Conditions: Skin and Subcutaneous Tissue Bacterial Infections Gram-Positive Bacterial Infections
Keywords: TNP-2092 ABSSSI Safety Efficacy
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 120
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate safety, tolerability, pharmacokinetic characteristics and efficacy of TNP-2092 in adults with ABSSSI suspected or confirmed to be caused by gram-positive pathogens.

Detailed description:
This Phase 2, double-blind, randomized, multicenter, parallel, controlled study is conducted to evaluate safety, tolerability, pharmacokinetics and efficacy of TNP-2092, and vancomycin in adults with ABSSSI suspected or confirmed to be caused by gram-positive pathogens. The duration of the treatment period is a minimum of 7 days and a maximum of 14 days.

Arms:
arm 1: TNP-2092 300 mg intravenous every 12 hours arm 2: vancomycin 1 g intravenous every 12 hours

Interventions: intervention 1: TNP-2092 intervention 2: Vancomycin
Intervention descriptions: intervention 1: TNP-2092 100mg/vial intervention 2: Vancomycin 1g/vial

Protocol document:
Prot_002.pdf: 
Protocol: PJI001-02
A Phase 2, Double-Blind, Randomized, Multicenter, Parallel, Controlled Study 
to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of 
TNP-2092 to Treat Acute Bacterial Skin and Skin Structure Infection in Adults
NCT03964493
Approval Date:  14-Feb-2019


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TI T L E P A G E  
P R O T O C O L TI T L E: A P H A S E 2 , D O U B L E -B LI N D, R A N D O MI Z E D, 
M U L TI C E N T E R, P A R A L L E L, C O N T R O L L E D  S T U D Y T O 
E V A L U A T E  T H E S A F E T Y, T O L E R A BI LI T Y, P H A R M A C O KI N E TI C S , 
A N D E F FI C A C Y O F T N P -2 0 9 2 T O T R E A T A C U T E B A C T E RI A L S KI N 
A N D S KI N S T R U C T U R E I N F E C TI O N  I N A D U L TS  
Pr ot oc ol N u m ber: P JI 0 0 1 -0 2  
A me n d me nt N u m ber: 1  
C o m p o u n d N u m ber: T N P -2 0 9 2  
St u d y P h ase: 2  
S h ort Title: S afet y , T ole r a bilit y, P h ar m ac o ki neti cs , a n d Effic ac y of T N P -2 0 9 2 t o Tre at 
Ac ute B acteri al S ki n a n d S ki n Str uct ure I nfecti o n  
S p o ns or N a me: 
Te n N or T her a pe utics  Li mite d  
Le g al Re gister e d A d dress: 
2 1 8 Xi n g h u Street, B uil di n g B 2, S uite 7 1 1  
S uz h o u I n d ustri al P ar k  
S uz h o u, C hi n a 2 1 5 1 2 3  
Re g ul a t or y A ge nc y I de ntifier N u m ber 
Re g ul at or y A ge nc y File  
I de ntif yi n g # 
I N D: 
A p pr o v al D ate  Ori gi n al P r ot oc ol : Se pte m be r  1 6 , 2 0 1 8  
A p pr o v al D ate A me n de d Pr ot oc ol: Fe br u ar y 1 4, 2 0 1 9  
T his d oc u me nt is t he c o nfi de ntial p r o pert y of T E N N O R T H E R A P E U TI C S LI MI T E D . N o 
part of it ma y be tra ns mitte d, re pr o d u ce d, p u blis he d, or use d b y ot her pers o ns wit h o ut pri or 
writte n a ut h oriz ati o n fr o m T E N N O R T H E R A P E U TI C S  LI MI T E D . 
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S p o ns or Si g n at or y:  
 
 
 
 
 
 
 
 
 
 
 
 
 
Date  
 
 
 
Date  
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INVESTIGATOR SIGNATURE PAGE 
Protocol Title:  Phase 2, Double-Blind, Randomized, Multicenter, Parallel, Controlled 
Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TNP-2092 
to Treat Acute Bacterial Skin and Skin Structure Infection in Adults   
 
 
Signature of Investigator 
 
 
Date 


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M E DI C A L M O NI T O R N A M E A N D C O N T A C T I N F O R M A TI O N  
 
 
 
 
 
 
 
 
 
 
 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
DOCUMENT HISTORY 
Amendment 
Date 
Amendment 1 
14 February 2019 
Amendment 1 Approval Date (14 February 2019) 
The TNP-2092 IV 450 mg dose was omitted from the original protocol and the 
randomization scheme was revised from 1:1:1 to 2:1 TNP-2092 (300 mg) IV versus 
vancomycin (1g) IV to reflect the change. This change was made to comply with an FDA 
request. Moreover, clarification on the timing and type of physical examinations and 
laboratory tests was made and typographical errors were corrected. Use of the local and 
central laboratories was clarified and a list of prohibited medications was provided. 
A description of substantive changes to the protocol are presented as follows: 
Section No. and Name 
Description of Change 
Brief Rationale 
1.1  Synopsis 
Dose and randomization changed in 
Table 1 and Table 2 
Match current study design 
1.2  Schema 
Figure 2 revised to remove one 
treatment arm 
Dose omitted 
1.3 Schedule of Activities 
Activity schedule and footnotes 
revised 
Update table and section 
numbers, and match study 
conduct  
3 
Objectives and 
 
Endpoints 
Table 4 omitted, hyperlink added to 
Table 1, and subsequent table 
numbers changed to reflect 
omission 
Remove redundant table 
4.1 Overall Design 
Dose omitted and 2:1 randomization 
added, omitted table, hyperlink 
added to identical table,  
To match current study design 
and remove redundant table 
4.2 Scientific Rationale … 
Dose omitted  
Match dose regimen 
4.3 Justification for Dose 
Dose omitted and added nonclinical 
data 
Match dose regimen and provide 
support for dose regimen 
4.3.2 Clinical Data 
One treatment arm removed  
Match dose regimen 
5.1 Inclusion Criteria 
Inclusion criteria (#3) revised  
Describe skin lesion 
measurement and clarify surgical 
procedures. 


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Section # and Name 
Description of Change 
Brief Rationale 
5.2 Exclusion Criteria 
Added exclusion criteria 
(Section 5.2) for body mass index 
≥30 kg/m2 (#1), list prohibited 
concomitant medications (#13), 
modified liver test criteria (#6) and 
added contraindications for 
fluoroquinolone use specified (#8), 
and deleted lesion description 
(former #10p) 
To refine patient population 
6.1 Study Interventions 
 
Administered   
2:1 randomization added, treatment 
arms revised, drug product storage 
clarification. Table 5 omitted, 
hyperlink added to Table 2, and 
subsequent table changed numbers 
to reflect omission 
Match current study design, 
clarify the duration of drug 
product storage, and remove 
redundant table  
6.4 Measures to Minimize 
 
Bias 
2:1 randomization added 
Match current study design  
6.6.2 Prohibited Medications 
Text to add prohibited medications 
modified 
Match text from prescribing 
information for approved 
fluoroquinolone (moxifloxacin) 
and rifamycin (rifampin) 
6.6.3 Adjunctive Therapy 
Text for surgical interventions 
added  
Clarify use of surgical 
intervention 
6.6.4 Rescue Medication 
Text for rescue medication and 
premature discontinuation of study 
intervention added 
Clarify use of rescue 
medications 
8.2.1 Physical Examinations 
Day 1 exam omitted 
Clarify timing of exam 
8.2.4 Clinical Safety 
 
Laboratory 
 
Assessments 
Text for central and local laboratory 
assessment separated  
Clarify use of local and central 
laboratory assessments 
8.4.1 Clinical Response and 
 
Table 8 (now Table 6) 
“No baseline gram-positive 
organisms for treatment of 
ABSSSI” statement deleted 
Statement untrue 
8.4.2 Microbiologic 
 
Evaluation 
Text regarding cellulitis added 
Clarify tissue collection from 
cellulitis lesions 
8.6 Pharmacokinetics 
One treatment arm omitted 
Dose omitted 
9.0 Statistical Considerations 
One treatment arm omitted 
Dose omitted 
9.2 Sample Size 
 
Determination 
New responder rate calculation 
added for randomization 
Randomization changed  
9.6 Safety Analyses 
One treatment arm omitted 
Dose omitted 
9.8 Pharmacokinetic 
 
Analyses 
One treatment arm omitted 
Dose omitted 


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Section # and Name 
Description of Change 
Brief Rationale 
9.9 Handling of Dropouts… 
“No baseline gram-positive 
organisms for treatment of 
ABSSSI” statement deleted 
Statement untrue 
10.2 Clinical Laboratory 
 
Tests 
Table 11: HIV testing deleted; 
allowed urine and serum pregnancy 
test type, and added measurement of 
haptoglobin 
Clarify laboratory assessments 
including HIV and pregnancy, 
and added haptoglobin 
measurements  
10.4 Prohibited Medications 
Added new section with table of 
prohibited medications (Table 20) 
Response to request for new 
Exclusion Criteria #13 
10.5 Pharmacokinetic 
 
Sample… (previously 
 
Section 10.4) 
One treatment arm omitted 
Treatment arm and dose omitted 
10.6 List of Abbreviations 
Revised abbreviations list 
Match protocol abbreviations 
10.7 Contraceptive Guidance 
 
and …. 
Pregnancy Report Form used to 
follow-up pregnancy outcome. 
Clarify where pregnancy 
outcome should be documented 
11 
References 
Prescribing information for 
moxifloxacin (2016) added and 
prescribing information for rifampin 
updated (2019) 
Needed in response to prohibited 
concomitant medications list 


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TABLE OF CONTENTS 
INVESTIGATOR SIGNATURE PAGE..........................................................................3 
TABLE OF CONTENTS ..................................................................................................8 
TABLE OF TABLES .......................................................................................................10 
TABLE OF FIGURES .....................................................................................................11 
1 
PROTOCOL SUMMARY .......................................................................................12 
1.1 
Synopsis .................................................................................................................12 
1.2 
Schema ..................................................................................................................17 
1.3 
Schedule of Activities ...........................................................................................17 
2 
INTRODUCTION ....................................................................................................20 
2.1 
Study Rationale ....................................................................................................20 
2.2 
Background ..........................................................................................................20 
2.2.1 
Nonclinical Data .............................................................................................21 
2.2.2 
Microbiology Data .........................................................................................22 
2.2.3 
Single-Dose and Multiple-Dose Studies in Healthy Subjects .....................22 
2.3 
Benefit/Risk Assessment ......................................................................................23 
3 
OBJECTIVES AND ENDPOINTS .........................................................................24 
4 
STUDY DESIGN ......................................................................................................24 
4.1 
Overall Design ......................................................................................................24 
4.2 
Scientific Rationale for Study Design .................................................................25 
4.3 
Justification for Dose ...........................................................................................26 
4.3.1 
Nonclinical Data .............................................................................................27 
4.3.2 
Clinical Data ...................................................................................................27 
4.4 
End of Study Definition .......................................................................................28 
5 
STUDY POPULATION ...........................................................................................28 
5.1 
Inclusion Criteria .................................................................................................28 
5.2 
Exclusion Criteria ................................................................................................30 
5.3 
Lifestyle Considerations ......................................................................................32 
5.4 
Screen Failures .....................................................................................................32 
6 
STUDY INTERVENTION ......................................................................................32 
6.1 
Study Interventions Administered .....................................................................32 
6.2 
Criteria for Intravenous to Oral Treatment Switch .........................................34 
6.3 
Preparation/Handling/Storage/Accountability .................................................34 
6.3.1 
IV Antibiotic ...................................................................................................34 
6.3.2 
Oral Antibiotic ...............................................................................................35 
6.4 
Measures to Minimize Bias: Randomization and Blinding..............................35 
6.5 
Study Intervention Compliance ..........................................................................36 
6.6 
Concomitant Therapy ..........................................................................................37 
6.6.1 
Other Medication Therapy ...........................................................................37 
6.6.2 
Prohibited Medications and Medications Requiring Special 
Consideration .................................................................................................37 
6.6.3 
Adjunctive Therapy .......................................................................................37 
6.6.4 
Rescue Medication .........................................................................................38 
6.7 
Dose Modification ................................................................................................38 
6.8 
Intervention After the End of the Study ............................................................38 


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7 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ...............................................................38 
7.1 
Discontinuation of Study Intervention ...............................................................38 
7.2 
Participant Discontinuation/Withdrawal from the Study................................38 
7.3 
Lost to Follow-up .................................................................................................39 
8 
STUDY ASSESSMENTS AND PROCEDURES ...................................................39 
8.1 
Protocol Adherence ..............................................................................................39 
8.2 
Safety Assessments ...............................................................................................41 
8.2.1 
Physical Examinations ...................................................................................41 
8.2.2 
Vital Signs .......................................................................................................41 
8.2.3 
Electrocardiograms........................................................................................41 
8.2.4 
Clinical Safety Laboratory Assessments ......................................................41 
8.3 
Adverse Events and Serious Adverse Events ....................................................43 
8.3.1 
Period and Frequency for Collecting AE and SAE Information ..............43 
8.3.2 
Method of Detecting AEs and SAEs .............................................................43 
8.3.3 
Follow-up of AEs and SAEs ..........................................................................43 
8.3.4 
Regulatory Reporting Requirements for SAEs ...........................................44 
8.3.5 
Pregnancy .......................................................................................................44 
8.3.6 
Death Events ...................................................................................................45 
8.3.7 
Disease-Related Events and/or Disease-Related Outcomes Not 
Qualifying as AEs or SAEs............................................................................45 
8.4 
Efficacy Assessments ...........................................................................................45 
8.4.1 
Clinical Response ...........................................................................................45 
8.4.2 
Microbiologic Evaluation ..............................................................................47 
8.5 
Treatment of Overdose ........................................................................................51 
8.6 
Pharmacokinetics .................................................................................................51 
8.7 
Pharmacodynamics ..............................................................................................52 
8.8 
Genetics .................................................................................................................52 
8.9 
Biomarkers ...........................................................................................................52 
8.10 
Health Economics/Medical Resource Utilization and Health Economics ......52 
9 
STATISTICAL CONSIDERATIONS ....................................................................52 
9.1 
Statistical Hypotheses ..........................................................................................52 
9.2 
Sample Size Determination .................................................................................52 
9.3 
Populations for Analyses .....................................................................................52 
9.4 
Analysis of Study Populations and Participant Characteristics ......................56 
9.5 
Study Intervention Exposure ..............................................................................56 
9.6 
Safety Analyses .....................................................................................................56 
9.7 
Efficacy Analyses – Secondary Endpoints .........................................................57 
9.7.1 
Clinical Outcomes ..........................................................................................57 
9.7.2 
Microbiological Outcomes.............................................................................58 
9.8 
Pharmacokinetic Analyses ..................................................................................58 
9.9 
Handling of Dropouts, Missing, Unused and Spurious Data ...........................58 
9.10 
Interim Analyses ..................................................................................................58 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ................................................................................................58 
10.1 
Regulatory, Ethical, and Study Oversight Considerations ..............................58 


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10.1.1 
Regulatory and Ethical Considerations .......................................................58 
10.1.2 
Financial Information ....................................................................................59 
10.1.3 
Data Protection...............................................................................................59 
10.1.4 
Informed Consent Process ............................................................................60 
10.1.5 
Dissemination of Clinical Study Data ..........................................................60 
10.1.6 
Data Quality Assurance .................................................................................60 
10.1.7 
Electronic Case Report Forms and Data Capture System.........................63 
10.1.8 
Source Data and Document Management ...................................................63 
10.1.9 
Study and Site Closure ..................................................................................64 
10.1.10 
Institutional Review Board Approval ..........................................................65 
10.1.11 
Publication Policy...........................................................................................65 
10.1.12 
Data Management and Monitoring ..............................................................65 
10.2 
Clinical Laboratory Tests....................................................................................66 
10.3 
Adverse Events: Definitions and Procedures for Recording, Evaluating, 
Follow-up, and Reporting ...................................................................................66 
10.3.1 
Definition of AE..............................................................................................66 
10.3.2 
Definition of SAE ...........................................................................................68 
10.3.3 
Recording and Follow-Up of AE and/or SAE .............................................69 
10.3.4 
Adverse Events of Interest ............................................................................71 
10.3.5 
Reporting of SAEs..........................................................................................72 
10.4 
Prohibited Medications .......................................................................................72 
10.5 
Pharmacokinetic Sample Schedule for Pharmacokinetic Assessments ..........74 
10.6 
List of Abbreviations ...........................................................................................75 
10.7 
Contraceptive Guidance and Collection of Pregnancy Information ...............76 
11 REFERENCES .........................................................................................................78 
 
TABLE OF TABLES 
Table 1 
Objectives and Endpoints........................................................................13 
Table 2 
Treatment Arms .......................................................................................16 
Table 3 
Schedule of Activities ...............................................................................18 
Table 4 
Preparation of Reconstituted TNP-2092 and Vancomycin ..................33 
Table 5 
Clinical Response Definitions – Programmatic Determination ...........46 
Table 6 
Clinical Response Definitions – Investigator’s Assessment .................47 
Table 7 
Microbiologic Outcome Categories ........................................................50 
Table 8 
Emergent Infections .................................................................................50 
Table 9 
Populations for Analysis ..........................................................................54 
Table 10 
Efficacy Evaluations by Analysis Population ........................................57 
Table 11 
Protocol-Required Safety Laboratory Assessments .............................66 
Table 12 
Definition of AE........................................................................................67 
Table 13 
Events Meeting the AE Definition ..........................................................68 
Table 14 
Definition of SAE .....................................................................................69 
Table 15 
Recording and Follow-Up of AE and/or SAE and Assessment of Intensity
....................................................................................................................70 
Table 16 
Assessment of Adverse Event/Serious Adverse Event Intensity ..........70 


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Table 17 
Assessment of Causality ..........................................................................71 
Table 18 
Assessment of Infusion Site Reactions ...................................................72 
Table 19 
SAE Reporting to the Sponsor ................................................................72 
Table 20 
List of Prohibited Concomitant Medications ........................................73 
Table 21 
Pharmacokinetic Sample Schedule ........................................................74 
 
TABLE OF FIGURES 
Figure 1 
Overview of Treatment Duration ...........................................................14 
Figure 2 
Overview of Study Design .......................................................................17 
Figure 3 
Overview of Analysis Populations ..........................................................55 
 


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1  P R O T O C O L S U M M A R Y  
1. 1  
S y n o psis  
Pr ot oc ol Title : A P hase 2, D o u ble -Bli n d, R a n d o miz e d , M ultic e nter, Par allel, C o ntr olle d 
St u d y t o E val u ate t he Safet y, T ol era bilit y, P har m ac o ki neti cs , a n d Effi cac y  of T N P -2 0 9 2 
t o Treat Ac ute B acterial S ki n a n d S ki n Str uct ur e I nfecti o n i n A d ults 
S h ort Title: Safet y , T oler a bilit y, P har ma c o ki netics a n d Effica c y of T N P -2 0 9 2 t o Treat 
Ac ute Bacteri al S k i n a n d S ki n Str u ct ure I nfe cti o n 
R ati o n ale:  
A nti bi oti c resista n ce p oses a seri o us t hre at t o p u blic healt h w orl d wi d e. Researc h eff orts 
i n rece nt years ha ve b ec o m e i ncr easi n gl y g eare d t o war d  disc o veri n g a n d de vel o pi n g ne w 
classes of a nti bi oti cs wit h m o des of acti o n disti nct fr o m t h ose of esta blis he d a g e nts a n d 
acti vit y a g ai nst resist a nt strai ns. A d diti o nal n o vel a nti bi oti c c h oi ces are ne e de d t o trea t 
bacterial i nfecti o ns  s us pecte d or c o nfir me d  t o be c a use d b y a nti bi otic-r esista nt, 
gra m -p ositi v e  pat h o g e ns  (e g, met hicilli n-r esista nt St a p hyl oc oc c us a ure us  [ M R S A]).  
T N P -2 0 9 2 is bei n g de vel o p e d f or t he treat me nt of seri o us or life -t hr eat e ni n g bacteri al 
i nfecti o ns i ncl u di n g t h ose c a use d b y gra m-p ositi ve p at h o ge ns t hat ha ve d e vel o pe d or 
ac q uire d r esista nce t o c o m m o nl y use d a nti bi otics. 
 
 
 
  
 
 
 
 
 
 
T N P -2 0 9 2 is pre dicte d t o be efficaci o us a gai nst ac ut e bact erial s ki n a n d s ki n str uct ur e 
i nfecti o ns (A B S S SI ) s us pecte d or c o nfir me d t o be ca use d b y a nti bi otic r esista nt gr a m -
p o siti ve pat h o ge ns, a n d bi ofil m-ass ociate d f or ei g n b o d y i nfecti o ns,  i ncl u di n g t h ose 
me dic ate d b y m ulti dr u g -resista nt pat h o ge ns. 
O bjecti ves a n d E n d p oi nts : 
T his is t he first st u d y i n w hic h T N P -2 0 9 2 is a d mi nist ere d t o parti ci pa nts wit h A B S S SI  
s us pecte d or c o nfir me d t o be ca use d b y gra m-p ositi v e pat h o ge ns . Safet y a n d t olera bilit y 
will be t h e pri m ar y o bje cti ves of t his st u d y, p har ma c o ki neti cs ( P K ) a n d efficac y will 
c o m prise sec o n d ar y o bjecti ves. T h e o bje cti v es a n d e n d p oi nts are prese nte d i n  Ta ble  1 . 
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All participants will be treated with IV study intervention for a minimum of 3 days 
(6 doses).  
Figure 1 
Overview of Treatment Duration 
 
IV = intravenous; Rx = treatment 
Note: The duration of the treatment period (IV or IV plus oral switch, if applicable) is a minimum of 7 days 
and a maximum of 14 days. Participants will be treated with IV study intervention for a minimum of 3 days 
(6 doses). Upon meeting protocol-specified switching criteria (Section 6.2), participants will continue 
treatment of ABSSSI with a commercially-available, open-label, oral antibiotic selected by the investigator.  
 
Upon meeting protocol-specified switching criteria (Section 6.2), participants will 
continue treatment of ABSSSI with a commercially-available, open-label, oral antibiotic 
selected by the investigator. An overview of the study design is presented in Section 4 
and the Schedule of Activities is presented in Section 1.3. 
Eligible participants will be randomized (2:1) to 1 of 2 treatment arms: TNP-2092 
300 mg IV q12h or vancomycin 1 g IV q12h. Randomization will be stratified by 
ABSSSI types to ensure proper balance between treatment arms. The types of eligible 
ABSSSI include cellulitis/erysipelas, wound infections, and major cutaneous abscesses; 
however, participants with major cutaneous abscess should not comprise >30% of 
randomized population. Participants with a minimum ABSSSI lesion surface area of 
75 cm2 will be enrolled. No prior systemic antibiotic treatment is permitted before 
enrollment in the study, and no other concomitant systemic or topical antibiotics are 
permitted during the study. If a participant enrolls and is subsequently found to have a 
gram-negative bacterial infection, they will remain in the study but may be switched to 
another antibiotic as appropriate. Participants will not be replaced. 
An adequate local ABSSSI site specimen must be collected from all participants with 
non-cellulitis ABSSSI for microbiologic evaluation at baseline. Local ABSSSI site 
specimens and blood cultures from 2 separate venipuncture sites, will be collected from 
all participants before administration of study intervention, whenever possible. All local 
ABSSSI site specimens will undergo Gram-stain and culture at the local laboratory and 
all blood cultures will be processed at the local laboratory. Specimens should be 


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processed according to standard recognized methods. All bacteria isolated from an 
adequate local ABSSSI site specimen or blood culture at the local laboratory will be sent 
to a designated central laboratory for confirmation of species identification and 
antimicrobial susceptibility testing. Microbiologic methods are described in Section 8.4.2 
and more details are presented in the laboratory manual. 
If local antimicrobial susceptibility testing of a baseline pathogen indicates possible 
non-susceptibility to study intervention (eg, intermediate susceptibility or resistance to a 
fluoroquinolone, rifamycin, and/or glycopeptide) but the participant is stable or clinically 
improving, the participant should remain on study intervention at the investigator’s 
discretion. In these cases, the investigator should discuss each situation with the medical 
monitor before discontinuation from study intervention. 
Screening assessments to determine study eligibility will be performed within 1 day 
before the first dose of study intervention is administered. Intravenous study intervention 
may be administered in a hospital or outpatient infusion center; outpatient administration 
of IV study intervention is limited to participants who are clinically stable and have 
adequate home support with reliable transportation to and from the hospital or clinic, as 
described in the Pharmacy Manual. 
Day 1 is the first day of study intervention; subsequent study days are consecutive 
calendar days. For purposes of analysis, study assessments will be performed during the 
treatment period on Day 1, Day 2, at early assessment (EA) 48 to 72 hours after IV 
treatment is started, at end of IV (EOIV, 3 to 14 days after IV treatment is started) at end 
of treatment (EOT, after a minimum of 7 days up to 14 days of intervention, IV or IV 
plus oral switch, if applicable), at posttreatment evaluation (PTE, 7 to 14 days after 
EOT), and at long-term follow-up (LTFU, 20 to 25 days after EOT) (Figure 2). 
The primary endpoint is assessment of safety and tolerability: incidence of adverse events 
(AEs), vital signs laboratory data, and ECG findings, and a qualitative assessment of 
local tolerability (including local infusion site reaction and thrombotic events) measured 
throughout the study. Secondary endpoints comprise PK (first dose and at EOIV 
treatment) and efficacy assessments (programmatic clinical response at EA aligns with 
the current FDA guidance [2013]). Secondary efficacy endpoints also include the 
investigator assessments of clinical response at designated timepoints and 
microbiological responses at PTE. 
Number of Participants: 
This protocol plans to enroll 120 participants who meet study entry criteria who will be 
randomly assigned to 1 of 2 treatment arms in a 2:1 ratio as presented in Table 2. A 
sample size of 80 participants who receive TNP-2092 is deemed sufficient to provide an 
initial assessment of safety and PK data to inform the future development of TNP-2092. 
Intervention Arms and Duration: 
The total duration of the study is up to 40 days from the screening visit to the LTFU. The 
screening period will be up to 1 day in duration before intervention, followed by a 


TNP-2092 
TenNor Therapeutics Ltd. 
Protocol PJI001-02 
Page 16 
 
  
 
treatment period of up to 14 days with at least 3 days (6 doses) of IV intervention and a 
minimum of 7 days and up to 14 days of treatment, a PTE visit 7 to 14 days after the 
EOT, and a LTFU visit comprising a telephone call, 20 to 25 days after the EOT to 
monitor continuing AEs and concomitant medications (Figure 2). 
The 2 treatment arms are presented in Table 2. 
Table 2 
Treatment Arms 
Arm 
Study Intervention, Dose, Duration 
Assigned Treatment 
Intervention 
Concentration 
Planned 
Number of 
Participants 
A 
TNP-2092 300 mg IV q12h Day 1 up to 
Day 14 (at least 3 days [6 doses] required) 
TNP-2092 (lyophilized red 
orange powder) 300 mg in 
200 mL D5W (1.5 mg/mL) 
for IV infusion 
80 
B 
Vancomycin 1 g IV q12h, Day 1 up to Day 14 
(at least 3 days [6 doses] required) 
Vancomycin 1 g in 200 mL 
D5W (5 mg/mL) for IV 
infusion 
40 
IV = intravenous; q12h = every 12 hours 
 
The treatment period can comprise IV treatment exclusively or a combination of IV plus 
oral switch treatment for a minimum of 7 days and up to 14 days of treatment. A switch 
from IV to oral open-label antibiotic treatment is permitted after at least 3 days (6 doses) 
of IV study intervention provided oral switch criteria and procedures are met 
(Section 6.2). 


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Protocol PJI001-02 
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1.2 
Schema 
An overview of the study design is presented in Figure 2. 
Figure 2 
Overview of Study Design 
 
 
EA = early assessment; EOIV = end of IV treatment; EOT = end of treatment; IV = intravenous; 
LTFU = long-term follow-up; PO = oral; PTE = posttreatment evaluation; q12h = every 12 hours 
Note: Participants receive a minimum of 3 days (72 hours, 6 doses) of IV study intervention. After 
72 hours, participants may begin oral antibiotic treatment upon meeting protocol-specified criteria 
(Section 6.2). 
*EA (48 to 72 hours after start of first dose of IV intervention) and EOIV (at least 72 hours, 6 doses after 
start of first dose of IV intervention) may occur simultaneously. EOT may be any day after at least 7 days 
of treatment initiation up to 14 days after treatment initiation. 
 
