Clinical trial NCT03032510
Conditions: Complicated Urinary Tract Infections
Sponsor: Tetraphase Pharmaceuticals, Inc
Start date: 2017-01-01; Completion date: 2018-01-01
Enrollment: 1205 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of eravacycline compared to ertapenem in treating participants with complicated urinary tract infections (cUTI).

Detailed description:
The purpose of this study is to assess the efficacy, safety, and pharmacokinetics of eravacycline compared to ertapenem in treating participants with complicated urinary tract infections (cUTI).

This is a phase 3, randomized, double-blind, double-dummy, multicenter, prospective study to assess the efficacy, safety and pharmacokinetics of eravacycline compared with ertapenem in the treatment of cUTI.

Randomization will be stratified based on two criteria: (1) by primary site of infection (pyelonephritis and normal urinary tract anatomy vs all other diagnoses) and (2) by the receipt of a single dose of effective non-study antibiotics for the acute cUTI within 72 hours prior to randomization. An enrollment cap of approximately 50% is planned for subjects with pyelonephritis with normal urinary tract anatomy. Also, an enrollment cap of approximately 20% is planned for subjects who have received a single dose of non-study antibiotics for the acute cUTI within 72 hours prior to randomization.

In this study subjects will be enrolled and randomized to one of two treatment arms in a 1:1 ratio: (i) eravacycline intravenously (IV) / levofloxacin (PO), or (ii) ertapenem (IV) / levofloxacin (PO).

Arms: arm 1: None arm 2: None
Interventions: intervention 1: Eravacycline intervention 2: Ertapenem intervention 3: Placebo intervention 4: Levofloxacin
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None

Protocol documents:
Prot_001.pdf: 







































































































































SAP_000.pdf: 
STATISTICAL ANALYSIS PLAN 
Investigating Gram-negative Infections Treated with Eravacycline (IGNITE) 3:  
A Phase 3, Randomized, Double-Blind, Double-Dummy, Multicenter, Prospective 
Study to Assess the Efficacy and Safety of IV Eravacycline Compared with 
Ertapenem in Complicated Urinary Tract Infections 
Protocol: TP-434-021 
Protocol Number: 
Protocol Version and Date: 
TP-434-021 
Version 1.1: 9 August 2016 
Name of Test Drug: 
Eravacycline (TP-434) 
Phase: 
Phase 3 
Methodology: 
Randomized, Double-Blind, Double-Dummy, Multicenter, 
Non-inferiority, Prospective Study 
Sponsor: 
Tetraphase Pharmaceuticals, Inc. 
480 Arsenal Way, Suite 110 
Watertown MA 02472 
Tel: 617-715-3600 
Fax: 617-926-3557 
Sponsor Representatives: 
Larry W. Tsai, MD 
Chief Medical Officer 
Anita F. Das, PhD 
Consultant Statistician 
Analysis Plan Date: 
22January2018 
Analysis Plan Version: 
Version 1.0 
Confidentiality Statement 
The information contained herein is confidential and the proprietary property of 
Tetraphase Pharmaceuticals, Inc., and any unauthorized use or disclosure  
of such information without the prior written authorization of  
Tetraphase Pharmaceuticals, Inc., is expressly prohibited. 




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TABLE OF CONTENTS 
1.
INFORMATION FROM THE STUDY PROTOCOL ...................................................8
1.1. 
Introduction and Objectives ................................................................................8 
1.1.1. 
Introduction ..........................................................................................8 
1.1.2. 
Study Objectives ..................................................................................9 
1.2. 
Study Design .......................................................................................................9 
1.2.1. 
Synopsis of Study Design ....................................................................9 
1.2.2. 
Stopping Rules and Unblinding .........................................................10 
1.2.3. 
Study Procedures ...............................................................................11 
2.
DATA MANAGEMENT ..............................................................................................13
3.
SUBJECT POPULATION ............................................................................................14
3.1. 
Population Definitions ......................................................................................14 
3.1.1. 
Intent-to-Treat (ITT) Population ........................................................14 
3.1.2. 
Safety Population ...............................................................................14 
3.1.3. 
All Treated (MITT) Population .........................................................14 
3.1.4. 
Microbiological Intent-to-Treat (micro-ITT) Population ..................14 
3.1.5. 
Modified Microbiological Intent-to-Treat (Micro-MITT) 
Population ..........................................................................................17 
3.1.6. 
Clinically Evaluable (CE) Populations ..............................................17 
3.1.7. 
Microbiologically Evaluable (ME) Populations ................................21 
3.2. 
Evaluability Review ..........................................................................................21 
3.2.1. 
Membership and Responsibilities ......................................................21 
3.2.2. 
Process for Determining Inclusion in Analysis Populations ..............21 
3.3. 
Protocol Deviations ...........................................................................................22 
4.
GENERAL STATISTICAL METHODS .....................................................................23
4.1. 
Sample Size Justification ..................................................................................23 
4.2. 
General Methods ...............................................................................................24 
4.3. 
Computing Environment ...................................................................................25 
4.4. 
Baseline Definitions ..........................................................................................25 
4.5. 
Withdrawals, Dropouts, Loss to Follow-up ......................................................25 
4.6. 
Missing, Unused, and Spurious Data ................................................................25 


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4.7. 
Interim Analyses ...............................................................................................26 
4.8. 
Visit Windows ...................................................................................................26 
5.
STUDY ANALYSES ...................................................................................................28
5.1. 
Subject Disposition ...........................................................................................28 
5.2. 
Demographics and Baseline Characteristics .....................................................28 
5.3. 
Medical History and Disease History ...............................................................28 
5.4. 
Baseline Microbiology ......................................................................................29 
5.5. 
Prior and Concomitant Medications..................................................................29 
5.6. 
Study Drug Exposure and Compliance .............................................................30 
5.7. 
Efficacy Evaluation ...........................................................................................31 
5.7.1. 
Primary Efficacy Analysis .................................................................31 
5.7.1.1. Additional Analyses of the Primary Efficacy Outcome ......34 
5.7.2. 
Secondary Efficacy Analyses.............................................................35 
5.7.3. 
Additional Efficacy Analyses ............................................................36 
5.7.3.1. Intravenous Only Responder Outcome ...............................36 
5.7.3.4. Clinical Outcome Measures ................................................36 
5.7.3.5. Microbiological Outcomes ..................................................36 
5.8. 
Safety Analyses .................................................................................................37 
5.8.1. 
Adverse Events ..................................................................................37 
5.8.2. 
Laboratory Data .................................................................................38 
5.8.3. 
Vital Signs and Physical Examination ...............................................41 
6.
CHANGES TO PLANNED ANALYSES ....................................................................43
7.
REFERENCES ..............................................................................................................44
5.7.3.2. Responder Outcome in Subjects with and without 
 
   Levofloxacin-Resistant Baseline Pathogens .......................36 
5.7.3.3. Responder Outcome in Subjects with and without 
 
   Ertapenem-Resistant Baseline Pathogens ...........................36 


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TABLES INCLUDED IN THE TEXT 
 
Page 
Table 1 
Study Drug Administration ............................................................................................. 10 
Table 2 
Schedule of Assessments ................................................................................................. 11 
Table 3 
Assumptions of Sample Size Calculations ...................................................................... 23 
Table 4 
Derived Analysis Visits for Efficacy and Safety Analyses ............................................. 27 
Table 5 
Primary Efficacy Outcome .............................................................................................. 32 
Table 6 
Presentation of Chemistry Parameters ............................................................................. 38 
Table 7 
Modified Division of Microbiology and Infectious Diseases Adult Toxicity 
Criteria (November, 2007) .............................................................................................. 39 
Table 8 
Clinically Notable Abnormal Vital Sign Threshold Values ............................................ 42 
 
 


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LIST OF ABBREVIATIONS AND DEFINITION OF TERMS 
Term 
Definition 
AE 
Adverse Event 
ALT (SGPT) 
Alanine Aminotransferase (Serum Glutamic Pyruvic Transaminase) 
AST (SGOT) 
Aspartate Aminotransferase (Serum Glutamic Oxaloacetic Transaminase) 
ATC 
Anatomical Therapeutic Chemical 
BUN 
Blood Urea Nitrogen 
CE 
Clinically Evaluable 
CFU 
Colony-Forming Unit 
CHF 
Congestive Heart Failure 
CI 
Confidence Interval 
cIAI 
Complicated Intra-abdominal Infections 
CN 
Clinically Notable 
CRA 
Clinical Research Associate 
CRO 
Contract Research Organization 
CSR 
Clinical Study Report 
cUTI 
Complicated Urinary Tract Infection 
DMID 
Division of Microbiology and Infectious Diseases 
eCRF 
Electronic Case Report Form 
EMA 
European Medicines Agency 
EOI 
End of IV 
EOT 
End of Treatment 
ERC 
Evaluability Review Committee 
FDA 
Food and Drug Administration 
FU 
Follow-Up 
IB 
Investigator’s Brochure 
ICH 
The International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use 
IGNITE 
Investigating Gram-Negative Infections Treated with Eravacycline 
ITT 
Intent-To-Treat 
IV 
Intravenous 
IWRS 
Interactive Web-Based Response System 


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Term 
Definition 
ME 
Microbiologically Evaluable 
MedDRA 
Medical Dictionary for Regulatory Activities 
MIC 
Minimum Inhibitory Concentration 
micro-ITT 
Microbiological Intent-To-Treat 
micro-MITT 
Modified Microbiological Intent-To-Treat 
MITT 
All Treated 
MRC 
Microbiology Review Committee 
PK 
Pharmacokinetic 
NI 
Non-Inferiority 
PO 
Per Oral 
RBC 
Red Blood Cell 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SI 
System International 
SOC 
System Organ Class 
TEAE 
Treatment-Emergent Adverse Event 
TOC 
Test of Cure 
ULN 
Upper Limit of Normal 
WBC 
White Blood Cell 
WHO 
World Health Organization 
 
 


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1. 
INFORMATION FROM THE STUDY PROTOCOL 
1.1. 
Introduction and Objectives 
1.1.1. 
Introduction 
The increasing incidence of multidrug resistance among Gram-positive and Gram-negative 
pathogens in complicated urinary tract infections (cUTIs) has raised concerns among experts, 
especially since there is a dearth of new antibiotics in the drug development pipeline and a 
limited number of marketed antibiotics with activity against these pathogens (1,2). The high 
degree of in vitro antibacterial activity against multidrug resistant Gram-positive and Gram-
negative pathogens and efficacy observed with eravacycline in established animal models of 
infection (3,4,5), as well as the results from initial clinical studies (6,7), warrant clinical 
development of intravenous (IV) eravacycline as a treatment option for cUTIs. A potential 
advantage of eravacycline, based on nonclinical and human pharmacokinetic (PK) data, is the 
possibility of convenient daily IV dosing. 
Eravacycline is a novel, synthetic, broad-spectrum fluorocycline antibiotic of the tetracycline 
class and is highly active in vitro against emerging pathogens. The full description of the in vitro 
antibacterial activity of eravacycline can be found in the Investigator’s Brochure (IB). 
The high degree and reliability of in vitro antibacterial activity against multidrug-resistant 
Gram-negative pathogens, the efficacy observed with eravacycline in established animal models 
of infection, and the efficacy and tolerability established in phase 2 and phase 3 studies of 
complicated intra-abdominal infections (cIAIs) warrant clinical development of eravacycline as a 
single daily dose IV treatment option for cUTIs. 
This statistical analysis plan (SAP) is designed to outline the methods to be used in the analysis 
of data from Study TP-434-021. Populations for analysis, data handling rules, statistical 
methods, and formats for data presentation are provided. The statistical analyses and summary 
tabulations described in this SAP will provide the basis for presentation and interpretation of the 
data in the clinical study report (CSR) for this trial. 
This SAP will also outline any differences in the currently planned analytical objectives relative 
to those planned in the study protocol. Changes, if any, made to the SAP after it has been signed 
but prior to database lock will be documented in an amendment. Any important changes made 
to the analysis will be described in the CSR. This SAP is based on protocol version 1.1 dated 
9 August 2016. 
Analysis of PK parameters is covered in a separate analysis plan. 
This protocol is designed to address the guidance requirements of the Food and Drug 
Administration (FDA; Complicated Urinary  Tract Infections: Developing Drugs for Treatment 
Guidance for Industry, CDER 2015) and European Medical Agency (EMA; Addendum to the 
guideline of the evaluation of medicinal products for the treatment of bacterial infections 
EMA/CHMP/351889/2013) on the development of treatment for cUTIs. The FDA supports the 
use of a responder outcome (clinical cure and microbiological success) at the End of IV (EOI) 
and Test of Cure (TOC) visit in the microbiological intent-to-treat (micro-ITT) population. For 
the EMA, the primary efficacy outcome is microbiologic response in the microbiological 
modified ITT (micro-MITT) and microbiologically evaluable (ME) populations. A separate 


