Conditions: Gonorrhea
Keywords: Urogenital Gonorrhea Gepotidacin Neisseria gonorrhoeae Efficacy Phase 3
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 628
Healthy volunteers: no

Brief summary:
This is a phase III, randomized, multicenter, open-label study which will be performed to evaluate efficacy and safety of oral Gepotidacin compared to intramuscular (IM) ceftriaxone plus oral azithromycin for the treatment of uncomplicated urogenital infection caused by Neisseria gonorrhoeae (N. gonorrhoeae) in adolescent and adult participants. In this study, participants will be randomly assigned to receive either oral gepotidacin or IM ceftriaxone plus oral azithromycin.

Detailed description:

Arms:
arm 1: Participants will receive Gepotidacin orally at the study site during the Baseline (Day 1) visit followed by self-administration of a second oral dose as an outpatient 10 to 12 hours after the first dose. arm 2: Participants will receive a single IM dose of Ceftriaxone plus a single oral dose of Azithromycin at the study site during the Baseline (Day 1) visit.

Interventions: intervention 1: Gepotidacin intervention 2: Ceftriaxone intervention 3: Azithromycin
Intervention descriptions: intervention 1: Gepotidacin will be administered as 3000 milligram (mg) oral dose (4 X 750 mg tablets) at the study site followed by 3000 mg oral dose (4 X 750 mg tablets) as an outpatient. Each dose should be taken after food consumption and with water. intervention 2: Ceftriaxone is available as sterile powder for reconstitution. It will be administered as one 500-mg IM dose at the study site. intervention 3: Azithromycin will be administered as 1000 mg oral dose (2 X 500 mg tablets) at the study site. Dose should be taken after food consumption and with water.

Protocol document:
Prot_000.pdf: 
TMF-16433266 
CONFIDENTIAL 
GSK group of companies 
 
BTZ116577 
 
1 
TITLE PAGE 
Protocol Title:  A Phase III, Randomized, Multicenter, Open-Label Study in Adolescent 
and Adult Participants Comparing the Efficacy and Safety of Gepotidacin to Ceftriaxone 
Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by 
Neisseria gonorrhoeae 
Protocol Number:  BTZ116577 / Amendment 3 
Short Title:  Phase III, Comparator-Controlled, Efficacy and Safety Study of 
Gepotidacin in the Treatment of Uncomplicated Urogenital Gonorrhea; Efficacy of 
Antibacterial Gepotidacin Evaluated (EAGLE-1) 
Compound 
Number: 
GSK2140944 
Sponsor Name and Legal Registered Address:  
GSK Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Sponsor Contact Address: 
GSK 
1250 South Collegeville Road 
PO Box 5089 
Collegeville, PA 19426-0989 
USA 
Medical monitor name and contact information can be found in local study contact 
information documents 
Regulatory Agency Identifying Numbers: 
IND 111885 
EudraCT 2018-001780-23 
Protocol Amendment Number:  3 
Sponsor Signatory: 
Salim Janmohamed, BSc, MBBS (Hons), FRCP, FACE 
Clinical Development Lead 
GSK  
Pharmaceutical Research and Development 
Approval Date: 10 Aug 2023 
Copyright 2019 the GSK group of companies. All rights reserved. Unauthorized copying 
or use of this information is prohibited.


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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date of Issue 
DNG Number 
Amendment 3 
10 Aug 2023 
TMF-16433266 
Amendment 2 
16 December 2022 
TMF-15064686 
Amendment 1 
14 December 2021 
TMF-14342295 
Original Protocol 
12 April 2019 
2017N317989_00 
Amendment 3 (10 Aug 2023) 
This global amendment is considered to be non-substantial. 
Overall rationale for the current Amendment:  
This global amendment revised the definition of the Microbiological ITT (micro-ITT) 
population to align with the reporting and analysis plan; reference to EUCAST 
breakpoints was deleted from this population definition in accordance with regulatory 
agency feedback. The amendment includes wording edits based on the above changes. 
Minor editorial edits have been done. Reference list has been updated as one reference 
was erroneously missed. 
 List of main change in the protocol and their rationale: 
Section # and Name 
Description of Change 
Brief Rationale 
10.3 Populations for 
Analyses  
The definition of the 
Microbiological Intent-to-Treat 
Population has been updated. 
Revisions were made to support 
the planned efficacy analyses 
per the reporting and analysis 
plan.  
11 References 
Reference list for erroneously 
missed reference has been 
updated  
Reference list has been updated 
as one reference was 
erroneously missed. 
 