1.3 
Schedule of Activities 
A Schedule of Activities is presented in Table 3. 


TNP-2092 
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Protocol PJI001-02 
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Table 3 
Schedule of Activities 
Study Visit 
Screening a 
Intravenous plus Oral Treatment Period b 
PTE d 
 
LTFU e 
 
Day -1 
Day 1b 
Day 2 
EA c 
After 48 to 
72 h  
EOIV (+ 1)  
After 72 h 
up to Day 14 
EOT c (+ 1) 
≥ Day 7 up 
to Day 14  
 7 to 14 Days 
after EOT 
20 to 25 
Days after 
EOT 
Informed consent, demographics, 
medical/surgical history, 
inclusion/exclusion criteria, CrCl f,g  
X 
 
 
 
 
 
 
 
Randomization h 
 
X 
 
 
 
 
 
 
Prior/concomitant medications i 
X 
X 
X 
X 
X 
X 
X 
X 
Physical exam/focused physical exam 
j 
X 
 
X 
X 
X 
X 
X 
 
Vital signs k 
X 
X 
X 
X 
X 
X 
X 
 
12-lead ECG l 
X 
 
 
X 
 
X 
X 
 
Serum or urine pregnancy test m 
X 
 
 
 
 
X 
 
 
Assess primary ABSSSI site n 
X 
X 
X 
X 
X 
X 
X 
 
Investigator assessment of clinical 
response o 
 
 
 
 
X 
X 
X 
 
Hematology/chemistry/urinalysis p 
X 
X 
X 
X 
X 
X 
X 
 
Administer study intervention up to 
14 days q 
 
X 
 
 
ABSSSI specimen, Gram-stain and 
culture, blood cultures r,s 
X 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
 
Record procedures (I&D) t 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
PK sample collection u 
 
X 
 
 
X 
 
 
 
Thrombotic and local infusion site 
reaction AE assessments 
 
X 
X 
X 
X 
 
 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
AEs = adverse events,β-HCG = beta-human chorionic gonadotropin; BP = blood pressure; CrCl = creatinine clearance; EA = early assessment; ECG = electrocardiogram; EOIV = end of IV 
assessment; EOT = end of treatment; HR = heart rate; I&D = incision and drainage; IV = intravenous; IWRS = interactive web response system; LTFU = long-term follow-up; 
PK = pharmacokinetic: PTE = posttreatment evaluation; SAE = serious adverse event 
a 
Screening assessments for study eligibility will occur within 1 day of the administration of the first dose of study intervention. 


TNP-2092 
TenNor Therapeutics Ltd. 
Protocol PJI001-02 
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b 
Day 1 is the first day for administration of IV study intervention and subsequent days are calendar days. Participants will receive IV infusion at the hospital or clinic for a minimum of 
3 days (6 doses) based on the investigator’s clinical judgment and after switching criteria are met (Section 6.2). The duration of the treatment period (IV or IV plus oral switch, if 
applicable) is a minimum of 7 days and a maximum of 14 days.  
c 
EA assessments will be performed 48 to 72 hours after the start of the first dose of IV study intervention. EOT assessments will be performed on the last calendar day of study 
intervention (IV or IV plus oral switch, if applicable). Participants who prematurely discontinue study intervention or withdraw from the study before EOT should have all EOT 
assessments performed on the day of withdrawal (+ 1 day). 
d 
Participants will attend the PTE 7 to 14 days after the EOT for collection of safety and efficacy data (clinical and microbiological response [Section 8.4.1 and Section 8.4.2]) . 
e 
Telephone contact will be made between 20 to 25 days after the EOT for participants who do not have symptoms of clinical relapse, ongoing AEs, new or ongoing SAEs, or laboratory 
 
abnormalities that require the attention of a healthcare provider at the clinic or hospital. Participants who fit into any of these listed categories will go to the clinic or hospital. 
f 
Written, informed consent must be obtained before any nonstandard of care screening assessments are performed.(Section 10.1.4) 
g 
CrCl will be calculated according to Cockcroft-Gault (Section 10.1.12). Participants with CrCl < 30 mL/minute will be excluded from the study. 
h 
All inclusion and exclusion criteria need to be met before randomization on Day 1. All participants will be centrally assigned to randomized study intervention via IWRS (Section 6.4) 
i 
All prior medications taken within 2 weeks before randomization will be recorded. All concomitant medications taken between Day 1 and EOT will be recorded to LTFU (Section 6.6). 
j 
A complete physical examination (ie, general appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest [heart, lungs], abdomen, skin/soft tissues, neurological, extremities, 
 
back, neck, musculoskeletal, lymph nodes) and height (screening only) and weight will be performed at screening, EOIV, EOT, and PTE (Section 8.2.1). Focused physical examinations 
 
(chest [heart, lungs], abdomen, skin, neurological and musculoskeletal examinations) are performed on Day 2, EA, and each subsequent day that IV treatment is administered but not 
 
including EOIV. 
k 
Vital signs comprises temperature [oral], pulse rate, respiratory rate, and blood pressure performed at all visits except LTFU (Section 8.2.2). 
l 
ECGs will be performed in triplicate within a 15-minute period at screening, EA, EOT, and PTE (Section 8.2.3). 
m 
Female participants of childbearing potential (< 2 years after menopause and not permanently sterile) must have a β-HCG pregnancy test at baseline and EOT (Section 8.3.5) 
n 
Direct evaluation of the primary ABSSSI site includes an assessment of the extent of infection as measured with a ruler (longest length by greatest perpendicular width) and an 
assessment of local  signs and symptoms (Section 8.4.1). 
o 
The investigator’s assessment of clinical response is defined in Table 6. 
p 
Laboratory assessments including hematology, coagulation, serum chemistry, and urinalysis testing will be performed to collect safety data at all visits except LTFU. Screening/baseline 
 
test samples will be collected and sent to local laboratory (to confirm eligibility) and central laboratory (screening and subsequent testing) (Section 8.2.4, Section 10.2, and  
Table 11). 
q 
On Day 1, the first dose of study intervention should be administered as quickly as possible after eligibility criteria are met. Participants receive an IV infusion over 60 minutes q12h for 
a minimum of 3 days (6 doses) followed by a switch to a commercially-available, oral antibiotic (criteria described in Section 6.2) for the remainder of the intervention, minimum 7 to 
14 days total. 
r 
Obtain appropriate ABSSSI site specimens from all subjects at screening and perform gram-stain and culture at the local laboratory The ABSSSI site specimen should be obtained 
before administration of antibacterial therapy, whenever possible. Repeat testing is only required (X) if a previous culture was reported as positive, if clinically indicated, or if the 
participant is deemed a clinical failure (Section 8.4.1 and Section  8.4.2). 
s. 
Two sets of blood cultures (each set comprises 1 aerobic and 1 anaerobic tube from 2 separate venipuncture sites, for a total of 4 tubes) will be collected from all participants at 
screening. The blood  cultures should be obtained before administration of antibacterial therapy, whenever possible. Repeat testing is only required (X) if a previous blood culture was 
reported as positive, if clinically  indicated, or if the participant is deemed a clinical failure (Section 8.4.1 and Section  8.4.2). 
t 
If required, surgical procedures to treat ABSSSI (eg, I&D) should be performed, before the first dose of study intervention up to 24 hours (Day 2) after the first dose of study 
 
intervention. After Day 2, surgical intervention will be captured (X); however, subject evaluability in analysis populations may be affected (Section 6.6.3).  
u 
Blood samples will be collected for PK analysis on Day 1 and at EOIV as described in Section 10.5


T N P -2 0 9 2  
T e n N or T hera pe utics Lt d.  
Pr ot oc ol PJI 0 0 1 -0 2  
Pa ge 2 0  
 
 
 
2  I N T R O D U C TI O N 
2. 1  
St u d y R ati o n ale  
A nti bi oti c resista n ce p oses a seri o us t hre at t o p u blic healt h w orl d wi d e. Researc h eff orts i n 
rece nt y ears ha ve bec o me i ncre asi n gl y ge are d t o war d  disc o veri n g a n d d e vel o pi n g ne w 
classes of a nti bi oti cs wit h m o des of acti o n disti nct fr o m t h ose of esta blis he d a g e nts a n d 
acti vit y a g ai nst resist a nt strai ns. A d diti o nal n o vel a nti bi oti c c h oi ces are ne e de d t o treat 
bacterial i nfecti o ns s us pecte d or c o nfir me d t o be c a use d b y a nti bi otic-r esista nt gr a m--p ositi ve 
pat h o ge ns , t he lea di n g ca use of ba cterial i nfecti o ns i n h u ma ns (Va n  Hal, 2 0 1 1 ). T he C e nter 
f or D isease C o ntr ol esti mates t hat great er t ha n  8 0, 0 0 0 i n vasi ve m et hi cilli n -resist a nt 
St a p hyl oc o cc us a ure us  (M R S A ) i nfecti o ns a n d great er t ha n 1 1, 0 0 0  relat e d deat hs oc c ur 
a n n uall y i n t he U nite d States. M ore o ver, a n u n k n o w n b ut m uc h hi g h er n u m ber of less se vere 
i nfecti o ns re q uire treat me nt i n c o m m u nit y a n d healt h care setti n gs (C D C, 2 0 1 3 ). 
T N P -2 0 9 2 is bei n g de vel o p e d f or t h e treat me nt of seri o us or life -t hr eat e ni n g bacteri al 
i nfecti o ns s us pecte d or c o nfir me d t o b e ca use d b y gr a m -p ositi v e pat h o g e ns t hat h a ve 
de vel o pe d or ac q uire d r esista nc e t o c o m m o nl y use d a nti bi otics. 
 
 
 
  
 
 
 
 
 
 
 
T N P -2 0 9 2 is pre dicte d t o be efficaci o us a gai nst A B S S SI s us pecte d or c o nfir me d t o be ca use d 
b y a nti bi otic r esista nt gr a m -p ositi ve pat h o g e ns, a n d bi ofil m -ass ociat e d f orei g n b o d y 
i nfecti o ns, i ncl u di n g t h ose m e dic ate d b y m ulti dr u g-r esista nt pat h o ge ns. 
2. 2  
B ac k gr o u n d  
Te n N or  T hera pe utics Li mit e d ( T e n N or)  is de vel o pi n g T N P-2 0 9 2 f or t he treat me nt of 
gra m -p ositi v e seri o us or lif e -t hreate ni n g b act erial i nf ecti o ns i n cl u di n g p at h o ge ns t h at ha ve 
de vel o pe d or ac q uire d r esista nc e t o c o m m o nl y use d a nti bi otics. Ke y t ar get p at h o ge ns f or 
T N P -2 0 9 2 i ncl u de st a p h yl oc oc ci, stre pt o c occi, a n d p ne u m oc oc ci  t h at e x hi bit resista nce or 
re d uce d s usce pti bilit y t o c urre ntl y mar kete d a nti ba ct erial a ge nts. P ote ntial uses i n t he 
h os pital setti n g i n cl u de treat me nt of A B S S SI a n d ot her ac ut e i nfecti o us disease s y n dr o m es, 
i ncl u di n g t h ose me diat e d b y m ulti dr u g resist a nt pat h o ge ns. 
 
 
C CI
C CI


T N P -2 0 9 2  
T e n N or T hera pe utics Lt d.  
Pr ot oc ol PJI 0 0 1 -0 2  
Pa ge 2 1  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
C CI


T N P -2 0 9 2  
T e n N or T hera pe utics Lt d.  
Pr ot oc ol PJI 0 0 1 -0 2  
Pa ge 2 2  
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C CI


T N P -2 0 9 2  
T e n N or T hera pe utics Lt d.  
Pr ot oc ol PJI 0 0 1 -0 2  
Pa ge 2 3  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
C CI
C C
I
C CI
C CI
C CI


TNP-2092 
TenNor Therapeutics Ltd. 
Protocol PJI001-02 
Page 24 
 
 
 
3 OBJECTIVES AND ENDPOINTS 
This is the first study in which TNP-2092 is administered to participants with ABSSSI 
suspected or confirmed to be caused by gram-positive pathogens. Safety and tolerability 
comprise the primary objectives, and PK and efficacy comprise the secondary objectives. 
The objectives and endpoints are presented in Table 1. 
4 STUDY DESIGN 
4.1 
Overall Design 
This Phase 2, double-blind, randomized, multicenter, parallel, controlled study will be 
conducted to evaluate safety, tolerability, and PK of TNP-2092 300 mg IV q12h, and 
vancomycin 1 g IV q12h in adults with ABSSSI suspected or confirmed to be caused by 
gram-positive pathogens. The duration of the treatment period (IV or IV plus oral switch, if 
applicable) is a minimum of 7 days and a maximum of 14 days as presented in Figure 1. 
All participants will be treated with IV study intervention for a minimum of 3 days (6 doses).  
Upon meeting protocol-specified switching criteria (Section 6.2), participants will continue 
treatment with a commercially-available, open-label, oral antibiotic selected by the 
investigator. The Schedule of Activities is presented in Table 3 (Section 1.3). 
Participants who meet the entry criteria (Section 5.1and Section 5.2) will be randomized 
(2:1) to 1 of 2 treatment arms: TNP-2092 300 mg IV q12h or vancomycin 1 g IV q12h 
(Table 2). Randomization will be stratified by ABSSSI types to ensure proper balance 
between treatment arms (Planned N = 120, n = 80 for TNP-2092 arm A and n = 40 for 
vancomycin arm B). The types of eligible ABSSSI include cellulitis/erysipelas, wound 
infections, and major cutaneous abscesses; however, participants with major cutaneous 
abscess should not comprise > 30% of randomized population. Participants with ABSSSI 
with a minimal lesion surface area of 75 cm2 will be enrolled (FDA Guidance, 2013). No 
prior antibiotic treatment for the current ABSSSI is permitted before enrollment in the study, 
and no other concomitant systemic or topical antibiotics are permitted during the study. If a 
participant enrolls and is subsequently found to have a gram-negative or anaerobic bacterial 
infection, they may remain in the study but may be switched to an appropriate antibiotic and 
will not be included in the modified intent-to-treat (mITT) population (excludes all 
participants with gram-negative pathogens) as described in Table 9. 
An adequate local ABSSSI site specimen must be collected from all participants with non-
cellulitis ABSSSI for microbiologic evaluation at baseline. Blood samples from local 
ABSSSI site specimens, and blood cultures from 2 separate venipuncture sites, will be 
collected from all participants before administration of study interventions, whenever 
possible. All local ABSSSI site specimens will undergo Gram-stain and culture at the local 
laboratory and all blood cultures will be processed at the local laboratory. Specimens should 
be processed according to standard recognized methods. All bacteria isolated from an 
adequate local ABSSSI site specimen or blood culture at the local laboratory will be sent to a 
designated central laboratory for confirmation of species identification and antimicrobial 
susceptibility testing. Microbiologic methods are described in Section  8.4.2 and more details 
are presented the laboratory manual. 


T N P -2 0 9 2  
T e n N or T hera pe utics Lt d.  
Pr ot oc ol PJI 0 0 1 -0 2  
Pa ge 2 5  
 
 
 
Scree ni n g assess me nts t o d eter mi ne st u d y eli gi bilit y will be perf or me d wit hi n 1 da y bef ore 
t he first d ose of st u d y i nter ve nti o n is a d mi nist ere d. I ntra ve n o us st u d y i nt er ve nti o n ma y b e 
a d mi nist ere d i n a h os pital or o ut patie nt i nf usi o n ce nt er; o ut patie nt  a d mi nistrati o n of I V st u d y 
i nter ve nti o n is li mite d t o p arti ci pa nts w h o are cli nicall y sta bl e a n d ha v e a de q uate h o m e 
s u p p ort wit h reli a ble tra ns portati o n t o a n d fr o m t he h os pital or cli ni c, as descri be d i n t he 
P har mac y Ma n ual.  
Da y 1  is t he first da y of st u d y i nter v e nti o n; s u bse q ue nt st ud y da ys are c o nse c uti v e  cal e n dar 
da ys. F or p ur p os es of a nal ysis, st u d y assess me nts will be perf or me d d uri n g t he tr e at m e nt 
peri o d o n Da y 1, Da y 2, at earl y assess me nt ( E A) 4 8 t o 7 2 h o urs after I V treat me nt is start e d, 
at E OI V (a n y cale n dar da y u p t o Da y  1 4 ) at t he e n d of treat me nt ( E O T, after a mi ni m u m of 
7  da ys a n d u p t o 1 4 da ys of tre at m e nt,  I V or I V pl us oral s witc h , if a p pli ca ble), at 
p osttreat me nt e val u ati o n ( P T E, 7 t o 1 4  da ys aft er E O T), a n d at l o n g-ter m f oll o w-u p ( L T F U, 
2 0 t o 2 5  da ys after E O T).  
Safet y assess me nts will b e perf or me d at e ac h visit fr o m scree ni n g t o L T F U as i n di cate d i n 
t he Sc he d ul e of A cti viti es (Secti o n  1. 3 ). Safet y will be assess e d b y A Es, p h ysical 
e xa mi n ati o ns, vital si g ns, l a b orat or y e val uati o ns ( he mat ol o g y, c he mistr y, c oa g ulati o n, 
uri nal ysis), a n d E C G par a meters. Pri mar y P K para m eters are sec o n d ar y e n d p oi nts a n d  bl o o d 
sa m ples will b e o btai ne d f or a nal ysis o n Da y 1 a n d E OI V visi ts at desi g nat e d ti mes 
(Secti o n  1 0. 4 ).  
Cli nic al a ssess me nts of t h e pri m ar y A B S S SI site  ( me as ure me nt of e xte nt of i nfecti o n a n d 
si g ns a n d s y m pt o ms ) will oc c ur at eac h visit fr o m t h e scree ni n g visit t o P T E , w he n cli nicall y 
i n dicate d, or if t he partici p a nt is de e me d a cli nic al fail ure (Secti o n  8. 4. 1 ). A B S S SI site 
s peci me n c ult ur es will be assess e d at scr ee ni n g,  w he n cli ni call y i n di cat e d, or if  t he 
partici pa nt is dee m e d a cli nic al fail ure. Bl o o d c ult ures will be assesse d at scre e ni n g wit h 
re peat testi n g if t he pre vi o us bl o o d c ult ure was re p orte d as p ositi v e, w he n  cli nic all y i n dicate d 
or if t he partici pa nt is dee me d a cli nic al fail ure (Se cti o n  8. 4. 1 ). 
4. 2  
Scie ntific R ati o n al e f or St u d y Desi g n  
A nti bi oti c resista n ce p oses a seri o us t hre at t o p u blic healt h w orl d wi d e. Researc h eff orts i n 
rece nt y ears ha ve bec o me i ncre asi n gl y ge are d t o war d  disc o veri n g a n d d e vel o pi n g ne w 
classes of a nti bi oti cs wit h m o des of acti o n disti nct fr o m t h ose of esta blis he d a g e nts a n d 
acti vit y a g ai nst resist a nt strai ns.  A d diti o nal a nti bi oti c c h oic es are nee d e d t o tr eat 
gra m -p ositi v e  bacterial i nfe cti o ns s us pect e d or c o nfir me d t o be ca use d b y a nti bi otic-resist a nt 
gra m -p ositi v e pat h o g e ns .  
 
 
 
 
 
 
 
C CI


T N P -2 0 9 2  
T e n N or T hera pe utics Lt d.  
Pr ot oc ol PJI 0 0 1 -0 2  
Pa ge 2 6  
 
 
 
 
lt h y s u bjects, treat me nt 
wit h T N P -2 0 9 2 was e val uat e d  bet wee n 1 0  m g a n d 6 0 0  m g  per da y . 
 
 
 
 
 
 
Base d o n t he prescri bi n g i nf or mati o n, v a nc o m y ci n is c o ntrai n dicate d i n patie nts wit h k n o w n 
h y perse nsiti vit y t o va n c o m yci n . War ni n gs a n d pr eca uti o ns after r a pi d b ol us a d mi nistr ati o n 
o ver se veral mi n ut es  i ncl u de e xa g ger ate d h y p ote nsi o n, i ncl u di n g s h oc k a n d rarel y car di ac 
arrest. I nf usi o ns s h o ul d be a d mi nister e d o ver a peri o d of n ot less t ha n 6 0 mi n utes t o a v oi d 
ra pi d i nf usi o n-relat e d reacti o ns, a n d d osa ge s h o ul d b e a dj uste d f or p ati e nts wit h re nal 
d ysf u ncti o n. Tr a nsi e nt or per ma ne nt ot ot o xi cit y h as occ urre d after va nc o m yci n i nf usi o n 
us uall y i n patie nts w h o recei ve e xcessi ve d oses, ha v e u n derl yi n g h eari n g l oss, or are 
recei vi n g c o nc o mita nt me dicati o ns wit h a n ot her ot ot o xic a ge nt. Va nc o m y ci n s h o ul d be use d 
wit h ca ut i o n i n patie nts wit h re nal i ns uffici e nc y t o a v oi d t he ris k of t o xicit y w hic h i n creases 
wit h hi g h, pr ol o n ge d bl o o d c o nc e ntrati o ns. Cl ostri di u m difficile  ass ociat e d diarr he a has bee n 
re p orte d wit h n earl y all a nti ba cterial a ge nts, i n cl u di n g va nc o m yci n.  
T he c urre nt st u d y is a P hase 2, d o u bl e -bli n d , ra n d o mize d, m ulti ce nt er, parallel, c o ntr olle d 
st u d y desi g ne d t o e v al uate t h e safet y, t olera bilit y, P K, a n d efficac y of I V a d mi nist ere d 
T N P -2 0 9 2 ( 3 0 0 m g q 1 2 h) a n d I V a d mi nist ere d va nc o m yci n ( 1 g q 1 2 h) i n a d ult p arti c i pa nts 
wit h A B S S SI. T he st u d y desi g n i nc or p orat es rec o m me n dati o ns fr o m t he U S F o o d a n d Dr u g 
A d mi nistrati o n 2 0 1 3 G ui da nc e f or I n d ustr y ( A B S S SI: De vel o pi n g Dr u gs f or Treat me nt) 
(F D A, 2 0 1 3 ). T he safet y an d t ol era bilit y par a meters m o nit ore d d uri n g t he st u d y are 
well -esta blis he d m eas ures of safet y i n cli nical st u d y partici pa nts. Bl o o d sa m ples will be 
c olle cte d t o det er mi ne t he P K para m eters of T N P -2 0 9 2 after t h e first d ose a n d E OI V i n t his 
st u d y p o p ulati o n. T he sec o n d ar y e n d p oi nts of pr o gra m matic cli ni cal r es p o nse at E A ali g ns 
wit h t he c urr e nt F D A g ui da nce  (2 0 1 3 ). Sec o n d ar y efficac y e n d p oi nts als o i ncl u de t he 
i n vesti gat or assess me nts of cli nic al res p onse at d esi g nate d ti me p oi nts a n d micr o bi ol o gical 
res p o nses at P T E.  
4. 3  
J ustific ati o n f or D ose  
 
 
 
 
 
C CI
C CI
C CI


T N P -2 0 9 2  
T e n N or T hera pe utics Lt d.  
Pr ot oc ol PJI 0 0 1 -0 2  
Pa ge 2 7  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
C CI
C CI
C CI
C CI
C CI


T N P -2 0 9 2  
T e n N or T hera pe utics Lt d.  
Pr ot oc ol PJI 0 0 1 -0 2  
Pa ge 2 8  
 
 
 
 
 
 
 
 
 
4. 4  
E n d of St u d y Def i niti o n 
A partici p a nt is c o nsi d ere d t o ha v e c o m plet e d tre at m e nt aft er recei vi n g  a mi ni m u m of 7  da ys 
a n d u p t o 1 4 da ys  of t he st u d y i nter v e nti o n. M ore o ver, a  parti ci pa nt is c o nsi dere d t o ha ve 
c o m plete d t h e st u d y w he n t he L T F U visit  has  bee n c o m plet e d as s h o w n i n t he Sc he d ule of 
Acti vities ( Secti o n  1. 3 ). T he e n d of t he st u d y is defi n e d as t he date of t h e last visit f or t he last 
pa rtici pa nt i n t he st u d y. 
5  S T U D Y P O P U L A TI O N  
T he p o p ulati o n of a d ult partici pa nts e nr olle d i n t his st u d y re q uire me di cal c are t o tre at t heir 
A B S S SI s us pecte d or c o nfir m e d t o be ca use d b y g ra m-p ositi ve p at h o ge ns .  
Pr os pecti ve a p pr o v al of pr ot oc ol de vi ati o ns t o r ecr uit me nt a n d e nr oll me nt criteria, als o 
k n o w n as pr ot oc ol wai vers or e xe m pti o ns, ar e n ot per mitt e d.  
5. 1  
I ncl usi o n Criteri a 
Partici p a nts are eli gi ble t o be i ncl u de d i n t he st u d y  if all criteria a p pl y  as f oll o ws : 
A ge  
1.  A d ult m al es or fe male s, 1 8 years of a ge or ol der  
T y pe of P artici p a nt a n d Dise ase C h ar acteristics  
2.  A B S S SI  s us pecte d or c o nfir m e d t o be ca use d b y  g ra m-p ositi ve p at h o ge ns t h at re q uires 
i niti al I V a nti bi otic tr eat me nt, w hic h p arti ci pa nts are willi n g t o r ecei ve f or at least 3  d a ys  
( 6 d oses) . Partici pa nts wit h 3 i nfe cti o n t y pes will be e nr olle d:  
a. Cell ulitis/ er ysi pel as - a diff use s ki n i nf ecti o n c hara ct erize d b y a s prea di n g ar ea of 
re d ness, e de ma, a n d/ or i n d urati o n 
b.  W o u n d i nfecti o n (tr a u matic or p osts ur gic al) - a n i nfe cti o n i n v ol vi n g s ki n a n d 
s u bc uta ne o us tiss ue, c h aract eriz e d b y p ur ule nt drai n a ge fr o m a w o u n d wit h 
s urr o u n di n g re d ness, e de ma, a n d/ or i n d urati o n  
c. Maj or c uta n e o us a bscess: a n i nfe cti o n c hara cterize d b y a c oll ecti o n of p us wit hi n t h e 
der mis or dee p er t hat is acc o m pa ni e d b y re d nes s, e de ma, a n d/ or i n d urati o n 
 
3.  S ki n i nfecti o n wit h a lesi o n s urface area at l east 7 5 c m2 (l o n gest l e n gt h a n d wi d est wi dt h 
per pe n dic ular t o t he le n gt h ma n u all y meas ure me nt wit h r uler). T he s urface area will be 
calc ulat e d b y m ulti pl yi n g t he le n gt h x wi dt h. T he l esi o n size will be m eas ure d b y are a of 
re d ness, e de ma, or i n d urati o n, w hi c he ver is great est.  
C CI


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For participants with more than 1 type of eligible lesion/wound or with multiple lesions 
of the same type, the investigator must clearly identify the lesion to be evaluated for 
study purposes. Surgical procedures to treat ABSSSI (eg, incision and drainage [I&D]) 
are permitted before the first dose of study intervention up to 24 hours after the start of 
the first dose of study intervention. 
4. At least 2 of the following local signs at the ABSSSI site: 
a.  Purulent or seropurulent drainage/discharge 
b. Erythema 
c. Fluctuance 
d. Heat/localized warmth 
e. Pain/tenderness to palpation 
f. Swelling/induration 
5. At least 1 marker of systemic inflammation: 
a. Fever or hypothermia (oral temperature ≥ 38.0ºC or ≤ 36.0ºC) 
b. White blood cell (WBC) count ≥10,000/mm3 or ≤4,000/mm3 
c. Immature neutrophils (bands) ≥15% irrespective of WBC count 
d. Presence of lymphangitis or lymphadenopathy proximal to the ABSSSI 
 
Note that there is no requirement for at least 1 marker of systemic inflammation in 
participants ≥ 70 years old or in participants with diabetes. 
Sex 
6. Females of childbearing potential, < 2 years postmenopausal who are not permanently 
sterile, must have a negative serum or urine pregnancy test (beta-human chorionic 
gonadotropin [β-HCG]) at baseline, and agree to use 2 highly effective methods of birth 
control (eg, abstinence, oral contraceptive, intrauterine device, barrier contraception 
[condom]) to PTE. Females who are not of childbearing potential (have had a tubal 
ligation, hysterectomy, or bilateral oophorectomy, or are ≥ 2 years postmenopausal) or 
have a partner who has had a vasectomy do not need to use any contraception. Males 
must use a highly effective method of birth control if female partner(s) is of childbearing 
potential and must not donate sperm from baseline through PTE. Contraception guidance 
is described further in Section 10.7. 
Informed Consent 
7. Capable of giving signed informed consent as described in Section 10.1.4 which includes 
compliance with the requirements and restrictions listed in the informed consent form and 
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5.2 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Body mass index ≥30 kg/m2 (obese) 
2. History or hypersensitivity or intolerability to any fluoroquinolone, rifamycin or 
glycopeptide class 
3. ABSSSI suspected or confirmed to be caused by pathogens that are resistant to the 
glycopeptide class  
4. Prior administration of systemic antibacterial therapy within 96 hours before 
randomization 
5. Pregnant or breastfeeding 
6. Evidence of significant hepatic, hematologic, or immunologic disease determined by the 
following: 
a. Acute hepatitis from any cause within the past year; participants with stable chronic 
hepatitis B and/or hepatitis C may be eligible provided they do not meet exclusion 
criteria  
b. Serum ALT, AST, or bilirubin greater than 2 times upper limit of normal 
c. Manifestations of end-stage liver disease, such as ascites or hepatic encephalopathy 
d. Current or anticipated neutropenia defined as < 500 neutrophils/mm3 
e. Known infection with human immunodeficiency virus (HIV) and a cluster of 
differentiation 4 (CD4) count that is unknown or documented to be < 200 cells/mm3 
within the last year, or an Acquired Immune Deficiency Syndrome (AIDS)-defining 
illness 
f. The receipt of cancer chemotherapy, radiotherapy, or potent noncorticosteroid 
immunosuppressant drugs (eg, cyclosporine, azathioprine, tacrolimus, 
immune-modulating monoclonal antibody therapy, etc.) within the past 3 months, or 
the receipt of corticosteroids equivalent to or greater than 40 mg of prednisone/day or 
for more than 14 days in the prior 30 days 
7. QT interval corrected with Fridericia’s formula (QTcF) > 450 msec based on the average 
of screening ECGs in triplicate; or history of QT prolongation, clinically significant 
hypokalemia, or other proarrhythmic conditions 
8. Has other contraindications to receive a systemic fluoroquinolone antibiotic, including 
confirmed or suspected peripheral neuropathy, tendon disorder, myasthenia gravis, 
cirrhosis, aortic aneurysm, or central nervous system disorder that may predispose the 
participant to seizures or lower the seizure threshold 
9. History of Clostridium difficile infection 
10. ABSSSI with any of the following characteristics: 