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SAP will be developed to address the different primary analysis populations for the EMA as 
well as other differences in the statistical analysis. 
1.1.2. 
Study Objectives 
The primary objective is to demonstrate that IV eravacycline is non-inferior to ertapenem in 
responder outcome (clinical cure and microbiologic success) in the micro-ITT population at the 
EOI visit (within 1 day of the completion of IV study drug treatment) and TOC visit (defined as 
14-17 days after randomization). 
The secondary objectives of the study are: 
• To compare responder outcomes in the treatment arms at Day 5 in the micro-ITT 
population 
• To compare clinical outcomes in the treatment arms at Day 5, EOI, End of Treatment 
(EOT), TOC, and Follow-up (FU) visits in the following populations: 
o ITT population 
o Clinically evaluable (CE) population 
o Micro-ITT population 
o Micro-MITT population 
o ME population 
• To compare microbiologic outcomes in the treatment arms at Day 5, EOI, EOT, TOC 
and FU visits in the following populations: 
o Micro-ITT population 
o Micro-MITT population 
o ME population 
• To assess safety and tolerability of IV eravacycline administration in the safety 
population 
• To explore PK parameters of IV eravacycline 
 
1.2. 
Study Design 
1.2.1. 
Synopsis of Study Design 
This is a non-inferiority (NI), phase 3, randomized, double-blind, double-dummy, multicenter, 
prospective study to assess the efficacy, safety, and PK of eravacycline compared with 
ertapenem. Dosing in the study arms is described in Table 1. 


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Table 1 
Study Drug Administration 
Treatment Arms 
For at Least the First 5 Doses 
After EOI through Study Drug 
Completion 
IV Infusion 
Oral Administration 
Eravacycline (IV) / 
Levofloxacin (PO) 
Eravacycline 1.5 mg/kg IV q24h 
Levofloxacin 750mg PO QD 
Ertapenem (IV) / 
Levofloxacin (PO) 
Ertapenem 1.0 g IV q24h 
Levofloxacin 750mg PO QD 
Key: EOI = End of IV Therapy; IV= Intravenous; q24h= every 24 hours; QD=once daily. Randomization Methodology 
Once an informed consent is obtained and study eligibility is established, a blinded study site 
member will obtain a subject number and a blinded study drug assignment for each subject from 
a computer-generated randomization scheme using an interactive web-based response system 
(IWRS). Randomization to eravacycline (1.5 mg/kg q24h) or ertapenem (1.0 g q24h) treatment 
arms will occur in a 1:1 ratio. For this study, enrollment is considered to occur at the time a 
subject is randomized. A subject is considered randomized when the IWRS issues a 
“confirmation of successful randomization” notification. 
Randomization will be stratified based on 2 criteria: (1) by primary site of infection 
(pyelonephritis and normal urinary tract anatomy vs all other diagnoses) and (2) by the receipt 
of a single dose of effective non-study antibiotics for the acute cUTI within 72 hours of 
enrollment (yes vs no). An enrollment cap of approximately 50% is planned for subjects with 
pyelonephritis with normal urinary tract anatomy. Also, an enrollment cap of approximately 
20% is planned for subjects who have received a single dose of effective non-study antibiotics 
for the acute cUTI within 72 hours of enrollment. 
Approximately 1200 subjects will be randomized to receive study drug. 
Subjects will be recruited at approximately 130 investigative sites worldwide. 
1.2.2. 
Stopping Rules and Unblinding 
There are no formal stopping rules for this study. 
The Sponsor designee (eg, study statistical team, IWRS vendor, etc) will have a designated 
randomization administrator who will maintain the randomization codes in accordance with 
standard operating procedures to ensure the blind is properly maintained, and that only 
personnel who require knowledge of treatment assignments will be unblinded (eg, staff involved 
in maintaining the clinical supplies or suspected unexpected serious adverse reaction reporting). 
Except for the responsible site pharmacist or designee and separate, unblinded clinical research 
associates (CRAs) to monitor drug supply and adherence to study drug blinding and 
randomization procedures, all study staff and subjects will be blinded to treatment assignment. 
The study drug treatment assignment will be unblinded only in emergency situations when 
knowledge of the treatment received is absolutely necessary for management of the subject or 
when it is in the best interest of the subject. The Investigator has unrestricted and immediate 
access to unblind the treatment code. The instructions for unblinding a subject can be found in 
the IWRS study manual. 


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In the event unblinding is necessary, the investigator is encouraged but not required to contact 
the appropriate Medical Monitor to discuss the situation and the subject’s medical status. 
When a subject’s treatment assignment is unblinded, a comprehensive source note must be 
completed by the unblinding Investigator that includes the date and time and the reason(s) the 
subject’s treatment code was unblinded. In the event the Investigator chooses to discuss the 
unblinding with the Medical Monitor, the source note must also include a record of the 
discussion. 
It is mandatory that all personnel who are involved in the unblinding and who have access to the 
unblinded treatment assignment information maintain the confidentiality of the information by 
not divulging the randomization code. 
After the database is locked and the SAP is final, the study blind codes will be broken. 
1.2.3. 
Study Procedures 
The schedule of assessments, as outlined in the study protocol, is provided in Table 2. 
Table 2 
Schedule of Assessments 
 
See footnotes below and on following page. 
Key: B/P = blood pressure; CFU = colony-forming unit; cUTI = complicated urinary tract infection; eCRF = electronic case 
report form; EOI = End of IV visit; EOT = End of Treatment visit; FU = Follow-up visit; HR = heart rate; 
IV = intravenous; PK = pharmacokinetic; PO = oral; RBC = red blood cell; RR = respiration rate; TOC = Test of Cure 
visit; WBC = white blood cell. 


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1. If Dose 1 and Screening occur on the same day then the signs and symptoms, physical exam, temperature, resting vital signs, 
and hematology/chemistry do not need to be repeated. Procedures performed as standard of care within 36 hours prior to 
randomization may be used to determine eligibility. Informed consent must be obtained prior to performing any study 
specific procedures that are not standard of care. However, urine and blood specimens collected during routine care prior to 
subject consent may be used for study purposes. If routine care results are used to determine eligibility, central laboratory 
blood tests must still be performed. 
2. If EOI occurs on the same day as a dosing day during hospitalization then the visit should be completed as an EOI visit. 
3. EOT assessments are to be performed at premature withdrawal or treatment failure and within 24-h of last dose. If EOT 
occurs on the same day as a dosing day during hospitalization then the visit should be completed as an EOT visit. 
4. A symptom directed Physical Exam should be conducted daily while in hospital. Complete physical exams should be 
performed at Screening, Day 5, EOI, EOT, TOC and FU visits. 
5. Temperature (oral, rectal, tympanic, or by temporal artery) should be assessed per institution guidelines while in hospital, 
and the highest daily value recorded in the eCRF. 
6. RR, HR, B/P at: (i) Screening, (ii) daily while in hospital, (iii) Day 5, (iv) EOI, (v) EOT, (vi) TOC, and (vii) FU. 
7. At screening visit, record all prior and concomitant medications, including all prescription, over-the-counter and herbal 
medications, taken within 1 week prior to randomization, including both day and time for all antibiotics administered in the 
72-h prior to randomization. The following subjects who have received previous/ongoing antibiotics are eligible for 
enrollment: (a) subjects with suspected acute cUTI who have received a single dose of effective non-study antibiotics for the 
acute cUTI; (b) subjects who developed signs and symptoms of cUTI while on an antibiotic for another indication. 
 
No concomitant systemic antibacterials effective in cUTI are permitted after the initial dose of study drug through the FU 
visit, other than subjects on rescue/non-study antibacterial therapy. See Protocol Section 10.6 for prohibited concomitant 
medications. 
8. Hematology and chemistry will be performed at: Screening, EOI, EOT, TOC, and FU. 
9. Urine microscopy for RBC, WBC, crystals, and casts performed at: (i) Screening, (ii) Day 5, (iii) EOI, (iv) EOT, (v) TOC, 
and (vi) FU. 
10. If creatinine clearance is <50 at Screening, creatinine clearance should be recalculated daily through Day 5 and thereafter as 
clinically indicated. Creatinine clearance should be calculated based upon local laboratory results in order to make timely 
dose adjustments, if needed; however, samples are also required to be sent to the central lab for assessment. 
Ertapenem/placebo and levofloxacin dosing should be increased or decreased according to the prescribing information. 
11. If a local serum pregnancy test is not available or results cannot be received within 4 hours of sampling at the investigative 
site then a urine pregnancy test may be utilized locally to obtain timely results for randomization. All female subjects of 
childbearing potential will have a serum pregnancy test performed by the central laboratory. 
12. Obtain a set of aerobic and a set of anaerobic samples from 2 separate venipuncture locations at Screening. Upon knowledge 
of a positive culture for a pathogen, blood cultures should be repeated until sterile (ie, both sets of cultures from 2 separate 
venipuncture sites are negative for pathogens) through the FU visit. Await results before drawing additional sets of blood 
cultures. If baseline cultures are negative, follow-up cultures should be obtained only if clinically indicated (eg, signs and 
symptoms of persistence, relapse, or new infection). 
13. Collected from a mid-stream urine specimen, a newly-placed urinary catheter, cystoscopy, suprapubic aspiration, or a 
properly disinfected collection port. 
 
Urine cultures should be processed using a calibrated loop to identify a quantitative count of bacteria at a lower limit of 103 
CFU/mL. The colony count and pathogenic microorganism(s) identification will be recorded and the purified isolate(s) will 
be sent to the central laboratory where species confirmation and antimicrobial susceptibility testing will be performed. 
14. Document any adverse events that occur from the signing of informed consent through study completion. Prior conditions 
should be documented as medical history 
15. Expected treatment duration is 7 days unless clinical failure occurs earlier; maximum treatment duration is ten days (total IV 
and PO). The 24-h interval between IV doses can be shortened (but not prolonged) by up to 2-h (ie, interval of 22-h to 24-h) 
from the first dose during doses 1-3 to adapt to a normal hospital schedule. After the third dose, the permitted IV 
administration window is q24h ± 90 minutes. At a minimum, the first 5 IV doses must be administered in an in-patient 
hospital setting; subsequent doses may be administered on an out-patient basis. Contact Medical Monitor for dosing beyond 
7 doses. 
16. Subjects should receive 7-10 days of treatment. Specific criteria for determining length of treatment are described in 
Protocol Section 11.3.3. 
17. Please refer to Protocol Section 24 for schedule of plasma PK sample collection on Day 1, Day 2, and Day 5. 


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2. 
DATA MANAGEMENT 
Data management procedures, including database design, development of the data dictionary, 
and coding of medical history, adverse events (AEs) and medications, will be performed at a 
Contract Research Organization (CRO). Data will be entered into an electronic case report form 
(eCRF) at the study sites. A series of logic and consistency checks will be conducted to ensure 
accuracy and completeness of the clinical database. One or more analysis databases, including 
detailed documentation, will be developed to support the analyses described in this SAP. Safety 
lab results, microbiology data, and pharmacokinetic data will be electronically transmitted from 
central labs. After database lock, randomization data will be provided electronically from the 
IWRS vendor. Refer to the Data Management Plan for further Data Management details. 


