample collection 
 
 
X 
(Day 3 
± 1 
day)w 
 
 
 
 
 
 
 
 
Reminder Contact 
 
 
 
 
 
 
 
 
X 
 
 
Access IXRS to Register Screening 
X 
 
 
 
 
 
 
 
 
 
 
Randomization by IXRS 
X 
 
 
 
 
 
 
 
 
 
 
Register oral switch status in IXRS 
 
 
 
 
 
 
X 
 
 
 
 
Register completion status in IXRS 
 
 
 
 
 
 
 
X 
 
 
 
Post treatment medications 
 
 
 
 
 
 
 
X 
Xx 
Adverse event evaluationy 
X 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
Abbreviations: ECR = Early Clinical Response; EOT = End of Treatment; TOC = Test of Cure; FU = Follow-Up; CABP = community-acquired bacterial pneumonia; 
MRSA = methicillin-resistant Staphylococcus aureus; CT = Computed tomography, PORT = Patient Outcomes Research Team; CURB-65 = scoring system based on 
confusion, urea, respiratory rate, blood pressure and age 65 or older; PK = pharmacokinetics; IXRS = interactive voice and web response system. 
a Screening procedures will occur within the 24 hours prior to the first dose. The first dose may be administered on the same day as Screening. If the first dose is 
administered the same day as screening, then the assessments listed for Day 1, but which were already completed for Screening will not be repeated. 
b The total duration of treatment (IV and oral) is 5 days up to 10 days if clinically indicated (minimum 10 doses and up to 20 delafloxacin/delafloxacin placebo doses). 
c Subjects who prematurely discontinue study drug or are completing treatment on day of visit can have EOT procedures performed that same day or up to 24 hours 
(+ 4 hours) after the last dose of study drug. Assessments already completed on the same day as the last dose of study drug can serve as EOT procedures and do not 
need to be repeated. Laboratory tests completed for a routine visit will not be repeated at EOT, if collected within 24 hours of the EOT visit.  
d A reminder contact will be done 3-9 days after the last dose of study drug. Subjects will receive a telephone call or contact via other interactive method, e.g., text or 
email, to remind the subject about the upcoming Test-of-Cure Visit. 
e TOC assessments will be performed 5 to 10 days after the last dose of study drug (see Section 3.3.2 for exception). 
f All efforts will be made to have subjects return to the clinic for a Follow-up Visit. Telephone contact is permissible for subjects unable, unwilling or not required (see 
Section 3.3.2) to return to the clinic.  


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g ECR Visit will occur 96 hours (± 24 hours) after the first dose of study drug. Procedures already completed as specified in Sections 3.4.1.3 or 3.4.1.5 do not need to be 
repeated unless outside the ECR 96-hour (± 24 hours) window.  
h Last day of IV therapy prior to oral switch. A minimum of 6 delafloxacin/delafloxacin placebo doses of IV study drug must be administered prior to oral switch. Refer 
to Schedule of Events for that day for assessments/procedures to be completed. 
i Clinical signs and symptoms of CABP will be assessed by the investigator using a 4-point severity scale (see Section 3.4.2.1). 
j Arterial blood gases can be obtained at Screening if clinically warranted. Body temperature can be measured via different routes and may include oral, rectal, tympanic 
and axillary. Pulse oximetry will be recorded for all subjects daily while on IV therapy and at ECR, and only if clinically indicated and/or for subjects on supplemental 
oxygen at Day 5, Day 7, EOT, and TOC. Vital signs should be measured at a consistent time each day while on IV therapy. 
k Electrocardiograms will be performed at screening and if clinically indicated as determined by the investigator after screening.  
l Targeted physical examinations will be performed during the study to assess changes from baseline parameters, adverse events, and other relevant safety information. 
m Will be performed only if lack of efficacy. 
n Local laboratory test results of pregnancy, hematology, serum chemistry, coagulation profile and urinalysis obtained within 24 hours before enrollment may be used for 
screening purposes and to verify entry criteria. Laboratory tests with exclusionary results judged by the investigator as not compatible with the subject’s clinical status 
may be repeated for eligibility purposes once. 
o Pregnancy tests to be performed for women of childbearing potential only. 
p Urinalysis and coagulation at screening only.  
q Two sets of blood cultures will be collected from all subjects at screening. Additional blood cultures will be collected if a previous culture was positive or if clinically 
indicated after Screening. Rapid test for MRSA identification methods are acceptable to use if S. Aureus is identified by the local/regional laboratory. 
r All reasonable efforts will be made to obtain a sputum specimen for Gram stain and culture. Other sources of respiratory specimens such as those obtained from 
bronchoalveolar lavage, protected specimen brush, transtracheal aspirate, and pleural fluid, if available, are acceptable to submit for culture. A Gram stain will be 
performed on all sputum and transtracheal aspirate samples. Rapid MRSA identification methods are acceptable to use if S. aureus is identified by the local/regional 
laboratory. 
s Results are not required prior to dosing. Refer to the laboratory manual for detailed instructions on collection, processing and shipment.  
t  If the first dose is started late in the day because of screening and eligibility verifications, a 1-time adjustment is allowed for a more customary dosing schedule that is 
within ± 4 hours of the normally scheduled second dose. The every-12-hours (± 2 hours) dosing schedule is set after the first dose (or dose adjustment). 
u Oral study drug treatment can be completed in the hospital or clinic. For subjects discharged to home, dispense study drug. Instruct subjects to bring study drug 
container(s) (empty and/or full) to the clinic at their next scheduled visit.  
v Study drug may be stopped at the discretion of the investigator after completing a minimum of 10 delafloxacin/delafloxacin placebo doses. Criteria for determination of 
appropriate treatment duration are described in Section 3.4.1.8.1.  
w Blood samples for PK analysis will be obtained from subjects at select sites on Day 3 (± 1 day) of treatment within the 30 minutes before study drug administration, and 
at 1.5 and 3 hours after the start of the infusion. Subjects should have received a minimum of 3 consecutive doses of study drug prior to the start of PK sample 
collection. All time points will have a ± 10-minute window. Subjects do not need to be fasted before dosing or during PK sample collections.  
x See Section 3.4.3.12 for collection of concomitant medications at FU. 
y Serious adverse events will be reported per protocol and recorded in the eCRF from the time subject provides informed consent through the FU visit.  


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7.2 
Appendix: PSI/PORT Score: Pneumonia Severity Index for CAP 
PSI/PORT Score: Pneumonia Severity Index for CAP 
 
 
Assigned Points 
Age (Years) 
 
Men 
Age (Years) 
Women 
Age (Years) −10 
Nursing home resident 
+10 
Neoplastic disease 
+30 
Liver disease history 
+20 
Congestive heart failure history 
+10 
Cerebrovascular disease history 
+10 
Renal disease history 
+10 
Altered mental status 
+20 
Respiratory rate > 29  
+20 
Systolic blood pressure < 90 mmHg 
+20 
Temperature < 35°C (95°F) or > 39.9°C (103.8°F) 
+15 
Pulse > 124 
+10 
Arterial pH < 7.35 
+30 
BUN > 29 mg/dL or urea > 10.9 mmol/L 
+20 
Sodium < 130 
+20 
Glucose > 249 (US) or > 13.8 (SI) 
+10 
Hematocrit < 30% 
+10 
Partial pressure of Oxygen < 60 mmHg* 
+10 
Pleural effusion on x-ray 
+10 
* An oxygen saturation of less than 90% on pulse oximetry or intubation before admission is also 
considered abnormal (Fine 1997). 
 


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Step 1: 
•
If the patient is > 50 years of age, assign to risk class II - V and proceed to step 2.
•
If the patient is < 50 years of age, but has a history of neoplastic disease, congestive
heart failure, cerebrovascular disease, renal disease or liver disease, assign to risk
class II - V and proceed to step 2.
•
If the patient has an altered mental status, pulse ≥ 125/minute, respiratory rate
≥ 30/minute, systolic blood pressure ≤ 90 mm Hg, or temperature < 35°C or ≥ 40°C,
assign to risk class II - V and proceed to step 2.
•
If none of the above apply, assign to risk class I = low risk.
Step 2: 
•
Assign points based on age, gender, nursing home residence, co-morbid illness,
physical examination findings, and laboratory and radiographic findings as listed
above.
•
Point distribution, score interpretation and suggested disposition based on local
standard of care:
Score 
Risk Class 
Risk 
Disposition 
≤70 
II 
Low 
Outpatient care 
71-90 
III 
Low 
Outpatient vs. Observation admission 
91-130 
IV 
Moderate 
Inpatient admission 
>130 
V 
High 
Inpatient admission 
Retrieved from http://www.mdcalc.com/psi-port-score-pneumonia-severity-index-adult-cap/ 


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7.3 
Appendix: CURB-65 
Each risk factor scores 1 point, for a maximum score of 5: 
CURB-65 
Symptom 
Points 
Confusion* 
1 
Urea > 7 mmol/L or BUN > 19 mg/dL 
1 
Respiratory Rate ≥ 30 breaths/min 
1 
Blood Pressure (SBP < 90 mmHG, DBP ≤ 60 mmHg) 
1 
Age ≥ 65 years 
1 
Abbreviations: SBP = systolic blood pressure, DBP = diastolic blood pressure 
*defined as a Mental Test Score of 8 or less, or new disorientation in person, place, or time 
Lim W, van der Eerden MM, Laing R, et al. Defining community acquired pneumonia severity on presentation 
to hospital: an international derivation and validation study. Thorax. 2003;58(5):377-382. 
doi:10.1136/thorax.58.5.377. 
 


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7.4 
Appendix: Child-Pugh Classification of Severity of Liver Disease 
Child-Pugh Classification of Severity of Liver Disease 
Clinical and Biochemical Measurements for 
Child-Pugh Classification of Severity of Liver 
Diseasea,b,c 
Points Scored for Increasing 
Abnormality 
1 
2 
3 
Hepatic encephalopathy (graded) 
None 
1 and 2 
3 and 4 
Ascites 
Absent 
Slight 
Moderatee 
Total bilirubin (mg/dL) 
< 2.0 
2.0-3.0 
> 3.0 
Serum albumin (g/dL) 
> 3.5 
2.8-3.5 
< 2.8 
Prothrombin timef 
 
 
 
Seconds prolonged over the ULN 
< 4 
4-6 
> 6 
International normalized ratio 
< 1.7 
1.7-2.3 
> 2.3 
Abbreviations: ULN, upper limit of normal. 
a 
Pugh RN, Murray-Lyon IM, Dawson JL, et al. Brit J Surg. 1973;60(8):646-9. 
b 
Lucey MR, Brown KA, Everson GT, et al. Liver Transpl Surg. 1997;3(6)628-37. 
c 
Classification is based on total points assigned for the degree of encephalopathy, the degree of ascites, the 
plasma concentrations of bilirubin and albumin, and prothrombin time: Grade A = 5-6 points; 
Grade B = 7-9 points; Grade C = 10-15 points. 
d 
Grading from Trey C, Burns DG, Saunders SJ. N Engl J Med. 1966;274(9):473-81. 
e 
Moderate or controlled by diuretics. 
f 
If there is a discrepancy for the points scored for the seconds prolonged over the ULN and the international 
normalized ratio, the points scored for the international normalized ratio should be used. 


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7.5 
Appendix: Cockcroft-Gault Formula 
The Cockcroft-Gault formula for estimating CrCl: 
 
• When serum creatinine (SCr) is measured in mg/dL: 
 
CrCl (mL/min) = {(140 – age) × weight (kg)} / 72 × SCr in mg/dL (× 0.85 if subject is 
female) 
 
• When SCr is measured in µmol/L: 
 
CrCl (mL/min) = {(140 – age) × weight (kg) × [1 – (0.15 × sex)]} / (0.814 × SCr), 
where, sex = 0 if male; sex = 1 if female 


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7.6 
Appendix: SF-12v2® Health Survey 
  


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7.7 
Appendix: Quality-of-Life Questions 
As a result of your infection, in the last 24 hours, have you experienced any difficulties in 
doing your usual daily activities?  
If you answer “yes” to any item, please use the scale provided to tell us how important it has 
been to you (1 = little difficulty to 5 = tremendous difficulty). 
 
Have you had difficulty doing 
the following activities?  
(check one) 
To what extent have you had 
difficulty? 
(1 = little difficulty to  
5 = tremendous difficulty) 
Doing your job 
(work, childcare, 
housework, etc.) 
[  ] yes     [  ] no 
1       2       3       4       5 
Earning an 
income 
[  ] yes     [  ] no 
 
[  ] not applicable (I do not work) 
1       2       3       4       5 
 
 
 


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7.8 
Appendix: Definitions of Symptom Intensity 
Symptom (Points) 
Absent (0) 
Mild (1) 
Moderate (2) 
Severe (3) 
Cough 
Absence of 
cough (or to pre-
CABP baseline) 
Transient, does 
not interfere 
with normal 
activity 
Frequent, 
interferes with 
normal activity 
or sleep 
Constant, 
interferes with 
most or all 
activities or 
sleep 
Dyspnea/ 
Shortness of 
Breath 
Absence of 
dyspnea (or to 
pre-CABP 
baseline) 
Dyspnea on 
exertion (e.g. 
climbing stairs) 
Dyspnea with 
normal/routine 
activities (e.g. 
walking) 
Dyspnea at rest 
or requiring 
oxygen therapy  
Chest Pain due to 
Pneumonia 
Absence of chest 
pain related to 
CABP  
Transient, does 
not interfere 
with normal 
activity 
Frequent, 
interferes with 
normal activity 
or sleep 
Constant, 
interferes with 
most or all 
activities or 
sleep 
Sputum 
Production 
Absence of 
sputum 
production (or to 
pre-CABP 
baseline) 
Sputum 
production 
rarely causes 
difficulty or 
distress 
Sputum 
production often 
causes difficulty 
or distress 
Constant 
difficulty with 
sputum 
production  
 


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7.9 
Appendix: Protocol Amendment 1 
The following sections detail the changes made to the original protocol dated 
03 September 2015.  
7.9.1 
Overview of Changes 
• To allow for the inclusion of PORT Risk Class V subjects in the study. 
• Added exclusion criterion to specify restrictions associated with use of linezolid: known 
uncontrolled arterial hypertension, pheochromocytoma, carcinoid thyrotoxicosis and 
restrictions associated with use of moxifloxacin (regional labeling): lactose intolerance, 
lactase deficiency and glucose-galactose malabsorption.  
• Revised to reflect that local laboratory results should be obtained within the 24 hours 
prior to first dose of study drug to verify entry criteria in order to more accurately assess 
the subject’s clinical condition at time of enrollment.  
• To clarify that oropharyngeal and nasopharyngeal specimens may include culture and/or 
PCR.   
• Revised to reflect CRP samples will not be collected.   
• Clarified that local/regional laboratory results will be used for patient care.  
• It was clarified that systemic steroid use during the treatment period is allowed for a short 
duration (e.g., steroid burst). Inhaled steroids are allowed without any restriction. 
• Treatment regimens clarified. 
• Description of delafloxacin was updated to be consistent with the Investigator Brochure.  
• The statistical analysis section was revised to reflect that a shift table will be not used to 
analyze change from baseline for physical exam findings. Worsening from baseline will 
be captured as adverse events.  
7.9.2 
Changes to the Protocol Text 
In this section, all affected protocol sections are detailed; the sequence of the sections follows 
the structure of the original protocol. Additions to the protocol text are shown in bold and 
deletions are shown in strikethrough text. Minor editorial and grammatical corrections are 
not specified. Any notes for the section are included in brackets. 
Title Page – Sponsor Contact 
Assistant Director of Clinical Operations 


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Title Page – Version of Protocol 
15 DecemberSeptember 2015 
Title Page – Previous Date and Version – [text added] 
03 September 2015, Original 
Protocol Synopsis – Study Population 
Adult male and female subjects 18 years of age or older with clinical and radiographic 
evidence of CABP and a Pneumonia Patient Outcomes Research Team (PORT) risk class of 
II, III, or IV, or V (Pneumonia Severity Index [PSI] score > 50 and ≤ 130). 
Protocol Synopsis – Inclusion criterion 4 and Section 3.2.1 Inclusion Criteria 
PORT risk class of II, III, or IV, or V PSI score (51 to 130, inclusive greater than 50). 
Subjects may be initially screened based on meeting CURB-65 score of 2 to 4. PORT risk 
class II will be limited to 25% of randomized subjects. 
Protocol Synopsis – Exclusion criterion 11 and Section 3.2.2 Exclusion Criterion 11 
corrected 
11.  Severe renal disease or creatinine clearance (CrCl) ≤ 29 mL/min using Cockcroft-Gault 
formula or need for hemodialysis or peritoneal dialysis. 
Protocol Synopsis –Exclusion criterion 22 and Section 3.2.2 Exclusion Criterion– added  
Patients with known uncontrolled hypertension, pheochromocytoma, carcinoid 
thyrotoxicosis; and rare hereditary problems of galactose intolerance, the Lapp lactase 
deficiency or glucose-galactose malabsorption.  
Subsequent exclusion criteria renumbered.  
Protocol Synopsis – Study Design and Section 3.1 Study Design 
Subjects may be initially screened based on meeting CURB-65 score of 2 to 4, but will be 
eligible for enrollment only if classified as PORT Risk Class II, III, or IV, or V.  A 
pretreatment sputum specimen will be collected for Gram stain and culture and susceptibility 
testing, if positive. Blood samples for procalcitonin C-reactive protein, and serology will be 
obtained at Day 1 as well as nasopharyngeal and oropharyngeal swabs for culture and/or 
polymerase chain reaction (PCR) testing and urine samples for antigen testing. 