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a. Suspected or confirmed infection caused by gram-negative or anaerobic organisms 
(eg, perineal wound infection, gluteal decubitus ulcer, wound infection associated 
with surgery on gastrointestinal tract or female genital tract, infection caused by a 
human or animal bite) 
b. Suspected or confirmed fungal, mycobacterial, parasitic, or viral pathogens 
c. Involving an ischemic ulcer due to peripheral vascular disease 
d. Involving a decubitus ulcer or perirectal abscess 
e. Involving a diabetic foot ulcer 
f. Involving a burn 
g. Involving an underlying inflammatory skin disease that may obscure determination of 
response (eg, chronic dermatitis) where inflammation may be prominent for an 
extended period, even after successful bacterial eradication has been achieved 
h. Involving a bite other than an arthropod bite (ie, human or animal bite) 
i. Involving a rapidly necrotizing process, such as necrotizing fasciitis 
j. Involving gangrene of any etiology 
k. Complicated by an immune deficiency (eg, development of ecthyma gangrenosum in 
neutropenic subject) 
l. Anatomically associated with prosthetic materials (eg, central venous catheters, 
permanent cardiac pacemaker battery packs, or joint replacement prostheses), even if 
the device is removed 
m. Requiring amputation 
n. Requiring significant surgical intervention (ie, procedures that would not normally be 
performed at the bedside) that cannot be performed within 24 h after initiating study 
intervention treatment (Inclusion Criterion 3) 
o. Minor cutaneous abscess or furuncle or any other condition with an estimated high 
cure rate after surgical incision alone or after aggressive local skin care 
p. Associated with infection at other anatomic sites or spaces, such as endocarditis or 
other endovascular infection, thrombophlebitis, osteomyelitis, or septic arthritis 
q. Anticipated need for antibacterial therapy for longer than 14 days 
11. History or evidence of severe renal disease or has a calculated creatinine clearance of 
< 30 mL/min, according to the Cockcroft-Gault equation (Section 10.2, Table 11) 
12. Presence of any other surgical or medical condition (including a clinically significant 
laboratory abnormality) as determined by the investigator and/or the sponsor’s medical 
monitor, that could interfere with the participant’s ability to participate in the study, the 
administration of study intervention, and/or the interpretation of study results. 
13. Anticipated need for concomitant use of medications from randomization to EOT: HIV 
protease inhibitors (eg, ritonavir-boosted or non-boosted saquinavir, atazanavir, 
darunavir, fosamprenavir, or tipranavir); praziquantel, halothane, and Class IA and III 


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anti-arrhythmics (eg, disopyramide, procainamide, quinidine, amiodarone, dofetilide, 
dronedarone, ibutilide, and sotalol) (Table 20). 
Prior/Concurrent Clinical Study Experience 
14. Previous enrollment in this study or previous treatment with TNP-2092 
15. Received an investigational medication within 30 days or 5 half-lives (whichever is 
longer) before the first dose of study intervention. 
5.3 
Lifestyle Considerations 
After switching to oral antibiotic treatment, food or drug restrictions (Section 6.6.2) may be 
necessary, depending on the antibiotic chosen. The investigator will inform the participants 
of any restrictions after reviewing the prescribing information for each antibiotic. 
5.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study but 
are not subsequently randomly assigned to study intervention. Individuals who do not meet 
the criteria for participation in this study (screen failure) can be rescreened. 
A minimal set of screen failure information is required and will be collected to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials publishing requirements and to respond to queries from regulatory 
authorities. Minimal information includes demography, screen failure details, eligibility 
criteria, and any SAE. 
6 STUDY INTERVENTION 
Study intervention is defined as any investigational intervention or marketed product, 
intended to be administered to a participant according to the protocol. During the first part of 
this study, each participant will receive an IV infusion q12h of study intervention for a 
minimum of 3 days (6 doses). Intervention comprising IV or IV plus oral medications switch 
(if applicable) will be administered for a minimum of 7 days up to 14 days. After the IV 
infusion part of the study is completed and participants meet switching criteria, they will be 
switched to a commercially-available, oral, open-label antibiotic selected by the investigator. 
6.1 
Study Interventions Administered 
One-hundred twenty participants who meet study entry criteria will be randomly assigned to 
treatment in 1 of 2 treatment arms in a 2:1 ratio as presented in Table 2. A sample size of 
80 participants who receive TNP-2092 is deemed sufficient to provide an initial assessment 
of safety and PK data to inform the future development of TNP-2092. 
The study intervention refers to supplied IV TNP-2092 and IV vancomycin and the 
commercially available, open-label, oral antibiotic. Infusions of study intervention will be 
administered as follows: 
• 
TNP-2092–300 mg IV q12h infusion will be administered over 60 minutes (treatment 
arm A) for a minimum of 3 days (6 doses) and a maximum of 14 days  


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• 
Vancomycin - 1 g IV q12h infusion will be administered over 60 minutes (treatment 
arm B) for a minimum of 3 days (6 doses) and a maximum of 14 days  
 
For all study interventions used in this study, the clinical label will identify the product by 
name, lot number, manufacturer, storage conditions, and expiry date. Administration of the 
IV study intervention is limited to investigational use only. Refer to the Pharmacy Manual 
for additional information. All supplies packed and labeled will be formally released in 
accordance with both Good Manufacturing Practice and Good Clinical Practice (GCP) 
guidelines. 
• 
Lyophilized TNP-2092 for IV administration will be provided in clear, glass vials (10 mL 
capacity) containing 100 mg TNP-2092. The vials should be kept frozen (-20ºC) until 
reconstitution. One vial of lyophilized TNP-2092 will be reconstituted in 5 mL of sterile 
Water for Injection, USP, for a final concentration of 20 mg/mL. Reconstituted 
TNP-2092 solution is injected into prepared IV bag at ambient temperature and diluted in 
5% dextrose solution as presented in Table 4. Once the drug product is reconstituted, it 
will be stored for no longer than 4 hours at ambient temperature.  
• 
Commercially-available, lyophilized vancomycin for IV administration will be provided 
in clear, glass vials containing 1 g vancomycin. The vials should be kept at ambient 
temperature until reconstitution. One vial of lyophilized vancomycin will be reconstituted 
in 20 mL of Sterile Water for Injection, USP, for a final concentration of 50 mg/mL. 
Reconstituted vancomycin solution is injected into the prepared IV bag, at ambient 
temperature, and diluted with 5% dextrose solution as presented in in Table 4. Once the 
drug product is reconstituted, it will be stored for no longer than 4 hours at ambient 
temperature.  
 
Table 4 
Preparation of Reconstituted TNP-2092 and Vancomycin 
Intervention 
Dose 
D5W 
Volume 
Added to 
IV Bag 
No. of 
Vials 
Needed 
Total 
Volume 
Withdrawn 
from Vial 
Total 
Volume 
Volume 
Infused 
Duration 
of 
Infusion 
TNP-2092 
300 mg 
185 mL 
3 
15 mL 
200 mL 
200 mL 
60 min 
Vancomycin 
1 g 
180 mL 
1 
20 mL 
200 mL 
200 mL 
60 min 
 
Packaging for the final ready-to-infuse infusion for TNP-2092 and vancomycin will not be 
identical in appearance. To maintain the blind, the unblinded pharmacist will cover the IV 
bag with an ultraviolet light impermeable overwrap to facilitate blinding of the parenteral 
drug product. The tubing used for the infusion will be impenetrable to light, so the color will 
not be seen. 
Treatment with study intervention will begin with the infusion of the IV formulation of study 
intervention on Day 1 as soon as possible after eligibility criteria are met. Treatment with the 
IV formulation will continue for at least 3 days (ie, 6 doses), after which participants may be 


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switched to the oral antibiotic only (Section 6.2). Participants will be hospitalized or will 
come to the clinic twice daily to receive study intervention. 
Study intervention will be dispensed to the sites as summarized in Schedule of Activities 
(Section 1.3). Returned study intervention must not be reused and must be disposed of 
according to instructions provided in the pharmacy manual. Upon completion of the IV 
infusion part of the study, the commercially-available, oral antibiotic treatment will be 
administered in an open-label manner after participants meet the switching criteria described 
in Section 6.2. The prescribing information provided by the manufacturer will be followed to 
ensure that it is administered appropriately. 
6.2 
Criteria for Intravenous to Oral Treatment Switch 
Following at least 3 days of study intervention (ie, 6 doses of TNP-2092 or vancomycin), 
participants may be switched from the twice daily IV study intervention to 
commercially-available, open-label, oral antibiotic therapy, if all of the following conditions 
are met: 
• 
In the previous 24 hours, the participant has had 4 temperature measurements, each 
separated by approximately 6 hours, and all 4 measurements are ≤ 37.6°C / 99.7°F. 
• 
Peripheral WBC count and immature neutrophils returning or have returned to normal 
range according to the local laboratory reference range 
• 
No increase from baseline or the previous visit in ABSSSI lesion area compared to the 
screening visit or a previous visit 
• 
No increase in severity of inflammatory findings at the primary site of infection 
(erythema, edema, induration) from baseline or a previous visit; in general, the severity of 
these findings should be mild 
• 
Unequivocal improvement in some or all clinical signs of ABSSSI under study; if some 
signs have not improved, none should have worsened (ie, stability for that sign is 
observed). 
• 
Ability to maintain oral intake 
 
Participants in any treatment arm may be switched to oral therapy, once the investigator’s 
assessment of clinical response is improvement, as described in Section 8.4.1. When the 
participant is switched to oral therapy, treatment will continue in an open-label manner with 
no attempt to blind the oral treatment. The IV antibiotic treatment will remain blinded until 
the database is unlocked. The oral antibiotic will be selected by the investigator and that part 
of the study will be conducted in an open-label manner. 
6.3 
Preparation/Handling/Storage/Accountability 
6.3.1 
IV Antibiotic 
All unit doses of study intervention, TNP-2092 IV and vancomycin IV, will be prepared at 
the study site by an unblinded pharmacist or by designated members of the clinical pharmacy 
staff. They will be responsible for maintaining the blind from other study personnel. 


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Preparation and administration of study intervention will be performed in accordance with 
the treatment schedule. 
1. The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit and storage for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
2. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study intervention 
must be stored in a locked, secure, environmentally controlled, and monitored (manual or 
automated) area in accordance with the labeled storage conditions (-20ºC) with access 
limited to the investigator and authorized site staff. 
3. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study intervention accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
4. Further guidance and information for the final disposition of unused study interventions 
are provided in the Pharmacy Manual. 
 
6.3.2 
Oral Antibiotic 
The investigator will select the type and dosage of commercially-available, antibiotic used. 
The oral antibiotic choice will not be blinded. 
6.4 
Measures to Minimize Bias: Randomization and Blinding 
Participants will be randomly assigned in a 2:1 ratio of the study interventions 
(TNP-2092: vancomycin). Randomization will be stratified by ABSSSI type 
(cellulitis/erysipelas, wound infection, or major cutaneous abscess); however, participants 
with major cutaneous abscess should not comprise > 30% of randomized population. All 
participants will be centrally assigned to randomized study intervention with an Interactive 
Web Response System (IWRS). Before the study is initiated, login information and 
directions for the IWRS will be provided to each site.  
Investigators will remain blinded to each participant’s assigned study intervention throughout 
the study. After informed consent has been obtained and study eligibility established, the 
study site’s pharmacist or designee will obtain the randomization number and the study 
intervention assignment from the IWRS and the participant is considered randomized. To 
maintain the blind, the study pharmacist will be responsible for the reconstitution and 
dispensation of all study intervention. The participant or legally authorized representative 
will also be instructed to avoid discussing the IV treatment or packaging of the study 
intervention with the investigator. 
This is a double-blind study. Those blinded to study intervention assignment include the 
sponsor, investigator, study statistician, clinical study personnel participating in direct 
participant care and those involved in all clinical evaluations. Those unblinded to study 
intervention assignment include the pharmacy personnel, the unblinded study monitor, and 
the bioanalytical laboratory. To minimize the potential for bias, treatment randomization 


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information will be kept confidential by and from the sponsor personnel and will not be 
released to the investigator, blinded investigator site personnel, or the blinded study monitor 
until the conclusion of the study. Procedures to ensure that the blind is maintained are 
detailed in the Study Blinding Manual. 
Unblinding Study Intervention 
If study intervention is determined not to be safe and/or not tolerated, the study intervention 
assignment for those participants with a significant safety concern may be unblinded. The 
investigator and medical monitor will review the participant’s data, discuss the findings, and 
jointly decide to unblind the treatment assignment, continue or terminate enrollment in the 
study. 
The blind may also be broken in the case of a medical emergency that requires the 
investigator to know the identity of the study intervention to appropriately guide the 
participant’s medical management. Before unblinding the treatment, the investigator is 
strongly advised to discuss options with the medical monitor or appropriate sponsor study 
personnel. If the blind is broken for any reason and the investigator is unable to contact the 
sponsor before unblinding the treatment, the investigator must notify the sponsor as soon as 
possible, without revealing the participant’s study intervention assignment (unless important 
to the safety of participants remaining in the study). All instances of treatment unblinding 
will be thoroughly investigated and documented by the unblinded study monitor. 
In the event of a quality assurance audit, the auditor will be allowed access to unblinded 
study intervention records at the sites to verify that randomization/dispensing has been done 
accurately. 
6.5 
Study Intervention Compliance 
Participant compliance with study intervention will be assessed at each visit. Each dose of IV 
study intervention will be administered by study staff, under direct medical supervision of the 
investigator, and recorded on the electronic case report form (eCRF). Participants who are 
not hospitalized during IV treatment will have to return to the clinic or hospital for each IV 
infusion. The following compliance information will be documented and reported in the 
eCRF: 
• 
The dates and times of administration of each IV study intervention. 
• 
For IV infusion, the time when infusion starts and when it ends is recorded along with the 
total volume of solution administered (if infusion is halted or interrupted for any reason, 
the time of premature discontinuation and re-initiation of infusion is recorded). 
Participants managed as outpatients who receive oral antibiotics will self-administer study 
intervention. At the EOT, unused study medication and used/empty bottles will be collected 
and used to determine compliance to treatment. Compliance will be calculated on the number 
of doses of study intervention administered, divided by the total number of expected doses 
from information obtained from the eCRF. Deviations from the prescribed dosage regimen 
will be recorded on the eCRF. 


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A further check of compliance will be the determination of blood concentrations of 
TNP-2092 during the analytical phase of the study (Section 10.4). 
6.6 
Concomitant Therapy 
6.6.1 
Other Medication Therapy 
All prescription medications and over-the-counter medications, including herbal, nutritional, 
and dietary supplements (eg, any antacid, iron supplement, or multivitamin) administered 
within 2 weeks (14 days) before randomization and during the study between Day 1 and 
LTFU will be documented in the eCRF. Any changes in prior or concomitant medications 
will also be recorded. 
In addition to the name of the medication, the following information will be collected and 
documented: 
• 
Reason for use 
• 
Dates of administration including start and end dates 
• 
Dosage information including dose and frequency 
 
The medical monitor should be contacted if there are any questions regarding concomitant or 
prior therapy. 
6.6.2 
Prohibited Medications and Medications Requiring Special Consideration 
Participants who received prior administration of systemic antibacterial therapy within 
96 hours before randomization are excluded from the study. No other concomitant systemic 
or topical antibacterial agents are permitted during the study. A list of prohibited medications 
is presented in Table 20 and Section 5.2, Exclusion Criterion 13.  
Caution is advised with concomitant use of medications that may have drug-drug interactions 
with rifamycin or fluoroquinolones. The investigators will receive the prescribing 
information for rifampin (2019) and moxifloxacin (2016). The investigators should review 
this information about these agents as representative examples from these drug classes. In 
addition, training sessions will be provided to the investigators regarding these drug classes. 
6.6.3 
Adjunctive Therapy 
The following non-drug adjunctive therapies are permitted: 
a. Local bedside wound care as per hospital protocol 
b. Lesion debridement at the bedside 
c. If required, surgical procedures to treat ABSSSI (eg, I&D) should be performed 
before the first dose of study intervention up to 24 hours (Day 2) after the first dose of 
study intervention. After Day 2, if performed, any surgical intervention will be 
captured; however, subject evaluability in analysis populations may be affected. 


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6.6.4 
Rescue Medication 
Concomitant or rescue antimicrobial medications are not permitted in this study, except in 
cases of failure of the study intervention and need for open-label antimicrobial therapy to 
continue treatment of the ABSSSI. If rescue medication is needed, study intervention should 
be prematurely discontinued and all EOT visit assessments should be completed, if possible, 
before rescue therapy is initiated. 
6.7 
Dose Modification 
No dose modifications will be permitted in this study. 
6.8 
Intervention After the End of the Study 
Continuation of study intervention beyond the 14-day treatment period is not permitted 
following the end of the study because participants with ABSSSI should be cured. For 
participants who withdraw from treatment because of lack of efficacy, all safety assessments 
from the EOT visit should be completed before rescue therapy with another antibiotic is 
initiated. 
7 DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Intervention 
Participants who prematurely discontinue treatment will remain in the study. Before 
premature discontinuation, the study site personnel should notify the medical monitor, time 
permitting. Efforts will be made by the site to complete all protocol-specified assessments 
listed for the EOT visit as appropriate, and to perform follow-up safety assessments as 
specified at the PTE visit and LTFU visit as scheduled. Ongoing AEs should be following to 
resolution or to a satisfactory outcome, as determined by the investigator. Participants who 
withdraw will not be replaced. See the Schedule of Activities for data to be collected at the 
time of intervention discontinuation and follow-up and for any further evaluations that need 
to be completed (Section 1.3). 
7.2 
Participant Discontinuation/Withdrawal from the Study 
Participants have the right to withdraw from the study without prejudice by request or may 
be withdrawn at any time at the discretion of the investigator. All participants should be 
encouraged to complete all study assessments before withdrawal, as shown in the Schedule 
of Activities (Section 1.3). Study assessments should be completed before any rescue therapy 
is initiated. After the study assessments are completed the participant will be permanently 
discontinued from the study. If the participant withdraws consent for disclosure of future 
information, the sponsor may retain and continue to use any data collected before consent is 
withdrawn. If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the investigator must document the request and destruction 
in the site study records. 
Data for all participants will be reviewed to ensure that the investigators are following the 
protocol-defined criteria for clinical response and queries will be issued as needed to clarify 
any response that does not meet the protocol definition. 


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7.3 
Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether the participant wishes to and/or should continue in the 
study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, 
if necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
 
Discontinuation of specific sites or of the study are handled as part of Section 10.1.9. 
8 STUDY ASSESSMENTS AND PROCEDURES 
8.1 
Protocol Adherence 
Each investigator must adhere to the protocol as detailed in this document and agree that the 
sponsor or sponsor representative must approve any change to the protocol before seeking 
approval from the Institutional Review Board (IRB). Each investigator will be responsible 
for enrolling only those participants who have met the protocol inclusion and exclusion 
criteria. 
• 
Study procedures and their timing are summarized in Section 1.3. Protocol waivers or 
exemptions are not allowed. 
• 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study intervention. 
• 
Adherence to the study design requirements, including those specified in the Schedule of 
Activities (Section 1.3), is essential and required for study conduct. 
• 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
• 
Procedures conducted as part of the participant’s routine clinical management (eg, blood 
count) and obtained before signing of the informed consent form (ICF) may be utilized 


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for screening or baseline purposes provided the procedures met the protocol-specified 
criteria and were performed within the time frame defined in the Schedule of Activities. 
• 
Blood samples will be collected from each participant over the duration of the study, and 
extra assessments will be collected as required. The sponsor anticipates that the total 
amount of blood will not exceed 200 mL. Repeat or unscheduled samples may be taken 
for safety reasons or for technical issues with the samples. 
 
Any changes in the timing or addition of time points for any planned study assessments must 
be documented and approved by the relevant study team member and then archived in the 
sponsor and site study files and will not constitute a protocol amendment. The IRB, IEC will 
be informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICF. 


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8.2 
Safety Assessments 
Planned time points for all safety assessments are provided in the Schedule of Activities 
(Section 1.3). 
8.2.1 
Physical Examinations 
Physical examinations, both complete and focused, will be performed as follows: 
• 
A complete physical examination comprises weight, height (screening only), general 
appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest (heart, lungs), 
abdomen, skin/soft tissues, neurological, extremities, back, neck, musculoskeletal, and 
lymph nodes. 
• 
A focused physical examination comprises chest (heart, lungs), abdomen, skin, 
neurological and musculoskeletal systems. 
Complete physical examinations will be performed at the screening, EOIV, EOT, and PTE 
visits. Focused physical examinations will be performed on Day 2, EA, and every subsequent 
day of IV treatment (minus EOIV). 
 
8.2.2 
Vital Signs 
Vital signs will be assessed preferably by the same observer and with the same instruments 
per participant at each visit from screening to PTE as follows: 
• 
Temperature (oral), pulse rate, respiratory rate, and blood pressure will be assessed. 
• 
Blood pressure and pulse measurements will be assessed in the sitting position with a 
completely automated device. Manual techniques will be used only if an automated 
device is unavailable. 
• 
Blood pressure and pulse measurements should be preceded by at least 5 minutes of rest 
in a quiet setting without distractions (eg, television, cell phones). 
• 
Vital signs (taken before blood collection for laboratory and PK assessments) will consist 
of 1 pulse and 3 blood pressure measurements (3 consecutive blood pressure readings 
will be recorded at intervals of at least 1 minute). The average of the 3 blood pressure 
readings will be recorded on the eCRF. 
 
8.2.3 
Electrocardiograms 
Triplicate 12-lead ECG recordings will be obtained within a 15-minute period, separated by 
at least 1 minute, before collection of blood for laboratory and PK assessments, and within 
4 hours (± 30 minutes) of study intervention administration. These assessments will be 
performed at screening, EA, EOT, and PTE. 
8.2.4 
Clinical Safety Laboratory Assessments 
Central laboratory safety assessments for hematology, coagulation, serum chemistry, and 
urinalysis will be performed at each visit from screening through PTE according to the 


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Schedule of Activities (Table 3). Specifically, central laboratory assessments include β-HCG 
pregnancy test at baseline and EOT, and hematology, coagulation, serum chemistry, and 
urinalysis testing at each visit from screening through PTE. Given the duration of time 
required to ship, receive, and analyze the central laboratory tests, the central laboratory 
results will not be available to immediately affect participant management in real-time. 
Therefore, local laboratory testing should be performed as needed according to local 
standards of care to appropriately manage participants. 
Local laboratory tests are required to ensure eligibility at screening (Section 5.1 and 
Section 5.2). Specifically, local laboratory testing for eligibility includes plasma WBC count 
and immature neutrophil percentage (potentially required to meet Inclusion Criterion 5); 
β-HCG pregnancy testing (Inclusion Criteria 6); serum ALT, AST, total bilirubin, and 
absolute neutrophil count (Exclusion Criterion 6); and serum creatinine for creatinine 
clearance calculation (Exclusion Criterion 11). Any other local laboratory samples may be 
collected as part of site-specific routine management of participants per local standards of 
care, whether at baseline or postbaseline.  
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study, including any value beyond PTE, should be repeated until the 
values return to normal or baseline or are no longer considered clinically significant by the 
investigator or medical monitor. Additional details of clinical laboratory testing are presented 
in the Laboratory Manual.  
A complete list of tests to be performed is presented in Section 10.2 (Table 11).  
The investigator duties regarding laboratory test results are as follows: 
• 
The investigator must review the laboratory report, document this review, and record any 
clinically significant changes occurring during the study in the AE section of the eCRF. 
The laboratory reports must be filed with the source documents. Clinically significant 
abnormal laboratory findings are those which are not associated with the underlying 
disease, unless judged by the investigator to be more severe than expected for the 
participant's condition. 
• 
All laboratory tests with values considered clinically significantly abnormal during 
participation in the study, including any value beyond PTE, should be repeated until the 
values return to normal or baseline or are no longer considered clinically significant by 
the investigator or medical monitor. 
• 
If such values do not return to normal/baseline within a period judged reasonable by the 
investigator, the etiology should be identified, and the sponsor notified. 
• 
All protocol-required laboratory assessments, as defined in Section 10.2, must be 
conducted in accordance with the laboratory manual and the Schedule of Activities 
(Section 1.3). 
• 
If values from laboratory assessments not specified in the protocol performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (eg, SAE or AE), then the results 
must be recorded in the eCRF. 


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8.3 
Adverse Events and Serious Adverse Events 
The definitions of an AE (Table 12), SAE (Table 14), and the types of events meeting the 
definition of AE (Table 13) are presented in Section 10.3. Adverse events will be reported by 
the participant during the study visits either in person or by telephone. The investigator and 
any qualified designees are responsible for detecting, documenting, and recording events that 
meet the definition of an AE or SAE as presented in Table 15. They remain responsible for 
following up AEs that are serious, considered related to the study intervention or study 
procedures, or that caused the participant to discontinue the study intervention or study. 
Thrombotic and infusion site AEs will be considered events of special interest and will be 
collected and documented separately from AEs from the screening to EOIV visits 
(Section 1.3). 
8.3.1 
Period and Frequency for Collecting AE and SAE Information 
All AEs and SAEs will be collected from the time the ICF is signed to the LTFU visit, 
20 to 25 days after the EOT, at the time points specified in the Schedule of Activities 
(Section 1.3). Medical occurrences that begin before the start of study intervention but after 
obtaining informed consent will be recorded on the Medical History/Current Medical 
Conditions section of the eCRF and not within the AE section. All SAEs will be recorded 
and reported to the sponsor or designee immediately within 24 hours of awareness, as 
presented in Table 19. The investigator will submit any updated SAE data to the sponsor 
within 24 hours of it being available. 
After the conclusion of the study (LTFU), investigators are not obligated to actively seek AE 
or SAE information. However, the investigator must promptly notify the sponsor if the 
investigator learns of any SAE, including a death, at any time after a participant has been 
discharged from the study, and he/she considers the event to be reasonably related to the 
study intervention or study participation. 
8.3.2 
Method of Detecting AEs and SAEs 
The method of recording, evaluating, and assessing the intensity and causality of AEs and 
SAEs and the procedures for completing and transmitting SAE reports are presented in 
Table 16 and Table 17, respectively. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
nonleading verbal questioning of the participant is the preferred method to inquire about AE 
occurrences. 
8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, AEs that lead to discontinuation, and AEs 
of special interest Section 10.3, will be followed until resolution, stabilization, the event is 
otherwise explained, or the participant is lost to follow-up (as defined in Section 7.3). Further 
information on follow-up procedures is given in Section 10.3.3. 


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8.3.4 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities toward the safety of participants and the safety of 
a study intervention under clinical investigation are met. 
• 
The sponsor has a legal responsibility to notify both the local regulatory authority and 
other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory requirements 
relating to safety reporting to the regulatory authority, IRB /Independent Ethics 
Committee (IEC), and investigators. 
• 
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
• 
An investigator who receives an investigator safety report describing a SAE or other 
specific safety information (eg, summary or listing of SAEs) from the sponsor will 
review and then file it along with the Investigator’s Brochure and will notify the 
IRBs/IECs, if appropriate according to local requirements. 
 
8.3.5 
Pregnancy 
A serum or urine β-HCG test will be performed at screening and at the EOT for all women of 
childbearing potential. 
• 
Details of all pregnancies in female participants and female partners of male participants 
will be collected after the start of study intervention until the outcome of the pregnancy is 
determined. 
• 
If a pregnancy is reported, the investigator should inform the sponsor within 24 hours of 
learning of the pregnancy and should follow the procedures described in Section 10.7. 
• 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
following the SAE reporting process (Section 10.3.5). 
 
The risks of treatment with TNP-2092 during pregnancy have not been fully evaluated. 
Therefore, females of childbearing potential, < 2 years postmenopausal who are not 
permanently sterile, must have a negative baseline serum or urine pregnancy test (β-HCG) at 
baseline, and agree to use 2 highly effective methods of birth control (eg, abstinence, oral 
contraceptive, intrauterine device, barrier contraception [condom]) to PTE. Females who are 
not of childbearing potential (have had a tubal ligation, hysterectomy, or bilateral 
oophorectomy, or are ≥ 2 years postmenopausal) or have a partner who has had a vasectomy 
do not need to use any contraception. Males must use a highly effective method of birth 
control if female partner(s) is of childbearing potential and must not donate sperm from 
baseline through PTE. Contraception guidance is described further in Section 10.7. 


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Female and male participants must be instructed to inform the investigator immediately if 
they or their female partner become pregnant during the study and follow the procedures 
described in Section 10.7. 
8.3.6 
Death Events 
Death is an outcome of an AE, but not an AE itself. All deaths from the start of the screening 
visit to the LTFU visit after the last dose of study medication must be reported, regardless of 
the cause or relationship to study medication. If a death occurs greater after the LTFU visit 
and is considered possibly related to study intervention, the investigator should report the 
death and associated event on the SAE Report Form. 
8.3.7 
Disease-Related Events and/or Disease-Related Outcomes Not Qualifying as 
AEs or SAEs 
Worsening of the primary ABSSSI for which the participant was enrolled is not considered 
an AE. All events that do not quality as an AE or SAE are presented in Table 12. 
8.4 
Efficacy Assessments 
Clinical response and microbiologic assessments of ABSSSI will be performed from the 
screening visit to the PTE visit as described below. 
8.4.1 
Clinical Response 
All participants must have their primary ABSSSI site evaluated by the investigator, including 
ABSSSI site measurements described below. At the screening visit, the primary anatomical 
site and predisposing cause for infection, if known (eg, trauma, arthropod bite, fungal 
dermatosis, surgery, spontaneous, etc.) should be recorded. 
When conducting a clinical examination of the primary ABSSSI site, the investigator will 
perform and record the following assessments: 
• 
Extent of the infection (area in cm2) as measured with a ruler provided by the sponsor. 
The area of redness, edema, or induration will be measured from the longest length 
multiplied by the greatest perpendicular width. Instructions for primary ABSSSI 
measurements are described in the Site Infection Assessment and Measurement Manual. 
• 
Local signs and symptoms of erythema (and any distant extension of erythema), 
swelling/edema, localized warmth, tenderness on palpation, drainage, fluctuance, and 
induration as described in the Site Infection Assessment and Measurement Manual. 
 