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3. 
SUBJECT POPULATION 
3.1. 
Population Definitions 
The subject populations defined in this section will be evaluated and used for presentation and 
analysis of the data. 
3.1.1. 
Intent-to-Treat (ITT) Population 
The ITT analysis set will consist of all randomized subjects regardless of whether or not the 
subject received study drug. 
3.1.2. 
Safety Population 
The Safety analysis set will consist of all randomized subjects who receive any amount of study 
drug. All safety analyses will be conducted in this population and will be presented in the 
summary tables by the treatment the subject actually received. A subject randomized to the 
ertapenem arm who mistakenly receives eravacycline will be included in the eravacycline arm. 
A subject randomized to the eravacycline arm who mistakenly receives ertapenem will be 
included in the ertapenem arm if ertapenem is given for the entire course of IV therapy and will 
be included in the eravacycline arm if both ertapenem and eravacycline are received. 
3.1.3. 
All Treated (MITT) Population 
The MITT population will consist of all randomized subjects who receive any amount of study 
drug. Analyses in this population will be presented in summary tables by the treatment arm to 
which the subject was randomized. 
3.1.4. 
Microbiological Intent-to-Treat (micro-ITT) Population 
The micro-ITT population will consist of all subjects in the ITT population who have at least 1 
baseline bacterial pathogen on culture of urine or blood that causes urinary tract infection 
against which eravacycline and ertapenem have expected antibacterial activity. As clinical 
breakpoints for eravacycline have not yet been determined, for the purpose of this analysis 
population, all baseline bacterial pathogens will be considered susceptible to eravacycline with 
the exception of Pseudomonas species. Analyses in this population will be presented in 
summary tables by the treatment arm to which the subject was randomized. 
To be considered a baseline pathogen, both of the following must be met: 
1. The organism must have been isolated from a suitable urine or blood specimen obtained 
between 36 hours prior to enrollment and the first dose of study drug). A suitable urine 
specimen is one collected from a clean-catch mid-stream urine specimen, a newly-placed 
urinary catheter (including uretheral catheters, supra pubic catheters, and nephrostomy 
tubes), cystoscopy, supra pubic aspiration, or a properly disinfected collection port. 
2. The baseline urine specimen must grow at least 1, but no more than 2 bacterial isolates at 
≥10^5 CFU/mL each (or at ≥10^4 CFU/mL if obtained via suprapubic aspiration, new 
nephrostomy or cystoscopy). If more than 2 bacterial isolates are identified, the urine 
culture will be considered uninterpretable unless the specimen is obtained via suprapubic 
aspiration, nephrostomy tube newly placed or cystoscopy, 1 of the isolates comprises 
≥80% of the total growth (predominant), or 1 or more isolates are also isolated 


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simultaneously from a blood culture. In the second case, only the predominant organism 
will be considered a baseline pathogen. In the latter case, only organisms isolated 
simultaneously from the urine culture and the blood culture will be considered baseline 
pathogens. 
All baseline urine cultures will be reviewed in a blinded manner by the Sponsor Microbiology 
Review Committee (MRC) for acceptability and final pathogen determination. The organism’s 
identity as determined at the local laboratory will be verified by the central laboratory. If the 
Genus identification is the same between the local and central microbiology laboratory but the 
species identification is discrepant, the central laboratory identification will be used. If the local 
laboratory grows an acceptable pathogen but the central laboratory is not able to grow the 
isolate, if isolates were lost during transportation or storage, or there are major discrepancies 
between the local and central laboratory in the identification of species, the central laboratory 
will request that the local laboratory resend the isolate. If the central laboratory is still not able 
to identify the isolate for any reason, the local laboratory determination of Genus and species 
will be used for pathogen identification. Any remaining major discrepancies in species 
identification between the central and local laboratory will be reviewed by the Sponsor MRC in 
a blinded manner for final identification of the isolate. 
There are 3 categories of pathogen identification as follows: 
1. Always a pathogen: 
• Escherichia coli 
• Klebsiella spp. 
• Proteus spp. 
• Citrobacter spp. 
• Enterobacter spp. 
• Serratia spp. 
• Providencia spp. 
• Morganella spp. 
• Other Enterobacteriaceae 
• Enterococcus spp. 
• Beta-hemolytic streptococci including: 
o Streptococcus agalactiae 
o Streptococcus pyogenes 
o Streptococcus bovis 
• Staphylococcus aureus 
• Staphylococcus saprophyticus 
• Acinetobacter spp. 


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• Corynebacterium urealyticum 
2. Not considered a pathogen: 
• Lactobacillus spp. 
• Corynebacterium spp. (EXCEPT Corynebactrium urealyticum) 
• Propionibacterium spp. 
• Viridans group streptococci, including: 
o Streptococcus oralis 
o Streptococcus mitis 
o Streptococcus salivarius 
o Streptococcus parasanguinis 
o Streptococcus milleri 
o Streptococcus constellatus 
o Streptococcus intermedius 
o Streptococcus anginosus 
o Streptococcus gordonii 
o Streptococcus sanguis 
o Streptococcus sanguinis 
o Streptococcus sobrinus 
o Streptococcus vestibularis 
o Streptococcus oralis 
o Streptococcus salivarius 
o Streptococcus mutans 
3. The following organisms will be considered pathogens if grown from urine culture at 
≥10^5 CFU/mL if obtained via a newly placed catheter or at ≥10^4 CFU/mL if obtained 
via suprapubic aspiration, new nephrostomy or cystoscopy. They will not be considered 
pathogens when grown from urine culture if obtained via midstream clean catch or a 
disinfected collection port. They will also not be considered pathogens when grown from 
blood cultures, unless simultaneously grown from urine culture at ≥10^5 CFU/mL if 


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obtained via a newly placed catheter or at ≥10^4 CFU/mL if obtained via suprapubic 
aspiration, new nephrostomy or cystoscopy: 
• Coagulase negative staphylococci, including: 
o Staphylococcus epidermidis 
o Staphylococcus hominis 
o Staphylococcus haemolyticus 
o Staphylococcus simulans 
o Staphylococcus capitis 
o Staphylococcus warneri 
• Bacillus spp. (other than B. anthracis) 
4. The following organisms will be considered non-susceptible to eravacycline or 
comparator and will NOT be analyzed as pathogens: 
o Pseudomonas spp.  
o Yeast and fungi  
5. Pathogens for MRC review: isolates will be reviewed in a blinded manner by the MRC 
on a case-by-case basis if none of rules 1 through 3 above apply. 
If more than 1 suitable urine culture specimen is obtained prior to the first dose of study drug 
therapy, and the same pathogen is isolated, the one with the highest MIC to study drug will be 
utilized in all analyses and the highest colony count will be used. If pathogens have the same 
MIC to study drug, the pathogens will be considered equivalent and a representative isolate will 
be selected from among them based on the lowest central laboratory accession number and the 
highest colony count will be used. 
3.1.5. 
Modified Microbiological Intent-to-Treat (Micro-MITT) Population 
The micro-MITT population will consist of all subjects in the micro-ITT population who receive 
at least 1 dose of study drug. Analyses in this population will be presented in summary tables by 
the treatment arm to which the subject was randomized. 
3.1.6. 
Clinically Evaluable (CE) Populations 
Five CE populations will be defined: the CE-Day 5, CE-EOI, CE-EOT, CE-TOC and CE-FU. 
Subjects will be included in or excluded from the CE populations based on the criteria listed 
below: 
1. Minimal Disease Criteria: 
Minimal disease is defined as meeting all of the following inclusion criteria: 
• Inclusion criterion 1: Male and female subjects with either: 
a. Pyelonephritis and normal urinary tract anatomy (approximately 50% of the 
total population), OR 


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b. cUTI with at least 1 of the following conditions associated with a risk for 
developing cUTI: 
i. 
Indwelling urinary catheter 
ii. 
Urinary retention (at least approximately 100 mL of residual urine 
after voiding) 
iii. 
History of neurogenic bladder 
iv. 
Partial obstructive uropathy (eg, nephrolithiasis, bladder stones, and 
ureteral strictures) 
v. 
Azotemia of renal origin (not Congestive Heart Failure (CHF) or 
volume related) such that the serum blood urea nitrogen (BUN) is 
elevated (> 20 mg/dL) AND the serum BUN: creatinine ratio is < 15 
vi. 
Surgically modified or abnormal urinary tract anatomy (eg, bladder 
diverticula, redundant urine collection system, etc) EXCEPT surgery 
within the last month (placing of stents or catheters is not considered 
to be surgical modification) 
• Inclusion criterion 4: At least 2 of the following signs or symptoms: 
a. Chills, rigors, or warmth associated with fever (oral, rectal, tympanic, or by 
temporal artery temperature > 100.4°F / 38°C) or hypothermia (oral, rectal, 
tympanic, or by temporal artery temperature < 95°F / 35°C) 
b. Flank pain (pyelonephritis) or pelvic pain (cUTI) 
c. Nausea or vomiting 
d. Dysuria, urinary frequency, or urinary urgency 
e. Costo-vertebral angle tenderness on physical examination 
• Inclusion criterion 5: Urine specimen with evidence of pyuria: 
a. Dipstick analysis positive for leukocyte esterase, OR 
b. ≥ 10 white blood cells per cubic millimeter, OR 
c. ≥ 10 white blood cells per high power field 
2. Prior Antibiotic Therapy: 
Subjects who receive only a single dose of effective non-study antibiotics in the 72 hours 
prior to randomization can be enrolled in the study. Subjects who receive more than a 
single dose of effective non-study antibiotics in the 72 hours prior to randomization will 
be excluded from the CE populations. 


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3. Concomitant Antibiotic Therapy: 
Subjects who receive any systemic concomitant antibiotic therapy from the first dose of 
study drug through the Day 5 Visit (CE-Day 5 population), EOI Visit (CE-EOI 
population), EOT Visit (CE-EOT population), TOC Visit (CE-TOC population) and FU 
Visit (CE-FU population) that is potentially effective against the baseline pathogen will 
be excluded from the CE populations with the following exceptions: 
• The subject is a clinical failure at Day 5 (CE-Day 5 population), EOI (CE-EOI 
population), EOT (CE-EOT population), TOC (CE-TOC population) or FU 
(CE-FU population) and received non-study antibiotics for insufficient 
therapeutic effect of the study drug 
• The subject received an oral antibiotic with no systemic absorption 
Subjects who do not have a pathogen isolated at baseline and receive an antibiotic with 
expected activity against cUTI pathogens will also be excluded from the CE populations 
unless considered a failure by the Investigator at Day 5, EOI, EOT, TOC or FU and 
received non-study antibiotics for insufficient therapeutic effect of the study drug. 
Subjects who receive a systemic concomitant antibiotic that is not effective against the 
baseline pathogen, or if no pathogen is isolated and the antibiotic does not have activity 
against cUTI pathogens, will be included in the CE populations. 
4. Study Drug Therapy: 
Subjects must meet all of the following to be included in the CE populations: 
• Received the correct study drug based on the randomization assignment for the 
entire treatment period 
• Study personnel involved in the assessment of efficacy or monitoring efficacy 
data remained blinded to treatment assignment, unless a treatment limiting AE 
occurred which required unblinding 
• The subject received at least 3 days of study drug 
• The subject was at least 80% compliant with study drug 
5. Clinical Outcome Assessment: 
Subjects must meet the following to be included in the CE populations: 
• For the CE-Day 5 population: 
o Completed the Investigator’s assessment of clinical response (ie, was not 
deemed an indeterminate outcome) at the Day 5 Visit 
o The Day 5 Visit occurred 4-6 days following randomization 
• For the CE-EOI population: 
o Completed the Investigator’s assessment of clinical response (ie, was not 
deemed an indeterminate outcome) at the EOI Visit 