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Protocol Synopsis – Criteria for Evaluation: Definitions 
Presumed Eradication: No sputum sample was available at TOC with a clinical assessment 
of Success.  
Persistence: The sputum and/or blood culture collected at the EOT TOC visit shows 
appearance of all causative pathogen(s) at enrollment. 
Protocol Synopsis – Microbiologic Measures 
The causative pathogen will be identified by isolation from a baseline specimen (either a 
sputum specimen or blood), by urinary antigen (S. pneumoniae and L. pneumophila), and/or 
serology and/or PCR (L. pneumophila and M. pneumonia). 
Protocol Synopsis – Date of Final Protocol 
03 September 15 December 2015 
List of Abbreviations 
CRP 
C-reactive protein [deleted] 
IXVRS/ IWRS 
Interactive voice response system and Interactive web-response system 
web response system 
RBC 
Red blood cell [added] 
Section 1.1.3 In Vivo Studies 
Against S. pneumoniae 5649, a multidrug-resistant strain, delafloxacin demonstrated a dose 
of vaccine required to protect 50% (PD50) of < 5.0 mg/kg/day, whereas levofloxacin and 
trovafloxacin resulted in PD50s of 12.9 and 10.2 mg/kg/day, respectively. 
Section 1.2.1 Pharmacokinetics, Safety, and Tolerability of IV and Oral Delafloxacin 
Single doses ranging from 50 tofrom 1200 mg were assessed for safety, tolerability, and 
pharmacokinetics (PK) in 5 Phase 1 studies with 4 different IV formulations. In the RX-
3341-108 study (Rib-X Study RX-3341-108), a maximum tolerated dose (MTD) for single 
IV administration was 900 mg given over 1 hour. 


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Figure 3-1  
Schematic of Study Design  
 
SCREENING 
 
TREATMENT PERIOD 
 
FOLLOW-UP PERIOD 
 
 
 
 
 
 
Screening and Enrollment 
Days –1 to 1 
 
Days 1 to 7 (up to 10 
days)  
 
End of 
Treatment 
(EOT) 
 
Test Of Cure 
Visit 5 to 10 days 
after last dose 
(TOC) 
 
Follow-
up Visit  
Day 28 
 
 
 
 
 
 
 
 
 
Obtain informed consent 
 
 
Blinded Study Drug 
Administration: 
One IV dose every 12 
hours (± 2 hours) for a 
total of 10 up to 20 doses* 
(IV alone or IV and oral) 
 
 
 
 
 
 
 
 
 
 
 
 
 
Screening procedures 
 
 
 
 
 
 
 
 
 
 
 Early Clinical Response 
at 96 hours (± 24 hours) 
after first dose of study 
drug 
 
 
Investigator Assessment of Clinical 
Outcome  
 
Capture 
post- 
study 
SAEs 
 
 
Enrollment and random assignment to 
treatment arm (1:1 ratio) via IVRS/IWRS 
IXRS 
 
 
  
 
 
 
Blinded delafloxacin 
 
Blinded 
moxifloxacin 
Day 5 and Day 7 
Assess the need to 
continue dosing up to 10 
days (20 doses)* 
 
 
 
Delafloxacin 300 mg 
IV BID option to 
switch to delafloxacin 
450 mg orally BID 
 
 
Moxifloxacin 400 mg 
IV administered QD 
option to switch to 
moxifloxacin 400 mg 
orally QD  
 
Optional switch to 
linezolid 600 mg 
IV/oralBID if 
MRSA is 
confirmed 
 
 
 
 
 
 
* delafloxacin/delafloxacin placebo doses  Abbreviations: EOT = End of Treatment; TOC = Test of Cure; IVRS/IWRSIXRS = interactive voice and-response system/interactive web response system; 
IV = intravenous; BID = every 12 hours; QD = every 24 hours; MRSA = methicillin-resistance Staphylococcus aureus 
Reminder Contact 
3–9 days after last 
dose 


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Table 3-1 Treatment Regimens 
Changes to previously bolded text are italicized. 
 
Regimens 
Given 
Subjects randomized to 
delafloxacin  
 
Subjects randomized to 
moxifloxacin  
WHILE ON 
IV 
THERAPY 
IV regimen 
given with 
blinding covers 
IV active delafloxacin 
twice daily  
 
IV active moxifloxacin 
once daily, alternative 
with IV placebo to 
maintain blind for BID 
dosing 
If linezolid is 
prescribed 
during IV 
dosing period 
Continue IV active 
delafloxacin twice daily  
 
Discontinue IV 
moxifloxacin/placebo 
and begin IV active 
linezolid twice daily 
 
 
 
 
 
WHILE ON 
ORAL 
THERAPY 
Delafloxacin 
Oral active delafloxacin 
twice daily 
and 
 
Oral placebo 
delafloxacin twice daily 
and 
Moxifloxacin 
Oral placebo 
moxifloxacin once 
daily 
 
Oral active 
moxifloxacin once daily  
If linezolid is 
prescribed for 
MRSA in 
moxifloxacin 
subjects (a 
partial switch 
back to IV 
applies) 
Oral placebo 
moxifloxacin will be 
discontinued (oral 
delafloxacin 
continues) and subjects 
randomized to 
delafloxacin will 
receive IV placebo 
linezolid twice daily 
 
Oral active 
moxifloxacin will be 
discontinued and 
subjects randomized to 
moxifloxacin will 
receive IV active 
linezolid twice daily 
and continue oral 
placebo delafloxacin 
twice daily 
 
Section 3.2 
Selection of Study Sample 
At least 860 male and female subjects, 18 years of age or older, with clinical and 
radiographic evidence of CABP and a pneumonia Patient Outcomes Research Team (PORT) 


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risk class of II, III, or IV, or V (pneumonia severity index score [PSI] greater than 501 -130 
inclusive) will be enrolled in the study. 
Section 3.2.2 Exclusion Criterion 9 
Severely compromised immune symptoms system, e.g.:   ………. 
Section 3.4.1 Study Visits 
……. Subjects may be treated as hospitalized inpatients or outpatients in accordance with 
local treatment guidelines for moderate to severe CABP, provided that all study-drug 
infusions are administered by study-site personnel or hospital staff who that have been 
trained on protocol specifics and the Sponsor-approved study drug-blinding plan. 
Section 3.4.1 Screening – bullet one 
• Access interactive voice-response system/interactive and web response system 
(IVRS/IWRS IXRS) to register screening. 
Section 3.4.1 Screening – bullet 10 
• Obtain blood samples for hematology, serum chemistry, and coagulation profile and 
urine sample for urinalysis (the results of any of these tests obtained within 48 24 hours 
of enrollment, may be used for screening purposes and to verify entry criteria by the local 
laboratory; however, blood and urine samples must be obtained at Screening (prior to the 
first dose) and sent to the central laboratory for analysis to serve as baseline values.  
Section 3.4.1.2 
Day 1 – bullet 7 
• Obtain blood samples for C-reactive protein (CRP), procalcitonin, and Mycoplasma 
pneumoniae and L. pneumophila serology.  
Section 3.4.1.5 
Day 5 – bullet 10 
• Subjects who continue oral treatment as an outpatient will be dispensed/administered 
study drug and instructed to return to the clinic on Day 7 with their study drug 
container(s).  
3.4.1.8.1 
Criteria for Determining Treatment Duration 
After completing 5 days of treatment (minimum of 10 doses of delafloxacin/delafloxacin 
placebo), the investigator will assess the subject for clinical response to treatment to 
determine adequate treatment duration. The following suggested criteria can be used to assess 
clinical response; however, the duration of therapy should be individualized based upon the 


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subject’s clinical response to treatment and comorbidities up to a maximum treatment of 10 
days (20 delafloxacin/delafloxacin placebo doses). 
Section 3.4.1.10 
TOC Visit (5–10 Days after Last Dose of Study Drug) – bullet 9 
• Obtain blood samples for M. pneumoniae and L. pneumophila serology, CRP, and 
procalcitonin. 
Section 3.4.1.11 
Follow-up Visit (Day 28 ± 2 Days) 
All efforts will be made to have subjects return to the clinic for a Follow-up visit. Telephone 
contact is permissible for subjects unable,or unwilling or not required (see Section 3.3.2) to 
return to the clinic. The following procedures will be performed at the Follow-up Visit on 
Day 28 (± 2 days). 
Section 3.4.3 Study Assessments 
The following assessments will be performed to collect data needed for this research study. It 
is expected that the investigator and hospital staff will follow the usual standard of patient 
care and that local/regional laboratory results will be used to manage patient care. 
Section 3.4.3.2 
Microbiological Assessments  
The following pathogens are examples of primary pathogens that will be used to determine 
the microbiological responses in the study: the typical bacterial pathogens include 
S. pneumoniae, H. influenzae, S. aureus, Klebsiella pneumoniae, and Moraxella catarrhalis 
and the atypical bacterial pathogens C. pneumoniae, M. pneumoniae, and L. pneumophila. 
The causative pathogen will be identified by isolation from a baseline specimen (either a 
sputum specimen or blood), by urinary antigen, and/or S. pneumoniae, L. pneumophila 
serology and/or PCR. The residual sputum sample and/or nasopharyngeal swabs may 
be sent to specialty laboratories for culture and/or PCR (S. pneumoniae, L. pneumophila, 
and M. pneumoniae). Respiratory and blood specimens will be sent to 
local/regional/specialty laboratories for culture, microorganism identification, and antibiotic 
sensitivity testing and will be processed according to standard recognized methods (Garcia 
2010, Murray 2007). Sites will use local/regional culture results for patient management. 
The Two Gram stain slides of the sputum specimen will be prepared by performed at the 
local/regional laboratories. One slide will be stained and read locally.  Both slides, read 
and unread, will be sent to the central laboratory to confirm results. An additional 
Gram stain slide may will be retained by the local microbiology laboratory, if required by 
local regulations. Culture will be performed at local or regional laboratories, as applicable. 
Rapid MRSA identification methods are acceptable to use if S. aureus is identified by the 


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local/regional laboratory. Isolates that are not considered contaminants will be forwarded to 
the central microbiology laboratory for confirmation of identity and antimicrobial 
susceptibility testing and any further molecular or phenotypic characterization (e.g., PCR for 
Panton-Valentine leukocidin and mecA genes, pulsed-field gel electrophoresis). Specific 
handling and shipping instructions that will maintain viability of all organisms will be 
provided in the laboratory manual. A duplicate sample of the isolate(s) (from all sources) 
submitted to the central microbiology laboratory will be maintained (in frozen state) by the 
local laboratory or sent to the central laboratory until the conclusion of the study. 
Directions for collection, processing and handling of specimen are included in the laboratory 
manual.  
Section 3.4.3.2.1 
Respiratory Culture 
All respiratory specimens will be sent for culture and susceptibility testing. Other sources of 
respiratory specimens such as those obtained from bronchoalveolar lavage (BAL), protected 
specimen brush (PSB), transtracheal aspirate, and pleural fluid, if available, are acceptable to 
submit for culture. In addition, a residual respiratory sample will be frozen and may be sent 
to a specialty lab for culture, antibiotic sensitivity testing, and/or serotyping.  
Section 3.4.3.2.3 
Urine Antigen Testing 
Urine samples will be obtained for L. pneumophila and S. pneumoniae urine antigen testing 
at baseline. The test kits will be provided by the sponsor and will be analyzed by the 
local/regional laboratory.  
Section 3.4.3.2.4 
Nasopharyngeal and Oropharyngeal Testing 
Nasopharyngeal swabs will be obtained at baseline for S. pneumoniae PCR analysis and/or S. 
pneumoniae culture and serotyping. Oropharyngeal swabs will be obtained at baseline for 
Mycoplasma culture and/or PCR antibiotic susceptibility testing at specialty microbiology 
laboratories.  
Section 3.4.3.5 
Clinical Laboratory Tests  
Other Chemistry:  CRP and Procalcitonin.  
Hematology: A hematology panel will be taken to include complete blood count with 
hematocrit, hemoglobin, platelet count, red blood cell count (RBC), RBC morphology and 
mean corpuscular volume, and white blood cell count with differential. 


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Urinalysis: A urine panel will be taken at screening to include pH, specific gravity, 
leukocytes, nitrite, leukocyte esterase, protein, urobilinogen, bilirubin, blood, glucose, and a 
microscopic examination. The urine samples will be analyzed by a central laboratory.  
Section 3.4.3.7 
Vital Sign Measurements 
Subjects who require pressor support should have regular blood pressure monitoring as per 
local standard of care.  
Section 3.4.3.10   Health-Related Quality-of-Life Assessment 
This survey will be completed at baseline, EOT, TOC, and FU based on availability of the 
validated survey in local language. 
Section 3.6.1   Method of Assigning Subjects to Treatment Groups 
Each subject will be randomly assigned in a 1:1 ratio to delafloxacin or moxifloxacin 
treatment group. 
The investigator or designee will enter the enrollment information in IVRS/IWRS IXRS. The 
unblinded pharmacist or unblinded designee will obtain the treatment assignment by the 
IVRS/IWRS IXRS as described in the study operations IXRS manual. 
Section 3.6.3   Description of Investigational Product   
Delafloxacin 
Delafloxacin for Injection, 300 mg/vial, is a light-yellow to tan-colored lyophilized cake 
powder provided in a 20 mL clear borosilicate glass vial. Each vial contains the following 
ingredients: 4332.9 mg delafloxacin meglumine equivalent of 300 mg free acid, 58.56 mg 
meglumine, 2400 mg sulfobutyl ether sodium beta cyclodextrin (Captisol®), and 2.6 mg 
ethylene-diamine-tetra-acetate disodium (as 2.6 EDTA, amount as acid) and water for 
injection.  It may also contain hydrochloric acid and/or sodim hydroxide for pH adjustment.  
When reconstituted with Sterile Water for Injection, USP, it forms a clear yellow to amber 
colored solution with a pH of 9.0, which will be further diluted into IV infusion bags.  
After reconstitution in the vial, the drug concentration is 25 mg/mL in an aqueous solution of 
12.4 mL (0.4 mL as overage). 
The delafloxacin tablet formulation consists of delafloxacin as the free acid in a traditional 
wet granulation of drug substance with commonly used excipients and a blend of basic 
buffering agents.  Each tablet contains the following ingredients: delafloxacin meglumine; 
povidone, as a binder; crospovidone as a disintegrant; microcrystalline cellulose as a filler; 
sodium bicarbonate; sodium phosphate monobasis; and citric acid for buffering effect; and 


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magnesium stearate as a lubricant.  The modified capsule shaped,s ingle-layer tablet is beige 
with tan spots, with “RX3341”embossed on 1 side.  
Oral delafloxacin is a capsule-shaped tablet in beige color with tan spots (delafloxacin 
particles) and with RX3341 debossed on one side. Each tablet contains the following 
ingredients: 649.35 mg delafloxacin meglumine equivalent of 450-mg free acid; cellulose; 
povidone; crospovidone; sodium bicarbonate; sodium phosphate; citric acid; and magnesium 
stearate. For more information on the description of delafloxacin, refer to the Investigator’s 
Brochure (Melinta IB 2015). 
Section 3.6.4.1   Study Drug Packaging and Storage 
Moxifloxacin (400 mg) for IV use is intended to be provided in glass bottles or infusion 
bags as local availability allows.  Moxifloxacin (400 mg) over-encapsulated tablets are 
intended to be supplied in daily dose bottles.  
….. 
Additional study drug will be supplied as needed based on information provided via the 
IVRS/IWRS IXRS. 
Section 3.6.4.3   Blinding 
….. 
Certain clinical research associate staff will not be blinded in order to monitor the pharmacy, 
administer study drug (if applicable), and monitor study administration records and will not 
reveal a subject’s treatment assignment to study staff. The statistician who creates the 
randomization code will not be involved otherwise in the conduct of the study. 
…… Bullet 3 
• Subjects in the moxifloxacin treatment arm will receive once-daily active IV therapy 
alternating doses of IV moxifloxacin and IV placebo every 12 hours (± 2 hours) BID.  
Section 3.6.7 Allowed Concomitant Treatment – [added text] Paragraph 2 
….. 
Systemic steroid use during the treatment period is allowed for a short duration (e.g., 
steroid burst). Inhaled steroids are allowed without any restriction. 
Section 3.7.2.2 
Clinical Outcome at EOT and TOC 
Indeterminate/Missing: A response cannot be determined because an efficacy assessment 
was not completed at the visit. Indeterminate/missing responses will be considered failures 