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Programmatic Determination of Clinical Response 
Objective evaluation of clinical response as determined programmatically will be made at the 
EA visit 48 to 72 hours after the study intervention begins. The lesion size will be a 
component of the clinical response and instructions for measuring lesions are provided in the 
Site Infection Assessment and Measurement Manual. Participants will be considered as 
responders, nonresponders, or indeterminate as defined in Table 5. 
Table 5 
Clinical Response Definitions – Programmatic Determination 
Timepoint 
Classification 
Definition 
At Early Assessment (48 to 72 hours after IV Treatment Starts) 
Responder 
Percent reduction in primary ABSSSI lesion size is ≥ 20% compared with baseline 
Did not die of any cause up to the specified visit 
Nonresponder 
Percent reduction in primary ABSSSI lesion size is < 20% compared with baseline 
Intercurrent antibacterial therapy administered for the treatment of the primary 
ABSSSI lesion that might have potential antibiotic activity directed toward the 
gram-positive pathogens implicated in the ABSSSI 
Did not die of any cause up to the specified visit 
Indeterminate 
Study data are unavailable for evaluation of efficacy for any reason (eg, missing data, 
lost to follow-up, did not attend the EA clinic appointment) 
ABSSSI = acute bacterial skin and skin structure infection; EA = early assessment; IV = intravenous 
 
Investigator’s Assessment of Clinical Response 
The investigator’s assessment of clinical response at EOIV, EOT, and PTE visits will be 
classified as defined in Table 6. Investigator assessed clinical failures at EOT will be carried 
forward as the clinical response at PTE. 


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Table 6 
Clinical Response Definitions – Investigator’s Assessment 
Timepoint 
 Classification 
Definition 
At EOIV 
Improvement 
The ABSSSI sufficiently improved such that further IV antibacterial therapy is not 
needed. These participants may have some residual clinical signs and symptoms 
related to ABSSSI requiring continued oral antibiotic stepdown therapy (provided the 
subject meets oral switch criteria, Section 6.2) or ancillary (ie, non-antibiotic) 
treatment, eg, bandages on a healing wound, debridement of uninfected tissue.  
Failure 
Investigator discontinued study intervention and indicated that the ABSSSI had 
responded inadequately such that alternative (rescue) nonstudy IV antibacterial therapy 
was needed 
The participant received antibacterial therapy for a different infection that may be 
effective for the ABSSSI under study 
The participant developed an AE that required discontinuation of study intervention 
before completion of the planned IV regimen 
Unplanned major surgical intervention (ie, procedures that would not normally be 
performed at the bedside) for the ABSSSI under study 
Died of any cause up to the specified visit 
Indeterminate 
Study data are unavailable for evaluation of efficacy for any reason (eg, missing data, 
lost to follow-up). 
EOT and PTE 
Success 
The ABSSSI sufficiently resolved such that further antibacterial therapy is not needed. 
These participants may have some residual changes related to infection requiring 
ancillary (ie, non-antibiotic) treatment, eg, bandages on a healing wound, debridement 
of uninfected tissue (ie, necrotic) 
Did not die of any cause up to the specified visit 
Failure 
Investigator discontinued study intervention and indicated that the ABSSSI had 
responded inadequately such that alternative (rescue) non-study antibacterial therapy 
was needed 
The subject received antibacterial therapy for a different infection that may be effective 
for the ABSSSI under study 
The subject developed an AE that required discontinuation of study intervention before 
completion of the planned treatment regimen 
Unplanned major surgical intervention (ie, procedures that would not normally be 
performed at the bedside) for the ABSSSI under study 
Died of any cause up to the specified visit 
Indeterminate 
Study data are unavailable for evaluation of efficacy for any reason (eg, missing data, 
lost to follow-up). 
ABSSSI = acute bacterial skin and skin structure infection; EOIV = end of IV treatment; EOT = end of 
treatment; PTE = posttreatment evaluation 
8.4.2 
Microbiologic Evaluation 
All participants enrolled with ABSSSI in this study must undergo microbiological 
assessments at screening, bacterial culture and Gram-stain, except microbiological 


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assessments from cellulitis lesions are optional (eg, invasive tissue samples are encouraged 
but not required from cellulitis lesions). Samples from local ABSSSI site specimens, and 
blood cultures from 2 separate venipuncture sites, will be collected from all participants 
before administration of study interventions, whenever possible. All ABSSSI site specimens 
will undergo Gram-stain and culture at the local laboratory and all blood cultures will be 
processed at the local laboratory. The screening microbiological assessments are critical, in 
that microbiological response against pathogens responsible for ABSSSI is an important 
secondary outcome of the study (Table 1). Similarly, participants with an infection suspected 
or confirmed to be caused by gram-negative bacteria (eg, Pseudomonas aeruginosa in burn 
patients), and anaerobic pathogens, mycobacteria, or fungi should not be enrolled, and 
participants with ABSSSI suspected or confirmed to be caused by gram-positive bacteria will 
be analyzed in the microbiological populations. If an enrolled participant is subsequently 
found to have a confirmed infection with gram-negative or anaerobic organisms, they may 
remain in the study but may be switched to the appropriate antibiotic. 
The ABSSSI site specimens are collected at screening, when clinically indicated, or if the 
participant is deemed a clinical failure. The following types of specimens are considered 
acceptable, in order of preference: 
• 
Biopsy of involved cutaneous or subcutaneous tissue, preferably from the advancing 
margin of the lesion 
• 
Debrided tissue 
• 
Tissue scraping (with curette or scalpel) 
• 
Needle aspirate of involved, nonpurulent cutaneous or subcutaneous tissue 
• 
Pus or infected tissue collected during an I&D procedure 
• 
Pus aspirated into a syringe 
• 
Deep swab of purulent material (only if collected from infected tissue that has been 
incised or is draining) 
 
Deep swabs of infected areas taken during significant surgical interventions are acceptable 
specimens. Superficial swabs of infected areas are not acceptable, due to the high probability 
that such specimens could be contaminated with clinically insignificant, and potentially 
misleading isolates. 
Two sets of blood cultures comprising 1 aerobic and 1 anaerobic culture bottle from 
2 separate venipuncture sites will be collected from all participants. When possible, the blood 
cultures should be obtained before administration of antibacterial treatment. Blood cultures 
must be repeated at the time that any previous blood culture was reported as positive, any 
time if clinically indicated, or if the participant is deemed a clinical failure. If repeat blood 
cultures remain positive with the causative bacteria initially isolated, the investigator must 
consider modifying the antibiotic treatment administered to the participant and discuss the 
case with the medical monitor. 


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All blood cultures and ABSSSI site specimens will be processed for Gram-stain and culture 
at the local laboratory. Laboratory reports on Gram-stain should include a semiquantitative 
description of the number of polymorphonuclear leukocytes per low power field (ie, 100×) 
and a description of bacterial morphologies. All bacterial isolates that are identified from an 
ABSSSI site specimen or blood culture at the local facilities collaborating laboratory will be 
sent to a designated central laboratory for confirmation of species identification and 
antimicrobial susceptibility testing. All microbiological specimen and processing details 
methods are described in the laboratory manual. 
Antimicrobial susceptibility testing should be performed at the local laboratory according to 
local standards of care; all clinically significant gram-positive pathogens should be tested 
locally for rifamycin, fluoroquinolone, and vancomycin susceptibility, as appropriate. 
Susceptibility testing for TNP-2092 will not be available at the local laboratory. Instead, the 
central laboratory will confirm and test all gram-positive isolates for both TNP-2092 and 
vancomycin susceptibilities. After the cultured isolates are sent to the central laboratory, the 
central laboratory will confirm and retest all gram-positive isolates for rifamycin, 
fluoroquinolone, and vancomycin susceptibilities. The local laboratory should retain all 
isolates until confirmation of a viable organism is received from the central laboratory. Back-
up cultures will be requested when the central laboratory does not receive a viable culture or 
recovers an organism different from the one recorded by the local laboratory. All necessary 
procedures for antimicrobial susceptibility testing are described in the laboratory manual. 
Per-Pathogen Microbiological Response 
A microbiological outcome at the PTE visit is determined for each pathogen isolated from 
the ABSSSI site or blood at screening from the categories defined in Table 7. Favorable 
microbiological outcomes include eradication or presumed eradication. Unfavorable 
microbiological outcomes include persistence or presumed persistence. 


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Table 7 
Microbiologic Outcome Categories 
Outcome 
Category 
Definition 
PTE 
Eradication 
An adequate source specimen demonstrates absence of the original screening 
pathogens 
Presumed 
Eradication 
An adequate source specimen was not available to culture and the participant was 
assessed as a clinical success by the investigator at PTE 
Persistence 
An adequate source specimen demonstrates continued presence of the original 
screening pathogens 
Presumed 
persistence 
An adequate source specimen was not available to culture and the participant was 
assessed as a clinical failure by the investigator at PTE 
Indeterminate 
An adequate source specimen was not available to culture and the participant’s clinical 
response was assessed as indeterminate 
PTE = posttreatment evaluation 
 
Per-Participant Microbiological Response 
An overall microbiological response at the PTE visit will be determined in the micro-ITT and 
ME population for each participant based on individual outcomes for each baseline pathogen. 
For a participant to have a favorable per-participant microbiological response, the outcome 
for each baseline pathogen must be favorable (eradicated or presumed eradicated, as defined 
in Table 7). For a participant to have an unfavorable per-participant microbiological 
response, the outcome for each baseline pathogen must be unfavorable (persistence, 
presumed persistence, as defined in Table 7). If the same pathogen is isolated from multiple 
sites (eg, blood and ABSSSI site culture), the worst response will be used to determine the 
per-participant microbiological response. 
Emergent Infections 
ABSSSI caused by pathogens first appearing after screening will be categorized as either 
superinfections or new infections as defined in Table 8. 
Table 8 
Emergent Infections 
Category 
Definition 
End of Intravenous Treatment 
Superinfection 
Isolation of a new pathogen other than the original screening pathogen from the 
primary ABSSSI site and from an appropriate ABSSSI specimen which is 
accompanied by signs and symptoms of infection requiring alternative systemic 
antimicrobial therapy during the period up to and including EOT 
New Infection 
Isolation of a new pathogen other than the original screening pathogen from the 
primary ABSSSI site and from an appropriate ABSSSI specimen which is 
accompanied by signs and symptoms of infection requiring alternative systemic 
antimicrobial therapy during the period after EOT 
ABSSSI = acute bacterial skin and skin structure infection; EOT = end of treatment 


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8.5 
Treatment of Overdose 
At the time this protocol was written, no known incidents of overdose with TNP-2092 were 
known. The highest single dose administered to humans was 400 mg in the CBR-2092-001 
Clinical Study, and the highest multiple-dose/day was 600 mg for 14 days in the 
CBR-2092-002 Clinical Study. 
An overdose is defined as deliberate or accidental administration of TNP-2092 at a dose 
greater than twice the daily dose assigned to that participant according to the protocol. In the 
event of a suspected overdose, the investigator should take the following steps: 
1. Contact the medical monitor immediately. 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities until study 
intervention can no longer be detected systemically (at least 30 days). 
3. Obtain a plasma sample for PK analysis within 2 days from the date of the last dose of 
study intervention if requested by the medical monitor (determined on a case-by-case 
basis). 
4. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
 
Decisions regarding dose interruptions or modifications will be made by the investigator in 
consultation with the CRO’s medical monitor based on the clinical evaluation of the 
participant. 
In case of overdose of vancomycin or commercially-available, open-label, oral antibiotic, the 
prescribing information (2018) should be consulted. 
8.6 
Pharmacokinetics 
Pharmacokinetic samples will be obtained from whole blood on Day 1 and at EOIV visits 
according to Table 21. Primary PK parameters will be calculated from concentration versus 
time data with noncompartmental techniques (Cmax, tmax, AUC versus time from time 0 to 
12 hours [AUC0-12], and CL [after last dose]). 
All participants from each treatment arm will have whole blood samples collected but only 
samples collected from participants in treatment arm A (TNP-2092 arm) will be analyzed 
(Section 10.5). Some degree of inference may be possible to the influence of baseline 
participant characteristics (eg, age, gender, weight, body mass index, race) on the clearance 
of the drug. 
The bioanalytical laboratory will measure plasma concentrations of TNP-2092 according to 
validated bioanalytical methods. Selected PK samples may be used in the identification of 
TNP-2092 metabolites. Specific instructions for the collection of plasma and urine drug 
concentration specimens will be described in the Laboratory Manual and should be reviewed 
before collection. 


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When multiple assessments are scheduled at any given timepoint, clinical assessments should 
precede all blood collection, including ECGs. 
The actual date and time (24-hour clock time) of each sample will be recorded. 
Approximately 5 mL/sample will be collected for measurement of TNP-2092. Drug 
concentration information that would unblind the study will not be reported to investigative 
sites or blinded personnel until after the study treatment has been unblinded.  
The PK population is defined in Section 9.8. Additional details regarding the collection and 
analysis of PK samples are described in the PK Analysis Plan. 
8.7 
Pharmacodynamics 
Pharmacodynamic parameters are not evaluated in this study. 
8.8 
Genetics 
Genetics are not evaluated in this study. 
8.9 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.10 
Health Economics/Medical Resource Utilization and Health Economics 
Health Economics/Medical Resource Utilization and Health Economics parameters are not 
evaluated in this study. 
9 STATISTICAL CONSIDERATIONS 
All data will be summarized separately by study intervention (TNP-2092 300 mg q12h or 
vancomycin 1 g q12h). Descriptive statistics (number, mean, standard deviation, median, 
minimum, and maximum) will be presented for continuous variables for each study 
intervention. Frequency distributions (counts and percentages) will be presented for 
categorical variables. Listings will be provided for individual participant study data. 
A comprehensive Statistical Analysis Plan (SAP) will be prepared and finalized before the 
database is locked. 
9.1 
Statistical Hypotheses 
No formal hypotheses testing will be conducted. 
9.2 
Sample Size Determination 
This study is not powered for inferential statistical analysis. If the responder rate in the 
TNP-2092 arm is 0.8 at EA (48 to 72 hours after start of study intervention) according to the 
programmatic clinical response, this results in a 95% CI of (0.7, 0.88) for the responder rate 
in the TNP-2092 arm at the EA visit (Clopper and Pearson, 1934). A sample size of 
80 participants who receive TNP-2092 is deemed sufficient to provide an initial assessment 
of safety and PK data to inform the future development of TNP-2092. 
9.3 
Populations for Analyses 
The analysis populations are defined as presented in Table 9 and Figure 3.  


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Inclusion in the ITT, safety, and PK populations will be determined programmatically from 
eCRF data. Inclusion in the mITT population will be determined by the medical monitor. The 
medical monitor will decide whether each isolate is considered a pathogen. All manual 
reviews and determinations of population inclusion/exclusion requirements will be done 
before the study is unblinded. 


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Table 9 
Populations for Analysis 
Population 
Description 
Intent-to-Treat (ITT) 
All randomized participants will be included, regardless of whether study 
intervention is administered. 
Safety 
All randomized participants who receive any amount of study intervention 
will constitute the safety population. Participants in the safety population 
will be analyzed according to study intervention received. 
Modified ITT (mITT) 
All randomized participants in the ITT population excluding those 
participants who have gram-negative pathogens only. 
Microbiologic ITT 
(micro-ITT) 
All randomized participants in the mITT population with culture evidence 
of a baseline gram-positive ABSSSI pathogens (exclude sole 
gram-negative and culture-negative participants) 
Clinically Evaluable (CE) 
All participants in the ITT population who meet the minimal clinical 
disease criteria for ABSSSI; do not have any major protocol deviations, 
receive at least 80% of the expected doses of study intervention; do not 
receive any potentially-effective systemic antibacterial therapies other than 
protocol-specified study intervention (except in cases of treatment failure). 
Included in the CE-EOIV population, if the following conditions are met: 
• 
Have an investigator's assessment of clinical response at EOIV 
(ie, neither response can be indeterminate) 
• 
Have an EOIV visit (+ 1 day)  
• 
Included in the CE-EOT population, if the following conditions are 
met: 
• 
Have an investigator's assessment of clinical response at EOT 
(ie, neither response can be indeterminate) 
• 
Have an EOT visit (+ 1 day)  
• 
Included in the CE-PTE population, if the following conditions are 
met: 
• 
Have an investigator's assessment of clinical response at PTE 
(ie, neither response can be indeterminate) unless the participant was 
defined as a clinical failure based on the assessment at EOT 
• 
Have a PTE visit 7 to 14 days after EOT, unless the participant was 
defined as a clinical failure based on the assessment at EOT 
Pharmacokinetic (PK) 
All participants who receive at least 1 dose of TNP-2092 and have a 
sufficient number of plasma samples for TNP-2092 PK analysis.  
Microbiologically Evaluable at 
PTE (ME-PTE) 
All participants in the micro-ITT population who belong to the CE-PTE 
population. 
ABSSSI = acute bacterial skin and skin structure infection; CE = clinically evaluable; EOIV = end of IV; 
EOT = end of treatment; ITT = intent-to-treat; mITT = modified ITT; micro-ITT = microbiological ITT; PTE 
= posttreatment evaluation 


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Figure 3 
Overview of Analysis Populations 
 
ABSSSI = acute bacterial skin and skin structure infection; CE = clinically evaluable; EOIV = end of IV; EOT 
= end of therapy; ITT = intent-to-treat; IV = intravenous; ME = microbiologically evaluable; mITT = modified 
intent-to-treat; micro-ITT = microbiological intent-to-treat; PK = pharmacokinetic; PTE = posttreatment 
evaluation; SAP = statistical analysis plan 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ITT Population 
All randomized participants 
Safety Population 
Participants who receive 
any amount of study 
intervention 
mITT Population 
Excludes participants with only 
gram-negative pathogens 
CE-EOIV/CE-EOT Population 
Participants with an EOIV or EOT 
visit and an Investigator’s assessment 
of clinical response at EOIV or EOT. 
ME-PTE Population 
Micro-ITT population who also are in 
the CE-PTE population 
CE-PTE Population 
Participants with a PTE visit and an 
Investigator’s assessment of clinical 
response completed at PTE  
CE Population 
• 
Minimal ABSSSI disease criteria 
• 
Receive ≥ 80% of study intervention,  
• 
No concomitant systemic antibacterial 
therapy between Day 1 and assessment 
timepoint (except in cases of treatment 
failure) 
• 
 No major protocol violations  
PK Population 
Participants with at least 1 
dose of TNP-2092 and 
sufficient PK samples for 
analysis 
Micro-ITT Population 
Participants with culture evidence 
of baseline gram-positive 
ABSSSI pathogens 


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9.4 
Analysis of Study Populations and Participant Characteristics 
Enrollment, study interventions administered, premature discontinuations from study 
interventions, withdrawals from the study, and protocol deviations will be summarized by 
treatment arm. A protocol deviation is defined as any variation from the protocol 
(eg, enrollment of a participant who did not meet all inclusion and exclusion criteria, failure 
to perform the assessments and procedures within the required time frame). 
Demographics (age, race, sex), description of the baseline ABSSSI type, medical history, and 
baseline clinical signs and symptoms of ABSSSI will be summarized by treatment arm. 
Baseline pathogens identified at the primary ABSSSI site will also be summarized by 
treatment arm. 
The number and percentage of participants in each population and reasons for exclusion from 
populations will be listed and summarized by treatment arm. 
The SAP will be developed and finalized before the database is locked and will describe the 
participant populations to be included in the analyses, and procedures for accounting for 
missing, unused, and spurious data.  
9.5 
Study Intervention Exposure 
By treatment arm summaries will be provided for the total number of doses, the number of 
IV doses of antibiotic, and the number of commercially-available oral antibiotic doses. 
Compliance to study intervention will be calculated based on the total number of doses taken, 
divided by the total number of expected doses. A further check of compliance will be the 
determination of blood concentrations of TNP-2092 during the analytical phase of the study 
(Section 10.5). 
9.6 
Safety Analyses 
Safety and tolerability of TNP-2092 IV, 300 mg q12h, will be assessed for a minimum of 
3 days (6 doses) and a maximum of 14 days to treat ABSSSI is the primary endpoint and the 
primary objective of this Phase 2 study. Safety will be assessed by AEs, physical 
examinations, vital signs, laboratory evaluations (hematology, chemistry, coagulation, 
urinalysis), and ECG parameters. For each safety parameter, the last assessment before the 
first administration of study intervention will be used as the baseline for all analyses. 
The incidence of treatment-emergent AEs (defined in Table 12) will be presented by system 
organ class and preferred terms according to Medical Dictionary of Regulatory Activities 
(MedDRA®); by system organ class, preferred term, and relationship to study intervention; 
and by system organ class, preferred term, and severity. In addition, the incidence of SAEs 
and treatment-emergent AEs leading to discontinuation of study intervention will be 
presented by system organ class, preferred term, and relationship to study intervention. If the 
incidence of SAEs and treatment-emergent AEs leading to discontinuation of study 
intervention is low, only a listing will be provided. 
Descriptive statistics of vital signs at each timepoint measured, as well as the change from 
baseline and potentially clinically significant changes, will be presented by treatment arm. 
Potentially clinically significant changes will be defined in the SAP. Descriptive statistics for 


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ECGs will also be presented for each timepoint measured by treatment arm. Abnormal 
physical examination data will also be summarized. Descriptive statistics for clinical 
laboratory tests and for the change from baseline will be presented by study visit and 
treatment arm. 
9.7 
Efficacy Analyses – Secondary Endpoints 
All secondary efficacy endpoints will be summarized by treatment arm by analysis 
populations presented in Table 10. 
9.7.1 
Clinical Outcomes 
Programmatic clinical response will be assessed at EA in the ITT, mITT, and micro-ITT 
populations. The number and percentage of participants with each outcome will be 
summarized by treatment arm. Confidence intervals (95%) will be provided for the responder 
rates at EA for each treatment arm. The difference between the responder/clinical response 
rates in the TNP-2092 treatment arm and the vancomycin treatment arm will be calculated 
and 95% CI for the difference between rates will be calculated (Miettinen and Nurminen, 
1985). 
The investigator’s assessment of clinical response at EOIV, EOT, and PTE will be 
summarized for the mITT, micro-ITT, CE-EOIV, CE-EOT, and CE-PTE populations, 
respectively. Success rates will be calculated for each analysis and differences in success 
rates between the TNP-2092 and vancomycin treatment arms will be calculated, along with 
corresponding 95% CI will be presented according to the same methods used for the 
programmatic response. The number and percentage of participants with sustained clinical 
response and clinical relapse will also be summarized at LTFU in the micro-ITT and CE-ME 
populations. 
Table 10 
Efficacy Evaluations by Analysis Population 
Efficacy Endpoints 
Efficacy Population 
ITT 
mITT 
Micro-
ITT 
CE-
EOIV 
CE-
EOT 
CE-
PTE 
ME-
PTE 
Secondary: 
Programmatic clinical response at EA 
 
√ 
 
√ 
 
√ 
 
 
 
 
 
 
 
 
Per participant microbiological response 
at PTE  
 
 
√ 
 
 
 
√ 
Microbiological response per baseline 
pathogen at PTE 
 
 
√ 
 
 
 
√ 
Investigator’s assessment of clinical 
response at EOIV 
 
√ 
√ 
√ 
 
 
 
Investigator’s assessment of clinical 
response at EOT  
 
√ 
√ 
 
√ 
 
 
Investigator’s assessment of clinical 
response at PTE 
 
√ 
√ 
 
 
√ 
 
Investigator’s assessment of sustained 
clinical response at LTFU 
 
√ 
√ 
 
 
 
 
CE = clinically evaluable; EA = early assessment; EOIV = end of IV treatment; EOT = end of treatment; IV 
= intravenous; mITT = modified intent-to-treat; ME = microbiologically evaluable; 
micro--ITT = microbiological intent-to-treat; PTE = posttreatment evaluation 


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9.7.2 
Microbiological Outcomes 
The number and percentage of participants with favorable microbiological responses will be 
summarized at PTE in the micro-ITT and ME-PTE populations. Responses include 
eradication, presumed eradication, persistence, presumed persistence, and indeterminate 
(Table 7). Of these responses, eradication and presumed eradication will be regarded as a 
favorable outcome. Persistence and presumed persistence will be regarded as an unfavorable 
outcome. If a participant has > 1 baseline pathogen, all pathogens must have a favorable 
response to have overall favorable response. 
The number and percentage of participants with a favorable outcome (eradication, presumed 
eradiation) will also be summarized for each baseline pathogen by treatment arm in the 
micro-ITT and ME-PTE populations. 
Emergent infections (eg, superinfection, new infection) will not be considered in the 
microbiological response and will be listed separately (Table 8). 
9.8 
Pharmacokinetic Analyses 
Characterization of the PK of TNP-2092 for a minimum of 3 days (6 doses) and a maximum 
of 14 days to treat ABSSSI is an important secondary objective for this study. Plasma 
samples from participants in the PK population (Section 10.5) will be analyzed for TNP-2092 
concentrations with a validated bioanalytical method. Key basic PK parameters will be 
assessed on Day 1 and at EOIV visits. Only PK samples collected from participants 
randomized to TNP-2092 (treatment arm A) will be analyzed. Further details of the PK 
sample collection and analyses are provided the Statistical Analysis Plan and Laboratory 
Manual. 
9.9 
Handling of Dropouts, Missing, Unused and Spurious Data 
Every effort will be made to collect all data at specified times. For secondary efficacy 
measures, the outcome will be classified as indeterminate if the data are unavailable for 
evaluation for any reason. A detailed description of the handling of dropouts and missing, 
unused, and spurious data will be provided in the SAP. 
9.10 
Interim Analyses 
No interim analysis or data monitoring committee is planned for this study. 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Regulatory, Ethical, and Study Oversight Considerations 
10.1.1 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with the following: 
◦ 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences CIOMS International Ethical Guidelines 
◦ 
Applicable ICH GCP Guidelines 


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◦ 
Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, IB, and other relevant documents (eg, 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed and 
approved by the IRB/IEC before the study is initiated. 
• 
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an 
immediate hazard to study participants. 
• 
The investigator will be responsible for the following: 
◦ 
Providing written summaries of the status of the study to the IRB/IEC annually or 
more frequently in accordance with the requirements, policies, and procedures 
established by the IRB/IEC 
◦ 
Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures 
◦ 
Providing oversight of the conduct of the study at the site and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 
536/2014 for clinical studies (if applicable), and all other applicable local 
regulations 
 
10.1.2 
Financial Information 
10.1.2.1 
Investigators and Subinvestigator Disclosure 
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators 
are responsible for providing information on financial interests during the study and for 
1 year after completion of the study. 
10.1.2.2 
Finance and Insurance 
The financing and insurance for this study are outlined in the Clinical Trial Agreement. 
10.1.3 
Data Protection 
• 
Participants will be assigned a unique identifier by the sponsor. Any participant records 
or datasets that are transferred to the sponsor will contain the identifier only; participant 
names or any information which would make the participant identifiable will not be 
transferred. 
• 
The participant must be informed that his/her personal study-related data will be used by 
the sponsor in accordance with local data protection law. The level of disclosure must 
also be explained to the participant. 
• 
The participant must be informed that his/her medical records may be examined by 
clinical quality assurance auditors or other authorized personnel appointed by the 
sponsor, by appropriate IRB/IEC members, and by inspectors from regulatory authorities. 


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10.1.4 
Informed Consent Process 
This study will be conducted in compliance with ICH E6 GCP: Consolidated Guidelines 
pertaining to informed consent. Participants will provide written consent to participate in the 
study at the first visit, before initiation of any study-related procedure after being informed of 
the purpose of the study as follows: 
• 
The investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions regarding 
the study. 
• 
Participants must be informed that their participation is voluntary. Participants will be 
required to sign a statement of informed consent that meets the requirements of 
21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study 
site. 
• 
The medical record must include a statement that written informed consent was obtained 
before the participant was enrolled in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
• 
In case of modifications, participants must reconsent to the most current version of the 
ICF during their participation in the study. 
• 
A copy of the ICF must be provided to the participant or the participant’s legally 
authorized representative. If applicable, it will be provided in certified translation for 
non-English speaking participants. 
Signed consent forms must remain in the participant’s study file and be available for 
verification by the sponsor or representatives of a competent regulatory agency at any time. 
The ICF will contain a separate section that addresses the use of remaining mandatory 
samples for optional exploratory research. The investigator or authorized designee will 
explain to each participant the objectives of the exploratory research. Participants will be told 
that they are free to refuse to participate and may withdraw their consent at any time and for 
any reason during the storage period. A separate signature will be required to document a 
participant's agreement to allow any remaining specimens to be used for exploratory 
research. Participants who decline to participate in this optional research will not provide this 
separate signature. 
10.1.5 
Dissemination of Clinical Study Data 
Publication planning and other activities related to nonpromotional, peer-reviewed 
publications, to ensure the scientific integrity of publication activities will be performed by or 
on behalf of the sponsor. Access may be granted to analyzable datasets from clinical studies 
through a secure system, following independent assessment of the scientific merit of a 
rigorously-defined research question from a third party. 
10.1.6 
Data Quality Assurance 
Written standard operating procedures from InClin will be followed to ensure that the study 
is conducted, data are generated, documented (recorded), and reported in compliance with 
the protocol, GCP, and the applicable regulatory requirements. Quality control will be 
applied to each stage of data handling. Regular monitoring, as defined in ICH GCP, 


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Section 1.8, “The act of overseeing the progress of a clinical trial, and of ensuring that it is 
conducted, recorded, and reported in accordance with the protocol, standard operating 
procedures, GCP, and the applicable regulatory requirement(s)”, will be conducted 
throughout the conduct of the study. 
Each investigator must adhere to the protocol as described in Section 8.1. The investigator 
will allow representatives of the sponsor or regulatory authorities to inspect facilities and 
records relevant to this study. 
The sponsor or sponsor representative will conduct site visits to inspect study data, 
participants’ medical records, and eCRFs in accordance with current ICH E6 GCP guideline, 
and regulations and guidelines, as applicable. Data for all participants will be reviewed to 
ensure the investigators are following the protocol-criteria for clinical response and queries 
will be issued as needed to clarify any response that does not meet the protocol definition. 
The sponsor or sponsor representative will also be able to review query status remotely, 
which may warrant additional communication with the investigator and the study site’s 
personnel. The investigator will make available to the sponsor, or sponsor representative, 
source documents, signed ICFs, and all other study-related documents. An unblinded monitor 
will be utilized for monitoring ongoing drug accountability and adherence to blinding 
procedures. 