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o The EOI Visit occurred within 1 day of the last dose of IV study drug 
• For the CE-EOT population: 
o Completed the Investigator’s assessment of clinical response (ie, was not 
deemed an indeterminate outcome) at the EOT Visit 
o The EOT Visit occurred within 1 day of the last dose of study drug (IV or 
PO) 
• For the CE-TOC population: 
o Completed the Investigator’s assessment of clinical response (ie, was not 
deemed an indeterminate outcome) at the TOC Visit, unless the patient 
was defined as a clinical failure at the EOT Visit 
o The TOC Visit occurred 13-18 days following randomization and at least 
5 days following the last dose of study drug, unless the subject was 
considered to be a clinical failure based on the Investigator’s assessment 
at the EOT Visit 
• For the CE-FU population: 
o Completed the Investigator’s assessment of clinical response (ie, was not 
deemed an indeterminate outcome) at the FU Visit, unless the patient was 
defined as a clinical failure at the EOT or TOC Visits. 
o The FU Visit occurred 20-29 days following randomization, unless the 
subject was considered to be a clinical failure based on the Investigator’s 
assessment at the EOT or TOC Visits. 
6. Baseline or Inter-Current Medical Events: 
Subjects will be excluded from the CE populations if the Investigator has documented in 
the eCRF that they meet any 1 of the following protocol-defined exclusion criteria at 
baseline (ie, prior to randomization): 
• Exclusion criterion 2: History of an ertapenem-resistant urinary tract infections 
within 1 year of consent 
• Exclusion criterion 3: Likely to require > 10 days of antibiotic treatment to cure 
the acute cUTI or likely to receive ongoing antibacterial drug prophylaxis prior 
to the FU visit (eg, subjects with vesiculo-ureteral reflux) 
• Exclusion criterion 6: Complicated pyelonephritis with complete obstruction or 
known or suspected renal or perinephric abscess, emphysematous pyelonephritis, 
OR Any condition likely to require surgery to achieve cure (this does NOT 
include procedure to place catheters or obtain diagnosis) 
• Exclusion 7: Known or suspected fungal infection 
• Exclusion 8: Uncomplicated lower urinary tract infection 


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• Exclusion 9: Suspected or confirmed active prostatitis, or currently under 
treatment for prostatitis 
• Exclusion 10: Subjects with high risk for cUTI due to Pseudomonas sp. (eg, 
History of prior cUTIs due to Pseudomonas, ≥ 20 mg QD prednisone or 
equivalent steroid, and other risk factors as perceived by the investigator) 
3.1.7. 
Microbiologically Evaluable (ME) Populations 
The ME-Day 5, ME-EOI, ME-EOT, ME-TOC and ME-FU populations will consist of all 
subjects in the micro-ITT and the CE-Day5, CE-EOI, CE-EOT, CE-TOC, CE-FU populations, 
respectively who also meet the following: 
• Had a suitable urine specimen (as defined in Section 3.1.4) collected at the Day 5 (ME-
Day 5), EOI (CE-EOI), EOT (ME-EOT), TOC (ME-TOC) and FU (ME-FU) Visits. 
Subjects who are microbiological failures prior to the TOC or FU Visit, and are 
otherwise evaluable, will be included in the ME-TOC and ME-FU populations 
regardless of when the TOC and FU visits occurred. 
• The urine culture at the Day 5 (ME-Day 5), EOI (ME-EOI), EOT (ME-EOT), TOC 
(ME-TOC) and FU (ME-FU) Visits is interpretable with respect to determining 
microbiological outcome. An interpretable urine culture is one that has a clearly 
identified pathogen or one where the baseline pathogen(s) can be excluded. A urine 
culture will be considered uninterpretable if more than 2 bacterial isolates are identified 
unless the specimen is obtained via suprapubic aspiration, nephrostomy tube newly 
placed or cystoscopy, 1 of the isolates comprises ≥80% of the total growth 
(predominant), 1 or more isolates are also isolated simultaneously from a blood culture, 
or there is <10^4 CFU/mL (including no growth) of the baseline pathogen(s). 
3.2. 
Evaluability Review 
3.2.1. 
Membership and Responsibilities 
The MRC will be responsible for reviewing microbiological data, including pathogen 
determination, as outlined in the Microbiological Outcomes Review Plan. The Evaluability 
Review Committee (ERC) will review clinical and microbiological data to assess inclusion in or 
exclusion from the CE populations as outlined in the Clinical Evaluability Review Plan. MRC 
and ERC members will be blinded to treatment assignment and will review the data concurrent 
with the conduct of the study. Final pathogen determinations and inclusion in analysis 
populations will be determined prior to database lock except for those criteria which require 
unblinded data (for example, determination of whether or not the subject received the study drug 
to which s/he was randomized). 
3.2.2. 
Process for Determining Inclusion in Analysis Populations 
Inclusion into the ITT and Safety populations will be determined programmatically from the 
eCRF data. Inclusion into the CE populations will be determined programmatically from the 
eCRF data and the manual review conducted by the ERC. 
Inclusion into the micro-ITT population will be determined programmatically by incorporating 
the outcome of the review of the isolates by the MRC. The MRC will determine whether each 


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isolate (baseline and post-baseline) is considered a pathogen based on a review of information 
regarding baseline samples such as method of collection of the specimen, CFU/mL, local and 
central genus and species identification. Inclusion into the ME and micro-MITT populations 
will be determined programmatically. 
3.3. 
Protocol Deviations 
Deviations will be reviewed by the Sponsor and categorized into general categories such as: 
informed consent, inclusion/exclusion criteria, randomization procedure, subject visit 
completion or timing, study procedure or assessment, study medication, excluded concomitant 
medication, and (serious) AE reporting. The number of subjects with at least 1 protocol 
deviation, the number of subjects with a minor protocol deviation, the number of subjects with a 
major deviation, and the number of subjects with at least 1 major deviation in each category will 
be presented by treatment group for the ITT population. A major deviation is defined as one that 
potentially affects the efficacy and/or safety analyses and will be determined by a review by the 
Sponsor in accordance with the Protocol Deviations Review Plan. 
All protocol deviations will be presented in a data listing. 


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4. 
GENERAL STATISTICAL METHODS 
4.1. 
Sample Size Justification 
This study is designed to demonstrate NI of eravacycline to ertapenem in the co-primary 
efficacy measures of responder outcome at the EOI and TOC visits in the micro-ITT population. 
An NI margin of 10% will be used which is based on historical data regarding the treatment 
effect of antibiotics. A 10% NI margin for the efficacy measure of responder outcome is robust 
and can sufficiently confirm a clinically meaningful treatment effect of eravacycline in the 
treatment of cUTI. 
The sample size calculation is based on ensuring sufficient power for the co-primary efficacy 
outcomes for the FDA as well as the co-primary efficacy outcomes for the EMA (which are 
secondary efficacy outcomes for the FDA). Using a 10% NI margin, one-sided alpha of 0.025, 
80% power, response rates at TOC of 71% in the eravacycline group and 72% in the ertapenem 
group, and the sample size methodology of Farrington and Manning, a total of 395 subjects per 
arm in the micro-ITT population is required. This sample size provides >90% power for the 
response rates at EOI assuming the response rates are 93% and 94% in the eravacycline and 
ertapenem groups, respectively. A sample size of approximately 1200 randomized subjects 
should provide sufficient numbers for this study, assuming 66% of enrolled subjects will meet 
the requirements for inclusion in the micro-ITT population. 
For the EMA, it is assumed that 65% of the randomized subjects will be in the micro-MITT 
population and 60% in ME population. The microbiological success rates at TOC are assumed 
to be 79% and 82% in both treatment groups in the micro-MITT and ME populations, 
respectively. With these assumptions, using an NI margin of 10%, a one-sided alpha of 0.005, 
and the sample size methodology of Farrington and Manning, there is at least 80% power to 
show NI for the co-primary efficacy outcomes. The power calculations are summarized in 
Table 3 based on a total of 1200 randomized subjects. 
Table 3 
Assumptions of Sample Size Calculations 
 
 
 
Outcome Rates 
 
 
Outcome/Pop
ulation 
Alpha level 
(one-sided) 
Evaluability 
Rate 
ERV 
ERT 
Total N 
Power 
FDA 
Outcomes 
 
 
 
 
 
 
Responder at 
EOI/ 
micro-ITT 
0.025 
66% 
93% 
94% 
790 
>99% 
Responder at 
TOC/ 
micro-ITT 
0.025 
66% 
71% 
72% 
790 
80.0% 
 
 
 
 
 
 
 
EMA 
Outcomes 
 
 
 
 
 
 
Microbiologica
l Success at 
0.005 
65% 
79% 
79% 
780 
79.8% 


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TOC / micro-
MITT 
Microbiologica
l Success at 
TOC / ME-
TOC 
0.005 
60% 
82% 
82% 
720 
84.7% 
Key: ERV = Eravacycline; ERT = Ertapenem; EMA = European Medicines Agency; FDA = Food and Drug Administration; 
ITT = Intent-to-Treat; ME = Microbiologically Evaluable; Micro-MITT = Modified Microbiological Intent-To-Treat;           
TOC = Test of Cure. 
4.2. 
General Methods 
All tabular summaries will present results by treatment. Listings will present data by treatment, 
country, subject number, and visit (as applicable). 
For purposes of all analysis and reporting, days will be numbered relative to the first day of 
dosing. Day 1 will be defined as the date on which a subject receives the first dose of study 
drug, as recorded on the eCRF. The day prior to the first dose of study drug is Day –1; there is 
no Day 0. 
Duration variables will be calculated using the general formula (end date - start date) +1. 
Appropriate descriptive statistics will be computed and displayed for both continuous and 
categorical variables. For continuous variables, descriptive statistics will include n (the number 
of subjects with non-missing data), mean, standard deviation (SD), median, minimum, and 
maximum values. For categorical parameters, the number and percentage of subjects within 
each category will be presented. The denominator for percentage will be based on the number of 
subjects with non-missing data appropriate for summary purposes. Unless otherwise noted, all 
percentages will be presented to 1 decimal place. 
Sort order for data listings will be subject number, visit, and time point where appropriate. 
All output will be incorporated into Microsoft Word or Excel files, or Adobe Acrobat PDF files, 
sorted and labeled according to the International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) recommendations, and formatted to 
the appropriate page size(s). 
If the reported value of a clinical laboratory parameter cannot be used in a statistical summary 
table (eg, a character string is reported for a parameter of the numerical type), a coded value 
must be appropriately determined and used in the statistical analyses. In general, a value or 
lower and upper limit of normal (ULN) range such as “<10” or “≤5” will be treated as “10” or 
“5” respectively, and a value such as “>100” will be treated as “100.” However, the actual 
values as reported in the database will be presented in data listings. Values that are out of range 
will be marked as ‘H’ or ‘L.’ 
Individual patient listings supporting the analyses specified in the SAP will be provided to 
facilitate the investigation of tabulated values and to allow for the clinical review of all efficacy 
and safety parameters. Available data at each time point will be presented. Missing data will not 
be imputed except as noted in Section 4.6. 