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for purposes of the primary ITT analysis and will be excluded from the CE and ME analysis 
populations. 
Section 3.8.5 Subgroup Analyses of the Primary Endpoint – bullet one 
• Demographic subgroups: age categories (age ≤ 65, > 65, > 75), gender, BMI categories 
(BMI < 30 and ≥ 30), baseline PORT score, prior systemic antimicrobial use, baseline 
CURB-65 Score, ethnicity, and race categories. 
Section 3.8.14 Physical Examination Findings 
Changes from Screening in physical examination results will be listed by subject for all 
subjects in the Safety set. Height and weight will be summarized by reporting the number of 
subjects evaluated, mean, median, standard deviation, minimum value, maximum value, and 
inner quartile percentiles. The number of baseline findings and the percentage of subjects 
with findings will be reported. A shift table will be provided for each of the body categories 
to report findings that represent changes from the baseline condition at each visit. 
Section 3.8.17 Missing Data – Number 5- [text added]  
5. 
Failure outcome due to LOE will be carried forward to later time points (i.e., TOC) if 
the subject discontinues the trial for LOE. These subjects will be considered evaluable if 
other factors of evaluability are met. 
IVRS/IWRS changed to IXRS in the following sections: 
Section 3.4.1.1   Screening – bullet 16 
Section 3.4.1.5   Day 5 – bullet 9 
Section 3.4.1.6   Day 7 – bullet 8 
Section 3.4.1.7   End of IV treatment – bullet 4 
Section 3.4.1.8.2   End of treatment or Early Termination Procedures – bullet 13 
Section 3.6.5   Breaking the Blind – Paragraph one 
Section 7.1   Appendix: Schedule of Events  
Section 7 
Appendices 
7.1 
Appendix: Schedule of Events 
7.2 
Appendix: PSI/PORT Score: Pneumonia Severity Index for CAP [added] 
7.3 
Appendix: CURB-65 


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7.4 
Appendix: Child-Pugh Classification of Severity of Liver Disease 
7.5 
Appendix: Cockcroft Gault Formula 
7.6 
Appendix: SF-12v2® Health Survey 
7.7 
Appendix: Quality-of-Life Questions 
7.7 
Appendix: Protocol Amendment 1 – [added]  
 


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Section 7.1 - Appendix: Schedule of Events [changed table cells are shaded gray] 
Assessment or Procedure 
Screeninga 
 
Treatment Periodb 
End of 
Treatment 
(EOT)/ 
Early 
Termc 
Reminder 
Contactd 
Test of 
Cure 
(TOC)e 
Follow-
Up 
Visitf 
Study Day(s) 
–1 to 1  
1a 
Daily 
while 
on IV 
96 hr 
± 24 
hrg 
ECR 
 
5 
(±+ 
1 
day) 
 
7 
(± 1 
day) 
 
End 
of 
IVh 
 
 
  
5 to 10 
days 
after last 
dose 
28 (± 2 
days) 
……….. 
Blood sample for procalcitonin and CRP 
 
X 
 
 
 
 
 
 
 
X 
 
Schedule of Events – Abbreviations 
Abbreviations: ECR = Early Clinical Response; EOT = End of Treatment; TOC = Test of Cure; CABP = community-acquired bacterial pneumonia; MRSA = 
methicillin-resistant Staphylococcus aureus; CT = Computed tomography, PORT = Patient Outcomes Research Team; CURB-65 = scoring system based on confusion, 
urea, respiratory rate, blood pressure and age 65 or older; CRP = C reactive protein; PK = pharmacokinetics; IVRS/IXRS IXRS = interactive web response system. 
Schedule of Events – footnote n 
n Local laboratory test results of pregnancy, hematology, serum chemistry, and coagulation profile and urinalysis obtained within 48 24 hours of enrollment may be used 
for screening purposes and to verify entry criteria by the local laboratory. Laboratory tests with exclusionary results judged by the investigator as not compatible with 
the subject’s clinical status may be repeated for eligibility purposes once. 
 


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7.2  Appendix: PSI/PORT Score: Pneumonia Severity Index for CAP [added] 
PSI/PORT Score: Pneumonia Severity Index for CAP 
 
Assigned Points 
Age (Years) 
 
Men 
Age (Years) 
Women 
Age (Years) −10 
Nursing home resident 
+10 
Neoplastic disease 
+30 
Liver disease history 
+20 
Congestive heart failure history 
+10 
Cerebrovascular disease history 
+10 
Renal disease history 
+10 
Altered mental status 
+20 
Respiratory rate > 29  
+20 
Systolic blood pressure < 90 mmHg 
+20 
Temperature < 35C (95F) or > 39C 
(103.8F) 
+15 
Pulse > 124 
+10 
Arterial pH < 7.35 
+30 
BUN > 29 
+20 
Sodium < 130 
+20 
Glucose > 249 (US) or 13.8 (SI) 
+10 
Hematocrit < 30% 
+10 
Partial pressure of Oxygen < 60 mmHg 
+10 
Pleural effusion on x-ray 
+10 
 


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Step 1: 
• 
If the patient is >50 years of age, assign to risk class II - V and proceed to step 2. 
• 
If the patient is <50 years of age, but has a history of neoplastic disease, 
congestive heart failure, cerebrovascular disease, renal disease or liver disease, 
assign to risk class II - V and proceed to step 2. 
• 
If the patient has an altered mental status, pulse ≥ 125/minute, respiratory rate ≥ 
30/minute, systolic blood pressure ≤ 90 mm Hg, or temperature < 35° C or ≥ 40° 
C, assign to risk class II - V and proceed to step 2 
• 
If none of the above apply, assign to risk class I = low risk. 
Step 2: 
• 
Assign points based on age, gender, nursing home residence, co-morbid illness, 
physical examination findings, and laboratory and radiographic findings as 
listed above. 
• 
Suggested disposition based on local standard of care: 
 
MDCalc© 2015. All Rights Reserved. 
 
Downloaded 28/November 2015 http://www.mdcalc.com/psi-port-score-pneumonia-
severity-index-adult-cap/ 
 


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7.10 Appendix: Protocol Amendment 2 
The following sections detail the changes made to the Amendment 1 of the protocol dated 
15 December 2015.  
7.10.1 
Overview of Changes 
• Revised inclusion criterion 2 as follows, to be consistent with the draft guidance for 
industry “Community-Acquired Bacterial Pneumonia: Developing Drugs for Treatment” 
o removed “…or a change in the character of the sputum,” from, “Production of 
purulent sputum or a change in the character of the sputum consistent with a 
bacterial infection” 
o separated out the vital sign abnormalities from the other clinical signs and 
laboratory abnormalities 
• Revised exclusion criterion 1 to include exclusion of medical history of significant 
hypersensitivity or allergic reaction to study drug excipients in the judgment of the 
investigator. 
• Revised exclusion criterion 4 to include criteria for documenting treatment failure based 
on clinical evidence and not pulmonary imaging alone. 
• Revised exclusion criterion 12 to include exclusion of known uncorrected 
hypomagnesemia at study entry.  
• Revised the primary efficacy endpoint definition of improvement to include no 
worsening of any of the other CABP symptoms as described in the references provided in 
the draft guidance for industry document.  
• Modified the suggested criteria for IV to oral switch to improved stability if vital sign 
indices, e.g. no worsening.   
• Revised the Responders definition to include no worsening of other symptoms. 
• The Nonresponders definition was revised to further clarify that additional antimicrobial 
treatment of the current CABP infection would only meet the Nonresponders definition if 
the reason for treatment was due to lack of efficacy.   
• The Failure definition was revised to clarify that additional antimicrobial treatment of the 
current CABP infection would only meet the Failure definition if the reason for treatment 
was due to lack of efficacy.   


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• Indeterminate/Missing definition was revised to clarify that a response could not be 
determined if the subject did not complete the planned course of study therapy for reason 
other than lack of efficacy.  
• Clarified that if ever utilized, any potential sample size recalculation would be based on 
pooled information across the 2 treatment arms. 
• Added a table that includes the definitions of symptom intensity ranging from absent (0 
points), to mild (1), moderate (2), and severe (3).  
7.10.2 
Changes to the Protocol Text 
In this section, all affected protocol sections are detailed; the sequence of the sections follows 
the structure of the original protocol. Additions to the protocol text are shown in bold and 
deletions are shown in strikethrough text. Minor editorial and grammatical corrections are 
not specified. Any notes for the section are included in brackets. 
Title Page – Version of Protocol 
15 December 2015 29 March 2016 
Title Page – Previous Date and Version – [text added] 
15 December 2015, Amendment 1 
Protocol Approval Page – Protocol Date 
15 December 2015 29 March 2016 
Protocol Synopsis – Inclusion criterion 2 and Section 3.2.1 Inclusion Criteria 
2.   Evidence of acute onset of CABP.  
Subjects must have at least 2 3  of the following clinical signs and symptoms (new or 
worsening): 
• Cough 
• Production of purulent sputum or a change in the character of the sputum consistent 
with a bacterial infection 
• Difficulty breathing (dyspnea) 
• Chest pain due to pneumonia 
AND 


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Subjects must also have at least 2 of the following findings: 
• Fever (oral temperature > 38°C or equivalent) within 24 hours prior to randomization 
• Hypothermia (oral temperature < 35°C or equivalent) within 24 hours prior to 
randomization  
• Tachycardia (> 100 beats per minute) 
• Tachypnea (elevated respiratory rate >18 breaths per minute 
AND 
Subjects must also have at least 1 of the following findings:  
• Hypoxemia (oxygen saturation < 90% or PaO2 < 60 mmHg on room air or with 
subject’s baseline [pre-CABP under study] supplemental oxygen flow rate) 
• Clinical evidence of pulmonary consolidation and/or presence of pulmonary rales 
• An elevated white blood cell count (WBC) > 10,000/mm3 or 15% immature 
neutrophils (bands), regardless of total peripheral WBC count or leukopenia with 
WBC < 4500/mm3 
Protocol Synopsis –Exclusion criterion 1 and Section 3.2.2 Exclusion criterion 1 
Medical history of significant hypersensitivity or allergic reaction to antibiotics of the 
quinolone or oxazolidinone class or study drug excipients in the judgment of the 
investigator. 
Protocol Synopsis – Exclusion criterion 4 and Section 3.2.2 Exclusion Criterion 4: 
4. Receipt of systemic antibiotic therapy in the 7 days before enrollment unless one of the 
following is documented: 
• The subject received at least 48 hours of antibiotic therapy for CABP and the clinic 
notes or pulmonary imaging  document treatment failure (i.e., not by patient history 
or pulmonary imaging alone) and/or isolation of a resistant pathogen with new or 
worsening signs or symptoms have developed while on pre-study therapy or 
identification of a respiratory pathogen that is resistant to a pre-study antibiotic, 
which would be susceptible to study drug (delafloxacin or moxifloxacin) in 
subjects with new or worsening signs and symptoms of CABP. 


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• The subject received 1 dose of a single, potentially effective, short-acting 
antimicrobial drug or a short-acting antimicrobial drug regimen for treatment of the 
CABP under study within 24 hours of enrollment. (Note: 1 dose of a regimen is 
defined as the standard therapy for CABP at the study site.) Subjects who received 
prior antimicrobial drug under this criterion will be limited to no more than 25% of 
total randomized subjects. 
Protocol Synopsis –Exclusion criterion 12 and Section 3.2.2 Exclusion criterion 12 
12. Uncorrected hypokalemia or known uncorrected hypomagnesemia at time of 
enrollment. 
Protocol Synopsis – Efficacy Endpoints  and Section 3.7.1.1 Primary Efficacy Endpoint 
Primary Efficacy Endpoint: The primary efficacy endpoint is the ECR defined as 
improvement at 96 hours (± 24 hours) after first dose of study drug in at least 2 of the 
following symptoms: chest pain, frequency or severity of cough, amount and quality of 
productive sputum and difficulty breathing and no worsening of any of the other 
symptoms in the ITT population. 
Protocol Synopsis – Criteria for Evaluation: Definitions and 3.7.2 Endpoint Definitions 
For Early Clinical Response: [Section 3.7.2.1] 
Responders: Improvement at 96 hours (± 24 hours) after first dose of study drug in at least 2 
of the following symptoms: chest pain, frequency or severity of cough, amount and quality of 
productive sputum, and difficulty breathing and no worsening in the other symptoms. 
Nonresponders: Improvement is not achieved at 96 hours (± 24 hours) after the first dose of 
study drug in at least 2 of the following symptoms (chest pain, frequency or severity of 
cough, amount and quality of productive sputum, and difficulty breathing); or there is use of 
additional nonstudy antimicrobial therapy for treatment of the current CABP infection due 
to lack of efficacy; or the subject dies from the current CABP infection. 
For Clinical Outcome at EOT and TOC: [Section 3.7.2.2] 
Failure: Symptoms of CABP present at study entry have not resolved, or new symptoms have 
developed, or the subject dies from pneumonia, or use of additional nonstudy antimicrobial 
therapy for treatment of the current CABP infection due to lack of efficacy.  
Subjects must receive at least 4 doses of study drug by the end of Day 3 to be called a 
Failure.  


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Indeterminate/Missing: A response cannot be determined because an efficacy assessment was 
not completed at the visit, including or subjects who did not complete the planned course 
of study therapy for reasons other than lack of efficacy.   
Protocol Synopsis – Date of Final Protocol 
15 December 2015 29 March 2016 
3.4.1.7   End of IV Treatment 
After a minimum of 6 delafloxacin/delafloxacin placebo doses, subjects can switch to oral 
treatment if, in the past 24 hours, the subject meets the following suggested criteria for 
switch to oral treatment:  
• Is able to ingest intact large tablets capsules, 
• Has a normally functioning gastrointestinal tract, and  
• Is clinically stable, and has improved stability of vital sign indices, such as, no 
worsening from entry vital signs.  
Does not have more than 2 of the following findings: 
o Oral temperature higher than 37.5°C (or equivalent) 
o Respiratory rate greater than 24 breaths per minute 
o Systolic blood pressure 90 mmHg or lower 
o Oxygen saturation under 90% or PaO2 < 60 mmHg on room air (or 
with subject’s pre-CABP under study supplemental oxygen flow rate) 
o Abnormal mental status 
3.4.2.1    Clinical Evaluation  
The following signs and symptoms of CABP will be assessed and evaluated: 
• 
Pleuritic chest pain  
• 
Frequency or severity of cough  
• 
Dyspnea  
• 
Sputum production (if present, change in character and quantity from baseline and 
purulence) 


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Symptom severity will be evaluated by the investigator on a 4-point scale (absent, mild, 
moderate, severe) with improvement defined as at least a 1-point improvement from baseline 
to the assessment at 96 hours (± 24 hours) after first dose of study drug (e.g., from severe to 
moderate, from moderate to mild, or from mild to absent).  See Appendix 7.8 for definitions 
of symptom intensity. 
Section 3.7.4 Sample Size Calculations 
At least 860 adult male and female subjects (430 subjects per treatment group) will be 
randomized. Use on a normal approximation approach (Miettinen and Nurminen’s 
Likelihood Score Test), 860 subjects in the ITT population will provide a 90% power to 
assess noninferiority of delafloxacin vs. moxifloxacin based on the following assumptions: 
(1) a rate of Early Clinical Response for moxifloxacin therapy and delafloxacin of 77% and 
74%, respectively; (2) 1-sided type I error (α) of 0.025; (3) a noninferiority margin of 12.5%. 
As Early Clinical Response is a new endpoint as new information arises (without unblinding 
the study) that informs sample size, this information may be used to reassess sample size.  If 
ever utilized, any potential sample size recalculation would be based on pooled 
information across the 2 treatment arms. 
Section 7    Appendices 
7.1 
Appendix: Schedule of Events 
7.2 
Appendix: PSI/PORT Score: Pneumonia Severity Index for CAP [added] 
7.3 
Appendix: CURB-65 
7.4 
Appendix: Child-Pugh Classification of Severity of Liver Disease 
7.5 
Appendix: Cockcroft Gault Formula 
7.6 
Appendix: SF-12v2® Health Survey 
7.7 
Appendix: Quality-of-Life Questions 
7.8 
Appendix: Symptom Severity Definitions – [added] 
7.9  
Appendix: Protocol Amendment 1 
7.9 
Appendix: Protocol Amendment 2 – [added]  
Section 7.1  Appendix: Schedule of Events 
Added footnote “y” to Screening Adverse Event Evaluation cell to clarify that serious 
adverse events will be reported per protocol and recorded in the eCRF. 