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The purpose of monitoring is to verify that: 
• 
Rights and well-being of the human participants are protected 
• 
The reported study data are accurate, complete, and verifiable from source documents 
• 
The conduct of the study is compliant with the currently approved protocol, with GCP, 
and with the applicable regulatory requirements 
• 
Monitoring is an integral role in the quality control of a clinical trial and is designed to 
verify the quality of the study 
To fulfill the quality assurance requirements of GCP, audits will be conducted to assess and 
ensure the reliability and integrity of the QC systems for the study and recognized standards. 
The purpose of an audit is to: 
• 
Ensure participant safety 
• 
Ensure compliance to study protocol procedures, regulatory requirements, and standard 
operating procedures 
• 
Ensure data quality 
Further instructions for the site and sponsor are presented below: 
• 
All participant data relating to the study will be recorded on an eCRF unless transmitted 
to the sponsor or designee electronically (eg, laboratory data). The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the eCRF. 
• 
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF. 
• 
Monitoring details describing strategy (eg, risk-based initiatives in operations and quality 
such as Risk Management and Mitigation Strategies and Analytical Risk-Based 
Monitoring), methods, responsibilities and requirements, including handling of 
noncompliance issues and monitoring techniques (central, remote, or on-site monitoring) 
are provided in the Monitoring Plan. 
• 
The sponsor or designee is responsible for the data management of this study including 
quality checking of the data. 
• 
The sponsor assumes accountability for actions delegated to other individuals (eg, 
Contract Research Organizations). 
• 
Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements. 
• 
Records and documents, including signed ICFs, laboratory test results, and medication 
inventory records pertaining to the conduct of this study must be retained by the 


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investigator for at least 2 years after the last approval of a marketing application in an 
ICH region and until there are no pending or contemplated marketing applications in an 
ICH region or at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational product unless local regulations or institutional 
policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor. 
10.1.7 
Electronic Case Report Forms and Data Capture System 
This study will be performed with an eCRF. All eCRF data are to be completed by 
designated site personnel. All data entry, modification, or deletion will be recorded 
automatically in the electronic audit trail. All electronic data entered by the site (including 
the electronic audit trail) will be maintained or made available at the site in compliance with 
21 CFR Part 11 and other applicable retention regulations. 
Before the first participant is treated with study intervention at an investigational site, the 
sponsor or sponsor representative will meet with the investigator and the study site’s 
personnel to train them to record the data on the eCRFs from an electronic data capture 
system. The investigator or designee will be responsible for reviewing eCRFs, resolving data 
queries generated by the sponsor via the system, providing missing or corrected data, and 
approving all changes performed on the participant data. This approval method will include 
applying an electronic signature, a uniquely assigned user name, and a password that together 
will represent a traditional handwritten signature. This electronic signature will be certified 
as outlined in 21 CFR Part 11. The sponsor will retain the original eCRF data and audit trail. 
An electronic or certified paper copy of all completed eCRF data, including query resolution 
correspondence, will be provided to the investigator at the end of the study. 
Queries may be issued electronically to the clinical study site and will be answered 
electronically by that study site’s personnel. The identifying information (assigned user 
name, date, and time) for both the originator of the query and the originator of the data 
change (if applicable) will be collected. 
10.1.8 
Source Data and Document Management 
All data collected on the eCRFs must have a source record. Source documents provide 
evidence for the existence of the participant and substantiate the integrity of the data 
collected and are filed at the investigator’s site. Data reported or entered in the eCRF that are 
transcribed from source documents must be consistent with the source documents or the 
discrepancies must be explained. The investigator may need to request previous medical 
records or transfer records, depending on the study. Also, current medical records must be 
available. The definition of what constitutes source data can be found in the Monitoring Plan. 
The investigator agrees that by his/her participation the results of this study may be used for 
submission to national or international registration. The sponsor or sponsor’s representative 
has ethical, legal, and scientific obligations to monitor this study in a detailed and orderly 
manner in accordance with established research principles and applicable local regulations. 
As part of a concerted effort to fulfill these obligations, the sponsor’s monitors or 


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representatives will visit the site during the study on a regular basis, in addition to 
maintaining telephone and written communication. 
The investigator is required to provide the sponsor with all study data, complete reports, and 
access to all study records. The investigator must retain a comprehensive and centralized 
filing system of all clinical study-related documentation that is suitable for inspection by the 
sponsor and representatives of regulatory authorities. The investigator will allow the sponsor 
or its representative, or an appropriate representative of the competent authorities, to inspect 
all clinical study-related documentation for confirmation of data throughout the study period. 
Data generated by this study must be available for inspection by any regulatory authorities, 
by the sponsor and by the IRB as appropriate. At a participant’s request, medical information 
may be given to his or her personal physician or other appropriate medical personnel 
responsible for his or her welfare. Medical information obtained from participants during the 
study is confidential and disclosure to third parties other than those noted above is prohibited. 
10.1.9 
Study and Site Closure 
The sponsor designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of the sponsor. The investigator may initiate study 
site closure at any time, provided there is reasonable cause and sufficient notice is given in 
advance of the intended termination. Reasons for the early closure of a study site by the 
sponsor or investigator may include but are not limited to: 
• 
Failure of the investigator to comply with the protocol, the requirements of the IRB/IEC 
or local health authorities, the sponsor's procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the investigator 
• 
Discontinuation of further study intervention development 
• 
Fabrication or alteration of data 
Study sites will be closed upon study completion. A study site is considered closed when all 
required documents and study supplies have been collected and a study site closure visit has 
been performed. The sponsor requires the availability of the following data and materials 
before a study can be considered complete or terminated: 
• 
Laboratory findings, clinical data, and all special test results from screening through 
LTFU for participants enrolled. 
• 
eCRFs (including queries) properly completed by appropriate study personnel and 
electronically signed and dated by the investigator. 
• 
Complete drug accountability records (drug inventory log and an inventory of returned or 
destroyed clinical material). 
• 
Copies of protocol and IRB approval and notification, if appropriate. 
• 
A summary of the trial conduct and ethical considerations of the study prepared by the 
investigator (an IRB summary letter is acceptable). 


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This study will be conducted in compliance with the ICH of Technical Requirements for 
Registration of Pharmaceuticals for Human Use E6 GCP: Consolidated Guidelines, the 
ethical principles of the Declaration of Helsinki, FDA GCP guidelines, and any additional 
IRB-required procedures. 
10.1.10 
Institutional Review Board Approval 
This study will be conducted in compliance with the protocol approved by the IRB and 
according to ICH and GCP consolidated guidelines and the ethical principles of the 
Declaration of Helsinki. 
No major deviation from the protocol will be implemented without the prior review and 
approval of the IRB except when it may be necessary to eliminate an immediate hazard to a 
research participant. In such case, the deviation will be reported to the IRB as soon as 
possible. 
This protocol, the informed consent document, and all relevant supporting data must be 
submitted to the IRB for approval. Approval of the protocol, ICF, and any advertisement 
used to recruit study participants must be obtained before study initiation. 
The investigator is responsible for informing the IRB of any changes made to the protocol, 
and to advise them, at least once a year, about the study progress. The investigator is also 
responsible for notifying the IRB of any SAEs and significant AEs that occur during the 
study. 
10.1.11 
Publication Policy 
The results of this study may be published or presented at scientific meetings. If this is 
foreseen, the investigator agrees to submit all manuscripts or abstracts to the sponsor before 
submission. This allows the sponsor to protect proprietary information and to provide 
comments. All personal data relating to the identity of the participant will not be disclosed 
without prior written authorization from the sponsor and participant. The sponsor will 
comply with the requirements for publication of study results. In accordance with standard 
editorial and ethical practice, the sponsor will generally support publication of multicenter 
studies only in their entirety and not as individual site data. In this case, a coordinating 
investigator will be designated by mutual agreement. Authorship will be determined by 
mutual agreement and in-line with International Committee of Medical Journal Editors 
authorship requirements. 
10.1.12 
Data Management and Monitoring 
Training sessions, regular monitoring of the investigative site by sponsor-designated 
personnel, instruction manuals, data verification, crosschecking, and data audits will be 
performed to ensure quality of all study data. 
It will be the responsibility of the investigator to ensure that essential documents are 
available in the investigator’s files or at the institutional site. All documents may be subject 
to, and should be available for, monitoring by the sponsor or inspection by regulatory 
authorities. 
















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Table 20 
List of Prohibited Concomitant Medications  
Drug Class 
Subclass 
Generic Name 
Anti-arrhythmics 
IA 
Disopyramide 
Procainamide 
Quinidine 
III 
Amiodarone 
Dofetilide 
Dronedarone 
Ibutilide 
Sotalol 
Antimicrobials 
Antiparasitics 
Praziquantel 
Anesthetics 
 
Halothane 
HIV-protease inhibitors 
 
Ritonavir-boosted saquinavir 
Saquinavir 
Atazanavir 
Darunavir 
Fosamprenavir 
Tipranavir 
HIV = human immunodeficiency virus 
Note: Medication use is prohibited by study entry criteria (Section 5.2). 
Source: Prescribing information for rifampin (2019) and moxifloxacin (2016). 


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10.5 
Pharmacokinetic Sample Schedule for Pharmacokinetic Assessments 
Primary PK parameters will be calculated from concentration versus time data with 
noncompartmental techniques. These parameters include Cmax, tmax, AUC0-12, and CL (after 
last dose). 
All participants from each treatment arm will have whole blood samples collected on Day 1 
and at the EOIV visit. Only PK samples collected from participants in treatment arm A 
(TNP-2092 arm) will be analyzed and is presented in Table 21. Bioanalytical testing will be 
performed by Bioanalytical Systems, Inc. 2701 Kent Avenue, West Lafayette, IN 47906 
USA. 
Table 21 
Pharmacokinetic Sample Schedule 
Collection Time 
Day 1 – First Dose 
EOIV – Last Dose a 
Predose at 0 minutes 
X 
X 
End of infusion, 57 to 60 minutes after infusion start 
X 
X 
1.5 to 3 hours after infusion start 
X 
X 
4 to 6 hours after infusion start 
X 
X 
12 hours after infusion start  
X 
X 
End of second infusion, 57 to 60 minutes after 
infusion start 
X 
Not Applicable 
EOIV = end of intravenous 
a 
Participants received an IV infusion for at least 3 days (6 doses) up to 14 days. The EOIV infusion will 
vary by participant from Day 4 to Day 14.  
 


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10.6 
List of Abbreviations 
ABSSSI 
acute bacterial skin and skin structure infection 
AE 
adverse event 
AIDS 
acquired immunodeficiency syndrome  
ALT 
alanine aminotransferase 
AST 
aspartate aminotransferase 
AUClast, AUCinf  
area under the curve vs. time from time 0 to last time point or to infinity 
β-HCG 
beta-human chorionic gonadotropin 
bid 
twice daily 
CD4 
cluster of differentiation 4 
CI 
confidence interval 
CL 
clearance 
Cmax  
maximum concentration 
D5W 
5% dextrose injection 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EOIV 
end of IV 
EOT 
end of treatment 
GCP 
good clinical practice 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
I&D 
incision and drainage 
IRB 
Institutional Review Board 
ITT 
intent-to-treat 
IV 
intravenous(ly) 
IWRS 
Interactive web response system 
Lesion response 
percent reduction in lesion size ≥20% compared with baseline 
LTFU 
long-term follow-up 
MedDRA 
Medical Dictionary of Regulatory Activities 
mITT 
modified intent-to-treat 
micro-ITT 
microbiologic intent-to-treat 
MRSA 
methicillin-resistant Staphylococcus aureus 
PI 
principal investigator 
PK 
pharmacokinetic 
PTE 
posttreatment evaluation 
q12h 
every 12 hours 
q24h 
every 24 hours 
QTcF 
QT interval calculated with Fridericia’s correction formula 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAR 
suspected adverse reaction 
SUSAR 
suspected unexpected serious adverse reactions 
t½  
terminal half-life 
tmax 
time to maximal concentration 
Vz  
volume of distribution 


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10.7 
Contraceptive Guidance and Collection of Pregnancy Information 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until she is postmenopausal unless 
permanently sterile (see below). 
If fertility is unclear (eg, amenorrhea in adolescents or athletes) and a menstrual cycle cannot 
be confirmed before first dose of study intervention, additional evaluation should be 
considered. 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
1. Documented hysterectomy 
Documented bilateral salpingectomy 
Documented bilateral oophorectomy 
 
For individuals with permanent infertility due to an alternate medical cause other than the 
above, (eg, mullerian agenesis, androgen insensitivity), investigator discretion should be 
applied to determine study entry. Documentation can come from the site personnel’s review 
of the participant’s medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
1. A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
i. A high follicle stimulating hormone level in the postmenopausal range may be 
used to confirm a postmenopausal state in women who do not use hormonal 
contraception or hormonal replacement therapy. However, in the absence of 
12 months of amenorrhea, confirmation with more than one follicle stimulating 
hormone measurement is required. 
ii. Females on hormone replacement therapy and whose menopausal status is in 
doubt will be required to use 1 nonestrogen hormonal highly effective 
contraception methods if they wish to continue their hormone replacement 
therapy during the study. Otherwise, they must discontinue hormone replacement 
therapy to allow confirmation of postmenopausal status before study enrollment. 
 


TNP-2092 
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Protocol PJI001-02 
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Collection of Pregnancy Information 
Male participants with partners who become pregnant 
• 
The investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. 
• 
After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the investigator will record pregnancy information on the appropriate form and 
submit it to the sponsor within 24 hours after learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and child will be forwarded to the sponsor. 
Generally, the follow-up will be no longer than 6 to 8 weeks following the estimated 
delivery date. Any termination of the pregnancy will be reported regardless of fetal status 
(presence or absence of anomalies) or indication for the procedure. 
 
Female Participants who become pregnant 
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the Pregnancy 
Report Form and submitted to the sponsor within 24 hours after learning of a participant's 
pregnancy. 
• 
Study medication should be stopped immediately. 
• 
Any female participant who becomes pregnant while participating in the study will be 
withdrawn from the study. 
• 
The investigator should counsel the participant regarding the possible effects of prior 
study medication exposure on the fetus and the need to inform the study site of the 
outcome of the pregnancy. 
• 
The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate and the 
information will be forwarded to the sponsor. Generally, follow-up will not be required 
for longer than 6 to 8 weeks beyond the estimated delivery date. Any termination of 
pregnancy will be reported, regardless of fetal status (presence or absence of anomalies) 
or indication for the procedure. The Pregnancy Report Form will be used to follow-up the 
outcome of the pregnancy. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or SAE. A 
spontaneous abortion is always considered to be an SAE and will be reported as such. 
Any poststudy pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.3.5. While the investigator is not obligated to actively seek this information in 
former study participants, he or she may learn of an SAE through spontaneous reporting. 


TNP-2092 
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Protocol PJI001-02 
Page 78 
 
 
 
11 REFERENCES 
1. Arciola CR, Campoccia D, Montanaro L. Implant infections: adhesion, biofilm formation 
and immune evasion. Nature Reviews/Microbiology. 2018; 
https://doi.org/10.1038/s41579-018-0019-y. 
2. Avelox® [prescribing information]. Wayne, NJ. Bayer Healthcare Pharmaceuticals Inc., 
September 2016. 
3. Centers for Disease Control and Prevention. Antibiotic resistance threats in the United 
States, 2013 (report). US Department of Health and Human Services, 2013. Available at 
http://www.cdc.gov/drugresistance/threat-report-2013/. Accessed 22 August 2018. 
4. Chaisson RE. Treatment of chronic infections with rifamycins: Is resistance likely to 
follow? Antimicrob Agents Chemther. 2003;47(10):3037–3039. 
5. Clopper CJ, Pearson ES. The use of confidence or fiducial limits illustrated in the case of 
the binomial. Biometrika. 1934;26:404–413. 
6. Food and Drug Administration, Center for Drug Evaluation and Research. Guidance for 
Industry—Acute Bacterial Skin and Skin Structure Infections: Developing Drugs for 
Treatment. Oct 2013. Available at: 
http://www.fda.gov/downloads/Drugs/.../Guidances/ucm071185.pdf 
7. Infusion Nurses Society. Infusion nursing standards of practice, Phlebitis Scale. J Infus 
Nurs 2011;34(1S):S65. 
8. Ma Z, Lynch AS. Development of a dual-acting antibacterial agent (TNP-2092) for the 
treatment of persistent bacterial infections. J Med Chem. 2016;59:6645–6657. 
9. Miettinen OS, Nurminen MM. Comparative analysis of two rates. Statistics in Medicine. 
1985;4 (2):213–226. 
10. Pace JL, Rupp ME, Finch RG. Biofilms, infection, and antimicrobial therapy. Boca 
Raton, FL CRC Press; 2006. 
11. Rifadin IV [prescribing information]. Bridgewater, NJ: Sanofi-Aventis, 2019. 
12. Robertson GT, Bonventre EJ, Doyle TB et al. In vitro evaluation of CBR-2092, a novel 
rifamycin-quinolone hybrid antibiotic: Studies of the mode of action in Staphylococcus 
aureus. Antimicrob. Agents Chemother. 2008;52(7):2313–2323. 
13. Robertson GT, Bonventre EJ, Doyle TB et al. In vitro evaluation of CBR-2092, a novel 
rifamycin-quinolone hybrid antibiotic: Studies of the mode of action in Staphylococcus 
aureus. Antimicrob. Agents Chemother. 2008;52(7):2324–2334. 
14. Tande AJ, Patel R. Prosthetic Joint Infection. Clinical Microbiology Reviews. 
2014;27(2):302–345. 


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15. TenNor Therapeutics Limited. Investigator’s Brochure. TNP-2092. Edition 2.0. 
September 2018.  
16. Vancomycin [prescribing information]. Lake Forest, IL: Hospira, 2018. 
17. Van Hal SJ, Peterson DL. New gram-positive antibiotics: Better than vancomycin? Curr 
Opin Infect Dis. 2011;24:515–520. 
18. Waldvogel, FA, Bisno, AL. Molecular basis of adherence of Staphylococcus aureus to 
biomaterials. In Waldvogel, FA, Bisno, AL eds. Infections Associated with Indwelling 
Medical Devices. 3rd ed. Washington, DC: ASM Press;2000:27–39. 

SAP_003.pdf: 
Statistical Analysis Plan: PJI001-02
A Phase 2, Double-Blind, Randomized, Multicenter, Parallel, Controlled Study 
to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of 
TNP-2092 to Treat Acute Bacterial Skin and Skin Structure Infection in Adults
NCT03964493
Approval Date: 19-Aug-2019


STATISTICAL ANALYSIS PLAN 
A PHASE 2, DOUBLE-BLIND, RANDOMIZED, MULTICENTER, PARALLEL, 
CONTROLLED STUDY TO EVALUATE THE SAFETY, TOLERABILITY, 
PHARMACOKINETICS, AND EFFICACY OF TNP-2092 TO TREAT ACUTE BACTERIAL 
SKIN AND SKIN STRUCTURE INFECTION IN ADULTS 
Study: PJI001-02 
CONFIDENTIAL 
August 19, 2019 


S T A TI S TI C A L A N A L Y SI S P L A N A P P R O V A L  
St u d y: P JI 0 0 1 -0 2  
V er si o n 1. 0  
C CI


T e n N or T h er a p e uti c s Lt d. ( Pr ot o c ol P JI 0 0 1 -0 2 ) 
St ati sti c al A n al y si s Pl a n –  V er si o n 1. 0  
A u g u st 1 9 , 2 0 1 9 
C o nfi d e nti al  
P a g e 3  of 5 2  
T A B L E O F C O N T E N T S  
1  
A B B R E VI A TI O N S A N D D E FI NI TI O N S  ........................................................................ 5  
1. 1  
A b br e vi ati o n s:  ........................................................................................................... 5  
1. 2  
D efi niti o n s of T er m s:  ................................................................................................. 6  
2  
I N T R O D U C TI O N .......................................................................................................... 7  
3  
S T U D Y D E SI G N ........................................................................................................... 7  
4  
S T U D Y O B J E C TI V E S  .................................................................................................1 1  
4. 1  
Pri m ar y O bj e cti v e s  ...................................................................................................1 1  
4. 2  
S e c o n d ar y O bj e cti v e s  ..............................................................................................1 1  
4. 3  
E n d p oi nt s  ................................................................................................................1 1  
5  
D A T A M A N A G E M E N T  ................................................................................................1 2  
6  
P A T H O G E N D E T E R MI N A TI O N  ..................................................................................1 2  
7  
D E FI NI TI O N O F A N A L Y S I S P O P U L A TI O N S .............................................................1 5  
7. 1  
I nt e nt-t o-Tr e at (I T T) P o p ul ati o n  ................................................................................1 6  
7. 2  
M o difi e d I nt e nt -t o-Tr e at ( MI T T) P o p ul ati o n  ..............................................................1 6  
7. 3  
S af et y P o p ul ati o n  ....................................................................................................1 6  
7. 4  
Mi cr o bi ol o gi c al I nt e nt -t o-Tr e at ( Mi cr o -I T T) P o p ul ati o n .............................................1 6  
7. 5  
Cli ni c all y E v al u a bl e P o p ul ati o n at E n d -of -I V ( E OI V), E n d-of -Tr e at m e nt ( C E -E O T) a n d 
t h e P o st-Tr e at m e nt E v al u ati o n ( C E -P T E)  ............................................................................1 6  
7. 6  
Mi cr o bi ol o gi c all y E v al u a bl e P o p ul ati o n ( M E -P T E) ....................................................1 8  
7. 7  
P h ar m a c o ki n eti c P o p ul ati o n ( P K)  ............................................................................1 8  
7. 8  
P at h o g e n a n d E v al u a bilit y D et er mi n ati o n  ................................................................1 8  
8  
D E FI NI TI O N O F O U T C O M E M E A S U R E S  ..................................................................1 9  
8. 1  
Cli ni c al O ut c o m e D efi niti o n s  ....................................................................................1 9  
8. 1. 1  Pr o gr a m m ati c Cli ni c al R e s p o n s e at E arl y A s s e s s m e nt ( E A)  ................................1 9  
8. 1. 2  I n v e sti g at or A s s e s s m e nt of Cli ni c al R e s p o n s e at E n d-of -I V ( E OI V) .....................1 9  
8. 1. 3  I n v e sti g at or A s s e s s m e nt of Cli ni c al R e s p o n s e at E n d-of -Tr e at m e nt ( E O T)  ..........2 0  
8. 1. 4  I n v e sti g at or-A s s e s s m e nt of Cli ni c al R e s p o n s e at P o st -Tr e at m e nt E v al u ati o n ( P T E)
2 1  
8. 2  
Mi cr o bi ol o gi c R e s p o n s e  ...........................................................................................2 2  
8. 2. 1  P er -P at h o g e n Mi cr o bi ol o gi c al R e s p o n s e at E O T a n d P T E Vi sit s  .........................2 2  
8. 2. 2  P er -S u bj e ct O v er all Mi cr o bi ol o gi c al R e s p o n s e at P T E  .........................................2 4  
8. 3  
E m er g e nt I nf e cti o n s  .................................................................................................2 5  
8. 4  
S af et y  O ut c o m e s  .....................................................................................................2 5  
8. 5  
P h ar m a c o ki n eti c O ut c o m e s  .....................................................................................2 5  


T e n N or T h er a p e uti c s Lt d. ( Pr ot o c ol P JI 0 0 1 -0 2 ) 
St ati sti c al A n al y si s Pl a n –  V er si o n 1. 0  
A u g u st 1 9 , 2 0 1 9 
C o nfi d e nti al  
P a g e 4  of 5 2  
9  
S T A TI S TI C A L M E T H O D S A N D G E N E R A L C O N SI D E R A TI O N S  ...............................2 6  
9. 1  
S a m pl e Si z e  ............................................................................................................2 6  
9. 2  
R a n d o mi z ati o n a n d M a s ki n g  ....................................................................................2 6  
9. 3  
I nt eri m A n al y si s .......................................................................................................2 7  
9. 4  
St a n d ar d C al c ul ati o n s  ..............................................................................................2 7  
9. 5  
H a n dli n g of Mi s si n g D at a  .........................................................................................2 8  
9. 6  
C o m m e nt s o n St ati sti c al A n al y si s  ............................................................................2 9  
1 0  S T A TI S TI C A L A N A L Y S E S  .........................................................................................3 0  
1 0. 1  
S u bj e ct Di s p o siti o n  ..................................................................................................3 0  
1 0. 2  
D e m o gr a p hi c s a n d B a s eli n e C h ar a ct eri sti c s  ............................................................3 1  
1 0. 3  
M e di c al a n d S ur gi c al Hi st or y  ...................................................................................3 1  
1 0. 4  
B a s eli n e Di s e a s e C h ar a ct eri sti c s  .............................................................................3 2  
1 0. 5  
B a s eli n e Mi cr o bi ol o g y  ..............................................................................................3 2  
1 0. 6  
P ri or a n d C o n c o mit a nt M e di c ati o n s .........................................................................3 3  
1 0. 7  
St u d y Dr u g E x p o s ur e a n d C o m pli a n c e  ....................................................................3 4  
1 0. 8  
Effi c a c y A n al y s e s .....................................................................................................3 5  
1 0. 8. 1  Eff i c a c y A n al y si s  ..................................................................................................3 6  
1 0. 8. 2  A d diti o n al Effi c a c y A n al y si s  .................................................................................3 7  
1 0. 8. 3  Mi cr o bi ol o gi c al O ut c o m e s  ....................................................................................3 8  
1 0 . 9 
S af et y A n al y s e s  .......................................................................................................3 8  
1 0. 9. 1  A d v er s e E v e nt s  ....................................................................................................3 8  
1 0. 9. 2  L a b or at or y V al u e s  ................................................................................................3 9  
1 0. 9. 3  V it al Si g n s ............................................................................................................4 1  
1 0. 9. 4  El e ctr o c ar di o gr a m  ................................................................................................4 2  
1 0. 9. 5  P h y si c al E x a mi n ati o n s  .........................................................................................4 2  
1 0. 9 . 6 P h ar m a c o ki n eti c A n al y s e s  ...................................................................................4 3  
1 0. 9. 7  Pr ot o c ol D e vi ati o n s  ..............................................................................................4 3  
1 1  D E VI A TI O N S F R O M T H E P R O T O C O L  ......................................................................4 4  
1 2  R E F E R E N C E LI S T  ......................................................................................................4 4  
A P P E N DI X A. S C H E D U L E  O F E V E N T S  ............................................................................4 5  
A P P E N DI X B. DI VI SI O N  O F MI C R O BI O L O G Y A N D  I N F E C TI O U S DI S E A S E S A D U L T 
T O XI CI T Y T A B L E  ...............................................................................................................4 7  
A P P E N DI X C. S A F E T Y L A B O R A T O R Y T E S T S  ................................................................4 9  
A P P E N DI X D. P R O HI BI T E D M E DI C A TI O N S  .....................................................................5 0  
A P P E N DI X E. L O C A L SI G N S A N D S Y M P T O M S O F A B S S SI  ..........................................5 1  
A P P E N DI X F. A S S E S S M E N T O F I N F U SI O N SI T E R E A C TI O N S  ......................................5 2  
A P P E N DI X G. P H A R M A C O KI N E TI C S A M P L E S C H E D U L E  .............................................5 2  


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1 
Abbreviations and Definitions 
1.1 
Abbreviations: 
ABSSSI 
Acute bacterial skin and skin structure infection 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANC 
Absolute Neutrophil Count 
AST 
Aspartate aminotransferase 
ATC 
Anatomical Therapeutic Chemical class 
BMI 
Body Mass Index 
CE 
Clinically evaluable 
CI 
Confidence interval 
CM 
Compartmental modeling 
CSR 
Clinical Study Report 
CRO 
Contract Research Organization 
CV 
Coefficient of Variation 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
GGT 
Gamma-glutamyl transferase 
H 
High 
ITT 
Intent-to-treat 
IV 
Intravenous (ly) 
IWRS 
Interactive web response system 
L 
Low 
LDH 
Lactate dehydrogenase 
LLN 
Lower Limit of Normal 
ME 
Microbiologically evaluable 
MedDRA 
Medical Dictionary of Regulatory Activities 


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MIC 
Minimum Inhibitory Concentration 
MIC50 
Minimum Inhibitory Concentration to inhibit 50% of the isolates 
MIC90 
Minimum Inhibitory Concentration to inhibit 90% of the isolates 
MIN 
Minimum 
MITT 
Modified intent-to-treat 
Micro-ITT 
Microbiological intent-to-treat 
MRSA 
Methicillin-resistant Staphylococcus aureus 
MSSA 
Methicillin-sensitive Staphylococcus aureus 
NCA 
Non-compartmental analysis 
PK 
Pharmacokinetic 
PO 
Oral 
q12h 
Every 12 hours 
QTcF 
Corrected QT interval using the Fridericia correction formula 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard Deviation 
TEAE 
Treatment-emergent adverse event 
ULN 
Upper limit of normal 
WBC 
White blood cell count 
1.2 
Definitions of Terms: 
Term 
Definition 
Day 1 
Day of administration of first IV dose 
Dose 
Any amount of study drug (IV or PO) taken at the time of dosing. 
EA 
Early assessment (48 - 72 hours after the start of the first dose of IV study 
drug) 
EOT 
End of Treatment (last day of study drug; Day 7 - Day 14) 
EOIV 
End of IV Treatment (3 - 14 days after treatment start) 


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Term 
Definition 
Lesion Response 
Percent reduction in lesion size ≥20% compared with baseline 
LTFU 
Long-Term follow-up (20 - 25 days after EOT) 
PTE 
Post treatment evaluation (7 - 14 days after EOT) 
Subject 
An individual who participates in a clinical trial, either as a recipient of the 
investigational product(s) or as a control 
TNP-2092 
The investigational medicinal product in this study which will be administered 
intravenously every 12 hours at dose equivalent of 300 mg.  
Vancomycin 
The comparator antibiotic which will be administered intravenously every 12 
hours at dose equivalent of 1 g. 
2 
Introduction 
This document presents the Statistical Analysis Plan (SAP) for the protocol PJI001-02, “A 
Phase 2, Double-Blind, Randomized, Multicenter, Parallel, Controlled Study to Evaluate the 
Safety, Tolerability, Pharmacokinetics, and Efficacy of Tnp-2092 to Treat Acute Bacterial 
Skin and Skin Structure Infection in Adults”. The statistical plan described is an a priori plan 
and no analyses have been conducted prior to the preparation of this plan. This SAP 
summarizes the study design and objectives and provides details of the outcome definitions 
and statistical methods that will be used to analyze the data from protocol PJI001-02. 
Changes made to the SAP after it has been signed but prior to study unblinding will be 
documented in an amendment. Any important changes made to the analyses will be 
described in the clinical study report (CSR). This SAP is based on the original protocol 
version dated September 16, 2018 and protocol amendment 1 dated February 14, 2019. 
3 
Study Design  
This Phase 2, double-blind, randomized, multicenter, parallel, controlled study will be 
conducted to evaluate safety, tolerability, pharmacokinetic (PK) and efficacy of TNP-2092 
300 mg IV q12h and vancomycin 1 g IV q12h in adults with acute bacterial skin and skin 
structure infection (ABSSSI) suspected or confirmed to be caused by gram-positive 
pathogens.    