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4.3. 
Computing Environment 
All descriptive statistical analyses will be performed using SAS statistical software Version 9.3 
or higher, unless otherwise noted. Medical history and AEs will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA) Version 20.0. Concomitant medications will be 
coded using the World Health Organization (WHO) Drug Dictionary Version March 2016 
Format B. 
4.4. 
Baseline Definitions 
The last assessments/measurements prior to the first dose of study drug will be used as the 
baseline reference for all analyses unless stated otherwise. 
4.5. 
Withdrawals, Dropouts, Loss to Follow-up 
Subjects who are randomized and withdraw prematurely from the study will not be replaced. 
4.6. 
Missing, Unused, and Spurious Data 
Missing data will be handled as outlined below: 
• All missing and partial dates for events occurring after randomization or for medications 
received after randomization will be queried for a value. If no value can be obtained, 
substitutions will be made as follows: 
o For date of cUTI diagnosis, if the day is missing, day will be defined as “01.” If 
the month and day are missing, no imputation will be made. For start dates, 
missing months and days will be defined by “01,” as long as this occurs on or 
after the first dose of study drug. If the algorithm produces a date prior to the first 
dose of study drug, the date of the first dose of study drug will be used for the 
partial date. For stop dates, missing months will be defined as “12” and days will 
be defined by the last day of the respective month. If the algorithm produces a 
date after the study discontinuation/completion date, the date of study 
discontinuation/completion will be used for the partial date. These substitutions 
will be used in calculations; however, the actual value recorded on the eCRF will 
be used for all listings. 
o Missing times for AEs will be queried for a value. If no value can be obtained 
and for all other times for events and assessments occurring after randomization, 
the time will not be imputed but will remain missing. 
• The severity and causality assessment for AEs should not be missing and will be queried 
for a value. Should there be missing data, AEs with missing severity will be considered 
severe and AEs with missing relationship to study drug will be considered related to 
study drug. 
• For clinical and microbiological response, missing data will be handled as follows: 
o For the outcome measure of clinical response: 
 Subjects will be defined as an indeterminate if the Investigator cannot 
determine whether the subject is a clinical cure or failure. Outcome will 
be defined as missing if the Investigator did not complete the assessment, 


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or if the subject did not complete the study visit. For the purposes of 
analysis missing data will be considered indeterminate, and by definition, 
subjects with an indeterminate response are included in the denominator 
for analyses in the ITT, micro-ITT and micro-MITT analysis sets, and 
thus, are considered failures. Subjects with an indeterminate response are 
excluded from the CE and ME populations. 
o For outcome measure of microbiologic response: 
 If no interpretable post-baseline specimen is available, the 
microbiological response is considered indeterminate. By definition, 
subjects with an indeterminate response are included in the denominator 
for analyses in the micro-ITT and micro-MITT populations and thus, are 
considered failures. Subjects with an indeterminate response are excluded 
from the ME populations. 
o Missing values for other individual data points will remain as missing. Missing 
values will not be imputed and only observed values will be used in data analyses 
and presentations. 
o Where individual data points are missing, categorical data will be summarized 
based on reduced denominators (ie, only subjects with available data will be 
included in the denominators). 
4.7. 
Interim Analyses 
A blinded assessment of the proportion of subjects qualifying for the micro-ITT population will 
be conducted after approximately 800 subjects have been randomized. If the micro-ITT 
proportion is lower than used in the sample size determination, the sample size may be 
increased to ensure the study is sufficiently powered. The sample size will not be reduced if the 
micro-ITT proportion is higher than expected. 
A blinded assessment of the overall (aggregated across treatment groups) responder rate 
(clinical cure and microbiological success) at the TOC visit will be conducted following the 
completion of approximately 800 subjects. If the overall blinded responder rate is less that the 
rate used in the sample size calculation for the eravacycline group (71%), the sample size will 
be increased as needed to ensure 80% power. The sample size will not be decreased if the 
overall blinded responder rate is greater than the rate used in the sample size calculation. No 
adjustment to the overall alpha level is required since the sample size adjustment is based on the 
overall (aggregated across treatment groups) responder rate. 
A separate analysis plan will be developed for the interim analysis.  
4.8. 
Visit Windows 
Visits will be planned to occur during the visit windows defined in Table 2. If visits occur 
outside of the defined windows, data will still be collected. All data will be included in by-
patient listings. For efficacy and safety analyses, analysis visits will be derived as outlined in 
Table 4. 


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Table 4 
Derived Analysis Visits for Efficacy and Safety Analyses 
Visit 
ITT, micro-ITT, and 
micro-MITT Efficacy 
Analysis Window1 
CE and ME Efficacy Analysis 
Window 
Safety Analysis Window2 
Day 5 
N/A 
4-6 Days after Randomization 
4-6 Days after Randomization 
EOI 
N/A 
Within 1 day of last dose of IV 
study drug 
Within 1 day of last IV dose of 
study drug 
EOT 
N/A 
Within 1 day of last dose of study 
drug (IV or PO) 
Within 1 day of last dose of study 
drug (IV or PO) 
TOC 
N/A 
13 – 18 Days after Randomization 
& >=5 Days after last dose 
14-17 Days after Randomization 
& >=5 Days after last dose 
FU 
N/A 
20-29 Days after Randomization 
21-28 Days after Randomization 
Key: EOI = End of IV; EOT = End of Treatment; FU = Follow-up; ITT = Intent-to-Treat; MITT = Modified Intent to Treat       
IV = Intravenous; N/A = Not Applicable; PO = Per Oral; TOC = Test of Cure. 
1. 
For ITT, micro-ITT, and micro-MITT analyses, visit windows are nominal. 
2. 
If out of window, the visit will be considered an unscheduled visit. 


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5. 
STUDY ANALYSES 
5.1. 
Subject Disposition 
The number and percentage of subjects included in each of the analysis populations (ie, ITT, 
Safety, MITT, micro-ITT, micro-MITT, CE-Day 5, CE-EOI, CE-EOT, CE-TOC, CE-FU, ME-
Day 5, ME-EOI, ME-EOT, ME-TOC, ME-FU) will be summarized by treatment group, 
geographic region and country. Regions are as follows: European Union (Austria, Bulgaria, 
Estonia, Hungary, Latvia, Poland, Romania, Slovakia), Non-European Union Europe (Republic 
of Moldova, Russia, and Ukraine, Georgia), and North America (United States). Tables will 
summarize the reasons for exclusion from each population and a listing will be provided that 
indicates each subject’s inclusion/exclusion from the analysis population and the reason for 
exclusion from each analysis population. The number and percentage of subjects enrolled at 
each site within each country will also be provided by treatment arm and overall. 
The number and percentage of subjects completing the study, prematurely discontinuing from 
study drug, and prematurely withdrawing from the study will be presented for each treatment 
group for the ITT, micro-ITT, micro-MITT and ME-TOC populations. Reasons for premature 
discontinuation of study drug and/or premature withdrawal from the study as recorded on the 
eCRF will be summarized (number and percentage) by treatment group. Percentages of subjects 
discontinued from study drug and withdrawals from the study will be compared between 
treatment groups using Fisher’s exact test. A listing of all subjects who prematurely 
discontinued from study drug or prematurely withdrew from the study will be presented, and the 
primary reason for discontinuation of study drug or withdrawal from the study will be provided. 
5.2. 
Demographics and Baseline Characteristics 
Demographic data and baseline characteristics will be presented by treatment group for the ITT, 
micro-ITT, micro-MITT and ME-TOC populations. A table will present the subject 
demographics (eg, gender, age, ethnicity and race) and baseline characteristics (height, weight, 
BMI, and creatinine clearance) collected before the start of study drug. Age, as collected on the 
eCRF, will be summarized as both a continuous and categorical variable (<65, 65-75 and >75 
years). Creatinine Clearance will be summarized as both a continuous and categorical 
(<15ml/min, 15 - <60ml/min, >=60, >=130ml/min) variable. 
5.3. 
Medical History and Disease History 
Medical history will be coded using the MedDRA classification, version 20.0. Medical history 
will be summarized by system organ class (SOC) and preferred term by treatment group for the 
ITT and micro-ITT populations. Subjects reporting the same SOC or preferred term more than 
once will be counted only once for that SOC and preferred term. 
The primary site of infection at baseline (pyelonephritis and normal urinary tract anatomy, cUTI 
with indwelling urinary catheter, urinary retention, neurogenic bladder, partial obstructive 
uropathy, with azotemia of renal origin or with surgically modified/abnormal urinary tract 
anatomy, or other diagnosis) will be summarized by treatment group for the micro-ITT, micro-
MITT and ME-TOC populations. 
Signs and symptoms related to the cUTI (chills rigors, fever, hypothermia, flank pain, pelvic 
pain, nausea, vomiting, dysuria, urinary frequency, urinary, urgency, cost-vertebral angle 


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tenderness) will be summarized as none, mild, moderate or severe at baseline by treatment 
group for the micro-ITT, micro-MITT and ME-TOC populations. Descriptive statistics (mean, 
SD, median, minimum and maximum value) for baseline temperature (highest daily 
temperature) will also be presented by treatment group. 
5.4. 
Baseline Microbiology 
The microbiological assessment of the baseline blood and urine specimens will be summarized 
by treatment group for the micro-ITT, micro-MITT and ME-TOC populations. The number and 
percentage of subjects with a suitable urine specimen obtained, the number of isolates obtained 
and whether or not the culture was interpretable will be summarized by treatment group. The 
distribution of the urine collection methods will also be presented. 
The pathogenic organisms identified from the baseline blood culture or urine culture specimens 
will be presented. The number and percentage of subjects with gram-negative organisms 
(aerobes), overall and within Enterobacteriaceae and non-Enterobacteriaceae, gram-positive 
organisms (aerobes) and all anaerobes will be presented by genus and species for the micro-ITT, 
micro-MITT and ME-TOC populations overall and by primary site of infection (pyelonephritis 
and normal urinary tract anatomy vs. all other diagnoses). The same pathogen identified from 
both the blood and the urine culture will be counted only once in the summary. The pathogenic 
organisms identified at baseline from a blood sample will also be presented separately for the 
micro-ITT population, micro-MITT and ME-TOC populations. The number and percentage of 
subjects with levofloxacin resistant and ertapenem resistant organisms will also be presented. 
The number and percentage of subjects with monomicrobial (gram-negative aerobe, gram-
positive aerobe, anaerobe) and poly-microbial infections (gram-negative aerobes only, gram-
positive aerobes only, anaerobes only, gram-negative aerobe and anaerobe, gram-positive 
aerobe and anaerobe, gram-negative and gram-positive aerobe, and gram-negative aerobe, gram-
positive aerobe and anaerobe) will be provided for specimens from the blood or urine culture. 
Several tables providing the frequency distribution of the minimum inhibitory concentrations 
(MIC) by pathogen as reported by the central laboratory will be provided for the micro-ITT, 
micro-MITT and ME-TOC populations: 
• The MIC distribution to eravacycline of the baseline pathogens. 
• The MIC distribution to ertapenem of the baseline pathogens. 
• The MIC distribution to levofloxacin of the baseline pathogens. 
• The MIC distribution to the study drug received of the baseline pathogens. For those 
subjects who received the wrong study drug, the summary will be based on actual 
treatment received. 
• MIC summary statistics (ie, range, MIC50 and MIC90) for baseline pathogens to the 
study drug received. Range will be reported for all pathogens, MIC50 and MIC90 will 
only be reported for those pathogens with at least 10 isolates in either treatment group. 
5.5. 
Prior and Concomitant Medications 
Prior medications will be summarized by WHODRUG (Version March 2016 Format B) 
Anatomical Therapeutic Chemical Classification (ATC) level 4 (fourth level indicates the 
chemical/therapeutic/pharmacologic subgroup) and 3 (third level indicates the 