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Section 7.1 Appendix: Schedule of Events – footnote ‘f” 
[Footnote ‘f’ was revised to include “not required” as a reason for telephone contact by 
follow-up.]  
All efforts will be made to have subjects return to the clinic for a Follow-up Visit. Telephone 
contact is permissible for subjects unable, or unwilling or not required to return to the 
clinic. 
Section 7.8 Appendix Definitions of Symptom Intensity [added] 
Symptom 
Absent (0) 
Mild (1) 
Moderate (2) 
Severe (3) 
Cough 
Absence of 
cough (or to pre-
CABP baseline) 
Transient, does 
not interfere 
with normal 
activity 
Frequent, 
interferes with 
normal activity 
or sleep 
Constant, 
interferes with 
most or all 
activities or 
sleep 
Dyspnea/Shortness
of Breath 
Absence of 
dyspnea (or to 
pre-CABP 
baseline) 
Dyspnea on 
exertion (e.g. 
climbing stairs) 
Dyspnea with 
normal/routine 
activities (e.g. 
walking) 
Dyspnea at rest 
or requiring 
oxygen therapy  
Chest Pain due to 
Pneumonia 
Absence of chest 
pain related to 
CABP  
Transient, does 
not interfere 
with normal 
activity 
Frequent, 
interferes with 
normal activity 
or sleep 
Constant, 
interferes with 
most or all 
activities or 
sleep 
Sputum 
Production 
Absence of 
sputum 
production (or 
to pre-CABP 
baseline) 
Sputum 
production 
rarely causes 
difficulty or 
distress 
Sputum 
production often 
causes difficulty 
or distress 
Constant 
difficulty with 
sputum 
production  
 


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7.11 Appendix: Protocol Amendment 3 
Amendment 3 is a global amendment which applies to all study sites, and all changes made 
in global Amendments 1 and 2, and in Administrative Change Numbers 1, 2, and 3 are 
incorporated into this amendment. The following sections detail the changes made in 
Amendment 3 of the protocol, dated 04 December 2017.  
7.11.1 
Overview of Changes 
• Administrative Change Number 1: to clarify that the procedures of chest radiography and 
clinical laboratory collection are to be performed prior to the first dose of study drug. 
• Administrative Change Number 2: to clarify that all screening procedures are to be 
performed in the 24 hour period prior to the first dose of study drug (unless otherwise 
noted). 
• Administrative Change Number 3:  
o To add serology testing for Chlamydia at Day 1, TOC, and Follow-up 
o In the PSI/PORT scoring appendix, to correct a minor discrepancy in Temperature, 
add a converted value from BUN to urea, and add the Risk Class to the scoring table. 
o To add a converted value from urea to BUN in the CURB-65 scoring appendix. 
• Primary and secondary objectives and endpoints, sample size calculations, populations 
and analyses were clarified for EMA submissions. 
• Clarifications were added to Inclusion 4 and Exclusions 4, 5, and 12. 
• Timing of vital signs was updated at all visits after first dose to clarify that they may be 
performed at any time, but should be consistent each day. 
• The window for the Day 7 (oral treatment) visit was updated from ± 1 day to + 1 Day so 
it would not coincide with the Day 5 (oral treatment) visit. 
• Procedures at the EOT and TOC visits were updated to clarify that a CXR or CT scan is 
also required to be done only for lack of efficacy. 
• General references to “sputum specimens” were changed to “respiratory specimens” 
throughout the protocol to clarify that other types of samples are accepted. 
• PK sections were updated to specify endpoints and analyses to be performed. 
• The Post-Treatment Medications section was updated to clarify which data should be 
recorded in the eCRF. 


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• The Adverse Events section was updated to clarify the required time period to record data 
in the CRF and to note that progression of disease under study is not recorded as an AE. 
• All references to ICH guideline E6(R1): Good Clinical Practice were updated to (R2) to 
align with global regulatory requirements. 
• Abbreviations were added or exchanged for text throughout the protocol as per the List of 
Abbreviations. These are not detailed in Section 7.11.2. 
• In-text citations and Section 6 References were updated to align with APA style. These 
are only detailed in Section 7.11.2 if a new or revised reference was added. 
• Minor grammatical and formatting changes were made throughout the text. These are 
only detailed in Section 7.11.2 if they altered the content of the protocol. 
7.11.2 
Changes to the Protocol Text 
In this section, all affected protocol sections are detailed; the sequence of the sections follows 
the structure of the protocol. Additions to the protocol text are shown in bold and deletions 
are shown in strikethrough text. Minor editorial and grammatical corrections are not 
specified. Any notes for the section are included in brackets [ ]. 
Title Page – CONFIDENTIAL, Sections 4.2 - Ethics Committee/Institutional Review, 4.3 - 
Subject Consent, 4.6 - Investigator Documentation, 4.7 - Study Conduct, 4.9 - Adherence 
to Protocol, 5.2.1 - Monitoring of the Study, 5.3.2 - Protocol Deviations 
[All references to the International Conference on Harmonisation (ICH) harmonised tripartite 
guideline E6(R1): Good Clinical Practice in the above listed sections were updated]  
E6(R12) 
Title Page – Sponsor Contact 
Jerri SwerdlowLaura Lawrence 
Director of Clinical Operations 
Telephone: 312-724-94020 
Email: clinicaltrials@melinta.com 
Title Page – Medical Monitor 
Telephone: 312-724-94010 
Title Page – Version of Protocol 
Amendment 23 


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Title Page – Date of Protocol 
294 MarchDecember 20162017 
Title Page – Previous Date and Version [text added] 
29 March 2016, Amendment 2 
Title Page – CONFIDENTIAL 
… 
The study will be conducted according to the International Conference on Harmonisation 
harmonised tripartite guideline E6(R2): Good Clinical Practice, FDA and EU clinical trial 
guidelines. (Sites in regions which have not yet implemented the E6(R2) addendum are 
subjecting themselves to it voluntarily.) 
Protocol Approval 
Protocol Date: 294 MarchDecember 20162017 
Protocol accepted and approved by: 
Sue Cammarata, MD 
Chief Medical Officer 
Melinta Therapeutics, Inc. 
300 George StreetTriState International, Suite 301272 
New Haven, CTLincolnshire, IL 0651160069, USA 


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Protocol Synopsis – Objectives 
FOR FDA 
Primary Objective: 
• To assess the noninferiority of clinical efficacy of intravenous (IV) to oral delafloxacin in 
adult subjects with community-acquired bacterial pneumonia (CABP) based on Early 
Clinical Response (ECR) defined as improvement at 96 hours (± 24 hours) after the first 
dose of study drug compared to IV to oral moxifloxacin in the Intent-to-Treat (ITT) 
population. 
… 
Secondary Objective(s): 
… 
• To assess the noninferiority of clinical efficacy of IV to oral delafloxacin in adult subjects 
with CABP based on ECR compared to IV to oral moxifloxacin in the microbiologic ITT 
(MITT) population. 
… 
FOR EMA 
Primary Objective: 
• To assess the clinical efficacy of IV to oral delafloxacin in adult subjects with CABP 
at 5 to 10 days after the last dose of study drug (TOC) compared to IV to oral 
comparator study drug arm in the Modified ITT (ModITT) and Modified CE 
(ModCE) populations.  
Secondary Objective(s): 
• To assess the clinical efficacy of IV to oral delafloxacin in adult subjects with CABP 
based on ECR defined as improvement at 96 hours (± 24 hours) after the first dose 
of study drug compared to IV to oral moxifloxacin in the ModITT and ModCE 
populations. 
• To assess the clinical efficacy of IV to oral delafloxacin in adult subjects with CABP 
at the TOC visit compared to IV to oral moxifloxacin in the Modified MITT 
(ModMITT) and Modified ME (ModME) populations. 
• To assess the microbiologic response to delafloxacin in respiratory pathogens in the 
ModMITT and ModME populations. 
• To assess the safety and tolerability of IV to oral delafloxacin in adult subjects with 
CABP in safety population. 
• To assess the all-cause mortality in adult subjects with CABP on Day 28 in ModITT. 
• To assess delafloxacin PK in adult subjects with CABP in PK population. 


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Protocol Synopsis – Inclusion Criteria 
4. PORT Risk Class of II, III, IV, or V (PSI Score greater than 50) (Fine 1997) 
(Appendix 7.2). Subjects may be initially pre-screened based on meeting CURB-65 
Score (Appendix 7.3) of 2 to 4. PORT Risk Class II will be limited to no more than 25% 
of randomized subjects. 
Protocol Synopsis - Exclusion Criteria 
4. Receipt of systemic antibiotic therapy in the 7 days before enrollment unless one or more 
of the following isare documented: 
… 
5. Respiratory infection confirmed or suspected to be secondary to hospital-acquired or 
ventilator-associated pneumonia or that requires treatment in an intensive care setting 
(because they are hemodynamically unstable, and/or likely to need mechanical 
ventilation) at the time of informed consent. 
12. Uncorrected hypokalemia, or known uncorrected hypomagnesemia, at the time of 
enrollment. If treatment normalizes the serum potassium or magnesium, confirmed 
by retest during the screening period, the patient may then be enrolled. 
Protocol Synopsis - Study Design 
… 
Subjects will be evaluated for baseline characteristics that include chest radiography within 
48 hours of before the first dose of study drug, and medical history, physical examination, 
and clinical laboratory evaluation, and blood cultures within 24 hours of before the first dose 
of study drug. Subjects may be initially pre-screened based on meeting CURB-65 score of 2 
to 4, but will be eligible for enrollment only if classified as PORT Risk Class II, III, IV, or V. 
A pretreatment respiratory specimen will be collected for Gram stain and culture and 
susceptibility testing, if positive. 
… 
Randomization will be stratified by PORT Class, medical history of chronic obstructive 
pulmonary disease (COPD)/asthma, and prior single-dose/regimen systemic antimicrobial 
use. Enrollment will be limited to no more than 25% PORT Class II and no more than 25% of 
subjects with prior antibacterial usewho received 1 dose of a single, potentially effective, 
short-acting antimicrobial drug or drug regimen for treatment of the CABP under 
study within 24 hours of enrollment. 
… 
The investigator may elect to switch subjects from moxifloxacin/moxifloxacin placebo to 


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linezolid (600 mg IV BID)/linezolid placebo if methicillin-resistant Staphylococcus aureus 
(MRSA) is confirmed (up to 10 days total moxifloxacin and linezolid duration of therapy). 
… 
Key visits will be ECR at (96 hours (± 24 hours) after the start of the first dose of study 
drug, at End of Treatment (EOT), and at TOC, 5-10 days after last dose. A Follow-up (FU) 
Visit or phone contact will also be conducted at Day 28to collect patient reported outcomes, 
capture serious adverse events, obtain a blood sample for convalescent serology and urine or 
serum pregnancy testing, if applicable. 
Protocol Synopsis - Pharmacokinetic Assessments 
Serial blood samples for PK analysis will be obtained at select investigative sites on Day 3 (± 
1 day) of treatment within the 30 minutes before the first study drug administration of the 
day and at 1.5 and 3 hours after the start of the infusion. All time points will have a ± 10 
minute window. Subjects should have received a minimum of 3 consecutive doses of study 
drug prior to the start of PK blood collection. Subjects do not need to be fasted before dosing 
or during PK sample collections. 
Protocol Synopsis - Sample Size 
FOR FDA PRIMARY ENDPOINT: At least 860 adult male and female subjects (430 
subjects per treatment group) will be randomized. 
… 
FOR EMA PRIMARY ENDPOINT: At least 860 adult male and female subjects 
(430 subjects per treatment group) will be randomized. Used on a normal 
approximation approach (Miettinen and Nurminen’s Likelihood Score Test), and 
assuming approximately 12% of patients will be in PORT Class II, and 80% of patients 
will be clinically evaluable, 755 subjects in the ModITT population and 604 subjects in 
the ModCE population will provide, respectively, a power of 91% and 83% to assess 
noninferiority of delafloxacin vs. moxifloxacin based on the following assumptions: (1) a 
rate of Clinical Outcome at the TOC visit for moxifloxacin and delafloxacin of 88% and 
86%, respectively; (2) 1-sided type I error (α) of 0.025; (3) a noninferiority margin of 
10%. 


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Protocol Synopsis - Efficacy Endpoints 
FOR FDA 
… 
Primary Efficacy Endpoint: The primary efficacy endpoint is the ECR defined as 
improvement at 96 hours (± 24 hours) after first dose of study drug in at least 2 of the 
following symptoms: chest pain, frequency or severity of cough, amount and quality of 
productive sputum, and difficulty breathing, and no worsening ofin any of the other 
symptoms in the ITT population. 
… 
FOR EMA 
All the primary and secondary endpoints will be analyzed for noninferiority with the 
possibility to switch to superiority.  
Primary Efficacy Endpoint: The Clinical Outcome responder rate at 5 to 10 days after 
the last dose of study drug (TOC) defined as resolution or near resolution of the 
symptoms of CABP present at study entry, and no use of additional antimicrobial 
therapy for the current infection, and no new symptoms associated with the current 
CABP infection (success) in the ModITT and ModCE populations. 
Secondary Efficacy Endpoint(s): 
• ECR defined as improvement at 96 hours (± 24 hours) after first dose of study drug 
in at least 2 of the following symptoms: chest pain, frequency or severity of cough, 
amount and quality of productive sputum and difficulty breathing and no worsening 
of any of the other symptoms in the ModITT and ModCE populations 
• ECR with the addition of improvement in vital signs and no worsening of the 4 
symptoms required as Response in the ModITT and ModCE populations 
• Clinical Outcome at EOT (ModITT and ModCE) 
• Clinical Outcome at TOC in the ModMITT and ModME populations 
• Microbiologic response (ModMITT and ModME) 
• All-cause mortality (ModITT) 
Protocol Synopsis - Pharmacokinetic Endpoints 
Pharmacokinetic results will be reported in a separate PK report. The time course of 
delafloxacin plasma concentrations will be assessed. 


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Protocol Synopsis - Analysis Populations 
… 
Modified ITT (ModITT): All randomized subjects who received at least one dose of 
study medication, classified as PORT Class III-V, analyzed according to the treatment 
arm to which they were randomized. 
Microbiological ITT (MITT): All subjects in the ITT population who had a baseline 
bacterial pathogen identified on culture of sputuma respiratory specimen or blood 
specimen, or a nonculture method of detection of bacterial pathogens (i.e., urinary antigen 
test, PCR, and serologic testing) identified that is known to cause CABP against which the 
study drug has antibacterial activity.  
Modified MITT (ModMITT): All subjects in the MITT population classified as PORT 
Class III-V. 
Clinically Evaluable (CE): All subjects in the ITT population who met the following criteria: 
… 
• Received 80% of the expected doses of study drug in the treatment period (e.g., for 
subjects receiving delafloxacin, at least 11 doses of delafloxacin for a 7-day treatment 
period). 
… 
Modified CE (ModCE): All subjects in the CE population classified as PORT 
Class III-V. 
… 
Modified ME (ModME): All subjects in the ME population classified as PORT 
Class III-V. 
Pharmacokinetic (PK): All subjects who receive at least 3 consecutive IV doses of study drug 
prior to the start of the blood sample collections on Day 3 (± 1 Day), and have sufficient 
plasma concentration data to facilitate calculation of PK parametersat least one delafloxacin 
plasma concentration data available. The PK population will be used for PK analyses. 
Protocol Synopsis - Criteria for Evaluation - Definitions 
For Early Clinical Response: 
Responders: Improvement at 96 hours (± 24 hours) after first dose of study drug in at least 2 
of the following symptoms: pleuritic chest pain, frequency or severity of cough, amount and 
quality of productive sputum, and dyspnea (difficulty breathing), and no worsening inof the 
other symptoms.  