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The screening period will be up to 1 day in duration before intervention, followed by a 
treatment period (IV or IV plus oral switch, if applicable) of between 7 to 14 days in duration 
as presented in Figure 1.   
Figure 1:  Overview of Treatment Duration 
IV = intravenous; Rx = treatment 
All subjects will be treated with IV study intervention for a minimum of 6 doses and upon 
meeting protocol-specified switching criteria, subjects may switch and continue treatment of 
ABSSSI with a commercially-available, open-label, oral antibiotic selected by the 
investigator.  The post treatment evaluation (PTE) visit is 7 to 14 days after the end of 
treatment (EOT) and a long-term follow-up (LTFU) visit to monitor continuing adverse events 
(AEs) and concomitant medications is comprised of a telephone call at 20 to 25 days after 
the EOT visit.  Hence the total duration of the study can be up to 40 days from the screening 
visit to the LTFU visit. 
Subjects who meet the entry criteria will be randomized (2:1) to 1 of 2 treatment arms: TNP-
2092 300 mg IV q12h or vancomycin 1 g IV q12h.  Randomization will be stratified by 
ABSSSI type to ensure proper balance between treatment arms (Planned N = 120, n = 80 
for TNP-2092 arm A and n = 40 for vancomycin arm B). Subjects who are randomized will 
not be replaced. 


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The types of eligible ABSSSI include cellulitis/erysipelas, wound infections, and major 
cutaneous abscesses; however, participants with major cutaneous abscess should not 
comprise > 30% of the randomized population. Participants with ABSSSI with a minimal 
lesion surface area of 75 cm2 will be enrolled. No prior antibiotic treatment for the current 
ABSSSI is permitted before enrollment in the study, and no other concomitant systemic or 
topical antibiotics are permitted during the study. If a participant enrolls and is subsequently 
found to have a gram-negative or anaerobic bacterial infection, they may remain in the study 
but may be switched to an appropriate antibiotic and will not be included in the modified 
intent-to-treat (MITT) population which excludes all participants with gram-negative 
pathogens. 
An adequate local ABSSSI site specimen must be collected from all participants with non-
cellulitis ABSSSI for microbiologic evaluation at baseline. Local ABSSSI site specimens and 
blood cultures from 2 separate venipuncture sites will be collected from all participants 
before administration of study intervention, whenever possible. All local ABSSSI site 
specimens will undergo Gram-stain and culture at the local laboratory and all blood cultures 
will be processed at the local laboratory. Specimens should be processed according to 
standard recognized methods. All bacteria isolated from an adequate local ABSSSI site 
specimen or blood culture at the local laboratory will be sent to a designated central 
laboratory for confirmation of species identification and antimicrobial susceptibility testing.  
If local antimicrobial susceptibility testing of a baseline pathogen indicates possible non-
susceptibility to study intervention (e.g., intermediate susceptibility or resistance to a 
fluoroquinolone, rifamycin, and/or glycopeptide) but the participant is stable or clinically 
improving, the participant can remain on study intervention at the investigator’s discretion. In 
these cases, the investigator should discuss each situation with the medical monitor before 
discontinuation from study intervention.  
Screening assessments to determine study eligibility will be performed within 1 day before 
the first dose of study intervention is administered. Intravenous study intervention may be 
administered in a hospital or outpatient infusion center; outpatient administration of IV study 
intervention is limited to participants who are clinically stable and have adequate home 
support with reliable transportation to and from the hospital or clinic.  


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Day 1 is the first day of study intervention; subsequent study days are consecutive calendar 
days. For purposes of analysis, study assessments will be performed during the treatment 
period on Day 1, Day 2, at early assessment (EA) 48 to 72 hours after IV treatment is 
started, at end of IV (EOIV, 3 to 14 days after IV treatment is started) at end of treatment 
(EOT, after a minimum of 7 days up to 14 days of intervention, IV or IV plus oral switch, if 
applicable), at posttreatment evaluation (PTE, 7 to 14 days after EOT), and at long-term 
follow-up (LTFU, 20 to 25 days after EOT) (Figure 2).  
Figure 2:  Overview of Study Design 
EA = early assessment; EOIV = end of IV treatment; EOT = end of treatment; IV = 
intravenous; LTFU = long-term follow-up; PO = oral; PTE = posttreatment evaluation; q12h = 
every 12 hours Note: Participants receive a minimum of 3 days (72 hours, 6 doses) of IV 
study intervention. After 72 hours, participants may begin oral antibiotic treatment upon 
meeting protocol-specified criteria. *EA (48 to 72 hours after start of first dose of IV 
intervention) and EOIV (at least 72 hours, 6 doses after start of first dose of IV intervention) 
may occur simultaneously. EOT may be any day after at least 7 days of treatment initiation 
up to 14 days after treatment initiation. 
The primary endpoint is the assessment of safety and tolerability: incidence of adverse 
events (AEs), vital signs laboratory data, and ECG findings, and a qualitative assessment of 
local tolerability (including local infusion site reaction and thrombotic events) measured 
throughout the study. Secondary endpoints comprise PK (first dose and at EOIV treatment) 
and efficacy assessments (programmatic clinical response at EA aligns with the current FDA 
guidance [2013]). Secondary efficacy endpoints also include the investigator assessments 
of clinical response at designated time points and microbiological responses at PTE. 
Clinical assessments of the primary ABSSSI site (measurement of extent of infection and 
signs and symptoms) will occur at each visit from the screening visit to PTE, when clinically 
indicated, or if the participant is deemed a clinical failure. ABSSSI site specimen cultures 


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will be assessed at screening, when clinically indicated, or if the participant is deemed a 
clinical failure. Blood cultures will be assessed at screening with repeat testing if the 
previous blood culture was reported as positive, when clinically indicated, or if the 
participant is deemed a clinical failure. 
4 
Study Objectives 
4.1 
Primary Objectives 
The primary objective is as follows: 

Evaluate safety and tolerability of TNP-2092 300 mg q12 formulation compared with
vancomycin 1g q12h
4.2 
Secondary Objectives 

To determine the PK of TNP-2092 300 mg q12h

To evaluate the efficacy of TNP-2092 300 mg q12h and vancomycin 1 g q12h
4.3 
Endpoints 
The primary endpoints are as follows: 

Incidence, causality, and severity of AEs

Investigator assessment of thrombotic events and local infusion site reactions and
tolerability

Assessment of vital signs, laboratory data, and ECG findings
The secondary endpoints are as follows: 

Characterize the PK of TNP-2092 300 mg q12h in adult subjects with ABSSSI.  PK
parameters will be calculated from the concentration versus time data using either
non-compartmental analysis (NCA) or compartmental modeling (CM).  Although the
final decision will be made once the data are available, based on the sampling
schedule in Table 21 of the study protocol, CM is more likely to be the applicable
method.

Evaluate early clinical response at:
-
EA in the intent-to-treat (ITT) population
-
EA in the modified intent-to-treat (MITT) population


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-
EA in the microbiological intent-to-treat (micro-ITT) population

Evaluate per-subject microbiological response at:
-
PTE in the in the microbiological intent-to-treat (micro-ITT) population
-
PTE in the in the microbiologically evaluable (ME-PTE) population

Evaluate per-pathogen microbiological response at:
-
PTE in the in the microbiological intent-to-treat (micro-ITT) population
-
PTE in the in the microbiologically evaluable (ME-PTE) population

Evaluate the Investigator’s assessment of clinical response at each time point:
-
End of IV (EOIV; last day of IV infusion) in the MITT, micro-ITT and CE-EOIV
populations
-
End of treatment (EOT; last day of study drug) in the MITT, micro-ITT and CE-
EOT populations
-
Post treatment evaluation (PTE; 7 to 14 days after EOT) in the MITT, micro-ITT
and CE-PTE populations
5 
Data Management 
Data management procedures, including database design, development of the data 
dictionary, and coding of medical history, adverse events and medications, will be 
performed at a Contract Research Organization (CRO). Data will be entered into an 
electronic case report form (eCRF) at the study sites. A series of logic and consistency 
checks will be conducted to ensure accuracy and completeness of the clinical database. 
Safety laboratory results, microbiology data, and pharmacokinetic data will be electronically 
transmitted from external vendors. After database lock and after the evaluability and 
pathogen review process has been completed, randomization data will be provided 
electronically from RTMS, interactive web response system (IWRS) vendor. Refer to the 
Data Management Plan for further Data Management details. 
6 
Pathogen Determination 
Pathogens will be identified based on the genus and species identification from the central 
laboratory. If the local laboratory grows an acceptable pathogen but the central laboratory is 
not able to grow the isolate, if isolates are lost during transportation or storage, or if there 
are any other major discrepancies between the local and central laboratory in the 
identification of species, the central laboratory or other Sponsor designee will request that 
the local laboratory resend the isolate. If the central laboratory cannot determine the genus 


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and species of the isolate for any reason, the local laboratory determination of genus and 
species will be used for pathogen identification.  
Screening/baseline samples are collected within 24 hours of the first dose of study drug on 
either Day 1 or Day -1. If more than one baseline ABSSSI site sample was obtained using 
an acceptable ABSSSI specimen or more than one baseline blood sample was obtained, 
isolates from all samples will be reviewed for pathogen determination. For subjects with 
cellulitis/erysipelas, if no acceptable baseline infectious material has been obtained, or if no 
pathogens have been identified from the baseline sample, then a Day 2 or 3 ABSSSI site 
sample can be used as baseline if the sample is considered acceptable.   
The organisms identified in Table 1 will always be considered an ABSSSI pathogen when 
isolated from an acceptable ABSSSI specimen.  Additional pathogens will be identified 
during pathogen review prior to unblinding of the study. 
Table 1:  ABSSSI Pathogens 

Methicillin-resistant Staphylococcus
aureus (MRSA)

Methicillin-susceptible Staphylococcus
aureus (MSSA)

Streptococcus pyogenes (Group A
streptococci)

Streptococcus anginosus

Streptococcus intermedius

Streptococcus constellatus

Streptococcus agalactiae

Streptococcus dysglactiae

Staphylococcus haemolyticus

Staphylococcus lugdunensis

Escherichia coli

Enterococcus faecalis

Enterococcus faecium

Proteus mirabilis

Pseudomonas aeruginosa

Klebsiella pneumoniae

Group C β-hemolytic streptococci

Streptococcus viridans group


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The following organisms in Table 2 will never be considered an ABSSSI pathogen when 
isolated from an ABSSSI specimen:  
Table 2: Not ABSSSI Pathogens 

Staphylococcus saprophyticus

Corynebacterium spp.

Staphylococcus epidermidis

Staphylococcus hominis

Staphylococcus warneri

Bacillus spp.

Micrococcus spp.

Candida spp. or other fungi
All other organisms not listed above will be assessed on a case-by-case basis via manual 
review by the Sponsor (e.g., Gram-negative organisms, anaerobes). If needed, subject 
clinical (e.g., type of infection, type of specimen, subject underlying conditions, etc.) and 
microbiological information (e.g., Gram stain, etc.) will be used to assist in determining if the 
isolate is a pathogen. In addition, all polymicrobial infections (i.e., ABSSSI caused by more 
than 1 pathogen) and all cases of bacteremia will be reviewed manually. 


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7 
Definition of Analysis Populations 
The relationship between the analysis sets is shown in Figure 3 below. 
Figure 3:  Overview of Analysis Populations 
ABSSSI = acute bacterial skin and skin structure infection; CE = clinically evaluable; EOIV = end of 
IV; EOT = end of therapy; ITT = intent-to-treat; IV = intravenous; ME = microbiologically evaluable; 
MITT = modified intent-to-treat; micro-ITT = microbiological intent-to-treat; PK = pharmacokinetic; 
PTE = posttreatment evaluation. 


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7.1 
Intent-to-Treat (ITT) Population 
The ITT population will consist of all randomized subjects regardless of whether or not the 
subject received study drug. A subject is considered randomized when the Investigator or 
Investigator’s designee receives the IWRS-generated randomization number. 
7.2 
Modified Intent-to-Treat (MITT) Population 
All randomized subjects in the ITT population, excluding subjects with only a Gram-negative 
pathogen(s) at baseline. 
7.3 
Safety Population 
The Safety population will consist of all randomized subjects who receive any amount of 
study drug. All safety analyses will be conducted in this population and will be presented in 
the summary tables by the treatment that the subject actually received. In the event that a 
subject received both TNP-2092 and vancomycin then that subject will be included in the 
TNP-2092 arm. 
7.4 
Microbiological Intent-to-Treat (Micro-ITT) Population 
The Micro-ITT population will consist of all subjects in the ITT population who have culture 
evidence of a baseline Gram-positive bacterial pathogen known to cause ABSSSI. Analyses 
in this population will be presented in summary tables by the treatment arm to which the 
subject was randomized. 
7.5 
Clinically Evaluable Population at End-of-IV (EOIV), End-of-Treatment (CE-EOT) 
and the Post-Treatment Evaluation (CE-PTE) 
The CE-EOIV, CE-EOT and CE-PTE populations will consist of all subjects in the ITT 
population who: 

meet the minimal clinical disease criteria for ABSSSI described in the study
Inclusion Criteria (Inclusion Criteria 2a, 2b, 2c, 3, 4a-4f, 5a-5d),

receive at least 80% of expected IV doses based on length of therapy,

did not receive any potentially-effective systemic or topical antibacterial therapies
other than protocol specified study drug(s) for an indication other than ABSSSI
between Day 1 and timepoint for assessment, where the timepoint for assessment is
EOIV for the CE-EOIV population, EOT for the CE-EOT population, and PTE for the
CE-PTE population.


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
Did not have any major protocol violation, including but not limited to:
o
Prior administration of systemic antibacterial therapy within 96 hours before
randomization
o
Received the wrong study drug or were unblinded before the timepoint of
assessment for reasons other than safety
In addition, to be included in the CE-EOIV population, the following conditions must be met: 

Have an Investigator’s assessment of clinical response at EOIV (i.e., response
cannot be indeterminate)

Had an EOIV visit within 1 calendar day of last dose of IV study drug (+1 day) [i.e.,
within 48 hours of the last dose of IV study drug]
In addition, to be included in the CE-EOT population, the following conditions must be met: 

Have an Investigator’s assessment of clinical response at EOT (i.e., response cannot
be indeterminate)

Had an EOT visit within 1 calendar day of last dose of study drug and/or follow up
open-label oral antibiotic (+1 day) [i.e., within 48 hours of the last dose of study drug]
To be included in the CE-PTE population, the following conditions must be met: 

Have an Investigator’s assessment of clinical response at PTE (i.e., response can’t
be indeterminate unless the subject is deemed a clinical failure at the EOT visit)

Had a PTE visit within 7-14 days after the EOT visit.  If the EOT visit is out of the
study window, then the PTE visit must still be within 7-14 days of the EOT visit.  If the
EOT visit is missed, then the PTE visit must be within 7-14 days of the last dose of
study drug and/or follow up open-label oral antibiotic.
Additional minimal dose requirements for clinical failure or success at EOIV, EOT or PTE: 

Subjects who are defined as clinical failures at EOIV, EOT or PTE with fewer than 3
doses of study drug are not included in the CE-EOIV, CE-EOT or CE-PTE
populations, respectively.

Subjects who are defined as clinical successes at EOIV, EOT or PTE with fewer than
4 doses of study drug are not included in the CE-EOIV, CE-EOT or CE-PTE
populations, respectively.


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7.6 
Microbiologically Evaluable Population (ME-PTE) 
The ME-PTE Population includes all subjects in the CE-PTE Population with culture 
evidence of a baseline Gram-positive bacterial pathogen known to cause ABSSSI (i.e., 
meets both CE-PTE and Micro-ITT Population definitions). 
7.7 
Pharmacokinetic Population (PK) 
All subjects who receive at least 1 dose of TNP-2092 and had a sufficient number of plasma 
samples for TNP-2092 PK analysis. 
7.8 
Pathogen and Evaluability Determination 
The Medical Monitor will review both clinical and microbiological data for determination of 
criteria used to assess inclusion in the analysis populations and for determination of 
baseline and post-baseline pathogens. The Medical Monitor will be blinded to treatment 
assignment and will review the data concurrent with the conduct of the study. 
Inclusion into the ITT, Safety, and PK Populations will be determined programmatically 
from the eCRF data. Inclusion into the CE-EOIV, CE-EOT, and CE- PTE Populations will 
be determined programmatically from the eCRF data and evaluability review conducted by 
the Medical Monitors. The Medical Monitor may review subject data to confirm that 
population criteria are satisfied.   
Inclusion into the MITT and ME-PTE Populations will be determined programmatically by 
incorporating the outcome of the pathogen review by the Medical Monitor. The Medical 
Monitor will determine whether each isolate (baseline and post-baseline) is considered an 
ABSSSI pathogen based on a review of information from samples including infection type, 
type of specimen, and local and central laboratory genus and species identification. In the 
event that a local culture is completed, but the reading from the central lab culture is not 
available, then the local lab result will be used. 
Additional details can be found in the Evaluability and Pathogen review process document 
and Section 7.8 of this document. 


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8 
Definition of Outcome Measures 
8.1 
Clinical Outcome Definitions 
8.1.1 Programmatic Clinical Response at Early Assessment (EA) 
Clinical response at EA will be determined programmatically based on data recorded on the 
eCRF. Note that the protocol EA visit window is 48-72 hours after the first dose of study 
drug. 
A subject will be classified programmatically as a ‘responder at EA’ if the percent reduction 
in the primary ABSSSI lesion area at EA is greater than or equal to 20% compared to 
baseline and the subject did not die of any cause within 72 hours of the first dose of study 
drug. 

A subject will be classified programmatically as a ‘non-responder at EA’ if the percent
reduction in the primary ABSSSI lesion size is less than 20% compared to baseline,
or the subject received a potentially-effective non-study antibacterial agent with
activity against gram-positive organisms for the treatment of ABSSSI through 72
hours, or died of any cause within 72 hours of the first dose of study drug.

A subject will be classified programmatically as ‘indeterminate at EA’ if study data
are unavailable for evaluation of efficacy for any reason (e.g., missing data, lost to
follow-up, did not attend the EA clinic appointment, or if the EA visit is out of the 48-
72 hour window).
If there is more than one ABSSSI measurement within the 48-72 hour window, the last 
measurement will be used to assess the clinical response at EA. If the baseline lesion 
measurement is missing and there is one within 6 hours of the first dose of study drug, this 
measurement may be considered the baseline measurement. 
8.1.2 Investigator Assessment of Clinical Response at End-of-IV (EOIV) 
Investigator-determined ‘clinical improvement at EOIV’ is defined by all of the following: 

ABSSSI sufficiently improved such that further IV antibacterial therapy is not needed

These subjects may have some residual clinical signs and symptoms related to
ABSSSI requiring continued oral antibiotic stepdown therapy (provided the subject


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meets oral switch criteria, or ancillary (i.e., non-antibiotic) treatment, e.g., bandages 
on a healing wound, debridement of uninfected tissue. 
Investigator-determined ‘clinical failure at EOIV’ is defined by any of the following: 

Investigator discontinued study intervention and indicated that the ABSSSI had
responded inadequately such that alternative (rescue) non-study IV antibacterial
therapy was needed,

The subject received potentially-effective non-study antibacterial therapy for a
different infection that may be effective for the ABSSSI under study

The subject developed an AE that required discontinuation of study intervention
before completion of the planned IV regimen,

Unplanned major surgical intervention (i.e., procedures that would not normally be
performed at the bedside) for the ABSSSI under study, or

Died of any cause up to the EOIV visit.
Investigator-determined ‘Indeterminate at EOIV’ is defined as: 

Study data are unavailable for evaluation of efficacy for any reason (e.g., missing
data, lost to follow-up).
8.1.3 Investigator Assessment of Clinical Response at End-of-Treatment (EOT) 
Investigator-determined ‘clinical success at EOT’ is defined by all of the following: 

ABSSSI sufficiently resolved such that further antibacterial therapy is not needed

These subjects may have some residual changes related to infection requiring
ancillary (i.e., non-antibiotic) treatment; e.g., bandages on a healing wound,
debridement of uninfected tissue (i.e., necrotic)

Did not die of any cause up to the EOT visit.
Investigator-determined ‘clinical failure at EOT’ is defined by any of the following: 

Investigator discontinued study intervention and indicated that the ABSSSI had
responded inadequately such that alternative (rescue) non-study antibacterial
therapy was needed,


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
The subject received potentially-effective non-study antibacterial therapy for a
different infection that may be effective for the ABSSSI under study,

The subject developed an AE that required discontinuation of study intervention
before completion of the planned treatment regimen,

Unplanned major surgical intervention (i.e., procedures that would not normally be
performed at the bedside) for the ABSSSI under study, or

Died of any cause up to the EOT visit.
Investigator-determined ‘Indeterminate at EOT’ is defined as: 

Study data are unavailable for evaluation of efficacy for any reason (e.g., missing
data, lost to follow-up).
8.1.4 Investigator-Assessment of Clinical Response at Post-Treatment Evaluation 
(PTE) 
Investigator-determined ‘clinical success at PTE’ is defined by all of the following: 

ABSSSI sufficiently resolved such that further antibacterial therapy is not needed

These subjects may have some residual changes related to infection requiring
ancillary (i.e., non-antibiotic) treatment, e.g., bandages on a healing wound,
debridement of uninfected tissue (i.e., necrotic)

Did not die of any cause up to the PTE visit.
Investigator-determined ‘clinical failure at PTE’ is defined by any of the following: 

Investigator discontinued study intervention and indicated that the ABSSSI had
responded inadequately such that alternative (rescue) non-study antibacterial
therapy was needed,

The subject received potentially-effective non-study antibacterial therapy for a
different infection that may be effective for the ABSSSI under study,

The subject developed an AE that required discontinuation of study intervention
before completion of the planned treatment regimen,

Unplanned major surgical intervention (i.e., procedures that would not normally be
performed at the bedside) for the ABSSSI under study, or


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
Died of any cause up to the PTE visit.
Investigator-determined ‘Indeterminate at PTE’ is defined as: 

Study data are unavailable for evaluation of efficacy for any reason (e.g., missing
data, lost to follow-up).
The following overall assessment of clinical response based on the Investigator’s 
Assessment will be determined at the PTE Visit based on the following rules. The Overall 
Assessment of Clinical Response at PTE will be summarized in all tables and the 
Investigator’s assessment of clinical response at the PTE as reported in the eCRF visit will 
only be listed. 
Table 3: Overall Assessment of Clinical Response 
EOT Visit 
PTE Visit 
Overall Assessment of Clinical 
Response  
Success 
Success 
Success 
Success 
Failure 
Failure 
Success 
Indeterminate 
Indeterminate 
Failure 
Success 
Failure 
Failure 
Failure 
Failure 
Failure 
Indeterminate 
Failure 
Indeterminate 
Success 
Indeterminate 
Indeterminate 
Failure 
Failure 
Indeterminate 
Indeterminate 
Indeterminate 
8.2 
Microbiologic Response 
8.2.1 Per-Pathogen Microbiological Response at EOT and PTE Visits 
Pathogen microbiological outcome categories are: eradication, presumed eradication, 
persistence, presumed persistence, and indeterminate and these as defined in the following 
table. Favorable microbiological outcomes include eradication or presumed eradication. 
Unfavorable microbiological outcomes include persistence or presumed persistence and are 
defined in Table 4. 


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Table 4:  Pathogen Microbiological Response at EOT and PTE Visits 
Eradication 
An adequate source specimen (from ABSSSI site and/or blood) 
demonstrates absence of the original screening/baseline 
pathogen(s). If there is a positive blood sample at 
screening/baseline, the last blood sample on or prior to the 
referenced visit (*) must be a negative. 
Presumed eradication 
An adequate source specimen was not available to culture and 
the subject was assessed as a clinical success by the 
Investigator at the referenced visit (*). If there is a positive 
blood sample at screening/baseline but there is no post-
baseline blood sample available and the subject was assessed 
a clinical success by the Investigator at the referenced visit (*), 
then categorize as presumed eradication. 
Persistence 
An adequate source specimen demonstrates continued 
presence of the original baseline pathogen(s) (i.e., presence of 
original baseline pathogen cultured from the site of ABSSSI or 
blood) at the referenced visit (*). 
Presumed persistence 
An adequate source specimen was not available to culture from 
site of ABSSSI or blood and the subject was assessed as a 
clinical failure by the Investigator at the referenced visit (*). 
Indeterminate 
An adequate source specimen was not available to culture from 
site of ABSSSI or blood and the subject’s clinical response was 
assessed as indeterminate at the referenced visit (*) 
Notes:  Should EA or EOIV pathogen show results of ‘no growth’ for a subject, but no subsequent 
pathogens captured for the same subject, then the ‘no growth’ (i.e. eradication) results will be carried 
forward to EOT and PTE. 
(*) the term ‘referenced visit’ is ‘EOT’ when defining the Pathogen Microbiological Response at EOT, 
and is ‘PTE’ when defining the Pathogen Microbiological Response at PTE. 


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8.2.2 Per-Subject Overall Microbiological Response at PTE 
In order for a subject to have a favorable per-subject microbiological response, the outcome 
for each baseline pathogen must be favorable (eradicated or presumed eradicated). In order 
for a subject to have an unfavorable per-subject microbiological response, the outcome for 
any baseline pathogen must be unfavorable (persistence, presumed persistence). 
The proportion of subjects with a favorable microbiological response is defined as: 
𝑃𝑀𝑖𝑐𝑟𝑜 𝐹𝑎𝑣 𝑅𝑒𝑠𝑝= (# 𝑠𝑢𝑏𝑗𝑒𝑐𝑡𝑠 𝑤𝑖ℎ 𝑒𝑟𝑎𝑑𝑖𝑐𝑎𝑡𝑖𝑜𝑛 𝑜𝑟 𝑝𝑟𝑒𝑠𝑢𝑚𝑒𝑑 𝑒𝑟𝑎𝑑𝑖𝑐𝑎𝑡𝑖𝑜𝑛)
𝐴𝑙𝑙 𝑠𝑢𝑏𝑗𝑒𝑐𝑡𝑠 (𝑖𝑛𝑐𝑙𝑢𝑑𝑖𝑛𝑔 𝑖𝑛𝑑𝑒𝑡𝑒𝑟𝑚𝑖𝑛𝑎𝑡𝑒𝑠)
The overall assessment of microbiological response will be implemented using responses 
at the EOT and PTE visits as identified in Table 5. Unless otherwise specified, all 
summaries of microbiological response are based on the overall microbiologic response at 
PTE. 
Table 5: Overall Assessment of Microbiological Response 
Microbiologic Response 
EOT Visit 
PTE Visit 
Overall Microbiologic 
Response at PTE 
Favorable 
Favorable 
Favorable 
Favorable 
Unfavorable 
Unfavorable 
Favorable 
Indeterminate 
Indeterminate 
Unfavorable 
Favorable 
Unfavorable 
Unfavorable 
Unfavorable 
Unfavorable 
Unfavorable 
Indeterminate 
Unfavorable 
Indeterminate 
Favorable 
Indeterminate 
Indeterminate 
Unfavorable 
Unfavorable 
Indeterminate 
Indeterminate 
Indeterminate 
Favorable is defined as eradication or presumed eradication. 