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therapeutic/pharmacologic subgroup). Medications are considered prior if taken prior to the first 
dose of study drug or if their start date is unknown. Subjects will be counted only once for an 
ATC class. Concomitant medications taken during the study treatment period will be similarly 
summarized. Medications are considered concomitant if taken on or after the first dose of study 
drug, or if their stop date is unknown or marked as continuing. 
The proportion of subjects who receive the following prior and concomitant medications will be 
summarized by treatment group: 
• Systemic antibacterial medications effective in cUTI taken prior to the first dose of study 
drug (micro-ITT, micro-MITT and ME-TOC populations) 
• Systemic antibacterial medications (excluding study drug) taken between first dose of 
study drug and the TOC visit (micro-ITT, micro-MITT and ME-TOC populations) 
• Non-antibacterial medications prior to the first dose of study drug (ITT and Safety 
populations) 
• Non-antibacterial medications taken from the first dose of study drug through the FU 
visit (Safety population) 
5.6. 
Study Drug Exposure and Compliance 
Exposure to study drug (IV and oral) will be characterized by the total duration of treatment (IV 
and oral), duration of IV treatment, the number of infusion days, the number of active doses (IV 
only), total IV dose received, the average daily dose over all infusion days, duration of PO 
treatment, and the number of PO days. Descriptive statistics for each measure of exposure to 
study drug will be summarized by treatment group for Safety, micro-ITT, and micro-MITT 
populations. 
Duration of treatment is defined as the number of days from when the subject first received 
study treatment until the day that they last received study treatment and is calculated as (date of 
last dose – date of first dose +1). Total duration of treatment (IV and PO), Duration of IV 
treatment and Duration of PO treatment will be calculated separately. 
An infusion day is the 24-hour period during which the full daily dose of study drug is to be 
administered. An infusion day can be coincidental with a calendar day or can start in the 
afternoon of 1 day and complete in the morning of the next day. 
Number of PO days would be calculated as: 
Number of PO days = [Duration of PO days – Number of days dose was missed] 
Study drug (IV only) is administered in mg/kg for the eravacycline arm and in g for the 
ertapenem arm. Actual daily dose in mg is dependent on the treatment received, weight (in the 
case of eravacycline), the volume of drug administered (recorded on the eCRF), and the volume 
of drug prepared (recorded on the eCRF), as follows: 
For eravacycline: 
actual daily dose (mg) = 1.5 * weight (kg) * (total volume of drug administered for dose) 
/ (total volume of drug prepared for dose) 


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For ertapenem: 
actual daily dose (mg) = 1000 * (total volume of drug administered for dose) / ( total 
volume of drug prepared for dose) 
The average daily dose of eravacycline, expressed as mg and as mg/kg, is based on the dose of 
active drug per infusion day, as follows: 
average daily dose (mg) = Σactual daily dose (mg) eravacycline over all doses / number 
of infusion days 
average daily dose (mg/kg) = average daily dose (mg) / screening weight (kg) 
It is expected that the average daily dose of eravacycline will be approximately 1.5 mg/kg. 
The average daily dose of ertapenem, expressed in mg, is based on the dose of active drug per 
infusion day, as follows: 
average daily dose (mg) = Σactual daily dose (mg) meropenem over all doses / number 
of infusion days 
The duration of infusions will be listed and deviations from the dosing regimen will be 
presented. 
Treatment compliance will be based on expected doses of study drug (IV and oral) received and 
will be calculated as the number of doses received/expected number of doses received. The 
expected number of active doses received is based on the number of days the subject received 
study drug. A dose is defined as receipt of any amount of study drug received regardless of 
whether the full volume was infused. 
Descriptive statistics of percent compliance as well as the number and percentage of subjects at 
least 80% compliant will be provided by treatment group for the Safety, micro-ITT, micro-
MITT and ME populations. 
5.7. 
Efficacy Evaluation 
For all efficacy analyses, subjects will be analyzed in the group to which they were randomized. 
By definition, subjects who receive the wrong study drug are not included in the CE and ME 
populations. For the primary analysis, subjects who are randomized to the wrong primary site of 
infection stratum will be analyzed in the stratum to which they were randomized. 
5.7.1. 
Primary Efficacy Analysis 
The primary outcome measure is a responder outcome derived from both clinical response and 
microbiological response at the EOI and the TOC Visit in the micro-ITT population. 
Clinical Response: 
Clinical response is based on the Investigator Responses on the CRF and is not derived 
programatically. Clinical response is classified by the Investigator as cure, failure or 
indeterminate based on the following definitions: 
• Clinical Cure: Clinical cure is defined as complete resolution or significant improvement 
of signs and symptoms of the infection such that no rescue/non-study antibacterial 
therapy is required to treat the cUTI that presented at study entry 


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• Clinical Failure: Subjects are classified as a clinical failure based on: 
o Death related to cUTI at any time point 
o Persistence of clinical symptoms of cUTI or new symptoms have developed 
o Initiation of rescue/non-study antibacterial drug therapy for cUTI 
• Indeterminate/Missing: If the subject’s outcome is neither clinical cure nor clinical 
failure, then the outcome should be listed as indeterminate/missing, including death 
where the cUTI is clearly noncontributory. If the Investigator did not complete an 
assessment or if the subject did not complete the study visit, the outcome is considered 
missing 
Subjects who are assessed as a clinical failure at the EOT visit or beyond will have the failure 
carried forward to all subsequent visits. 
Data for all subjects will be reviewed to ensure the Investigators are following the protocol 
defined criteria for clinical response and queries will be issued as needed to clarify any response 
that does not meet the protocol definition. 
Microbiologic Response: 
Per-subject microbiological response is defined as follows: 
• Microbiological success: 
o Reduction of the baseline pathogen(s) to <10^4 CFU/mL 
• Microbiological failure: 
o Blood cultures are positive for the baseline pathogen(s), or 
o Urine culture grows ≥10^4 CFU/mL of the baseline pathogen(s) 
• Microbiological Indeterminate/Missing: No interpretable urine culture data are available 
The primary efficacy outcome is defined in Table 5. 
Table 5 
Primary Efficacy Outcome 
Primary Efficacy Outcome 
Clinical Response 
Microbiological Response 
Responder Outcome 
Cure 
Success 
Responder 
Cure 
Failure 
Non-responder 
Cure 
Indeterminate / Missing 
Indeterminate 
Failure 
Success 
Non-responder 
Failure 
Failure 
Non-responder 
Failure 
Indeterminate / Missing 
Non-responder 
Indeterminate / Missing 
Success 
Indeterminate 
Indeterminate / Missing 
Failure 
Non-responder 
Indeterminate / Missing 
Indeterminate / Missing 
Indeterminate 


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For the micro-ITT population, the proportion of micro-ITT subjects with a response is defined 
using the following formula (where the denominator adds to the total number of subjects in the 
micro-ITT population): 
Number of subjects with response 
(Number of subjects with a response + Number of subjects with a non-response + Number of 
subjects with an indeterminate response) 
The primary efficacy analyses will be based on the micro-ITT population. The NI test will be a 
one-sided hypothesis test performed at the 2.5% level of significance. This NI test will be based 
on the lower limit of the two-sided 95% confidence interval (CI) for both EOI and TOC Visits. 
The primary efficacy outcome is the percentage of subjects with an outcome of responder 
(clinical cure and microbiological success) at the EOI and TOC Visits. The primary analysis is 
unadjusted. 
The number and percentage of subjects in each treatment group defined as a responder, non-
responder and indeterminate/missing will be tabulated. The null and alternative hypotheses are 
as follows: 
𝐻𝐻0: 𝑝𝑝1 −𝑝𝑝2 ≤−∆ and 𝐻𝐻1: 𝑝𝑝1 −𝑝𝑝2 > −∆ 
Where p1 is the responder rate in the eravacycline treatment group, p2 is the responder rate in 
the ertapenem treatment group, and Δ is the NI margin of 10%. Note: For H0, outcomes at both 
EOI and TOC visits will be considered. For H1, outcomes at EOI or TOC visits will be 
considered. 
To test the null hypothesis, two-sided 95% CIs for the observed difference in responder rates 
(eravacycline treatment group minus ertapenem treatment group) will be calculated for the 
micro-ITT population for the EOI and TOC Visits. If the lower limit of both (EOI and TOC 
Visits) 95% CIs for the difference in responder rates in the micro-ITT analysis set exceeds –
10%, then the null hypothesis will be rejected and the NI of eravacycline to ertapenem will be 
declared. 
The two-sided 95% CIs for NI testing based on the difference of responder rates at the EOI and 
TOC Visits, will be computed using the method proposed without stratification by Miettinen 
and Nurminen (Miettinen 1985). For notation purposes, assume 1 represents the eravacycline 
group (Group 1) and 2 represents the ertapenem group (Group 2). 
Based on Miettinen and Nurminen, the 2-sided 95% CI is given by the roots for 
𝑅𝑅𝑅𝑅= 𝑝𝑝1 −𝑝𝑝2of the following equation: 
𝜒𝜒𝛼𝛼
2 = (𝑝𝑝̂1 −𝑝𝑝̂2 −𝑅𝑅𝑅𝑅)2
𝑉𝑉
 
Where 𝜒𝜒𝛼𝛼
2 is the cut point of size 𝛼𝛼 from the chi-square distribution (𝜒𝜒𝛼𝛼
2 = 3.84 for 2-sided 95% 
CI), 𝑅𝑅𝑅𝑅 is the difference between the 2 true rates (𝑅𝑅𝑅𝑅= 𝑝𝑝1 −𝑝𝑝2), 𝑝𝑝̂1is the observed average 
proportion in the eravacycline group (Group 1), 𝑝𝑝̂2 is the observed average proportion in the 
ertapenem group (Group 2), and 


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𝑉𝑉= ቈ𝑝𝑝෤1(1 −𝑝𝑝෤1)
𝑛𝑛1
+ 𝑝𝑝෤2(1 −𝑝𝑝෤2)
𝑛𝑛2
቉
𝑛𝑛1 + 𝑛𝑛2
𝑛𝑛1 + 𝑛𝑛2 −1 
Where 𝑛𝑛1 is the number of subjects in the eravacycline group (Group 1), 𝑛𝑛2 is the number of 
subjects in the ertapenem group (Group 2), and 𝑝𝑝෤1 and 𝑝𝑝෤2 are the maximum likelihood 
estimators for the responder rates in the eravacycline and ertapenem groups, respectively, and 
computed under the constraint that 𝑝𝑝෤1 −𝑝𝑝෤2 = 𝑅𝑅𝑅𝑅. 
As stated above, the 2-sided 95% CI for the difference in rates is given by the roots for 𝑅𝑅𝑅𝑅=
𝑝𝑝1 −𝑝𝑝2 from the equation above, but this equation does not allow for explicit solution for 𝑅𝑅𝑅𝑅. 
Therefore, a numerical algorithm will be used to obtain the 2 roots (CI) for 𝑅𝑅𝑅𝑅. This CI 
approach corresponds to the NI test (a p-value approach) proposed by Farrington and Manning. 
5.7.1.1. 
Additional Analyses of the Primary Efficacy Outcome 
If eravacycline is determined to be non-inferior to ertapenem, superiority of eravacycline to 
ertapenem will be assessed. A step-wise analysis will be conducted in which superiority at TOC 
will be tested first. If the lower bound of the 2-sided 95% CI is greater than 0, superiority of 
eravacycline for response (clinical cure and microbiological success) at the TOC visit will be 
concluded and superiority at EOI will be tested. If the lower bound of the 2-sided 95% CI is 
greater than 0, superiority of eravacycline for response (clinical cure and microbiological 
success) at the EOI visit will be concluded. If superiority is not concluded at the TOC visit, 
superiority at the EOI visit will not be tested. 
The reasons for non-response and for an indeterminate response at the EOI and TOC visits will 
be summarized by treatment group for the micro-ITT population. The primary efficacy outcome 
will also be assessed separately across the randomization stratification factors of primary site of 
infection and receipt of a single dose of effective non-study antibiotics. For each infection site 
stratum and each antibiotic stratum, a 2-sided 95% CI for the observed difference in the 
responder rate at the EOI and TOC visits will be calculated for the micro-ITT population using 
the same method as for the primary efficacy analysis. In addition, the primary analysis results 
will also be assessed separately across geographical region and country by treatment group to 
assess for consistency of results across regions. For each geographical region and country, a 
2-sided 95% CI for the observed difference in the response rate at the EOI and TOC visits will 
be calculated for the micro-ITT population. 
Sensitivity analyses of the primary outcome will also be conducted. The first analysis will be an 
adjusted analysis (adjusted for the stratification factor of primary site of infection and receipt of 
a single dose of effective non-study antibiotics). A 2-sided stratified 95% CI will be computed 
for the difference in responder rate at the EOI and TOC visits between the eravacycline and 
ertapenem treatment groups using the method of Miettinen and Nurminen (9). Cochran-Mantel-
Haenszel weights will be used for the stratum weights in the calculation of the CI as follows: 
𝑊𝑊𝑖𝑖= 𝑛𝑛1𝑖𝑖𝑛𝑛2𝑖𝑖
𝑛𝑛1𝑖𝑖+𝑛𝑛2𝑖𝑖
 