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Non-responders: Improvement is not achieved at 96 hours (± 24 hours) after first dose of 
study drug in at least 2 of the following symptoms: (pleuritic chest pain, frequency or 
severity of cough, amount and quality of productive sputum, and dyspnea (difficulty 
breathing); or there is use of additional non-study antimicrobial therapy for treatment of the 
current CABP infection due to lack of efficacy; or the subject diesd from the current CABP 
infection. Indeterminate/missing assessments will be mapped to Non-responders in the 
statistical analysis of the ITT population.  
Symptoms for the Early Clinical Response will be evaluated on a 4-point scale (absent, mild, 
moderate, severe) with improvement defined as at least a 1-point improvement (decrease) 
from baseline to the assessment at 96 hours (±24 hours) after the first dose of study drug 
(e.g., from severe to moderate, from moderate to absentmild, or from mild to absent).  
For Clinical Outcome at EOT and TOC: 
Success: Resolution or near resolution of the symptoms of CABP present at study entry, and 
no use of additional antimicrobial therapy for the current infection, and no new symptoms 
associated with the current CABP infection. 
Failure: Symptoms of CABP present at study entry have not resolved, or new symptoms of 
CABP have developed, or the subject diesd from pneumonia, or use of additional non-study 
antimicrobial therapy for treatment of the current CABP infection due to lack of efficacy. 
Subjects must receive at least 4 doses of study drug by the end of Day 3 to be called a 
Failure. 
Indeterminate/Missing: A response cannot be determined because an efficacy assessment was 
not completed at the visit, or subject did not complete the planned course of study therapy for 
reasons other than lack of efficacy. Indeterminate/missing responses will be considered 
failures for purposes of the primary ITT/ModITT analysies and will be excluded from the 
CE and ME populations. 
For Microbiologic Response 
Eradication: The sputumrespiratory and/or blood specimen at the TOC Visit shows all 
causative pathogen(s) at enrollment eradicated and no use of additional antimicrobial therapy 
for the current infection. 
Presumed Eradication: No sputumrespiratory and/or blood samplespecimen was available 
at TOC with a clinical assessment of Success.  
Persistence: The sputumrespiratory and/or blood culture collectedspecimen at the TOC visit 
shows appearance of all causative pathogen(s) present at enrollment. 


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Presumed Persistence: No sputumrespiratory and/or blood samplespecimen was available 
for a case classified as clinical failure.  
Superinfection: A culture taken during treatment shows appearance of a new pathogen 
causing respiratory infection associated with clinical failure. 
Colonization/Contamination: A culture taken post-baseline through the TOC visit 
shows appearance of a new pathogen(s), with a clinical assessment of Success and no 
use of additional antimicrobial therapy for the current infection. 
Protocol Synopsis - Microbiologic Measures 
The following pathogens are examples of primary pathogens that will be used to determine 
the microbiological responses in the study: the typical bacterial pathogens include but may 
not be limited to Streptococcus pneumoniae, Haemophilus influenzae, S. aureus, Klebsiella 
pneumoniae, and Moraxella catarrhalis, and the atypical bacterial pathogens Chlamydophila 
pneumoniae, Mycoplasma pneumoniae, and Legionella pneumophila. The causative 
pathogen will be identified by isolation from a baseline culture specimen (either a 
sputumrespiratory specimen or blood), by urinary antigen, and/orby serology, and/or by 
PCR. 
List of Abbreviations 
CLSI 
Clinical Laboratory Standards Institute 
CV 
Coefficient of variation 
EUCAST 
European Committee on Antimicrobial Susceptibility Testing 
ModCE 
Modified clinically evaluable 
ModITT 
Modified intent-to-treat 
ModME 
Modified microbiologically evaluable 
ModMITT 
Modified microbiological intent-to-treat 
QSSP 
Quinolone-susceptible S.treptococcus pneumoniae 
SD 
Standard deviation 
Section 1.1.2 - In Vitro Studies - Comparative Antibacterial Activity 
In a recent survey of 2014 US and European isolates, delafloxacin’s MIC50 and MIC90 were 
0.008 µg/mL and 0.015 µg/mL, respectively for S.treptococcus pneumoniae. 
… 


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Section 1.1.3 - In Vivo Studies 
… 
Against S. pneumoniae 5649, a multidrug-resistant strain, delafloxacin demonstrated a dose 
required to protect 50% (PDED50) of < 5.0 mg/kg/day, whereas levofloxacin and 
trovafloxacin resulted in PDED50s of 12.9 and 10.2 mg/kg/day, respectively. Against 
H. influenzae, all compounds were highly efficacious in this rat lung-infection model, with 
delafloxacin, levofloxacin, and trovafloxacin demonstrating PDED50s of 2.1, 6.9, and 
5.9 mg/kg/day, respectively.  
Section 1.2.2 - Phase 2 Study for Community-Acquired Pneumonia: Study M01-344 
… 
The primary endpoint of this trial was the investigators’ assessment of clinical response rate 
at the TOC time point in the Clinically Evaluable (CE) group. 
… 
Table 1-1 
Proportion of Patients Achieving Endpoints in (Study M01-344) 
Table 1-2 
Target Pathogen Eradication Rates at the TOC Visit (Study M01-344) 
Section 1.2.3 - Treatment of Acute Bacterial Skin and Skin Structure Infections: 
Study RX-3341-302 
Table 1-3 
Proportion of Patients Achieving Endpoints in (Study RX-3341-302) 
Section 1.3 - Dose Selection of Delafloxacin for This Study 
• Delafloxacin has shown evidence of efficacy in a completed phase 2 community-acquired 
pneumonia (CAP) trial (M01-344 [Abbott 2003]). In addition, a phase 2 trial in acute 
bacterial exacerbation of chronic bronchitis (M01-298 [Abbott 2003]) and 2 phase 2 
ABSSSI trials (studies RX-3341-201 [Rib-X 2009] and RX-3341-202 [Rib-X 2014]) 
provide evidence of efficacy of delafloxacin in these indications. 
• Delafloxacin has shown evidence of efficacy in a completed Phase 3 ABSSSI trial 
(RX-3341-302 [Melinta 2015]) using the intended 300 mg IV BID dose. 
• Delafloxacin has been well tolerated at the 300 mg IV BID dose used in 2 phase 2 
ABSSSI trials (studies RX-3341-201 [Rib-X 2009] and RX-3341-202 [Rib-X 2014]) and 
1 Phase 3 ABSSSI trial (study RX-3341-302). 


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Section 2.1 - Primary Objective [table format added] 
The primary objective is: 
FDA 
EMA 
To assess the noninferiority of clinical 
efficacy of IV to oral delafloxacin in adult 
subjects with CABP based on Early Clinical 
Response (ECR) defined as improvement at 
96 hours (± 24 hours) after the first dose of 
study drug compared to IV to oral 
moxifloxacin in the ITT population. 
To assess the clinical efficacy of IV to oral 
delafloxacin in adult subjects with CABP 
at 5 to 10 days after the last dose of study 
drug (TOC) compared to IV to oral 
comparator study drug arm in the 
Modified ITT (ModITT) and Modified CE 
(ModCE) populations. 
 
Section 2.2 - Secondary Objective(s) [table format added] 
The secondary objectives are: 
FDA 
EMA 
To assess the clinical efficacy of IV to oral 
delafloxacin in adult subjects with CABP 
based on clinical outcome at the TOC visit, 5 
to 10 days after the last dose of study drug 
compared to IV to oral comparator study 
drug arm in the CE and ITT populations. 
To assess the clinical efficacy of IV to oral 
delafloxacin in adult subjects with CABP 
based on ECR defined as improvement at 
96 hours (± 24 hours) after the first dose of 
study drug compared to IV to oral 
moxifloxacin in the ModITT and ModCE 
populations. 
To assess the noninferiority of clinical 
efficacy of IV to oral delafloxacin in adult 
subjects with CABP based on ECR compared 
to IV to oral moxifloxacin in the 
Microbiological ITT (MITT) population 
To assess the clinical efficacy of IV to oral 
delafloxacin in adult subjects with CABP 
at the TOC visit compared to IV to oral 
moxifloxacin in the Modified MITT 
(ModMITT) and Modified ME (ModME) 
populations. 
To assess the microbiologic response to 
delafloxacin in respiratory pathogens. 
To assess the microbiologic response to 
delafloxacin in respiratory pathogens in 
the ModMITT and ModME populations. 


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FDA 
EMA 
To assess the safety and tolerability of IV to 
oral delafloxacin in adult subjects with 
CABP  
To assess the safety and tolerability of IV 
to oral delafloxacin in adult subjects with 
CABP in safety population. 
To assess the all-cause mortality in adult 
subjects with CABP on Day 28 
To assess the all-cause mortality in adult 
subjects with CABP on Day 28 in ModITT 
population. 
To assess delafloxacin PK in adult subjects 
with CABP 
To assess delafloxacin PK in adult subjects 
with CABP in PK population. 
Section 3.1 - Study Design 
This is a Phase 3, randomized, double-blind, comparator-controlled, multicenter, global 
study. Subjects who consent to the study will have screening procedures performed. Subjects 
will be evaluated for baseline characteristics that include chest radiography within 48 hours 
of before the first dose of study drug, and medical history, physical examination, clinical 
laboratory evaluation, and blood cultures within 24 hours of before the first dose of study 
drug. Subjects may be initially pre-screened based on meeting CURB-65 score of 2 to 4, but 
will be eligible for enrollment only if classified as Pneumonia Patient Outcomes Research 
Team (PORT) Risk Class II, III, IV or V. A pretreatment sputumrespiratory specimen will be 
collected for Gram stain and culture, and susceptibility testing, if positive.  
… 
Subjects who meet the entry criteria will be randomly assigned in a 1:1 ratio to receive 
delafloxacin or moxifloxacin. Randomization will be stratified by PORT Class, medical 
history of COPD/asthma, and prior single-dose/regimen systemic antimicrobial use. 
Enrollment will be limited to no more than 25% PORT Class II and no more than 25% of 
subjects with prior antibacterial usewho received 1 dose of a single, potentially effective, 
short-acting antimicrobial drug or drug regimen for treatment of the CABP under 
study within 24 hours of enrollment.  
… 
The investigator may elect to switch subjects from moxifloxacin/moxifloxacin placebo to 
linezolid (600 mg IV BID)/ linezolid placebo if MRSA is confirmed (up to 10 days total 
moxifloxacin and linezolid duration of therapy). 
Section 3.2.1 - Inclusion Criteria 
2. Evidence of acute onset of CABP. 
… 


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• Tachypnea (elevated respiratory rate > 18 breaths per minute) 
4. PORT Risk Class of II, III, IV, or V (PSI Score greater than 50) (Fine 1997) 
(Appendix 7.2). Subjects may be initially pre-screened based on meeting CURB-65 
Score (Appendix 7.3) of 2 to 4. PORT Risk Class II will be limited to no more than 25% 
of randomized subjects. 
Section 3.2.2 - Exclusion Criteria 
4. Receipt of systemic antibiotic therapy in the 7 days before enrollment unless one or more 
of the following isare documented: 
… 
5. Respiratory infection confirmed or suspected to be secondary to hospital-acquired or 
ventilator-associated pneumonia or that requires treatment in an intensive care setting 
(because they are hemodynamically unstable, and/or likely to need mechanical 
ventilation) at the time of informed consent. 
12. Uncorrected hypokalemia, or known uncorrected hypomagnesemia, at the time of 
enrollment. If treatment normalizes the serum potassium or magnesium, confirmed 
by retest during the screening period, the patient may then be enrolled. 
Section 3.3.2 - Handling of Withdrawals 
Subjects who discontinue study drug and receive a non-study antibiotic for CABP will have 
EOT visit procedures performed with clinical assessment, but will not return for further 
on-site visits. Additional specimens for microbiological cultures and chest radiographCXR 
should be collected before initiation of any rescue therapy and/or if the subject is a clinical 
failure, if possible. These subjects should be contacted by phone for the FU visit. 
Subjects who discontinue study drug and do not receive additional non-study antibiotic for 
CABP will have EOT visit procedures performed and should return to the site for the TOC 
and FU visits. Every attempt will be made to collect all-cause mortality data on Day 28 for 
all subjects who receive at least 1 dose of study drug. [sentence moved below] 
Should a subject’s study participation be discontinued after receiving study drug, efforts must 
be made to perform all required EOT procedures with corresponding data recorded in the 
electronic case report form (eCRF). Subjects who prematurely discontinue study 
treatment should be encouraged to return to the study site for these safety evaluations. 
Subjects who withdraw consent will not be contacted after withdrawal. [sentence moved 
below] 


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Every attempt will be made to contact all subjects who received at least 1 dose of study 
drug to collect all-cause mortality data on Day 28 (FU visit). Subjects who withdraw 
consent will not be contacted after withdrawal. 
… 
Section 3.4.1.1 - Screening 
Screening procedures will occur within the 24 hours of prior to the first dose of study 
drug. 
… 
• Obtain posteroanterior (PA) and lateral chest radiograph (CXR). A CT scan of the thorax 
is an acceptable alternative, if available per local standard of care. The CXR or CT scan 
obtained per local standard of care will not be repeated if obtained within 48 hours of 
before the first dose of study drug. 
… 
• Obtain blood samples for hematology, serum chemistry, and coagulation profile and 
urine sample for urinalysis. The results of any of these tests obtained within 24 hours 
ofbefore enrollment may be used for screening purposes and to verify entry criteria by 
the local laboratory; however, blood and urine samples must be obtained at Screening 
(prior to the first dose of study drug) and sent to the central laboratory for analysis to 
serve as baseline values. 
Section 3.4.1.2 - Day 1 
Treatment may begin immediately after enrolling the subject via the IXRS. Subjects must 
begin study drug within 24 hours after the start of Screening procedures. If the first dose is 
administered the same day as Screening, then assessments that are required on Day 1, but 
already completed for Screening, will not be repeated unless otherwise specified below 
(assessments should be recorded in the Screening eCRF and NOT duplicated in the Day 1 
eCRF). If not already performed on that day as part of the Screening visit, the following 
procedures will be performed on Day 1 prior to dosing: 
… 
• Record vital signs, body temperature, and pulse oximetry ataround the time of the first 
daily dose. 
• Collect deep cough sputum specimen for Gram stain and culture prior to dosing if not 
collected or determined to be not acceptable at Screening (if possible). Additionally, 
other respiratory sources are acceptable if available (refer to Section 3.4.3.2.1). 
… 


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• Obtain blood samples for procalcitonin and Chlamydia pneumoniae, M.ycoplasma 
pneumoniae and L. pneumophila serology.  
• Obtain nasopharyngeal and oropharyngeal swabs prior to dosing. 
… 
• Administer second dose of study drug after 12 hours (± 2 hours). If the first dose is 
started late on Day 1in the day because of screening and eligibility verifications, a 1-time 
adjustment is allowed for a more customary dosing schedule that is within ± 4 hours of 
the normally scheduled second dose. The every-12-hour (± 2 hours) dosing schedule is 
set after the first dose (or dose adjustment).  
Section 3.4.1.3 - Daily While on IV Therapy 
The following procedures will be performed daily only while on IV therapy: 
… 
• Record vital signs, body temperature, and pulse oximetry at a consistent time of first 
daily dose each day. 
… 
• For sites participating in PK assessments, blood samples for PK analysis will be obtained 
on Day 3 (± 1 day) of treatment within the 30 minutes before the first study drug 
administration, and at 1.5 and 3 hours after the start of the infusion. All time points have 
a ± 10-minute window. Subjects should have received a minimum of 3 consecutive doses 
of study drug prior to the start of PK blood sample collections. Subjects do not need to be 
fasted before dosing or during PK sample collections. Refer to Section 3.4.3.6 
Pharmacokinetic Blood Sample Collections for details.  
Section 3.4.1.4 - Early Clinical Response at 96 Hours (± 24 hours) 
• Subjects who continue oral treatment as an outpatient will be 
dispensed/administered study drug and instructed to return to the clinic on Day 5 (if 
applicable) with their study drug container(s). [bullet 9 added] 
Section 3.4.1.5 - Day 5 (+ 1 Day) 
The assessments that are required on Day 5, but already completed as specified in 
Section 3.4.1.3 or 3.4.1.4 do not need to be repeated. Assessment should be recorded in the 
Day 5 eCRF and NOT duplicated in the Daily IV eCRF. If not already performed on that day, 
the following procedures will be performed: 
… 


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• Administer study drug every 12 hours (± 2 hours) to total 10 delafloxacin/delafloxacin 
placebo doses. 
• Perform study drug accountability on returned oral drug (outpatient subjects). 
… 
Section 3.4.1.6 - Day 7 (+ 1 Day) 
[Section heading updated to change the visit window from ± 1 Day to + 1 Day.] 
The assessments that are required on Day 7 but already completed as specified in 
Section 3.4.1.3 do not need to be repeated. If not already performed on that day, the 
following procedures will be performed:  
• Perform study drug accountability on returned oral drug (outpatient subjects). 
… 
• Study drug may be stopped at the discretion of the investigator on Day 7. Subjects may 
be evaluated and study drug may be administered/dispensed as described above 
until the subject completes the investigator’s planned course of therapy, up to a 
maximum 10 days of treatment (20 doses delafloxacin/delafloxacin placebo). Criteria 
for determination of appropriate treatment duration isare described in Section 3.4.1.8.1. 
EOT procedures are detailed in Section 3.4.1.8.2. 
… 
• Subjects who continue on treatment will be dispensed/administered sufficient quantity of 
study drug to complete treatment and will be instructed to return to the clinic (outpatient 
patientssubjects) onfor the planned EOT dayvisit (Day 8, 9, and/or 10) with their study 
drug container(s).  
• Subjects may be evaluated and study drug may be administered/dispensed as described 
above until the subject completes 10 days of treatment (20 doses 
delafloxacin/delafloxacin placebo). [moved to bullet above] 
Section 3.4.1.7 - End of IV Treatment 
… 
Register the IV to oral switch in the IXRS. For subjects completing treatment as an 
outpatient, dispense oral study drug. Outpatient subjects will be instructed to return to the 
clinic on Day 5 (+ 1 day), Day 7 (+ 1 day) as applicable, and at EOT with their study drug 
container(s). Refer to Section 3.6.6. 