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8.3 
Emergent Infections 
Microbiological definitions of superinfections or new infections are defined in Table 6. 
Table 6: Superinfections and New Infections 
Category 
Definition 
Superinfection 
Isolation of a new pathogen(s) (other than the original 
screening/baseline pathogen[s]) from the primary ABSSSI site (culture) 
which is accompanied by signs and symptoms of infection requiring 
alternative systemic antimicrobial therapy during the period up to and 
including EOT, based on the Investigator’s assessment of clinical 
response.  
New infection 
Isolation of a new pathogen(s) (other than the original 
screening/baseline pathogen[s]) from the primary ABSSSI site (culture) 
which is accompanied by signs and symptoms of infection requiring 
alternative systemic antimicrobial therapy after EOT, based on the 
Investigator’s assessment of clinical response. 
8.4 
Safety Outcomes 
Safety will be assessed through the determination and recording of the occurrence of 
adverse events (AEs) and AEs of special interest (Thrombotic and infusion site AEs), as well 
as by changes in vital signs, ECG parameters, and laboratory data. Additional safety events 
that occur after PTE will be assessed at LTFU. Adverse events will be evaluated by 
relationship to study drug and severity. Serious adverse events (SAEs) will be identified. 
8.5 
Pharmacokinetic Outcomes 
Sampling for pharmacokinetic analysis (with evaluation of TNP-2092 levels) will occur at the 
time points shown in “Pharmacokinetic Sample Schedule” of Appendix G.  Details of the 
analysis of this data will be provided separately by the pharmacokineticist in the CSR. 


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9 
Statistical Methods and General Considerations 
9.1 
Sample Size 
This study is not powered for inferential statistical analysis. With N=80, if the responder rate 
in the TNP-2092 arm is 0.8 at EA (48 to 72 hours after start of study intervention) according 
to the programmatic clinical response, this results in a 95% confidence interval (CI) of (0.7, 
0.88) for the responder rate in the TNP-2092 arm at the EA visit (Clopper and Pearson, 
1934). A sample size of 80 participants who receive TNP-2092 is deemed sufficient to 
provide an initial assessment of safety and PK data to inform the future development of 
TNP-2092.  Hence 120 (80 TNP-2092: 40 vancomycin) adult subjects with ABSSSI will be 
enrolled in this study. 
9.2 
Randomization and Masking 
Fixed block randomization using an interactive response system (IWRS) will be used to 
assign subjects (2:1) to TNP-2092 or vancomycin. Randomization will be stratified by 
infection type (cellulitis/erysipelas, wound infection, or major cutaneous abscess). After 
informed consent has been obtained and study eligibility established, the study site’s 
Pharmacist or Pharmacist’s designee will obtain the subject number and the study drug 
assignment from a computer-generated randomization code via IWRS. A subject is 
considered randomized when the Pharmacist or Pharmacist’s designee receives the 
randomization number or study drug assignment. 
This is a double-blind study. Those blinded to study drug assignment include the Sponsor, 
Investigator, study statistician, clinical study personnel participating in subjects’ care or 
clinical evaluations, and the subjects. Those unblinded to study drug assignment include the 
pharmacy personnel, the unblinded study monitor, and the bioanalytical laboratory. Blinded 
personnel must not make any effort to determine which study drug therapy is being 
administered. Blinded personnel will remain blinded to study drug assignment until all 
subjects have completed the study and the database is locked. Procedures to ensure that 
the blind is maintained are detailed in the Sponsor, CRO and Vendor Blinding plan, the 
Blinded Clinical Monitoring Plan, and the Site-Specific Blinding Plans. 
If study drug is determined not to be safe and tolerated, the study drug assignment for those 
subjects with a safety concern may be unblinded after discussion between the Investigator 
and Sponsor. The blind may also be broken in the case of a medical emergency requiring 


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the Investigator to know the identity of the study drug to appropriately guide the subject’s 
medical management. Prior to any unblinding, the Investigator is strongly advised to discuss 
options with the Medical Monitor or appropriate Sponsor study personnel. If the blind is 
broken for any reason and the Investigator was unable to contact the Sponsor before 
unblinding, the Investigator must notify the Sponsor as soon as possible, without revealing 
the subject’s study drug treatment assignment (unless important to the safety of subjects 
remaining in the study). All instances of unblinding will be thoroughly investigated and 
documented by the unblinded study monitor. 
After the database is locked and the SAP is final, and all analysis populations have been 
determined, the study will be unblinded. 
9.3 
Interim Analysis 
There is no formal interim analysis of efficacy or safety for this study and a Data Monitoring 
Committee will not be utilized. 
9.4 
Standard Calculations 
Variables requiring calculation will be derived using the following formulas: 

Baseline - A baseline value is the last non-missing value recorded prior to the first dose
of study drug. For subjects who never get dosed, the screening measurements will be
considered the baseline assessment. If an assessment has both a date and time that
exactly match the date and time of first dose of study drug, the assessment will be
counted as baseline.
o
Baseline pathogens however will include any pathogens identified from samples
during the baseline/screening visit. For subjects with cellulitis/erysipelas, if no
acceptable baseline infectious material has been obtained, or if no pathogens
have been identified from the baseline sample, then a Day 2 or 3 ABSSSI site
sample can be used as baseline if the sample is considered acceptable.
o
In the event of missing baseline lesion measurements, a lesion size baseline
measurement may include a measurement up to 6 hours after the first dose.

Change from baseline - Change from baseline will be calculated for each subject at the
specified time point as the value at the specified time point minus that subject’s baseline
value.


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
Study day – For a given date (date), the study day is calculated as days since the date
of first dose of study drug (firstdose).
Study day = date – firstdose + 1, where date ≥ firstdose 
Study day = date – firstdose, where date < firstdose 

Days – Durations, expressed in days, between one date (date1) and another later date
(date2) are calculated using the following formula: duration in days = (date2-date1+1).

Body Mass Index (BMI) - BMI (kg/m2) = weight (kg) / [[height (cm)/100]2].

Age, in years, will be computed from the date of birth to the date of informed consent.
9.5 
Handling of Missing Data 
All missing data and missing and partial dates for events occurring after randomization or for 
medications received after randomization will be queried for a value.  If no value can be 
obtained missing data will be handled as outlined below:  

All AEs with partial or missing dates and times will be considered treatment emergent
unless a partial start date and/or time indicates the AE began prior to the start of study
medication or a stop date indicates the AE ended prior to the start of study medication.

The severity and causality assessment for adverse events must not be missing and will
be queried for a value. Should there be missing data, adverse events with missing
severity will be considered severe and adverse events with missing relationship to study
drug will be considered related to study drug.

Missing start and stop times for antibiotics will be queried for a value. The actual value
(blank) will be recorded on the eCRF and will be used in the listings.

All other (non-antibiotic) medications with partial or missing dates and times recorded on
the concomitant medication eCRF will be considered concomitant unless a partial stop
date and time clearly indicates it was stopped before the first dose of study treatment.
For clinical and microbiological response, missing data will be handled as follows: 

For the primary efficacy outcome measure (early clinical response at 48 to 72 hours):

The subject will have missing data if there is no lesion size measurement (either
length or width) at the EA visit and will be defined as an indeterminate response.


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


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
Continuous variables will be summarized using number (n), mean, standard
deviation (SD), median, minimum, and maximum.  Summaries of blood concentration
will also include the geometric mean (GM) and coefficient of variation (CV).

Frequency counts and percentages will be reported for all categorical data.

Duration variables will be calculated using the general formula
(end date - start date) +1.

If the reported value of a clinical laboratory parameter cannot be used in a statistical
summary table (e.g., a character string is reported for a parameter of the numerical
type), a coded value must be appropriately determined and used in the statistical
analyses. In general, a value or lower and upper limit of normal range such as ‘<10’
or ‘≤ 5’ will be treated as ‘10’ or ‘5’ respectively, and a value such as ‘>100’ will be
treated as ’100’. However, the actual values as reported in the database will be
presented in data listings.

For all “by visit” safety tables (e.g., laboratory values, vital signs, electrocardiograms
(ECGs)), nominal visits will be summarized. In addition within tables that summarize
changes from baseline, the minimum and maximum post-baseline values will be
summarized to take unscheduled visits into account.

Version 9.4 of SAS statistical software package will be used to provide all
summaries, listings, graphs, and statistical analyses.

The analyses described in this plan are considered a priori, in that they have been
defined prior to database lock. Any analyses performed subsequent to this will be
considered post-hoc and exploratory. Post-hoc analyses will be labeled as such on the
output and identified in the CSR.
10 Statistical Analyses 
10.1 Subject Disposition 
The number and percentage of subjects included in each of the analysis populations (ITT, 
MITT, Safety, Micro-ITT, CE-EOIV, CE-EOT, CE-PTE, ME-PTE) will be summarized by 
treatment group and the number of subjects screened and the reasons for screen failures 
will also be summarized.  A table will summarize the reasons for exclusion from each 


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


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10.4 Baseline Disease Characteristics 
The primary disease diagnosis at baseline (cellulitis/erysipelas, wound infection, or major 
cutaneous abscess), location of infection, symptoms of infection, and size of infection 
(<=300 cm2, >300-600 cm2, >600-1000 cm2 and >1000 cm2) will be summarized by 
treatment group for the ITT, Micro-ITT, CE-EOIV, CE-EOT, and CE-PTE Populations.  The 
location of infection will be categorized as follows: head or face or neck, chest or shoulder 
or back or abdomen, groin or buttock, arm or hand (upper extremities), and leg or thigh or 
knee or lower leg or ankle or foot (lower extremities). 
Baseline information about each ABSSSI including mean infection area, mean infection 
area by disease diagnosis, and the signs and symptoms of disease will be summarized by 
treatment group for the ITT, Micro-ITT, CE-EOIV, CE-EOT, and CE-PTE populations. 
10.5 Baseline Microbiology 
The number and percentage of subjects with each type of ABSSSI site specimen obtained, 
whether or not there was Gram stain, whether there was growth, whether there was culture 
grown, the type of bacteria (Gram-positive cocci, Gram-negative cocci, Gram-positive 
bacilli, Gram-negative bacilli), and the presence of white blood cells from the local 
laboratory will be provided by treatment group in the Micro-ITT and ME-PTE populations. 
Baseline blood specimen results from the local laboratory will be summarized similarly for 
the Micro-ITT and ME-PTE populations.  All ABSSSI site specimen and blood specimen 
Gram stain results will be listed. 
The pathogenic organisms identified by the central or local laboratory from the baseline 
blood culture or culture of the ABSSSI specimen will be presented.  If there is disagreement 
between the central and local organism, the pathogen will be identified as described in the 
Evaluability and Pathogen Review process document.  The number and percentage of 
subjects with Gram positive and Gram negative organisms will be presented by genus and 
species for the Micro-ITT and ME-PTE populations overall and by infection type; 
additionally for the Staphylococcus aureus genus and species, the resistance phenotype 
will also be presented for Methicillin, Rifampin and Ciprofloxacin. The same pathogen 
identified from both the blood and the ABSSSI culture will be counted only once in the 
summary. The pathogenic organisms identified at baseline from blood sample(s) will also 
be presented for the Micro-ITT and ME-PTE populations.  


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The number and percentage of subjects with monomicrobial Gram-positive, polymicrobial 
Gram-positive, mixed (Gram positive and Gram negative) infections, will be presented by 
treatment group, and provided for specimens from blood or ABSSSI culture for both the 
Micro-ITT and ME-PTE populations. When per-subject counts of S. aureus are presented, 
subjects with both MRSA and MSSA are counted only once. 
A listing will be provided that includes all baseline and post-baseline isolates obtained from 
the blood and primary ABSSSI site specimen and will indicate the type of specimen and 
pathogenic organism identified from both the local and central laboratories.  Gram stain 
results will also be listed. 
The minimum inhibitory concentration (MIC) of TNP-2092 to baseline pathogens from the 
primary ABSSSI site or blood culture will be summarized by genus, species and treatment 
group in the Micro-ITT and ME-PTE populations.  The MIC of vancomycin will be 
summarized similarly. If available, the baseline MIC of other available antibacterial 
medications (e.g., Rifampin, Ciprofloxacin and Methicillin) will be summarized for the all 
pathogen genus and species by treatment group in the Micro-ITT population. Summary 
Statistics (range, MIC50, MIC90) will be presented for the study drug received to baseline 
pathogens from the primary ABSSSI site or blood culture will be summarized by treatment 
group in the Micro-ITT and ME-PTE populations. MIC50 and MIC90 values will only be 
presented for a particular pathogen if there are >=10 pathogens identified within a 
treatment arm. The MIC50 and MIC90 are the MICs required to inhibit the growth of 50% and 
90% of organisms, respectively. For subjects with more than one baseline pathogen of the 
same genus and species, the one with the highest MIC to study drug received will be 
selected for analysis; thus subjects are counted only once for that pathogen. If there is a 
tie, the MIC with the lowest disk diffusion (if applicable) to study drug received will be 
chosen. Otherwise, the highest accession number is chosen. 
10.6 Prior and Concomitant Medications 
All prescription medications and over-the-counter medications, including herbal, nutritional, 
and dietary supplements (e.g., any antacid, iron supplement, or multivitamin) administered 
within 2 weeks (14 days) prior to randomization and during the study between Day 1 and 
LTFU will be documented in the eCRF. 
Verbatim terms on case report forms will be mapped to Anatomical/Therapeutic/Chemical 
(ATC) class and Generic Drug Names using the World Health Organization (WHODrug 


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Global B3, March 2019) dictionary. Anatomical Therapeutic Chemical Classification (ATC) 
level 4 (fourth level indicates the chemical/therapeutic/pharmacologic subgroup) and 3 
(third level indicates the therapeutic/pharmacologic subgroup). 
Prior medications are those medications taken before the first dose of study drug.  
Concomitant medications are those medications taken at the start of study drug or initiated 
after the initial dose of study drug, or medications that were initiated prior to the start of 
study drug and continue to be taken after study drug is administered. (See the “Handling of 
Missing Data” section for details on handling in the event of missing medication dates.) 
The proportion of subjects who receive the following prior and concomitant medications will 
be summarized by ATC level 3 class, preferred term, and treatment group: 

Concomitant systemic or topical antibacterial medications (excluding study drug)
taken between time of the first administration of study drug on Day 1, the EOIV visit
(ITT, MITT, CE-EOIV populations), the EOT Visit (ITT, MITT, CE-EOT populations)
and the PTE Visit (ITT, MITT, CE-PTE populations)

Prior medications (including antibacterial) taken  (ITT, Safety populations)

Concomitant non-antibacterial medications (ITT, Safety Population)
Subjects will be counted only once for an ATC class and preferred term. 
All prior and concomitant antibacterial medications will be listed.  All prior and concomitant 
non-antibacterials will also be listed  
10.7 Study Drug Exposure and Compliance 
The active study drugs TNP-2092 (300 mg IV q12h infusion) and vancomycin (1 g IV q12h 
infusion), will be administered for at least 6 doses up to a maximum of 14 days.  The 
maximum of 14 days would result when subjects receive the IV formulations for the entire 
treatment duration. Alternatively, subjects may be switched to a commercially-available, 
open-label, oral antibiotic (as selected by the investigator) after 6 doses and will continue 
oral antibiotic treatment through the EOT visit. The Intervention comprising IV or IV plus oral 
medications switch (if applicable) will be administered for a minimum of 7 days up to 14 
days. 


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By treatment group summaries will be provided for total number of IV doses in the ITT, 
MITT, Safety, CE-EOIV, CE-EOT and CE-PTE populations.  The number of days and doses 
of IV dosing, until switch to PO, will also be summarized. 
Duration of treatment is defined as the number of calendar days from when the subject first 
received study treatment until the day that they last received study treatment (IV or PO) and 
is calculated as (date of last dose – date of first dose +1).  Duration of treatment will be 
looked at overall, and then also by route (IV or PO), where the duration of oral dosing is 
defined as the last day of oral dosing minus the first day of oral dosing + 1. 
Compliance to IV study drug will be calculated based on the total number of IV doses taken, 
divided by the total number of expected IV doses, in the time period between the dates of 
the first and last IV doses of study drug.   
𝑪𝒐𝒎𝒑𝒍𝒊𝒂𝒏𝒄𝒆𝑰𝑽= 100 ∗(𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑜𝑠𝑒𝑠 𝑟𝑒𝑐𝑒𝑖𝑣𝑒𝑑 (𝐼𝑉))
(𝐸𝑥𝑝𝑒𝑐𝑡𝑒𝑑 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑑𝑜𝑠𝑒𝑠 (𝐼𝑉))
Descriptive statistics of percent compliance as well as the number and percentage of 
subjects at least 80% compliant by number of IV doses will be provided by treatment group 
for the ITT, MITT, Safety, CE-EOIV, CE-EOT, and CE-PTE populations.  
Descriptive statistics of study drug exposure by route of administration will also summarized 
by treatment group, for the ITT, MITT, Safety, CE-EOIV, CE-EOT, and CE-PTE populations.  
This entails days of dosing for the IV and PO dosing regimens as well as IV doses for the 
intravenous portion. 
10.8 Efficacy Analyses 
For all efficacy analyses, subjects will be analyzed in the group to which they were 
randomized. By definition, subjects who receive the wrong study drug are not included in 
the CE and ME-PTE populations. The secondary efficacy endpoints are identified in Table 
7. 
All confidence intervals for responder rates or rates of success will be computed using the 
Exact (Clopper-Pearson) Confidence Limits. The differences in responder or success rates 
will be calculated and the confidence intervals for these differences will be computed using 
the method developed by Miettinen and Nurminen (Miettinen and Nurminen, 1985, 
Reference 2).  Confidence intervals will not be calculated for by pathogen results. 


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Table 7: Secondary Efficacy Endpoints 
Efficacy Endpoints 
Efficacy Population 
ITT 
MITT 
Micro-
ITT 
CE-
EOIV 
CE-
EOT 
CE-
PTE 
ME-
PTE 
Programmatic clinical response at EA 
√ 
√ 
√ 
Per-subject microbiological response at 
PTE  
√ 
√ 
Microbiological response per baseline 
pathogen at PTE 
√ 
√ 
Investigator’s assessment of clinical 
response at EOIV 
√ 
√ 
√ 
Investigator’s assessment of clinical 
response at EOT  
√ 
√ 
√ 
Investigator’s assessment of clinical 
response at PTE 
√ 
√ 
√ 
CE = clinically evaluable; EA = early assessment; EOIV = end of IV treatment; EOT = end of 
treatment; IV = intravenous; MITT = modified intent-to-treat; ME = microbiologically evaluable; Micro-
ITT = microbiological intent-to-treat; PTE = post treatment evaluation 
10.8.1 Efficacy Analysis 
The efficacy analysis of interest is an examination of the percentage of subjects with early 
Clinical Response at the EA visit in the TNP-2092 treated group vs the percentage in the 
vancomycin group in the ITT population. This aligns with the FDA’s primary efficacy 
endpoint of interest in ABSSSI studies (reference 1). The number and percentage of 
responders, non-responders and indeterminate responses will be summarized by treatment 
group and an exact 95% CI will be provided for the responder rates in each treatment 
group. The difference between the responder rates will be calculated and the difference 
between rates will be calculated. A summary of reasons for programmatic non-responder 
and indeterminate response at the EA Visit will also be summarized in the ITT population.  
Additional secondary efficacy analyses will also be included for the early clinical response 
at EA for the MITT and Micro-ITT populations. Similarly the reasons for programmatic non-
responder and indeterminate response at the EA Visit will also be provided. 
The Investigator’s assessment of clinical response will be classified as described in the 
“Clinical Outcome Definitions” section of this SAP. The number of subjects with an 


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Investigator’s assessment of ‘clinical improvement’, ‘clinical failure’, and ‘indeterminate’ at 
EOIV will be summarized for both treatment groups in the MITT, Micro-ITT and CE-EOIV 
populations. The number of subjects with an Investigator’s assessment of ‘clinical success’, 
‘clinical failure’, and ‘indeterminate’ at EOT will be summarized for both treatment groups in 
the MITT, Micro-ITT and CE-EOT populations. The Overall Assessment of Clinical 
Response based on the Investigator’s assessment at PTE will be summarized for both 
treatment groups in the MITT, Micro-ITT and CE-PTE populations.   
Note that subjects with an indeterminate response will be excluded from summaries in the 
CE-EOIV, CE-EOT and CE-PTE populations. The 95% CI will be provided for the rate of 
clinical success or improvement for each treatment group. The 95% CI will also be provided 
for the difference in rates of improvement at EOIV in the MITT, Micro-ITT and the CE-EOIV 
populations.  The 95% CI will also be provided for the difference in rates of success at EOT 
in the MITT, Micro-ITT and the CE-EOT populations.  Similarly the 95% CI will be provided 
for the difference in rates of success at PTE in the MITT, Micro-ITT and the CE-PTE 
populations. The reasons for ‘failure’ and ‘indeterminate’ will be summarized as well for the 
clinical responses at EOIV, EOT and PTE for the indicated populations as well as for the 
MITT and Micro-ITT populations. 
The Overall Assessment of Clinical Response based on the Investigator’s assessment at 
PTE will also be summarized by baseline pathogen in the Micro-ITT and ME-PTE 
populations.  The Overall Assessment of Clinical response at PTE will also be summarized 
by the MIC of TNP-2092 and MIC of Vancomycin by treatment group in the Micro-ITT and 
ME-PTE populations. 
10.8.2 Additional Efficacy Analysis 
Early clinical response will be summarized in the ITT, MITT, and Micro-ITT populations, 
excluding subjects who did not receive any study drug. Early clinical response at the EA visit 
will also be summarized by ABSSSI type in the ITT and MITT populations.  Also early 
clinical response at EA will be summarized by pathogen and baseline MIC of TNP-2092 and 
vancomycin, by treatment group in the Micro-ITT and ME-PTE populations.  


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Clinical response at EOIV, EOT and overall assessment of clinical response at PTE will also 
be summarized by ABSSSI type in the MITT and CE-PTE populations.  Also clinical 
response at EOIV, EOT and the overall assessment of clinical response at PTE will be 
summarized by pathogen and baseline MIC of TNP-2092 and vancomycin, by treatment in 
the Micro-ITT and ME-PTE populations. 
10.8.3 Microbiological Outcomes 
The number and percentage of subjects with favorable, unfavorable, and indeterminate 
microbiological responses will be summarized for the overall response at PTE in the micro-
ITT and ME-PTE populations. A 2-sided exact 95% CI will be constructed for the percentage 
of subjects with favorable response and a 95% CI will be calculated for the difference in the 
per-subject favorable microbiological response. 
Microbiologic response will be summarized by baseline pathogen and treatment randomized 
to, for each pathogen isolated at baseline from the primary ABSSSI site or from blood in the 
Micro-ITT and ME-PTE populations.  
A listing will be provided that presents the subjects with a superinfection or a new infection. 
10.9 Safety Analyses 
All safety analyses will be conducted in the Safety population. 
10.9.1 Adverse Events 
Verbatim descriptions of AEs will be coded using Version 21.1 of MedDRA. Summary 
tables will be provided for all treatment-emergent adverse events (TEAEs). A treatment-
emergent AE is defined as any AE that newly appeared, increased in frequency, or 
worsened in severity following initiation of study drug and up through the last study visit or 
evaluation, or an SAE that occurs during or after the first administration of study drug up 
through 30 days after the final administration of study drug.  
An overall summary of AEs will include number and percentage of subjects in each 
treatment group who experienced at least one AE of the following categories: any AE, any 
TEAE, any drug-related TEAE (defined as possibly, probably or definitely related to study 
drug), any severe or life-threatening TEAE, any serious TEAE (SAE), any drug-related 


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SAE, any SAE leading to death, and any TEAE leading to premature discontinuation of 
study drug and any SAE leading to premature study drug discontinuation. 
All remaining adverse event tables will be summarized by treatment group and treatment 
type at start of adverse event: IV, oral, post-oral, and overall. Adverse events associated 
with IV administration, includes all AEs that started between the time of first IV dose and 
before the first oral dose (or last IV dose if subject never switched).  Adverse events 
associated with oral administration, includes all AEs that started between the first oral dose 
to the last oral dose.  Post-oral includes all AEs that started after the last oral dose. The 
number and percentage of subjects reporting a TEAE in each treatment group and 
treatment type will be tabulated by system organ class and preferred term; by system organ 
class, preferred term, and severity (mild, moderate, and severe/life-threatening/death); and 
by system organ class, preferred term, and relationship (unrelated [defined as unrelated or 
unlikely related to study drug] or related to study drug). 
Summary tables will be presented alphabetically by system organ class and preferred term 
within system organ class. For all analyses of TEAEs, if the same AE (based on preferred 
term) is reported for the same subject more than once, the AE is counted only once for that 
preferred term and at the highest severity and strongest relationship to study drug.  
The number and percentage of subjects reporting a SAE and reporting a TEAE leading to 
premature discontinuation of study drug in each treatment group will be summarized by 
system organ class and preferred term. 
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 TNP-2092 group. 
Infusion related AEs (e.g., thrombosis, phlebitis) will be considered AEs of special interest 
and will be summarized by treatment groups over the period these are collected (D1 to 
EOIV visits). 
In addition, all AEs (including non-TEAEs), serious AEs (SAEs), and TEAEs leading to 
study drug discontinuation will be provided in listings.   
10.9.2 Laboratory Values 


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Summaries of laboratory data will include hematology, chemistry, coagulation and C-
reactive protein laboratory parameters. Laboratory parameters will be presented in 
alphabetic order with the following exceptions: differentials of white blood cell (WBC) counts 
will be presented following the WBC results, and chemistry parameters will first be grouped 
by organ class (renal, liver, electrolytes, and other) and presented alphabetically within each 
of these classes, as shown in Table 8. 
Several analyses of the laboratory data will be presented. Descriptive statistics (based on 
standard units) for chemistry, hematology, and coagulation values and the change from 
baseline will be summarized by treatment group at Day 1, Day 2, EA, EOIV, EOT, and PTE 
visits, and for the overall minimum and maximum post-baseline values (which includes 
unscheduled visits). Change from baseline will be calculated for each subject at the 
specified time point as the value at the specified time point minus the baseline value. 
Table 8:  Laboratory Parameters
Renal 
Blood urea nitrogen 
Creatinine 
Liver 
Alkaline phosphatase 
ALT 
AST 
Bilirubin direct 
Bilirubin total 
GGT 
LDH 
Electrolytes 
Bicarbonate 
Calcium 
Chloride 
Magnesium 
Potassium 
Sodium 
Other 
Albumin 
Creatine kinase 
Glucose, nonfasting 
Phosphorus 
Total protein 
Toxicity grade will be determined based on the modified DMID criteria (Appendix B). Shift 
tables will be presented to show the number of subjects with a chemistry or hematology 
laboratory value with a grade of 1, 2, 3 or 4 at baseline versus the worst post-baseline value. 
Post-baseline substantially abnormal clinical laboratory values will also be summarized. For 
hematology, where substantially abnormal is defined as <75% of the lower limit of normal 


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(LLN) (<50% of ANC) for values normal at baseline, and <75% of the LLN (<50% for ANC) 
and of baseline for values abnormal at baseline.  For chemistry substantially abnormal is 
defined as 2 x the upper limit of normal (ULN) for values normal at baseline and 2 x the ULN 
and 2 x the baseline. 
The number and percentage of subjects with elevated liver function assessments will also 
be summarized by visit using the following categories: >3-5 xULN, >5-10 xULN, and >10 
xULN, where ULN is the upper limit of normal. 
A listing will be presented identifying all subject records meeting the substantially abnormal 
hematology, chemistry criteria. This same listing will also contain any abnormal liver function 
results that meet the laboratory criteria of Hy’s law, which is: AST or ALT > 3xULN, alkaline 
phosphatase (ALP) < 2xULN, and total bilirubin > 2 ULN (reference 3).   
A general detailed subject listing of all laboratory data collected during the study will be 
provided. Laboratory values outside normal limits will be identified in the subject data 
listings with flags for low (L) and high (H) as will laboratory values that meet the clinically 
notable thresholds. 
10.9.3 Vital Signs 
Blood pressure (systolic and diastolic), respiration rate, heart rate, and temperature will be 
summarized using descriptive statistics by treatment group at each time point at which they 
were measured. Descriptive statistics of the change from baseline to each post-baseline 
time visit will also be provided.  
The number and percentage of subject abnormal values, identified by the threshold levels 
provided in Table 9, will be summarized by treatment group. Only subjects with both 
baseline and post-baseline values will be summarized for diastolic blood pressure 
increases.  All vital signs will also be provided in by-subject listings.  