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Where 𝑛𝑛1𝑖𝑖 is the number of subjects in the eravacycline treatment group (Group 1) in the i-th 
stratum, and 𝑛𝑛2𝑖𝑖 is the number of subjects in the ertapenem treatment group (Group 2) in the i-th 
stratum. 
The second sensitivity analysis will analyze those subjects who are considered indeterminates in 
the primary analysis as responders. Additional sensitivity analyses will be stratified analyses for 
the following combinations: primary site of infection and geographic region, primary site of 
infection and receipt of a single dose of effective non-study antibiotics, and geographic region 
and receipt of a single dose of effective non-study antibiotics. Two-sided 95% CIs will be 
computed for the difference in responder rate at the EOI and TOC visits between the 
eravacycline and ertapenem treatment groups within each stratum using the method of Miettinen 
and Nurminen. 
5.7.2. 
Secondary Efficacy Analyses 
Responder outcome will also be analyzed at the Day 5 visit. A 2-sided 95% CI for the observed 
difference in the responder rate at the Day 5 visit will be calculated for the micro-ITT 
population using the same method as for the primary efficacy analysis. 
The number and percentage of subjects in each treatment group with an outcome of clinical 
cure, clinical failure and indeterminate/missing (by definition the CE and ME populations do 
not include subjects with an indeterminate/missing response) will be presented for the following 
time points and analysis populations: 
• Day 5 - ITT, CE-Day 5, micro-ITT, micro-MITT, ME-Day 5 populations 
• EOI Visit - ITT, CE-EOI, micro-ITT, micro-MITT, ME-EOI populations 
• EOT Visit – ITT, CE-EOT, micro-ITT, micro-MITT, ME-EOT populations 
• TOC Visit – ITT, CE-TOC, micro-ITT, micro-MITT, ME-TOC populations 
• FU Visit – ITT, CE-FU, micro-ITT, micro-MITT, ME-FU populations 
Two-sided 95% unadjusted CIs will be constructed for the observed difference in the clinical 
cure rates between the treatment groups for descriptive purposes; no conclusion of NI will be 
made. Analyses at the TOC visit will also be presented by primary infection site and receipt of a 
single dose of effective non-study antibiotics in the ITT and CE-TOC populations. 
Per-subject microbiological response will be summarized as success, failure and indeterminate 
at the Day5, EOI, EOT, TOC and FU visits in the micro-ITT, micro-MITT and ME populations. 
Two-sided 95% unadjusted CIs will be constructed for the observed difference in the success 
rates between the treatment groups for descriptive purposes; no conclusion of NI will be made. 
Time to resolution of signs and symptoms is defined as the number of days from the start of 
study treatment to the visit where all signs and symptoms are reported as absent or have at least 
a 2-grade decrease in severity (chills, rigor or warmth associated with fever or hypothermia, 
flank or pelvic pain, nausea or vomiting, dysuria, urinary frequency or urinary urgency, costo-
vertebral angle tenderness on physical examination). Subjects who discontinue the study prior to 
having all signs and symptoms resolved will be censored at the last evaluation at which sign and 
symptoms were assessed. 


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Time to resolution of signs and symptoms will be analyzed using Kaplan-Meier methods in the 
micro-ITT population. The median, 25th and 75th percentile will be presented by treatment 
group and Kaplan-Meier curve will be presented by treatment group. 
5.7.3. 
Additional Efficacy Analyses 
5.7.3.1. 
Intravenous Only Responder Outcome 
Responder outcome will be analyzed at the EOT, TOC and FU visits in the micro-ITT 
population among subjects who only received IV study drug and did not transition to PO study 
drug for any reason (including treatment failures who did not receive PO study drug). The 
analysis will be conducted using the same methods as the primary efficacy analysis. 
5.7.3.2. 
Responder Outcome in Subjects with and without Levofloxacin-Resistant Baseline 
Pathogens 
Responder outcome will be analyzed at the EOI and TOC visits in subjects with levofloxacin-
resistant baseline pathogens. A 2-sided 95% CI for the observed difference in the responder rate 
at the EOI and TOC visits will be calculated for the micro-ITT population using the same 
method as for the primary efficacy analysis. 
5.7.3.3. 
Responder Outcome in Subjects with and without Ertapenem-Resistant Baseline 
Pathogens 
Responder outcome will be analyzed at the EOI and TOC visits in subjects with ertapenem-
resistant baseline pathogens. A 2-sided 95% CI for the observed difference in the responder rate 
at the EOI and TOC visits will be calculated for the micro-ITT population using the same 
method as for the primary efficacy analysis. 
5.7.3.4. 
Clinical Outcome Measures 
A summary (number and percentage of subjects) of the shift from baseline to each visit (Day 5, 
EOI, EOT, TOC and FU Visits) in the signs and symptoms of cUTI will be presented by 
treatment group for the micro-ITT population. 
5.7.3.5. 
Microbiological Outcomes 
Microbiologic response by baseline pathogen will be determined as the proportion of subjects 
with a microbiological success at the EOI (micro-ITT and ME-EOI populations) and TOC 
(micro-ITT and ME-TOC populations) visits for each pathogen isolated at baseline.  
Microbiologic response for levofloxacin resistant and ertapenem resistant baseline pathogens 
will also be presented. 
For subjects with baseline pathogens obtained from blood culture (ie, for bacteremic subjects), 
microbiologic success by baseline pathogen will also be summarized separately for the micro-
ITT population. 
In addition, a table will list all subjects in each treatment group with at least 1 baseline pathogen 
obtained from blood culture, including the per subject clinical response, per subject 
microbiological response, and the per-pathogen microbiological response for each pathogen. 


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Per-pathogen microbiological success will also be summarized by baseline pathogen and MIC 
to study drug received for those pathogens with a sample size of at least 10 in 1 of the treatment 
groups in the micro-ITT population. 
Microbiological categories for pathogens identified after baseline assessment are superinfection 
and new infection, which are defined as follows: 
• Superinfection: Emergence of a new pathogen during therapy, from urine or blood 
cultures, with emergence or worsening of signs and symptoms of infection (ie, is 
determined by the Investigator to be a clinical failure) 
• New infection: Emergence of a new pathogen after completion of therapy, from urine or 
blood cultures, with emergence or worsening of signs and symptoms of infection (ie, is 
determined by the Investigator to be a clinical failure) 
The number and percentage of subjects with a superinfection or new infection after baseline will 
be presented by treatment group. A listing will be provided that presents the subjects with a 
superinfection and new infection including the type of specimen and pathogen. 
Decreasing susceptibility of a pathogen is defined as continued presence of the baseline 
pathogen at ≥10^4 CFU/mL with a > 2-fold (at least 2 dilutions) increase from baseline to any 
subsequent study time point in the MIC of the study drug received. The number and percentage 
of subjects in the micro-ITT population with a pathogen showing decreasing susceptibility will 
be tabulated for each treatment group. In addition, a table will list all subjects in each treatment 
group with a pathogen showing decreasing susceptibility, including the type of specimen, 
pathogen, and MIC values for the drug received. 
5.8. 
Safety Analyses 
5.8.1. 
Adverse Events 
Verbatim descriptions of AEs will be coded using Version 20.0 of MedDRA. Summary tables 
will be provided for all treatment-emergent AEs (TEAEs). A TEAE is defined as any AE that 
newly appeared, increased in frequency, or worsened in severity following initiation of study 
drug. An AE is considered treatment emergent if the AE starts on or after the first dose of study 
drug. In addition, all AEs (including non-TEAEs), serious TEAEs, and TEAEs leading to study 
drug discontinuation will be provided in listings by treatment group, site, subject, verbatim term, 
MedDRA SOC and preferred term, start and end date, seriousness flag, severity, relationship to 
study drug, action taken with study treatment, frequency and outcome. All AEs will be coded 
using the MedDRA coding system and displayed in tables and data listings using SOC and 
preferred term. 
An overall summary of AEs will include number and percentage of subjects in each treatment 
group who experienced at least 1 AE of the following categories: any AE, any TEAE, any drug-
related TEAE (defined as possibly, probably or definitely related to study drug), any severe 
TEAE, any serious TEAE (SAE), any drug-related SAE, any SAE leading to death, any TEAE 
leading to premature discontinuation of study drug, and any SAE leading to premature study 
drug discontinuation. 
The number and percentage of subjects reporting a TEAE in each treatment group will be 
tabulated by SOC and preferred term; by SOC, preferred term, and severity (mild, moderate, 


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and severe); and by SOC, preferred term, and relationship (unrelated [defined as unrelated or 
unlikely related to study drug] or related to study drug). The number and percentage of subjects 
reporting a SAE and reporting a TEAE leading to premature discontinuation of study drug in 
each treatment group will also be summarized by SOC and preferred term. Summary tables will 
be presented alphabetically by SOC and preferred term within SOC. The incidence of TEAEs 
that occur in at least 2% of subjects in either treatment group will be summarized by preferred 
term and treatment group, sorted by decreasing frequency in the eravacycline group. For all 
analyses of TEAEs, if the same AE (based on preferred term) is reported for the same subject 
more than once, the AE is counted only once for that preferred term and at the highest severity 
and strongest relationship to study drug. Events with missing severity will be considered severe 
and events with missing relationship to study drug will be considered related to study drug. 
5.8.2. 
Laboratory Data 
Summaries of central laboratory data will include hematology (erythrocyte count [RBC], 
hematocrit, hemoglobin, mean cell hemoglobin [MCH], mean cell hemoglobin concentration 
[MCHC], mean cell volume [MCV], leukocyte count [WBC], absolute and differential 
basophils, absolute and differential eosinophils, absolute and differential lymphocytes, absolute 
and differential monocytes, absolute and differential neutrophils, and absolute and differential 
platelets), chemistry (tests included in Table 6), coagulation (fibrinogen, partial thromboplastin 
time, and prothrombin time), and urinalysis (bilirubin, casts, crystals, glucose, ketones, pH, 
protein, RBC, urobilinogen, and WBC) laboratory parameters. Laboratory parameters will be 
presented in alphabetic order with the following exceptions: differentials of WBC counts will be 
presented following the WBC results, and chemistry parameters will first be grouped by organ 
class (renal, liver, electrolytes and other) and presented alphabetically within each of these 
classes, as shown in Table 6. Clinical laboratory values will be expressed in System 
International (SI) units. Box plots showing the minimum, maximum, and quartile values will be 
presented for all visits by treatment group. 
Table 6 
Presentation of Chemistry Parameters 
Renal 
Blood urea nitrogen 
Creatinine 
Liver 
Alkaline phosphatase 
ALT 
AST 
Bilirubin indirect 
Bilirubin total 
GGT 
LDH 
Electrolytes 
Bicarbonate 
Calcium 
Chloride 
Magnesium 
Potassium 
Sodium 
Other 
Albumin 
Amylase 