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Section 3.4.1.8.2 - End of Treatment or Early Termination Procedures 
Subjects who prematurely discontinue study drug or are completing treatment will have EOT 
procedures performed that same day or up to 24 hours (+4 hours) after the last dose of study 
drug. Assessments already completed on the same day as the last dose of study drug is 
administered can serve as EOT procedures, and do not need to be repeated.  
… 
• ONLY FOR LACK OF EFFICACY, obtain collect repeat deep cough sputum 
specimen for Gram stain and culture, if possible. Additionally, other respiratory 
sources are acceptable if available (refer to Section 3.4.3.2.1). 
• ONLY FOR LACK OF EFFICACY, and obtain a repeat CXR. 
Section 3.4.1.10 - Test of Cure (TOC Visit, 5–10 Days After Last Dose of Study Drug) 
… 
• Collect deep cough sputum specimen for culture, if possible. Additionally, other 
respiratory sources are acceptable if available (refer to Section 3.4.3.2.1). 
• ONLY FOR LACK OF EFFICACY, obtain a repeat CXR. 
… 
• Obtain blood samples for C. pneumoniae, M. pneumoniae and L. pneumophila serology 
and procalcitonin. 
Section 3.4.1.11 - Follow-up Visit (FU, Day 28 ± 2 Days) 
… 
• Obtain blood sample for C. pneumoniae, M. pneumoniae and L. pneumophila serology 
(for subjects who return to the clinic). 
… 
• Record post-treatment medications in the subject’s source, particularly any antibiotics 
taken after EOT (only post-treatment medications associated with and SAE will be 
collected in the eCRF). 
Section 3.4.2.1 - Clinical Evaluation 
… 
Symptom severity will be evaluated by the investigator on a 4-point scale (absent, mild, 
moderate, severe, see Section 7.8 for definitions) with improvement defined as at least a 
1-point improvement (decrease) from baseline to the assessment at 96 hours (± 24 hours) 


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after first dose of study drug (e.g., from severe to moderate, from moderate to mild, or from 
mild to absent). See Appendix 7.8 below for definitions of symptom intensity. 
Section 3.4.3.1 - Chest Radiography 
A chest radiograph (chest x-ray; posteroanterior and lateral preferred; single view acceptable 
if conclusive) must be obtained prior to randomization with initial interpretation and 
included in the source documents. Computed tomography of the thorax may be used as an 
alternative, if available as per local standard of care. The presence of lobar, multilobar, or 
patchy parenchymal infiltrate(s) consistent with acute bacterial pneumonia on a pulmonary 
imaging study is required for study entry. Chest radiography should be performed before the 
first dose of study drugrandomization and repeated at the end of treatmentEOT or TOC 
only for lack of efficacy. Chest radiography obtained per local standard of care will not be 
repeated if obtained within 48 hours before the first dose of study drug. Findings will be 
recordinged in the eCRF. Radiologic films must have a formal interpretation available in the 
source documents. Source, i.e., radiologist report and imaging, will be maintained by the site. 
3.4.3.2 - Microbiological Assessments 
The following pathogens are examples of primary pathogens that will be used to determine 
the microbiological responses in the study: the typical bacterial pathogens include but may 
not be limited to S. pneumoniae, H. influenzae, S. aureus, K.lebsiella pneumoniae, and 
Moraxella catarrhalis, and the atypical bacterial pathogens C. pneumoniae, M. pneumoniae, 
and L. pneumophila. The causative pathogen will be identified by isolation from a baseline 
culture specimen (either a sputum respiratory specimen or blood), by urinary antigen, 
and/orby serology, and/or by PCR.  
Residual sputum respiratory samples, and/or nasopharyngeal swabs, and oropharyngeal 
swabs maywill be sent to specialty laboratories for possible culture, and/or PCR, serotyping, 
and/or susceptibility testing (S. pneumoniae, L. pneumophila, M. pneumoniae).  
… 
Pathogens will be specifically identified to the genus and species levels. In vitro 
susceptibility of target pathogens to delafloxacin and moxifloxacin will be determined at the 
central laboratory according to Clinical Laboratory Standards Institute (CLSI) and 
European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines for 
broth and agar dilution and disk diffusion. Susceptibility to additional antibiotics may will 
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Section 3.4.3.2.1 - Respiratory Culture 
The collection of an adequate sputum samples for Gram stain, culture, and susceptibility 
testing, as applicable, will be attempted in all subjects at baseline and. Other sources of 
respiratory specimens such as those obtained from bronchoalveolar lavage (BAL), 
protected specimen brush (PSB), transtracheal aspirate, and pleural fluid, if available, 
are acceptable to submit for culture. All respiratory specimens will be sent to the 
local/regional laboratoriesy for gram stain, culture and susceptibility testing, as 
applicable. 
All sputum and transtracheal aspirate samples will be evaluated to determine quality. A 
Gram stain will be performed immediately after the sample is delivered to the microbiology 
laboratory. A microscopic examination of the slide will be performed. A “good” sputum 
sample is one with polymorphonuclear leukocytes but few (or no) squamous epithelial cells 
on Gram stain. All efforts will be made to obtain a sputum or transtracheal aspirate 
specimen that yields an acceptable Gram-stain, defined as < 10 squamous epithelial cells 
and/or > 25 polymorphonuclear cells per low-power field. 
All respiratory specimens will be sent for culture and susceptibility testing. Other sources of 
respiratory specimens such as those obtained from bronchoalveolar lavage (BAL), protected 
specimen brush (PSB), transtracheal aspirate, and pleural fluid, if available, are acceptable to 
submit for culture.[sentence moved up] In addition, any residual respiratory sample will be 
frozen and may be sent to a specialty labthe central laboratory for culture, L. pneumophila 
identification, antibiotic sensitivity susceptibility testing, and/or serotyping at a specialty 
microbiology laboratory. The respiratory culture, if positive, will be used to identify and 
freeze isolates for subcultures submission to the central microbiology laboratory and to 
freeze for back-up storage. 
Collection of a repeat respiratory specimen for culture should be attempted at EOT only for 
lack of efficacy, prior to any rescue therapy, and at TOC if possible, or if clinically indicated.  
… 
NOTE: References to sputum culture in the protocol are intended apply to culture from 
respiratory specimens as well. 
Section 3.4.3.2.2 - Blood Culture 
Two sets (aerobic and anaerobic) of blood specimens for culture will be obtained at 
baseline from anatomically different locations. Additional blood samples will be collected 
for culture at subsequent visits only if a previous culture was positive, or if clinically 
indicated. If positive, blood cultures will be repeated daily until they are negative. The 2 sets 


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of blood cultures should be obtained from anatomically different locations. Culture will be 
performed at a local or regional laboratory, as applicable. The blood culture, if positive, 
will be used to identify isolates for submission to the central microbiology laboratory 
and to freeze for back-up storage. 
Section 3.4.3.2.3 - Urine Antigen Testing 
Urine samples will be obtained for L. pneumophila and S. pneumoniae urine antigen testing 
at baseline and forwarded to the central laboratory. 
Section 3.4.3.2.4 - Nasopharyngeal and Oropharyngeal Testing 
A nasopharyngeal swabs will be obtained at baseline and forwarded to the central 
laboratory for S. pneumoniae PCR analysis and/or S. pneumoniae culture, and serotyping 
and antibiotic susceptibility testing at a specialty microbiology laboratory. Two 
oropharyngeal swabs will be obtained at baseline and forwarded to the central laboratory 
for M.ycoplasma pneumoniae culture and/or PCR analysis, antibiotic susceptibility testing at 
a specialty microbiology laboratoriesy. 
Section 3.4.3.2.5 - Serology 
Serum serology samples will be tested for identification of atypical pathogens 
C. pneumoniae, M.ycoplasma pneumoniae and L.egionella pneumophila at baseline, TOC, 
and FU. 
Section 3.4.3.3 - Demographic Data/Medical History 
… 
The medical history should include clinically significant medical, pulmonary or surgical 
history ongoing at baseline or with onset in the previous 2 years, as well as hospitalizations 
of more than 2 days within the last 90 days.  
… 
Section 3.4.3.5 - Clinical Laboratory Tests 
Clinical laboratory testing will be performed according to the Schedule of Events 
(Appendix 7.1). Local results of pregnancy test, serum chemistry and coagulation profile, 
hematology, and urinalysis tests obtained within 24 hours of before enrollment may be used 
for screening purposes and to verify entry criteria. However, blood and urine samples will 
be collected either at Screening or and on Day 1 prior to the first dose of study drug and will 
be sent to the central laboratory and willto serve as baseline values. Directions for collection, 


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processing, and handling of specimens are included in the laboratory manual. 
… 
Other Chemistry: Procalcitonin will be analyzed by a central laboratory. 
Section 3.4.3.6 - Pharmacokinetic Blood Sample Collections 
Serial blood samples for PK analysis will be obtained at select investigative sites on Day 3 
(± 1 day) of treatment within the 30 minutes before the first study drug administration of the 
day and at 1.5 and 3 hours after the start of the infusion. All time points will have a 
± 10 minute window. Subjects should have received a minimum of 3 consecutive doses of 
study drug prior to the start of PK blood collection. Subjects do not need to be fasted before 
dosing or during PK sample collections. Samples will be processed according to the 
laboratory manual and sent to the central laboratory for analysis.  
All plasma samples will be assayed using a validated liquid chromatography coupled 
with tandem mass spectrometry assay for delafloxacin. 
Section 3.4.3.7 - Vital Sign Measurements 
Vital signs including body temperature, heart rate, respiratory rate, systolic and diastolic 
blood pressure, and pulse oximetry will be obtained according to the Schedule of Events 
(Appendix 7.1). Arterial blood gases can be obtained at Screening if clinically warranted. 
Any Daily supplemental oxygen at the time of pulse oximetry will be recorded. Blood 
pressure and pulse rate will be measured after subjects have been in a sitting position for at 
least 5 minutes. Respirations will be counted and documented in breaths per minute. Body 
temperature can be measured via different routes methods and may includeing oral, rectal, 
tympanic, and axillary. Vital signs should be measured around the at a consistent time of the 
first daily dose of study drug each day while on IV therapy. Subjects who require pressor 
support should have regular blood pressure monitoring as per local standard of care. 
Section 3.4.3.10 - Health-Related Quality-of-Life Assessment 
Quality-of-Life Questions  
Quality-of-life questions will be asked/administered to determine the effect of the subject’s 
CABP under study and its effect on his/her usual daily activities of doing their job and 
earning income. The questions require the patient’ssubject to recall of the patient’stheir 
status in the 24 hours prior to questioning.  
… 


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Section 3.4.3.11 - Concomitant Medications 
All concomitant medications will be recorded in the source and eCRF from the time the 
subject signs informed consent through the EOT.  
… 
Section 3.4.3.12 - Post-Treatment Medications 
All medications, including nonprescription medications and dietary supplements, taken once 
or more from the End of TreatmentEOT Visit assessments through the TOC Visit and only 
medications associated with an SAE from the TOC Visit through Follow-upFU Visit will be 
recorded in the subject source. The post-treatment medications recorded in the eCRF will 
be limited. Enter any antibiotics taken after EOT in the eCRF for all subjects. All other 
medications will only be entered in the eCRF through the TOC Visit, will be recorded in the 
eCRF and only medications associated with an SAE from the TOC Visit through the Follow-
upFU Visit will be recorded in the eCRF. For subjects not required to have or missing the 
TOC Visit, post-treatment medications other than antibiotics will only be recorded in 
the eCRF if associated with an SAE through the Follow-up Visit. 
Section 3.4.4.1 - Adverse Event Definitions 
… 
A TEtreatment-related AE is defined as any event with suspected causality to study drug. 
… 
Section 3.4.4.2 - Eliciting and Documenting Adverse Events 
… 
In addition to subject observations, AEs will be documented from any data collected in the 
eCRF or other source documents (e.g., laboratory values, physical examination findings, 
ECG changes), or other documents (e.g., subject diaries) that are relevant to subject safety. 
An allergic reaction to study drug must be reported as an AE. 
Section 3.4.4.3 - Reporting Adverse Events 
All AEs reported or observed during the study will be recorded in the AE eCRF from the 
time that the subject is first administered double-blind study drug through the EOT or TOC 
Visit, whichever is later. Only SAEs will be collected from the TOC Visit through the 
Follow-up Visit. All Serious adverse eventAEs will be collected recorded in the eCRF from 
the time the subject or authorized representative signs the ICF through the Follow-upFU 
Visit. 
… 


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Insufficient clinical response (lack of efficacy): 
Insufficient clinical response, efficacy, or pharmacological action should NOT be recorded as 
an AE. The principal investigator must make the distinction between exacerbation of 
preexisting illness and lack of therapeutic efficacy. Progression of the current CABP due to 
lack of efficacy of the study drug will be recorded on the Clinical Response eCRF. 
Section 3.5 - Overdose Management 
Single oral doses of delafloxacin as high as 1600 mg and multiple doses of 1200 mg have 
been administered to subjects in Phase 1 trials. Single IV doses as high as 1200 mg have been 
administered to subjects in Phase 1 trials. In study RX-3341-302, 3 patients received 600 mg 
IV BID for up to 13 days due to pharmacy error (Rib-X 2015). 
… 
Section 3.6.1 - Method of Assigning Subjects to Treatment Groups 
… 
The investigator or designee will enter the enrollment information in the IXRS. The 
unblinded pharmacist or unblinded designee will obtain the treatment assignment by from 
the IXRS as described in the IXRS manual. A statistician who is not otherwise involved in 
the conduct of the study will create the randomization code. Randomization will be stratified 
by PORT Risk Class, medical history of COPD/asthma, and by prior single-dose/regimen 
antibiotic use.  
Subjects in PORT Risk Class II will be limited to no more than 25% of total randomized 
subjects, and prior single-dose/regimen antibiotic use limited to no more than 25% of total 
randomized subjects.  
Section 3.6.7 - Allowed Concomitant Treatment 
… 
Any concomitant medication deemed necessary for the welfare of the subject during the 
study may be given at the discretion of the investigator. However, it is the responsibility of 
the principal investigator to ensure that details regarding the medication are recorded in full 
in the source and on the eCRF. 
Section 3.6.8 - Prohibited Medications and Restrictions 
Concurrent systemic antimicrobial treatments are prohibited. Any subject who requires 
additional (i.e., nonstudy) antibiotics for any of the following reasons will be considered a 
treatment failure: lack of efficacy after at least 4 doses of study drug by the end of Day 3, 
treatment related AE requiring a nonstudy antibiotic, antibiotic therapy required for more 


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than 20 delafloxacin/delafloxacin placebo doses. Study drug should be stopped for all 
treatment failures, and the subject should complete end of treatment procedures. 
… 
Section 3.7.1 - Endpoints 
For FDA, in order to control Type 1 error rate of 5%, a gate-keeping statistical method of a 
fixed sequence procedure will be used to test for the secondary efficacy endpoints once the 
primary efficacy endpoint is claimed to be successful. If the noninferiority of delafloxacin is 
declared in the primary analysis, in order to control type 1 error, the secondary endpoints will 
be tested for superiority in a sequential (hierarchical) fashion using a fixed sequential 
procedure.  
For EMA, all the primary and secondary endpoints will be analyzed for noninferiority 
with the possibility to switch to superiority.  
The difference (delafloxacin – moxifloxacin) and CIs for all secondary endpoints will be 
reported. The primary and secondary efficacy endpoints are presented in the following text. 
Section 3.7.1.1 - Primary Efficacy Endpoint [table format added] 
The primary efficacy endpoint is: 
FDA 
EMA 
The ECR defined as improvement at 
96 hours (± 24 hours) after first dose of 
study drug in at least 2 of the following 
symptoms: chest pain, frequency or 
severity of cough, amount and quality of 
productive sputum, and difficulty 
breathing, and no worsening in the other 
symptoms in the ITT population. 
The Clinical Outcome responder rate at 5 to 
10 days after the last dose of study drug 
(TOC) defined as resolution or near 
resolution of the symptoms of CABP present 
at study entry, and no use of additional 
antimicrobial therapy for the current 
infection, and no new symptoms associated 
with the current CABP infection (success) in 
the ModITT and ModCE populations. 
 