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Table 9: Abnormal Vital Threshold Values
Vital Sign 
Threshold 
Diastolic blood pressure 
> 20 mmHg increase from baseline
Systolic blood pressure 
≥ 140 mmHg 
Heart rate 
< 60 beats/min 
Heart rate 
> 120 beats/min
Temperature 
>102.3° F
10.9.4 Electrocardiogram 
ECGs will be recorded in triplicate at each visit, where all three measurements are taken 
within a 15 minute period. The mean of available triplicate values will be calculated and 
reported for each time point. If there are no triplicate values, the mean of the duplicate or 
single value will be used. ECGs are local only (no central ECGs) and the only parameter 
captured is the QT interval using the Fridericia correction formula (QTcF).  Descriptive 
statistics for QTcF as well as the changes from baseline will be presented by treatment 
group at each scheduled visit.   
A distribution showing counts and percentages for the maximum increase post-baseline to 
EOT, and then to PTE, will be provided for QTcF using the following categories:  <0, ≥1 - 
<30 msec, ≥30 - <60 msec, ≥60 - <90 msec, >=90 msec. Actual QTcF visit values will also 
be summarized using counts and percentages for the following categories: ≤ 450, > 450 - ≤ 
480, >480 - ≤ 500, and >500 msec). 
The shift from baseline to each post-baseline visit will be summarized for the overall ECG 
interpretation.  ECG interpretation categories include:  normal, abnormal not clinically 
significant, and abnormal clinically significant.  If there are differences in the interpretation 
for any of the triplicate values at a visit, the most severe interpretation will be summarized. 
A listing of electrocardiogram data will also be provided. 
10.9.5 Physical Examinations 
Physical examination results will be presented in by-subject listings. 


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10.9.6 Pharmacokinetic Analyses 
PK parameters will be calculated from the concentration versus time data using either NCA 
or CM.  Although the final decision will be made once the data are available, based on the 
sampling schedule in Table 21 of the study protocol, CM is more likely to be the applicable 
method.  If CM is used, then the estimated parameters will be: Central compartment 
clearance (CL), intercompartmental clearance (CLD2), volume of the central (V1) and 
peripheral (V2) compartments, distribution and elimination rate constants and their 
associated t½s, steady-state maximum plasma drug concentration (Cmax) and area under the 
curve (AUC), where AUC is over a dosing interval (12 hr).  If NCA is used, then the 
estimated parameters will be: Cmax, time to maximum observed plasma concentration (tmax), 
AUC versus time from time 0 to 12 hours [AUC0-12], and CL [after last dose]. 
Summaries for TNP-2092 blood concentrations and PK parameters will include descriptive 
statistics (including the geometric mean and geometric CV% for all parameters except tmax) 
If NCA is used, then figures for TNP-2092 plasma concentrations will display geometric 
mean concentrations versus time on linear and semi-logarithmic axes.  Nominal blood 
sampling times will be used to calculate the geometric mean concentrations at each time 
point.  Individual subject plasma concentrations versus time will be displayed on linear and 
semi-logarithmic axes.  Boxplots comparing select PK parameters, for Day 1 (first dose) 
versus EOIV (last dose), will also be displayed.   
If CM is used, then individual subjects observed and model-predicted plasma concentrations 
will be plotted on linear and semi-logarithmic axes. 
Subject plasma concentrations for TNP-2092 and PK parameters values will be listed. 
10.9.7 Protocol Deviations 
A listing of all protocol deviations will be provided. Protocol deviations will also be reviewed 
by the Sponsor and categorized into general categories such as: randomization, at least 
one inclusion criterion not met, at least one exclusion criterion met, study procedures/visits 
not done, study visit outside window, noncompliance with dose, and use of prohibited 
medications or treatments. The number of subjects with at least one protocol deviation, the 
number of subjects with a minor protocol deviation, the number of subjects with a major (or 


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important) deviation, and the number of subjects with at least one deviation in each 
category will be presented by treatment group for the ITT Population. A major (or important) 
deviation is defined as one that potentially affects the efficacy and/or safety analyses and 
will be determined by a review by the Sponsor. The study Medical Responsibility Plan and 
the InClin standard operating procedure 02-06.03 (Review and Reporting of Deviations 
from Clinical Protocol) will be followed for the reporting, review, and management of 
protocol deviations. 
11 Deviations from the Protocol 
The SAP and the population definition sections of the protocol specify that the Clinically 
Evaluable populations include subjects who “did not receive any potentially-effective 
systemic antibacterial therapies other than protocol specified study drug(s) between Day 1 
and timepoint for assessment”; however Figure 3 of the protocol incorrectly omits inclusion 
of the words “potentially-effective”. 
Table 10 of the protocol specified that the investigator’s assessment of sustained clinical 
response would be summarized at LTFU.  The investigator’s assessment is not collected at 
LTFU and cannot be summarized. 
12 Reference List 
1. Food and Drug Administration, Center for Drug Evaluation and Research. Guidance
for Industry - Acute Bacterial Skin and Skin Structure Infections: Developing Drugs
for Treatment. Oct 2013. Available at:
http://www.fda.gov/downloads/Drugs/.../Guidances/ucm071185.pdf
2. Miettinen O, Nurminen M.  Comparative analysis of two rates.  Statistics in Medicine.
1985;4(2):213-226.
3. Food and Drug Administration Guidance Document.  Drug- Induced Liver Injury:
Premarketing Clinical Evaluation.  July 2009.  Available at:
https://www.fda.gov/media/116737/download
4. Qin Z.  Protocol Clarification Letter.  April 24, 2019


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Appendix A. Schedule of Events 
Note:  All table and section references in the appendices are referring to the protocol. 
The calendar day on which the first dose of study drug is administered is Day 1.   


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Appendix B. Division of Microbiology and Infectious Diseases Adult Toxicity Table 
The DMID Adult Toxicity Table (November 21, 2007) was modified to exclude the clinical component of the toxicity grading because 
clinical signs and symptoms related to abnormal laboratory values are not collected in this study. In addition, Grade 0 was added to 
the table so that shifts from normal could be analyzed. For toxicity grades based on a multiple of the ULN, the normal range from the 
central laboratory will be applied. For toxicity grades based on fixed values, the grades will be assigned regardless of the normal 
actual range values from the central laboratory. For example, a hemoglobin value of 10.0 gm/dL will be assigned a grade of 1 
toxicity, even if the lower limit of normal from the laboratory was 9.8 gm/dL. 
ENZYMES 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
AST (SGOT) 
<1.25xULN 
1.1-2.0xULN 
2.0-3.0xULN 
3.0-8.0xULN 
>8.0xULN
ALT (SGPT) 
<1.25xULN 
1.1-2.0xULN 
2.0-3.0xULN 
3.0-8.0xULN 
>8.0xULN
GGT 
<1.25xULN 
1.1-2.0xULN 
2.0-3.0xULN 
3.0-8.0xULN 
>8.0xULN
Alkaline Phosphatase 
<1.25xULN 
1.1-2.0xULN 
2.0-3.0xULN 
3.0-8.0xULN 
>8.0xULN
HEMATOLOGY 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin (gm/dL) 
>10.5
9.5-10.5 
8.0-9.4 
6.5-7.9 
<6.5 
Absolute Neutrophil Count 
(count/mm3) 
>1500
1000-1500 
750-999
500-749
<500 
Platelets (count/mm3) 
≥100,000 
75,000-99,999 
50,000-74,999 
20,000-49,999 
<20,000 
WBCs (count/mm3) 
1000-10,999 
11,000-12,999 
13,000-14,999 
15,000-30,000 
>30,000
% Polymorphonuclear Leucocytes 
+ Band Cells
80% 
>80%-90%
>90–95%
>95%
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CHEMISTRY 
Grade 0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hyponatremia (mEq/L) 
>135
130-135
123-129
116-122
<116 
Hypernatremia (mEq/L) 
<146 
146-150
151-157
158-165
>165
Hypokalemia (mEq/L) 
>3.4
3.0-3.4 
2.5-2.9 
2.0-2.4 
<2.0 
Hyperkalemia (mEq/L) 
<5.6 
5.6-6.0 
6.1-6.5 
6.6-7.0 
>7.0
Hypoglycemia (mg/dL) 
65 
55-64
40-54
30-39
<30 
Hyperglycemia (mg/dL) (nonfasting 
and no prior diabetes)* 
<116 
116-160
161-250
251-500
>500
Hypocalcemia (mg/dL) (corrected 
for albumin) 
>8.4
8.4-7.8 
7.7-7.0 
6.9-6.1 
<6.1 
Hypercalcemia (mg/dL) (correct for 
albumin) 
10.5 
10.6-11.5 
11.6-1.5 
12.6-13.5 
>13.5
Hypomagnesemia (mEq/L) 
>1.4
1.4- 1.2 
1.1-0.9 
0.8-0.6 
<0.6 
Hypophosphatemia (mg/dL) 
2.5 
2.0-2.4 
1.5-1.9 
1.0-1.4 
<1.0 
Hyperbilirubinemia (when 
accompanied by any increase in 
other liver function test) 
<1.1xULN 
1.1 - <1.25xULN 
1.25 - <1.5xULN 
1.5 – 1.75xULN 
> 1.75xULN
Hyperbilirubinemia (when other 
liver function are in the normal 
range) 
<1.1xULN 
1.1 - <1.5xULN 
1.5 - <2.0xULN 
2.0 – 3.0xULN 
> 3.0xULN
BUN 
<1.25xULN 
1.25-2.5xULN 
2.6-5xULN 
5.1-10xULN 
>10xULN
Hyperuricemia (uric acid) (mg/dL) 
<7.5 
7.5–10.0 
10.1–12.0 
12.1–15.0 
>15.0
Creatinine 
<1.1xULN 
1.1-1.5xULN 
1.6-3.0xULN 
3.1-6xULN 
>6xULN
* The DMID toxicity table reports hyperglycemia detected in nonfasting specimens obtained from subjects with no prior diabetes.


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Appendix C. Safety Laboratory Tests 


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Appendix D. Prohibited Medications 
No concomitant systemic or topical antibacterial agents are permitted during the study. In 
addition, a list of prohibited concomitant medications is presented below: 


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


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Appendix F. Assessment of Infusion Site Reactions 
Appendix G. Pharmacokinetic Sample Schedule 


CONFIDENTIAL 
Page 1 of 13 
Phase 2, Double-Blind, Randomized, Multicenter, Parallel, Controlled Study to 
Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of TNP-2092 to 
Treat Acute Bacterial Skin and Skin Structure Infection in Adults   
Protocol: PJI001-02 
EVALUABILITY REVIEW PROCESS 
Version 1.0, 10September2019 


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Table of Contents 
1.0 
INTRODUCTION..............................................................................................................3 
2.0 
DEFINITIONS OF PATIENT POPULATIONS ............................................................3 
3.0 
REVIEW TEAM ................................................................................................................3 
4.0 
OVERVIEW OF PROCESS FOR DETERMINING EVALUABILITY .....................3 
4.1 
ITT AND SAFETY POPULATIONS ..............................................................................3 
4.2 
MICRO-ITT POPULATION ...........................................................................................3 
4.3 
CE POPULATIONS ..........................................................................................................4 
5.0 
DATA REVIEW.................................................................................................................7 
6.0 
PROGRAMMING AND REVIEW DETAILS ...............................................................8 
7.0 
APPENDIX A ...................................................................................................................13 


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1.0 
INTRODUCTION 
This document presents the Evaluability Review Process for protocol PJI001-02, “Phase 2, 
Double-Blind, Randomized, Multicenter, Parallel, Controlled Study to Evaluate the Safety, 
Tolerability, Pharmacokinetics, and Efficacy of TNP-2092 to Treat Acute Bacterial Skin and 
Skin Structure Infection in Adults.”  The evaluability review process and the detailed patient 
population definitions provided in the Statistical Analysis Plan (SAP) are finalized prior to 
determination of patient evaluability.  
2.0 
DEFINITIONS OF PATIENT POPULATIONS 
Detailed definitions of the patient analysis populations are provided in the SAP. 
3.0 
REVIEW TEAM 
One evaluability review team (ERT) will be organized and will consist at a minimum of the 
study Medical Monitors (Paul Eckburg and Zhijie Qin). A study biostatistician will be in charge 
of consolidating comments and will facilitate the review meetings.  Other sponsor staff may 
participate in the review as required.  The review team will review isolates for pathogen 
determination and patient inclusion in the micro-ITT population and also clinical data for 
inclusion in or exclusion from the CE-EOIV, CE-EOT, and CE-PTE populations, including a 
review of the programmatic assessment of patient inclusion in or exclusion from the CE-EOIV, 
CE-EOT, and CE-PTE populations.  
Review of data and determination of evaluability will be performed in a blinded manner prior to 
database lock.  All pathogens must be identified and finalized prior to unblinding.  A subject’s 
CE population classification will be considered locked at database unblinding and may only be 
changed programmatically for those subjects who did not receive the correct study drug (i.e., 
randomized study drug) or for those subjects who were unblinded during the study.  
4.0 
OVERVIEW OF PROCESS FOR DETERMINING EVALUABILITY 
4.1 
ITT and Safety Populations 
Inclusion in the Intent-to-Treat (ITT), modified Intent-to-Treat (MITT), Pharmacokinetic (PK), 
Safety, and Microbiologically Evaluable (ME-PTE) populations is determined programmatically 
and does not require review by the ERT.  
4.2 
Micro-ITT Population 
Inclusion in the Micro-ITT population will be determined programmatically using pathogen 
determinations provided by the review team.  The review team will be provided with an EXCEL 
spreadsheet that will include the specimen source (ABSSSI site specimen, blood), the date, time, 
and study day (relative to the date of the first dose of study drug) of specimen collection, local 
laboratory specimen number, central laboratory isolate accession number, local laboratory genus 


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and species identification, central laboratory genus and species identification, final identification 
of genus and species, the programmed pathogen flag, and the programmed baseline pathogen 
flag. 

The programmed pathogen flag will have a value of “Yes” if any of the pathogens
identified in Table 2 of the SAP are identified.  When there is a central laboratory result,
the central laboratory result will be used.  When there is only a local laboratory result, the
local result will be used.  If there are discrepancies between the local and central
laboratory, then a manual override can be used during the review process to specify the
pathogen.  The programmed baseline pathogen flag will be programmed similarly and
will have a value of “Yes” if the pathogen was identified at baseline.

The programmed pathogen flag will have a value of “No” if the organism is identified in
Table 3 of the SAP or there is no organism identified (no growth).  The programmed
baseline pathogen flag will be programmed similarly.

All other cases will be reviewed manually.
The review team will confirm the pathogen status of isolates whose pathogen status could not be 
programmatically determined according to the rules specified above and in Section 6 of the SAP 
and will confirm the final identification of genus and species for those cases where there is a 
discrepancy between the local and central laboratory identification of genus and species. Further 
details regarding the programming of the EXCEL spreadsheet are provided in Section 6.0 of this 
document. 
4.3 
CE Populations 
The review team will be provided with an EXCEL spreadsheet that will include an indication of 
whether or not the patient met or did not meet each criterion for inclusion in or exclusion from 
the CE-EOIV, CE-EOT, and CE-PTE populations listed in the SAP and in Table 1, below, along 
with all systemic or topical antibacterial medications received on or after the date of the first 
dose of study drug through the PTE assessment date.  For those patients who must be reviewed 
on a case-by-case basis, the review team will review the spreadsheet to determine whether the 
patient should be included in the CE-EOIV, CE-EOT, and CE-PTE populations.  The decision 
will be noted on the EXCEL spreadsheet.  If it is determined that a patient should be excluded 
from the CE populations, the reason(s) for exclusion from the CE populations will also be 
provided.  Further details regarding the programming of the EXCEL spreadsheet are provided in 
Section 6.0 of this document. 
Table 1 summarizes the eligibility criteria for the CE populations.  Inclusion in or exclusion from 
the CE populations will be determined programmatically for those criteria that always result in 
inclusion in or exclusion from the CE populations.   


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Table 1: Eligibility Criteria for CE Populations 
Criteria 
Number Criteria 
Determined 
Programmatically 
Reviewed 
Manually 
1 
Met the minimal clinical disease criteria 
for ABSSSI described in the study 
Inclusion Criteria (See Inclusion criteria 
in Protocol- Inclusion Criteria 2a- 2c, 3, 
4a-4f, 5a-d).   
X 
2 
Receive at least 80% of expected IV 
doses based on length of IV therapy 
X 
3 
Did not have any major protocol 
deviation including but not limited to: 
Violated Exclusion 4 (prior
administration of systemic
antibacterial therapy within 96
hours before randomization)
Received the wrong study drug
or unblinded before the
timepoint of assessment for
reasons other than safety
X 
X 
4 
Did not receive any potentially-
effective systemic or topical 
antibacterial therapies other than 
protocol specified study drug(s) 
between Day 1 and EOIV (CE-EOIV), 
EOT (CE-EOT) or PTE (CE-PTE), 
except in cases of treatment failure.   
X 
X 
5 
For the CE-EOIV analysis population: 
a.
Completed the CE-EOIV Visit
within 1 calendar day of the last
dose of IV drug (+1 day) [i.e.,
within 48 hours of the last dose
of study drug].
b. Must not have had a clinical
response of indeterminate based
X 


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Table 1: Eligibility Criteria for CE Populations 
Criteria 
Number Criteria 
Determined 
Programmatically 
Reviewed 
Manually 
on the Investigator’s assessment 
at EOIV.  
For the CE-EOT analysis population: 
c.
Completed the EOT Visit within
1 calendar day of the last dose
of study drug (+1 day) [i.e.,
within 48 hours of the last dose
of study drug].
d. Must not have had a clinical
response of indeterminate based
on the Investigator’s assessment
at EOT
For the CE-PTE analysis population: 
a. Completed the 7-14 after the
EOT visit.  If the EOT visit is
out of the study window, then
the PTE visit must still be within
7-14 days of the EOT visit.  If
the EOT visit is missed, then the
PTE visit must be within 7-14
days of the last dose of study
drug unless the patient was
considered a failure at EOT.
b. Must not have had a clinical
response of indeterminate based
on the overall assessment of
clinical response (based on the
Investigator assessment at PTE)
unless the subject was a failure
at EOT.


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Table 1: Eligibility Criteria for CE Populations 
Criteria 
Number Criteria 
Determined 
Programmatically 
Reviewed 
Manually 
6 
Subjects who are clinical failures at 
EOIV, EOT or PTE (by overall 
assessment at PTE), but don’t have at 
least 3 doses of IV study drug are not 
included in the CE-EOIV, CE-EOT or 
CE-PTE populations respectively.   
X 
7 
Subjects who are clinical successes at 
EOT or PTE (overall assessment at 
PTE) but have fewer than 4 doses of IV 
study drug are not included in the CE-
EOT or CE-PTE, populations, 
respectively. Subjects who have clinical 
improvement at EOIV but have fewer 
than 4 doses of IV study drug are not 
included in the CE-EOIV population. 
X 
Some subjects may only receive IV study drug. For these subjects, their end of treatment (EOT) 
visit information is recorded in the EOT visit only and not the EOIV visit within study database. 
Efficacy data at EOT will be duplicated for EOIV and these subjects will be summarized at both 
visits within study tables and the evaluability spreadsheet. Similarly, these subjects will be 
considered for inclusion in both the CE-EOT and CE-EOIV populations. 
5.0 
DATA REVIEW 
EXCEL spreadsheets will be provided to the review team prior to database soft-lock and once 
after database soft-lock.  If a data query results in a change to any of the data fields used for 
either pathogen determination, inclusion in or exclusion from the patient populations, then re-
determination (either programmatically or by the review teams) of the patient’s population 
classifications and/or pathogen review will be conducted. The patient study population 
classification will not be locked or finalized until there are no outstanding queries that affect 
population determination for the patient. 


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The review process will result in two final spreadsheets, the first with final pathogen 
determinations and the second with final population determinations, including the reasons 
patients are not included in the CE-EOIV, CE-EOT, and CE-PTE populations.  The pathogen 
determination, CE population flags, and reviewer comments from the spreadsheets will be 
included as part of the final clinical analysis datasets as detailed in Section 6.0. These 
spreadsheets will also be converted into datasets and will be merged with the study ADaM 
datasets, as appropriate. 
6.0 
PROGRAMMING AND REVIEW DETAILS 
EXCEL spreadsheets will be generated by InClin for the following relevant data: 
1. Isolates for pathogen determination
2. All of the relevant clinical evaluability criteria flags with final CE-EOIV, CE-EOT, and
CE-PTE flags for inclusion in or exclusion from the CE populations
Each of these spreadsheets will be sent to the review team for review. The following details 
provide a description of each step of the evaluability process and the associated data spreadsheets 
(see Figure 1 for a detailed algorithm).  All data spreadsheets, as well as associated SAS datasets, 
are saved on the InClin server. 
Pathogen Determination 

The project programmer will generate an EXCEL spreadsheet that includes the patient
ID,  specimen source (ABSSSI site specimen or blood), nominal visit identifier (e.g.,
screening, the date, time, and study day (relative to the date of the first dose of study
drug) of specimen collection, method of collection (e.g. needle aspiration, deep swab,
etc), central laboratory isolate accession number, local laboratory genus and species
identification, central laboratory genus and species identification, final identification of
genus and species, a final genus and species override column, the programmed pathogen
flag  (“PATHPROG” heading), and the programmed baseline pathogen flag
(“BPATHPRG” heading), and override columns for both the pathogen and baseline
pathogen flags.  In addition, placeholder columns will be provided in the spreadsheet for
reviewer comments (“PATHCOMM” heading), reviewer initials (“PATHINIT” heading),
and date of review (“PATHDATE” heading).

The review team will independently confirm the pathogen status of isolates whose genus
and species are not identified in the SAP and the final identification of genus and species
for those cases where there is a discrepancy between the local and central laboratory
identification of genus and species, and will indicate his/her agreement or disagreement
in the following columns:

'Final Genus & species - Override' (F_ORGREV)

'Programmed Pathogen Flag - Override'(PATHREV)

'Programmed Baseline Pathogen Flag - Override' (BPATHREV)
The review team will also provide comments in the comment column (“PATHCOMM” ) 

The manual pathogen determinations will then be sent to the project statistician.


TenNor Therapeutics Ltd.  
Evaluability and Pathogen Review 
Process for Protocol PJI001-02 
Confidential
Page 9 of 13 
The project statistician will consolidate the independent evaluations from each member 
of the ERT and will highlight any discrepancies. This consolidated list of discrepant 
pathogen determinations will be sent back to the ERT for reconciliation. 

The ERT will review and discuss the discrepancies and provide the project statistician
with the resolved final pathogen determinations.

The EXCEL spreadsheet with the final suitable specimen and pathogen determinations
will be saved as a PDF and archived.

The EXCEL spreadsheet with the final pathogen determinations will be sent to the
project programmer and a new final pathogen flag (“PATHYN”) will be generated taking
into consideration the “PATHPROG” and “PATHREV” columns and saved as a SAS
dataset.  A new final baseline pathogen flag (“BPATHYN”) will be generated taking into
consideration the “BPATHPROG” and “BPATHREV” columns and saved as a SAS
dataset.   In cases where the programmatic pathogen determination (“PATHPROG”/
“BPATHPROG”) flags are discrepant with the reviewer pathogen determination flags
(“PATHREV”/ “BPATHREV”), the reviewer pathogen flags will be used for
determination of the final pathogen flags (“PATHYN”/“BPATHYN”).  The SAS dataset
will also contain as variables final comments from the ERT.
CE Population Determinations 

The project programmer will generate another EXCEL spreadsheet that includes the
patient ID with all the flags for each CE criterion from Table 1 and a programmatically-
determined CE population flags (“CEEOIVPRG”, “CEEOTPRG”, and “CEPTEPRG”
headings).  In addition, placeholder columns with the following headings will be
provided in the spreadsheet for ERT determinations of  the CE population
(“CEEOIVREV” ,“CEEOTREV”, and “CEPTEREV“ headings), confounding
concomitant antibiotics (“CABXREV” heading), CABXPROG (confounding antibiotic
override) and any comments regarding the yes/no determination of CE population
(“CEEOIVCOM” ,“CEEOTCOM”, and “CEPTECOM” headings), reviewer initials
(“REVINIT” heading), and date of review (“REVDATE” heading).

The above spreadsheet will be sent to ERT members for independent review. All of the
CE criteria will be reviewed and each member of the ERT will independently review the
programmatically-determined CE population flags (“CEEOIVPRG” ,“CEEOTPRG”, and
“CEPTEPRG” columns) and will indicate his/her agreement or disagreement with the
programmatically-determined CE population flags in the “CEEOIVREV”,
“CEEOTREV”, and “CEPTEREV“ columns as well as provide comments in the
“CECOMM” column.  Each member of the ERT will also review concomitant systemic
antibiotics and the programmatic determination of whether or not the concomitant
antibiotics are considered potentially confounding of the clinical outcome (in the
“CABXPROG” column) and will indicate his/her agreement with the programmatically
determined confounding concomitant antibiotic flag in the “CABXREV” column.

The project statistician will consolidate the independent evaluations from each member
of the ERT and will highlight any discrepancies. This consolidated list of discrepant CE
determinations will be sent back to the ERT for reconciliation.


TenNor Therapeutics Ltd.  
Evaluability and Pathogen Review 
Process for Protocol PJI001-02 
Confidential
Page 10 of 13 

The ERT will review and discuss the discrepancies and provide the project statistician
with the resolved final CE population determinations.

The EXCEL spreadsheet with the final CE population determinations will be saved as a
PDF and archived.

The ERT-reviewed spreadsheet will be sent to the project programmer and new final CE
population flags (“CEEOIVFL”, “CEEOTFL” and “CEPTEFL”) will be generated by the
programmer taking into consideration the “CEEOIVPRG”/“CEEOTPRG”/
“CEPTEPRG” and “CEEOIVREV” /“CEEOTREV”/ “CEPTEREV” columns and saved
as a SAS dataset.  In cases where the programmatic CE population flags) and the
reviewer CE population flags) are discrepant, the reviewer CE population flags will be
used as the final CE population flags (“CEEOIVFL” ,“CEEOTFL”, and “CEPTEFL”).
The SAS dataset will also contain as variables within the dataset as well as final
comments from the committee review of the discrepant CE determinations, along with
the reviewers’ initials and date of review.  The final CE population flags (“CEEOIVFL”,
“CEEOTFL”, and “CEPTEFL”) will be used by the programmer for final implementation
of inclusion or exclusion of patients into/from CE populations.

A manual review of the final CE population determinations in the SAS dataset versus the
PDF of the final CE population determinations will be conducted by the project
statistician.
The pathogen review EXCEL spreadsheet will be created as specified, below: 
1. Merge local specimen culture and serology information (mb1o.sas7bdat, mb2o.sas7bdat)
with the central laboratory microbiology data (jmimicrodata.sas7bdat) by subject ID, date,
and central laboratory accession number.  Pathogens are then programmatically determined
using Tables 2 and 3 of the Statistical Analysis Plan.
Program 
Pathogens.sas 
Input data 
SAS datasets: mb1o, mb2o, jmimicrodata and EXCEL 
spreadsheet: “organism list.xls”   
Output 
PJI001-02_PathReview_Date.xls 
Location 
F:\Biometrics\SASFiles\TenNor\ PJI001-02 \data\Excel 
Document type 
EXCEL spreadsheet 
2. Pathogen status and final pathogen identification reviewed and confirmed by the ERT.
Output 
PJI001-02_ PathReview_Date.xls, reviewed and 
completed by ERT. 
Location 
F:\Biometrics\SASFiles\TenNor\ PJI001-02 \data\excel 
Document type 
EXCEL spreadsheet 
The CE review EXCEL spreadsheet will be created as specified, below: 


TenNor Therapeutics Ltd.  
Evaluability and Pathogen Review 
Process for Protocol PJI001-02 
Confidential
Page 11 of 13 
1. A SAS dataset will be generated that will include the programmed clinical evaluable (CE)
population flags along with all CE population criteria.  It is then converted to a spreadsheet
for clinical review.
Program 
CE_Criteria.sas 
Input data 
RAW SAS datasets: IE, IEP  
SDTM datasets: DM, SV, FA, EX, suppEX, DV, CM, 
suppCM 
Output 
PJ1001-02 _EvalReview_Date.xls 
Location 
F:\Biometrics\SASFiles\TenNor\ PJI001-02 \data\excel 
Document type 
EXCEL spreadsheet 
2. The reviewed spreadsheet with CE population overrides and comments will be sent back to
InClin.
Output 
PJ1001-02 _EvalReview_Date.xls 
Location 
F:\Biometrics\SASFiles\TenNor\PJI001-02 \data\excel 
Document type 
EXCEL spreadsheet 


TenNor Therapeutics Ltd.  
Evaluability and Pathogen Review 
Process for Protocol PJI001-02 
Confidential
Page 12 of 13 
Figure 1: Process and flow of spreadsheets used for pathogen and evaluability 
determinations. 
Pathogen Review Spreadsheet 
 (To Identify Baseline and Post-Baseline Pathogens) 
Spreadsheet Name:  
PJI001-02_PathReview_Date.xls 
CE Criteria Review Spreadsheet  
(To Confirm CE Populations) 
Spreadsheet Name:  
PJI001-02_EvalReview_Date.xls 
ERT reviews Pathogen Review Spreadsheet and 
specifies pathogen determination override(s), 
comments containing reason for override(s), and 
final identification of organisms 
ERT review CE Criteria Review Spreadsheet 
and specifies CE population override(s) and 
comments containing reason for override(s) 
Create SAS datasets from the Pathogen Review and CE 
Criteria Review Spreadsheets 
Pathogen Review and CE Criteria Review Spreadsheets 
are read into ADaM domains and used in combination 
with all other study datasets to create all 
tables/figures/listings specified in the SAP. 


Te n N or T her a pe utics Lt d.   
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Pr ocess  f or Pr ot oc ol P JI 0 0 1 -0 2  
C o nfi de nti al
P a g e 1 3  o f 1 3  
7. 0  
A P P E N DI X  A  
PJI 0 0 1 -0 2 _ Pat h Re vie w _ Date. xls  
PJI 0 0 1 -0 2 _ E v a lRe vie w _ Date. xls  
C CI