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Cholesterol (total) 
Creatine kinase 
Glucose, non-fasting 
Lipase 
Phosphorus 
Total protein 
Uric acid 
Key: ALT = Alanine Aminotransferase; AST = Aspartate Aminotransferase; GGT = Gamma-Glutamyl Transferase; 
LDH = Lactate Dehydrogenase. 
Baseline is defined as the value closest to but prior to the start of study drug administration. 
Analyses will utilize assessments occurring during safety analysis windows (see Table 2). Thus, 
if a subject has a visit outside the window, for example, a TOC visit on Day 11, the laboratory 
assessment will not be summarized with the TOC visit but will be considered an unscheduled 
assessment. If more than 1 measurement is taken during the visit window, the value taken on the 
scheduled visit will be utilized or if no scheduled visit was done, the first (earliest) measurement 
will be used. If more than 1 measurement is taken on the same day, the last measurement on the 
day will be used. For worst overall post-baseline analyses, all laboratory assessments including 
those obtained from unscheduled visits will be included. 
Several analyses of the laboratory data will be presented. Descriptive statistics (based on SI 
units) for chemistry, hematology and coagulation values and the change from baseline will be 
summarized by treatment group at Day 5, EOI, EOT, TOC and FU visits, and for the overall 
worst value post-baseline (which includes unscheduled visits). Change from baseline will be 
calculated for each patient at the specified time point as the value at the specified time point 
minus the baseline value. 
Toxicity grade will be determined based on the modified Division of Microbiology and 
Infectious Diseases (DMID) criteria in Table 7. The DMID Adult Toxicity Table (November 21, 
2007) was modified to exclude the clinical component of the toxicity grading. In addition, 
Grade 0 was added to the table so that shifts from normal could be analyzed. For toxicity grades 
based on a multiple of the ULN, the normal range from the central laboratory will be applied. 
For toxicity grades based on fixed values, the grades will be assigned regardless of the normal 
actual range values from the central laboratory. For example, a hemoglobin value of 10.0 gm/dL 
will be assigned a grade of 1 toxicity, even if the lower limit of normal from the laboratory was 
9.8 gm/dL. Shift tables will be presented to show the number of subjects with a laboratory value 
with a grade of 0, 1, 2, 3 or 4 at baseline versus the worst post-baseline value. 
Table 7 
Modified Division of Microbiology and Infectious Diseases Adult Toxicity 
Criteria (November, 2007) 
Hematology 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin (gm/dL) 
>10.5 
9.5-10.5 
8.0-9.4 
6.5-7.9 
<6.5 
Absolute Neutrophil 
Count (count/mm3) 
>1,500 
1,000-1,500 
750-999 
500-749 
<500 
Platelets (counts/mm3) 
≥100,000 
75,000-99,999 
50,000-74,999 
20,000-49,999 
<20,000 
WBC (count/mm3) 
1,000-10,999 
11,000-12,999 
13,000-14,999 
15,000-30,000 
>30,000 


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% Polymorphonuclear 
Leucocytes  
≤80% 
>80%-90% 
>90-95% 
>95% 
-- 
Key: WBC = White Blood Cell Count. 
Chemistry 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hyponatremia (mEq/L) 
>135 
130-135 
123-129 
116-122 
<116 
Hypernatremia (mEq/L) 
<146 
146-150 
151-157 
158-165 
>165 
Hypokalemia (mEq/L) 
>3.4 
3.0-3.4 
2.5-2.9 
2.0-2.4 
<2.0 
Hyperkalemia (mEq/L) 
<5.6 
5.6-6.0 
6.1-6.5 
6.6-7.0 
>7.0 
Hypoglycemia (mg/dL) 
≥65 
55-64 
40-54 
30-39 
<30 
Hyperglycemia (mg/dL) 
(nonfasting and regardless 
of prior history of 
diabetes)* 
<116 
116-160 
161-250 
251-500 
>500 
Hypocalcemia (mg/dL) 
(corrected for albumin) 
>8.4 
7.8-8.4 
7.0-7.7 
6.1-6.9 
<6.1 
Hypercalcemia (mg/dL) 
≤10.5 
10.6-11.5 
11.6-12.5 
12.6-13.5 
>13.5 
Hypomagnesemia (mEq/L) 
>1.4 
1.2-1.4 
0.9-1.1 
0.6-0.8 
<0.6 
Hypophosphatemia (mg/dL) 
≥2.5 
2.0-2.4 
1.5-1.9 
1.0-1.4 
<1.0 
Hyperbilirubinemia (total 
bilirubin) 
<1.1×ULN 
1.1-
1.5×ULN 
1.6-2.5×ULN 
2.6-5.0×ULN 
>5.0×ULN 
BUN 
<1.25×ULN 
1.25-
2.5×ULN 
2.6-5.0×ULN 
5.1-
10.0×ULN 
>10.0×ULN 
Hyperuricemia (uric acid) 
(mg/dL) 
<7.5 
7.5-10.0 
10.1-12.0 
12.1-15.0 
>15.0 
Creatinine 
<1.1×ULN 
1.1-
1.5×ULN 
1.6-3.0×ULN 
3.1-6.0×ULN 
>6.0×ULN 
Key: BUN = Blood Urea Nitrogen; ULN = Upper Limit of Normal. 
* The DMID toxicity table reports hyperglycemia detected in nonfasting specimens obtained from patients with no prior 
diabetes. 
Enzymes 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
AST (SGOT) 
<1.25×ULN 
1.25-2.5×ULN 
2.6-5×ULN 
5.1-10×ULN 
>10×ULN 
ALT (SGPT) 
<1.25×ULN 
1.25-2.5×ULN 
2.6-5×ULN 
5.1-10×ULN 
>10×ULN 
GGT 
<1.25×ULN 
1.25-2.5×ULN 
2.6-5×ULN 
5.1-10×ULN 
>10×ULN 
Alkaline Phosphatase 
<1.25×ULN 
1.25-2.5×ULN 
2.6-5×ULN 
5.1-10×ULN 
>10×ULN 
Amylase 
<1.1×ULN 
1.1-1.5×ULN 
1.6-2.0×ULN 
2.1-5.0×ULN 
>5.1×ULN 
Lipase 
<1.1×ULN 
1.1-1.5×ULN 
1.6-2.0×ULN 
2.1-5.0×ULN 
>5.1×ULN 
Key: ALT (SGPT) = Alanine Aminotransferase (Serum Glutamic Pyruvic Transaminase); AST (SGOT) = Aspartate 
Aminotransferase (Serum Glutamic Oxaloacetic Transaminase); GGT = Gamma-Glutamyl Transferase; ULN = Upper 
Limit of Normal. 


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COAGULATION 
 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Fibrinogen 
(mg/dL) 
>200 - <400 
100-200 (low) or 
400-600 (high) 
50 - <100 (low) 
or >600 (high) 
<50 (low) 
Fibrinogen 
associated with 
gross bleeding 
or with 
disseminated 
coagulation 
Activated Partial 
Thromboplastin 
(APPT) 
<1.01×ULN 
1.01-1.66×ULN 
1.67-2.33×ULN 
2.34-3×ULN 
>3×ULN 
Prothrombin Time 
(PT)/International 
Normalized Ratio 
(INR) 
<1.01×ULN 
1.01-1.25×ULN 
1.26-1.5×ULN 
1.51-3.0×ULN 
>3×ULN 
Key: ULN = Upper Limit of Normal. 
Number and percentage of subjects with at least a 2-grade increase from baseline or a post-
baseline grade 4 abnormality (based on DMID criteria) will be summarized by treatment arm. 
Percentages for each lab test will be based on the number of subjects with a post-baseline 
evaluation of that laboratory test. A table will be provided which gives all laboratory results for 
a given laboratory test for subjects who have at least one 2-grade increase from baseline or a 
post-baseline grade 4 abnormality. 
The number and percentage (based on the number of subjects with a normal level at baseline) of 
subjects in each treatment group with an elevated transaminase level (>3 × ULN, >5 × ULN, 
and >10 × ULN), an elevated bilirubin level (>1.5 × ULN and >2 × ULN) will be presented by 
study visit. A table of subjects who meet the laboratory criteria for Hy’s law will also be 
provided. The laboratory criteria for Hy’s law is defined as ALT or AST >3 ×ULN, ALP ≤2.0 × 
ULN, and total bilirubin >2 × ULN. 
Detailed patient listings of all laboratory data collected during the study will be provided. 
Laboratory values outside normal limits will be identified in the patient data listings with flags 
for low (L) and high (H) as will laboratory values that meet the clinically notable (CN) 
thresholds. 
5.8.3. 
Vital Signs and Physical Examination 
Blood pressure (systolic and diastolic), respiration rate, and heart rate will be summarized using 
descriptive statistics by treatment group at each time point at which they were measured. 
Descriptive statistics of the change from baseline to each post-baseline time point will also be 
provided. Change from baseline will be calculated for each subject at the specified time point as 
the value at the specified time point minus the baseline value. Visit windows will be determined 
in the same manner as described for the laboratory data.  Clinically significant physical 
examination findings will be reported, analyzed and presented as AEs. 
A summary of abnormal values, identified by the threshold levels provided in Table 8 will be 
analyzed using the methodology described for CN laboratory values with the exception that only 
subjects with both baseline and post-baseline values will be evaluable for the analysis of a 
diastolic blood pressure increase >20 mmHg. 


Tetraphase Pharmaceuticals, Inc. 
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22 January 2018, Version 1.0 
 
 
 
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Table 8 
Clinically Notable Abnormal Vital Sign Threshold Values 
ABNORMAL VALUES 
Vital Sign 
Threshold 
Reference 
Diastolic blood pressure 
> 20 mmHg increase from baseline 
CTCAE Grade 2 
Systolic blood pressure 
≥ 140 mmHg 
CTCAE Grade 2 
Heart rate 
< 60 beats/min 
Noble et al 1990 
Heart rate 
> 120 beats/min 
- 
Key: CTCAE = Common Terminology Criteria for Adverse Events, Version 4.0 
Detailed patient listings of all vital signs results will be provided. 


Tetraphase Pharmaceuticals, Inc. 
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22 January 2018, Version 1.0 
 
 
 
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6. 
CHANGES TO PLANNED ANALYSES 
This is Version 1.0 of the SAP. 


Tetraphase Pharmaceuticals, Inc. 
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22 January 2018, Version 1.0 
 
 
 
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7. 
REFERENCES 
1. Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, et al. Bad bugs, no 
drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 
Off Publ Infect Dis Soc Am. 2009 Jan 1;48(1):1–12.  
 
2. Infectious Diseases Society of America. The 10 x ’20 Initiative: pursuing a global commitment 
to develop 10 new antibacterial drugs by 2020. Clin Infect Dis Off Publ Infect Dis Soc Am. 
2010 Apr 15;50(8):1081–3.  
 
3. Murphy T, Slee A, Sutcliffe J. TP-434 is highly efficacious in animal models of infection. 
Boston, MA: 50th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy; 
2010 Sep. Report No.: Abstract F1-2161. 
 
4. Sutcliffe J. TP-434 has potential to treat complicated urinary tract infections (cUTI) - F1-1858. 
In Chicago, IL; 2011.  
 
5. Morrissey I, Hackel M. Surveillance of the activity of eravacycline against bacteria collected 
from European and USA hospitals in 2013-2014. IHMA Epalinges, Switzerland and 
Schaumburg, IL: International Health Management Report IHMA 2300; 2015 Oct.  
6. Cesnauska G and Horn P. A Phase 2, Randomized, Double-Blind, Double-Dummy, Multicenter, 
Prospective Study to Assess the Efficacy, Safety, and Pharmacokinetics of 2 Dose Regimens of 
TP 434 Compared With Ertapenem in Adult Community Acquired Complicated Intra-abdominal 
Infections. New Hope, PA: INC Research, Inc; 2012 Sep. Report No.: TP-434-P2-cIAI-1.  
7. Slepavicius A, Horn P. A Phase 3, Randomized, Double-Blind, Double-Dummy, Multicenter 
Prospective Study To Assess The Efficacy And Safety Of Eravacycline Compared With 
Ertapenem In Complicated Intra-Abdominal Infections. Watertown, MA: Tetraphase 
Pharmaceuticals; 2015 Aug. Report No.: TP-434-008 Clinical Study Report, Version 1. 
8. Nicolle LE, AMMI Canada Guidelines Committee*. Complicated urinary tract infection in 
adults. Can J Infect Dis Med Microbiol J Can Mal Infect Microbiol Médicale AMMI Can. 2005 
Nov;16(6):349–60. 
9. Miettinen O, Nurminen M. Comparative analysis of two rates. Statistics in Medicine. 
1985;4(2):213-22