3.7.1.2 - Secondary Efficacy Endpoints [table format added] 
The secondary efficacy endpoints are: 
FDA 
EMA 
ECR with the addition of 
improvement in vital signs and 
ECR defined as improvement at 96 hours (± 24 hours) 
after first dose of study drug in at least 2 of the 


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FDA 
EMA 
no worsening of the 4 symptoms 
required as Response in the ITT 
population 
following symptoms: chest pain, frequency or severity 
of cough, amount and quality of productive sputum 
and difficulty breathing and no worsening of any of 
the other symptoms in the ModITT and ModCE 
populations 
Clinical Outcome at TOC  
(CE and ITT populations) 
ECR with the addition of improvement in vital signs 
and no worsening of the 4 symptoms required as 
Response in the ModITT and ModCE populations 
Clinical Outcome at the EOT 
Clinical outcome at EOT (ModITT and ModCE) 
ECR in the MITT population 
Clinical Outcome at TOC in the ModMITT and 
ModME populations 
Microbiologic Response  
(ME and MITT) 
Microbiologic response (ModMITT and ModME)  
All-cause mortality (ITT) 
All-cause mortality (ModITT)  
 
Section 3.7.1.5 - Pharmacokinetic Endpoints 
Pharmacokinetic results will be reported in a separate PK report. The time course of 
delafloxacin plasma concentrations will be assessed. 
Section 3.7.2.1 - Early Clinical Response 
Symptoms for the Early Clinical Response will be evaluated by the investigator on a four-
point scale (absent, mild, moderate, severe, see Section 7.8 for definitions) with 
improvement defined as at least a 1-point improvement (decrease) from baseline to the 
assessment at 96 hours (± 24 hours) after first dose of study drug (e.g., from severe to 
moderate, from moderate to absentmild, or from mild to absent). 
Responders: Improvement at 96 hours (± 24 hours) after first dose of study drug in at least 
2 of the following symptoms: pleuritic chest pain, frequency or severity of cough, amount 
and quality of productive sputum, and dyspnea (difficulty breathing), and no worsening of 
the other symptoms.  
Non-responders: Improvement is not achieved at 96 hours (± 24 hours) after first dose of 
study drug in at least 2 of the following symptoms: (pleuritic chest pain, frequency or 
severity of cough, amount and quality of productive sputum, and dyspnea (difficulty 
breathing); or there is use of additional non-study antimicrobial therapy for treatment of the 


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current CABP infection due to lack of efficacy; or the subject diesd from the current CABP 
infection. Indeterminate/missing assessments will be mapped to Non-responders in the 
statistical analysis of the ITT Population. 
Section 3.7.2.2 - Clinical Outcome at EOT and TOC 
… 
Success: Resolution or near resolution of the symptoms of CABP present at study entry, at 
and no use of additional antimicrobial therapy for the current infection, and no new 
symptoms associated with the current CABP infection. 
Failure: Symptoms of CABP present at study entry have not resolved, or new symptoms of 
CABP have developed, or the subject diesd from pneumonia, or use of additional non-study 
antimicrobial therapy for treatment of the current CABP infection due to lack of efficacy. 
Failure outcome due to Lack of Efficacy (LOE) will be carried forward to later time points if 
the subject discontinues the trial for LOE. Subjects must receive at least 4 doses of study 
drug by the end of Day 3 to be called a Failure. 
Indeterminate/Missing: A response cannot be determined because an efficacy assessment was 
not completed at the visit, or subject did not complete the planned course of study therapy for 
reasons other than lack of efficacy. Indeterminate/missing responses will be considered 
failures for purposes of the primary ITT/ModITT analysises and will be excluded from the 
CE and ME analysis populations. 
Section 3.7.2.3 - Microbiologic Response 
Microbiological response for subjects in the MITT and ME set will be based on results of the 
baseline and follow up cultures and susceptibility testing or serology. When follow-up 
culture results are missing, the clinical response assigned by the investigator will be 
considered. Microbiological responses will be generated at the TOC assessments at both the 
subject and the pathogen levels. The following microbiological responses will be considered: 
Eradication: The sputumrespiratory and/or blood specimen at the TOC Visit shows all 
causative pathogen(s) present at enrollment eradicated and no use of additional antimicrobial 
therapy for the current infection. 
Presumed Eradication: No sputum samplerespiratory and/or blood specimen was available 
at TOC with a clinical assessment of Success.  
Persistence: The sputumrespiratory and/or blood culture collectedspecimen at the TOC 
Visit shows appearance of all causative pathogen(s) present at enrollment. 


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Presumed Persistence: No sputum samplerespiratory and/or blood specimen was available 
for a case classified as clinical failure.  
Superinfection: A culture taken during treatment shows appearance of a new pathogen 
causing respiratory infection associated with clinical failure. 
Colonization/Contamination: A culture taken post-baseline through the TOC visit 
shows appearance of a new pathogen(s), with a clinical assessment of Success and no 
use of additional antimicrobial therapy for the current infection. 
Section 3.7.4 - Sample Size Calculations [table format added] 
FDA 
EMA 
At least 860 adult male and female 
subjects (430 subjects per treatment 
group) will be randomized. Used on a 
normal approximation approach 
(Miettinen and Nurminen’s Likelihood 
Score Test), 860 subjects in the ITT 
population will provide a 90% power to 
assess noninferiority of delafloxacin vs. 
moxifloxacin based on the following 
assumptions: (1) a rate of Early Clinical 
Response for moxifloxacin therapy and 
delafloxacin of 77% and 74%, 
respectively; (2) 1-sided type I error (α) 
of 0.025; (3) a noninferiority margin of 
12.5%. 
At least 860 adult male and female subjects 
(430 subjects per treatment group) will be 
randomized. Used on a normal approximation 
approach (Miettinen and Nurminen’s 
Likelihood Score Test), and assuming 
approximately 12% of patients will be in PORT 
Class II, and 80% of patients will be clinically 
evaluable, 755 subjects in the ModITT 
population and 604 subjects in the ModCE 
population will provide, respectively, a power 
of 91% and 83% to assess noninferiority of 
delafloxacin vs. moxifloxacin based on the 
following assumptions: (1) a rate of Clinical 
Outcome at the TOC visit for moxifloxacin and 
delafloxacin of 88% and 86%, respectively; 
(2) 1-sided type I error (α) of 0.025; (3) a 
noninferiority margin of 10%. 
… 
Section 3.7.5 - Analysis Populations 
Data analysis will be based on different analysis populations according to the purpose of the 
analysis (e.g., safety or efficacy). Within the efficacy analysis, different combinations of 
analysis sets will be used for the clinical response and the microbiologic response. The 
analysis for clinical response will be generally presented using the ITT, MITT, CE, and ME 
populations for FDA and the ModITT, ModMITT, ModCE and ModME populations for 
EMA. The analysis for microbiologic response will be presented using the MITT and ME 


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populations for FDA and the ModMITT and the ModME populations for EMA. 
… 
Modified ITT (ModITT) Population 
All randomized subjects who received at least one dose of study medication, classified as 
PORT Class III-V, analyzed according to the treatment arm to which they were 
randomized. 
Microbiological ITT (MITT) Population 
All subjects in the ITT population who had a baseline bacterial pathogen identified on 
culture of sputum specimena respiratory or blood specimen, or a nonculture method of 
detection of bacterial pathogens (i.e., urinary antigen test, PCR and serologic testing) 
identified that is known to cause CABP against which the study drug has antibacterial 
activity. 
Modified MITT (ModMITT) Population 
All subjects in the MITT population classified as PORT Class III-V. 
… 
Modified CE (ModCE) Population 
All subjects in the CE population classified as PORT Class III-V. 
… 
Modified ME (ModME) Population 
All subjects in the ME population classified as PORT Class III-V. 
Pharmacokinetic (PK) Population 
All subjects who receive at least 3 consecutive IV doses of study drug prior to the start of the 
blood sample collections on Day 3 (± 1 Day) and have sufficient plasma concentration data 
to facilitate calculation of PK parametersat least one delafloxacin plasma concentration 
data available. The PK population will be used for PK analyses. 
Section 3.8.1 - Demographics and Other Baseline Characteristics 
Demographics and other baseline characteristics including gender, age, race, ethnicity, 
height, weight, BMI and the data for baseline infection types at Screening PORT Class and 
CURB-65 score will be summarized for the ITT, Safety, ModITT, MITT, ModMITT, CE, 
ModCE, ME and ModME populations to assess the comparability of the treatment groups. 
Medical history data including pulmonary and hospitalization history will be summarized for 
the ITT and ModITT populations using the number of observations and percentage of 


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subjects reporting each category. Baseline radiograph findings and signs and symptoms 
required for study entry will be summarized for the ITT and ModITT populations using the 
number of observations and percentage of subjects reporting each category. 
Section 3.8.3 - Primary Efficacy Analysis [table format added] 
The primary efficacy endpoint is: 
FDA 
EMA 
The Early Clinical ResponseECR defined as 
improvement at Day 4 96 hours 
(± 24 hours) in at least 2 of the following 
symptoms: chest pain, frequency or severity 
of cough, amount and quality of productive 
sputum, and difficulty breathing, and no 
worsening of the other symptoms in the ITT 
population. 
Each treatment group’s response rate will be 
defined as: (# Responders) / (# Responders 
+ Non-responders). 
The treatment difference (delafloxacin – 
moxifloxacin) in the rates of this endpoint 
will be presented, and the Miettinen-
Nurminen test, without stratification, will be 
used for the 2-sided 95% confidence interval 
(CI) on the difference in response rate. This 
analysis will be performed using the ITT 
population. 
The lower bound of this CI will demonstrate 
the maximum extent to which the response 
rate for moxifloxacin may exceed that for 
delafloxacin. If the lower bound is greater 
than -12.5%, it will be concluded that 
delafloxacin is noninferior to moxifloxacin 
for treating patients with CABP. In addition, 
superiority will be claimed if the lower 
bound of the 95% CI exceeds 0. 
An indeterminate/missing response will be 
The Clinical Outcome at TOC. 
For the assessment of Clinical Outcome at 
TOC, each treatment group’s Clinical 
Outcome rate will be defined as: 
(# Success) / (# Success + Failure). 
The treatment difference (delafloxacin – 
moxifloxacin) in the rates of this endpoint 
will be presented, and the Miettinen-
Nurminen test, without stratification, will 
be used for the 2-sided 95% CI on the 
difference in response rate. This analysis 
will be performed using the ModCE and 
ModITT analysis populations, and the 
result at TOC will be tested for 
noninferiority with the possibility to 
switch to superiority. 
The lower bound of this CI for 
delafloxacin – moxifloxacin will 
demonstrate the maximum extent to 
which the response rate for moxifloxacin 
may exceed that for delafloxacin. If the 
lower bound is greater than 10%, it will be 
concluded that delafloxacin is noninferior 
to moxifloxacin for treating patients with 
CABP. In addition, superiority will be 
claimed if the lower bound of the 95% CI 
exceeds 0.  
A missing response will be classified as 
failure for purposes of the primary 


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FDA 
EMA 
classified as Non-responders for purposes of 
the primary analysis. 
ModITT analysis. 
 
Section 3.8.4 - Sensitivity Analysis of the Primary Endpoint for each Region 
(FDA and EMA) 
The following sensitivity analyses for the primary endpoint will be performed:  
… 
• The primary analysis performed on the MITT/ModMITT, CE and ME/ModME 
analysis populations as per the corresponding region. 
• For EMA region, in order to control the possible age influence on the clinical 
evaluation, the primary endpoint will be tested including the age class, defined as 
Age < 65 and Age ≥ 65, as an additional factor in the model. 
… 
Section 3.8.5 - Subgroup Analyses of the Primary Endpoint for each Region 
(FDA and EMA) 
… 
• Demographic subgroups: age categories (age < 65, ≥ 65, ≥ 75), gender, BMI categories 
(BMI < 30 and ≥ 30), baseline PORT scoreRisk Class, baseline CURB-65 Score, 
ethnicity, region, and race categories. 
… 
• Presence or absence of: baseline bacteremia, multilobar pneumonia, diabetes, history of 
COPD/asthma, history of hepatitis, renal impairment/disease, baseline MRSA 
S. pneumoniae infection, baseline adequate Gram stain adequacy. 
These subgroup analyses will be performed using the ITT/ModITT population for the 
primary efficacy endpoint. 
Section 3.8.6 - Secondary Efficacy Analyses 
For each of the FDA submissions, in order to control Type 1 error rate of 5%, a gate-
keeping statistical method of a fixed-sequence procedure will be used to test for the 
secondary efficacy endpoints once the primary efficacy endpoint is claimed to be successful. 
For each of the FDA (and EMA) submissions, If the noninferiority of delafloxacin is 
declared in the primary analysis, the secondary endpoints will be tested for superiority in a 


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sequential (hierarchical) fashion using a fixed sequential procedure, in the order given in 
Section 3.7.1.2. Unless specified otherwise in the endpoint definition, the testing will be 
performed in the ITT analysis population.  
For EMA, all the primary and secondary endpoints will be tested for noninferiority 
with the possibility to switch to superiority.  
Each test, both for FDA and EMA, will be performed using the type 1 error rate of 0.05. 
The secondary endpoints with proportion will be tested, both for FDA and EMA, using 
Miettinen-Nurminen test for delafloxacin – moxifloxacin, without stratification;. Superiority 
for the corresponding study endpoint will be claimed using a 5% significance level. 
Section 3.8.6.1 - Early Clinical Response with the Addition of Improvement in Vital Signs 
and No Worsening of the 4 Symptoms Required as Response 
The treatment difference (delafloxacin – moxifloxacin) of ECR with the addition of 
improvement in vital signs and no worsening of the 4 symptoms required as response will be 
presented, and the Miettinen-Nurminen test, without stratification, will be used for the 
2-sided 95% CI on the difference in ECR with the addition of improvement in vital signs and 
no worsening of the 4 symptoms required as response rate. This analysis will be performed 
using the ITT and ModITT/ModCE population, respectively for FDA and EMA. 
Section 3.8.6.2 - Clinical Outcome at EOT and TOC 
The treatment difference (delafloxacin – moxifloxacin) in the rates of this endpoint will be 
presented, and the Miettinen-Nurminen test, without stratification, will be used for the 2 
sided 95% CI on the difference in response rate. This analysis of clinical outcome at EOT 
and TOC will be performed using the CE and ITT analysis populations for FDA. The 
ModCE and ModITT analysis populations will be used to perform the analysis of 
clinical outcome at EOT for EMA. The ModMITT and ModME analysis populations 
will be used to perform the analysis of the EMA secondary endpoint of clinical outcome, 
and the result at TOC will be tested for noninferiority for EMA use, which will be outlined in 
the statistical analysis plan (SAP). 
The lower bound of this CI for delafloxacin – moxifloxacin will demonstrate the maximum 
extent to which the response rate for moxifloxacin may exceed that for delafloxacin. If the 
lower bound is greater than 12.5%, it will be concluded that delafloxacin is noninferior to 
moxifloxacin for treating patients with CABP. 


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A missing response will be classified as failure for purposes of the primary ITT analysis. For 
the assessment of Clinical Outcome at EOT and TOC, each treatment group’s Clinical 
Outcome rate will be defined as: (# Success) / (# Success + Failure). 
The assessment of Clinical Outcome at TOC will be performed stratified by baseline PORT 
classification, medical history of COPD/asthma and prior systemic antimicrobial use. In 
addition, this analysis will be performed on the MITT, CE, and ME analysis populations at 
TOC. In addition, subgroup analyses listed in Section 3.8.5 will also be performed for the 
assessment of Clinical Outcome at the TOC for EMA use. 
Section 3.8.6.3 - Early Clinical Response for Subjects in the MITT, ModITT and 
ModCE Populations 
The treatment difference (delafloxacin – moxifloxacin) of ECR for patients in the MITT and 
ModITT/ModCE populations respectively for FDA and EMA will be presented, and the 
Miettinen-Nurminen test, without stratification, will be used for the 2-sided 95% CI on the 
difference in ECR rate. This analysis will be performed using the ITT population for patients 
in the MITT population. 
Section 3.8.6.4 - Microbiologic Response 
The treatment difference (delafloxacin – moxifloxacin) of microbiologic response rate will be 
presented, and the Miettinen-Nurminen test, without stratification, will be used for the 
2-sided 95% CI on the difference in microbiologic response rate. This analysis will be 
performed using the ME and the MITT populations for FDA, and the ModME and 
ModMITT populations for EMA. 
Section 3.8.6.5 - All-Cause Mortality 
All-cause mortality in adult subjects with CABP on Day 28 will be assessed and compared 
between the two treatment groups. Kaplan-Meier estimates will be used to summarize the 
time to all-cause mortality on Day 28. Patients who dohave not died atby Day 28 will be 
censored at Day 28.  
… 
The Cox proportional hazards regression model will be used to evaluate the difference 
between the 2 treatment groups adjusting for the baseline covariates including baseline 
PORT classification, history of COPD/asthma, and prior systemic antimicrobial use. 
Interactions between treatment and each covariate will be evaluated at the 0.10 significance 
level; if not significant, they will be removed from the final model. These analyses will be 
performed for ITT and ModITT populations respectively for FDA and EMA. 


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Section 3.8.7 - Exploratory Analyses 
… 
Exploratory efficacy analyses will include summaries for the primary and secondary 
endpoints measured at additional study time points and for different analysis population. As 
other exploratory analyses, secondary analyses of secondary endpoints that used nonstratified 
Miettinen-Nurminen CIs will be repeated using the same method but stratified by PORT 
Class/PSI score, medical history of COPD/asthma, and prior systemic antimicrobial use. 
In addition, the following shift analyses will be performed as exploratory analyses using a 
chi-squared test if appropriate: 
… 
Section 3.8.16 - Pharmacokinetic Analyses 
Pharmacokinetic analyses will be detailed in the separate PK report. Summary statistics will 
be calculated for the plasma concentration-time data including N, mean, standard 
deviation (SD), coefficient of variation (CV), median, minimum, maximum, and 
geometric mean.  
Plasma concentration data will be subjected to a separate population PK analysis. 
Section 3.8.17 - Missing Data 
… 
2. Missing data for Clinical Response based on the investigator assessment of signs and 
symptoms of pneumonia will be considered a Failure in the ITT/ModITT analysis. 
3. For each secondary and exploratory efficacy endpoint, missing data will be imputed as 
the worst possible response. For instance, subjects missing assessment data at either the Early 
Clinical Response time point or the TOC will be considered as Failures or Non responders in 
the ITT/ModITT analysis. 
… 
Section 5.1 - External Data Monitoring Groups 
An external data monitoring group (data safety monitoring board) may be employed in this 
study. In that event, the membership, activities, and responsibilities of the safety 
monitoring committee will be described in detail in a separate charter document 
established for this study. 


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Section 6. – References 
Abbott Laboratories (Abbott Park, IL). A phase 2b comparative study of the safety and 
efficacy of three oral doses of RX-3341ABT-492 for the treatment of subjects with 
community acquired pneumonia. 2003 Dec 15. Clinical Study Report R&D/03/393. (Study 
Protocol M01-344). 
Abbott Laboratories (Abbott Park, IL). A phase 2a comparative study of the safety and 
efficacy of ABT-492 100 mg QD, 200 mg QD, 400 mg QD and levofloxacin 500 mg QD 
for the treatment of subjects with acute bacterial exacerbation of chronic bronchitis. 
2003 Dec 16. Clinical Study Report R&D/03/392. Protocol M01-298. 
Department of Health and Human Services (DHHS), Food and Drug Administration 
(FDA), Center for Drug Evaluation and Research (US). Draft guidance. Community-
Acquired Bacterial Pneumonia: Developing Drugs for Treatment. January 2014. 
Available from: https://www.fda.gov/downloads/drugs/guidances/ucm123686.pdf. 
European Medicines Agency (EMA). Committee for Human Medicinal Products 
(CHMP). Addendum to the guideline on the evaluation of medicinal products indicated 
for treatment of bacterial infections. London, 24 October 2013. 
EMA/CHMP/351889/2013. Available from: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2013/11/
WC500153953.pdf. 
… 
Melinta Study Report EF-3341-006. Melinta Therapeutics, Inc. (New Haven, CT). 
Evaluation of delafloxacin in a murine respiratory tract infection model against 
S. pneumoniae D39. 2015 Apr 28. Melinta Report #EF-3341-006. 
[moved up from below]Rib-X Study RX-3341-302. Rib-X Pharmaceuticals, Inc. Melinta 
Therapeutics, Inc. (New Haven, CT). A phase 3, multicenter, randomized, double-blind, 
active-controlled study to evaluate the efficacy and safety of delafloxacin compared with 
vancomycin + aztreonam in patients with acute bacterial skin and skin structure infections. 
2015 Nov 04. Clinical Study Report. Protocol RX-3341-302. 
Melinta Therapeutics, Inc. (Melinta) (New Haven, CT). A phase 3, multicenter, 
randomized, double-blind, active-controlled study to evaluate the efficacy and safety of 
IV and oral delafloxacin compared with vancomycin + aztreonam in patients with acute 
bacterial skin and skin structure infections. 2017 Jan 06. Clinical Study Report: 
Amendment No. 1. Protocol RX-3341-303. 


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Melinta IB 2015. Melinta Therapeutics, Inc. (Melinta) (New Haven, CT). 
Investigator’s Brochure: Edition 21. Investigational New Drug: Delafloxacin (RX-3341). 
Edition Date: 082 JuneDecember 20156. 
Study R&D 01/135. Meulbroek J. Efficacy of ABT-492 against Streptococcus pneumoniae 
and Haemophilus influenzae in the rat pulmonary infection model. 2001 Feb 27. Research 
and Development Report R&D/01/135. 
… 
Rib-X Study RX-3341-108. Rib-X Pharmaceuticals, Inc. (Rib-X) (New Haven, CT). A Phase 
1, single-dose, safety, tolerability, and pharmacokinetic study of IV and oral formulations, 
and a maximum tolerated dose study of delafloxacin in healthy subjects. 2011 Sep 21. 
Clinical Study Report. Protocol RX-3341-108. 
Rib-X Pharmaceuticals, Inc. (New Haven, CT). A randomized, double-blind, 
multicenter study of the safety and efficacy of RX-3341 compared with tigecycline for 
the treatment of complicated skin and skin structure infections. 2009 Jul 21. Clinical 
Study Report. Protocol RX-3341-201. 
Rib-X Study RX-3341-202. Rib-X Pharmaceuticals, Inc. (Rib-X) (New Haven, CT). A phase 
2 exploratory study of objective endpoints in subjects with acute bacterial skin and skin 
structure infections treated with delafloxacin, vancomycin, or linezolid. 2014 Aug 11. 
Clinical Study Report. Protocol RX-3341-202. 
Section 7. - Appendices 
… 
7.11 Appendix: Protocol Amendment 3 [added] 


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Section 7.1 - Appendix: Schedule of Events 
[Only updated table rows are shown. Changed table cells are shaded gray.]  
[In header, abbreviations updated, and Day 7 visit window changed from ± 1 day to + 1 day. Chest radiograph or CT scan added at 
TOC with footnote m. Footnote m added to Sputum for Gram stain and culture at EOT. Chlamydia added to serology. Footnote y 
added to Adverse event evaluation and removed from Screening and FU] 
Assessment or Procedure 
Screeninga 
Treatment Periodb 
End of 
Treatment 
(EOT)/ 
Early Termc 
Reminder 
Contactd 
Test of 
Cure 
(TOC)e 
Follow-
Up 
(FU)f 
Study Day(s) 
–1 to 1 
1a 
Daily 
while 
on IV 
ECR 
96 hrs 
± 24 hrg 
5 
(+ 1 
day) 
7 
(+ 1 
day) 
End 
of IVh 
 
 
5 to 10 
days after 
last dose 
28  
(± 2 
days) 
Chest radiograph or CT scan 
X 
 
 
 
 
 
 
Xm 
 
Xm 
 
SputumRespiratory specimen for  
Gram stain and culturer 
X 
X 
 
 
 
 
 
Xm 
 
X 
 
Chlamydia/Legionella/Mycoplasma serology  
 
Xs 
 
 
 
 
 
 
 
X 
X 
Adverse event evaluationy 
Xy 
X 
X 
X 
X 
X 
 
X 
 
X 
Xy 
Abbreviations: ECR = Early Clinical Response; EOT = End of Treatment; TOC = Test of Cure; FU = Follow-Up; CABP = community-acquired bacterial 
pneumonia; MRSA = methicillin-resistant Staphylococcus aureus; CT = Computed tomography, PORT = Patient Outcomes Research Team; CURB-65 = 
scoring system based on confusion, urea, respiratory rate, blood pressure and age 65 or older; PK = pharmacokinetics; IXRS = interactive voice and web 
response system. 
a Screening procedures will occur within the 24 hours ofprior to the first dose. The first dose may be administered on the same day as Screening. If the first 
dose is administered the same day as screening, then the assessments listed for Day 1, but which were already completed for Screening will not be repeated. 
b The total duration of treatment (IV and oral) is 5 days up to 10 days if clinically indicated (minimum 10 doses and up to 20 delafloxacin/delafloxacin placebo 
doses). 
c Subjects who prematurely discontinue study drug or are completing treatment on day of visit can have EOT procedures performed that same day or up to 24 
hours (+ 4 hours) after the last dose of study drug. Assessments already completed on the same day as the last dose of study drug is administered can serve as 
EOT procedures and do not need to be repeated. Laboratory tests completed for a routine visit will not be repeated at EOT, if collected within 24 hours of the 
EOT visit.  
d A reminder contact will be done 3- 9 days after the last dose of study drug. Subjects will receive a telephone call or contact via other interactive method, e.g., 
text or email, to remind the subject about the upcoming Test-of-Cure Visit. 
e TOC assessments will be performed 5 to 10 days after the last dose of study drug (see Section 3.3.2 for exception). 


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f All efforts will be made to have subjects return to the clinic for a Follow-up Visit. Telephone contact is permissible for subjects unable, unwilling or not 
required (see Section 3.3.2) to return to the clinic.  
g ECR Visit will occur 96 hours (± 24 hours) after the first dose of study drug. Procedures already completed as specified in Sections 3.4.1.3 or 3.4.1.5 do not 
need to be repeated unless outside the ECR 96-hour (± 24 hours) window.  
h Last day of IV therapy prior to oral switch. A minimum of 6 delafloxacin/delafloxacin placebo doses of IV study drug must be administered prior to oral switch. 
Refer to Schedule of Events for that day for assessments/procedures to be completed. 
i Clinical signs and symptoms of CABP will be assessed by the investigator using a 4-point severity scale (see Section 3.4.2.1). 
j Arterial blood gases can be obtained at Screening if clinically warranted. Body temperature can be measured via different routes and may include oral, rectal, 
tympanic and axillary. Pulse oximetry will be recorded for all subjects daily while on IV therapy and at ECR, and Day 5 and Day 7, EOT, and TOC only if 
clinically indicated and/or for subjects on supplemental oxygen at Day 5, Day 7, EOT, and TOC. Vital signs should be measured around theat a consistent 
time of the first daily dose of study drugeach day while on IV therapy. 
k Electrocardiograms will be performed at screening and if clinically indicated as determined by the investigator after screening.  
l Targeted physical examinations will be performed during the study to assess changes from baseline parameters, adverse events, and other relevant safety 
information. 
m Will be performed only if lack of efficacy. 
n Local laboratory test results of pregnancy, hematology, serum chemistry, and coagulation profile and urinalysis obtained within 24 hours ofbefore enrollment 
may be used for screening purposes and to verify entry criteria. Laboratory tests with exclusionary results judged by the investigator as not compatible with the 
subject’s clinical status may be repeated for eligibility purposes once. 
o Pregnancy tests to be performed for women of childbearing potential only. 
p Urinalysis and coagulation at screening only.  
q Two sets of blood cultures will be collected from all subjects at screening. Additional blood cultures will be collected if a previous culture was positive or if 
clinically indicated after Screening. Rapid test for MRSA identification methods are acceptable to use if S. Aureus is identified by the local/regional laboratory. 
r All reasonable efforts will be made to obtain a sputum specimen for Gram stain and culture. Other sources of respiratory specimens such as those obtained 
from bronchoalveolar lavage, protected specimen brush, transtracheal aspirate, and pleural fluid, if available, are acceptable to submit for culture. A Gram stain 
will be performed on all sputum and transtracheal aspirate samples. Rapid test for MRSA identification methods are acceptable to use if S. aureus is identified 
by the local/regional laboratory. 
s Results are not required prior to dosing. Refer to the laboratory manual for detailed instructions on collection, processing and shipment.  
t  If the first dose is started late on Day 1in the day because of screening and eligibility verifications, a 1-time adjustment is allowed for a more customary dosing 
schedule that is within ± 4 hours of the normally scheduled second dose. The every-12-hours (± 2 hours) dosing schedule is set after the first dose (or dose 
adjustment). 
u Oral study drug treatment can be completed in the hospital or clinic. For subjects discharged to home, dispense study drug. Instruct subjects to bring study drug 
container(s) (empty and/or full) to the clinic at their next scheduled visit.  
v Study drug may be stopped at the discretion of the investigator after completing a minimum of 10 delafloxacin/delafloxacin placebo doses. Criteria for 
determination of appropriate treatment duration isare described in Section 3.4.1.8.1.  
w Blood samples for PK analysis will be obtained from subjects at select sites on Day 3 (± 1 day) of treatment within the 30 minutes before the first study drug 
administration, of the day and at 1.5 and 3 hours after the start of the infusion. Subjects should have received a minimum of 3 consecutive doses of study drug 
prior to the start of PK sample collection. All time points will have a ± 10-minute window. Subjects do not need to be fasted before dosing or during PK 
sample collections.  
x See Section 3.4.3.12 for collection of concomitant medications at FUassociated with serious adverse events will be entered in the eCRF. 


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y Serious adverse events will be reported per protocol and recorded in the eCRF from the time of subject provides informed consent through the FU visit.  


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Section 7.2 - Appendix: PSI/PORT Score: Pneumonia Severity Index for CAP 
[Only updated table rows are shown. Changed table cells are shaded gray.] 
 
Assigned Points 
Temperature < 35°C (95°F) or > 39.9°C (103.8°F) 
+15 
BUN > 29 mg/dL or urea > 10.9 mmol/L 
+20 
Glucose > 249 (US) or > 13.8 (SI) 
+10 
Partial pressure of Oxygen < 60 mmHg* 
+10 
* An oxygen saturation of less than 90% on pulse oximetry or intubation before admission is 
also considered abnormal (Fine 1997). 
… 
Step 2: 
• 
Assign points based on age, gender, nursing home residence, co-morbid illness, 
physical examination findings, and laboratory and radiographic findings as listed 
above. 
• 
Point distribution, score interpretation and suggested disposition based on local 
standard of care: 
Score 
Risk Class 
Risk 
Disposition 
≤70 
II 
Low 
Outpatient care 
71-90 
III 
Low 
Outpatient vs. Observation admission 
91-130 
IV 
Moderate 
Inpatient admission 
>130 
V 
High 
Inpatient admission 
[Risk Class was added to the table] 
MDCalc© 2015. All Rights Reserved. 
Downloaded Retrieved from28/November 2015 http://www.mdcalc.com/psi-port-score-
pneumonia-severity-index-adult-cap/ 


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Section 7.3 - Appendix: CURB-65 
[Only updated table rows are shown. Changed table cells are shaded gray.] 
CURB-65 
Symptom 
Points 
Urea > 7 mmol/L or BUN > 19 mg/dL 
1 
 
Section 7.6 - Appendix: SF-12v2® Health Survey 
[Sample questionnaire replaced with actual United States (English) version of questionnaire] 
Section 7.8 - Appendix: Definitions of Symptom Intensity 
[Only updated table rows are shown. Changed table cells are shaded gray.] 
Symptom (Points) 
Absent (0) 
Mild (1) 
Moderate (2) 
Severe (3) 
 

SAP_001.pdf: 
NCT02679573