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TABLE OF CONTENTS 
PAGE 
1. 
SYNOPSIS ............................................................................................................... 6 
2. 
SCHEDULE OF ACTIVITIES ................................................................................. 10 
3. 
INTRODUCTION .................................................................................................... 13 
3.1. 
Study Rationale .......................................................................................... 13 
3.2. 
Background ................................................................................................ 14 
3.3. 
Benefit/Risk Assessment ............................................................................ 15 
3.3.1. 
Risk Assessment ......................................................................... 16 
3.3.2. 
Benefit Assessment ..................................................................... 23 
3.3.3. 
Overall Benefit:Risk Conclusion ................................................... 23 
4. 
OBJECTIVES AND ESTIMANDS/ENDPOINTS ..................................................... 24 
5. 
STUDY DESIGN .................................................................................................... 30 
5.1. 
Overall Design ............................................................................................ 30 
5.2. 
Number of Participants ............................................................................... 33 
5.3. 
Participant and Study Completion ............................................................... 33 
5.4. 
Scientific Rationale for Study Design .......................................................... 33 
5.5. 
Dose Justification ........................................................................................ 35 
6. 
STUDY POPULATION ........................................................................................... 37 
6.1. 
Inclusion Criteria ......................................................................................... 37 
6.2. 
Exclusion Criteria ........................................................................................ 38 
6.3. 
Lifestyle Restrictions ................................................................................... 41 
6.3.1. 
Meals and Dietary Restrictions .................................................... 41 
6.4. 
Screen Failures........................................................................................... 41 
7. 
TREATMENTS ....................................................................................................... 42 
7.1. 
Treatments Administered ............................................................................ 42 
7.2. 
Dose Modification ....................................................................................... 43 
7.3. 
Method of Treatment Assignment ............................................................... 43 
7.4. 
Blinding ....................................................................................................... 44 
7.5. 
Preparation/Handling/Storage/Accountability .............................................. 44 
7.6. 
Treatment Compliance ................................................................................ 45 
7.7. 
Concomitant Therapy.................................................................................. 45 
7.7.1. 
Permitted Medications and Nondrug Therapies ........................... 46 
7.7.2. 
Prohibited Medications and Nondrug Therapies........................... 46 
7.8. 
Treatment After the End of the Study .......................................................... 47 
8. 
DISCONTINUATION CRITERIA ............................................................................. 48 
8.1. 
Discontinuation of Study Treatment ............................................................ 48 
8.1.1. 
Liver Chemistry Evaluation Criteria .............................................. 48 
8.1.2. 
QTc Stopping Criteria .................................................................. 49 
8.1.3. 
Gastrointestinal Evaluation Criteria .............................................. 50 
8.2. 
Withdrawal From the Study ......................................................................... 50 
8.3. 
Lost to Follow-Up ........................................................................................ 51 
9. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 51 


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9.1. 
Efficacy Assessments ................................................................................. 54 
9.1.1. 
Bacteriology Samples for Culture ................................................. 54 
9.1.2. 
NAAT Assay ................................................................................ 55 
9.2. 
Adverse Events........................................................................................... 57 
9.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 57 
9.2.2. 
Method of Detecting AEs and SAEs ............................................. 58 
9.2.3. 
Follow-up of AEs and SAEs ......................................................... 58 
9.2.4. 
Regulatory Reporting Requirements for SAEs ............................. 58 
9.2.5. 
Adverse Events of Special Interest .............................................. 59 
9.2.6. 
Cardiovascular and Death Events ................................................ 59 
9.2.7. 
Pregnancy ................................................................................... 59 
9.3. 
Treatment of Overdose ............................................................................... 59 
9.4. 
Safety Assessments ................................................................................... 60 
9.4.1. 
Physical Examinations ................................................................. 60 
9.4.2. 
Vital Signs .................................................................................... 60 
9.4.3. 
Electrocardiograms ...................................................................... 61 
9.4.4. 
Clinical Safety Laboratory Assessments ...................................... 61 
9.5. 
Pharmacokinetics ....................................................................................... 62 
9.6. 
Pharmacodynamics .................................................................................... 62 
9.7. 
Genetics ..................................................................................................... 62 
9.8. 
Biomarkers ................................................................................................. 62 
9.9. 
Health Economics or Medical Resource Utilization and Health 
Economics .................................................................................................. 62 
10. STATISTICAL CONSIDERATIONS ........................................................................ 63 
10.1. 
Statistical Hypothesis .................................................................................. 63 
10.2. 
Sample Size Determination ........................................................................ 63 
10.2.1. 
Justification of Sample Size ......................................................... 63 
10.2.2. 
Sample Size Sensitivity ................................................................ 64 
10.3. 
Populations for Analyses ............................................................................ 65 
10.4. 
Statistical Analyses ..................................................................................... 66 
10.4.1. 
General Considerations ............................................................... 66 
10.4.2. 
Efficacy Analyses ......................................................................... 66 
10.4.3. 
Safety Analyses ........................................................................... 67 
10.4.4. 
Other Analyses ............................................................................ 68 
10.5. 
Interim Analysis .......................................................................................... 68 
10.6. 
Data Monitoring Committee or Other Review Board ................................... 68 
11. REFERENCES ....................................................................................................... 69 
12. APPENDICES ........................................................................................................ 71 
12.1. 
Appendix 1: Abbreviations and Trademarks ................................................ 71 
12.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 74 
12.3. 
Appendix 3: Study Governance Considerations .......................................... 76 
12.4. 
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 82 
12.5. 
Appendix 5: Division of Microbiology and Infectious Diseases Adult 
Toxicity Tables for Adverse Event Assessment........................................... 87 
12.6. 
Appendix 6: Contraceptive Guidance and Collection of Pregnancy 
Information .................................................................................................. 95 
12.7. 
Appendix 7: Genetics .................................................................................. 98 


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12.8. 
Appendix 8: Liver Safety: Required Actions and Follow-up 
Assessments .............................................................................................. 99 
12.9. 
Appendix 9: Additional Guidance on Permitted and Prohibited 
Medications and Crediblemeds.org ........................................................... 103 
12.10. Appendix 10: Clostridium Difficile Testing Procedure and Algorithm ......... 106 
12.11. Appendix 11: COVID-19 Protocol Information ........................................... 107 
12.11.1. Overall Rationale for this Appendix ............................................ 107 
12.11.2. Study Procedures During the COVID-19 Pandemic ................... 107 
12.12. Appendix 12: Protocol Amendment History ............................................... 109 
 


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1. 
SYNOPSIS 
Protocol Title:  A Phase III, Randomized, Multicenter, Open-Label Study in Adolescent 
and Adult Participants Comparing the Efficacy and Safety of Gepotidacin to Ceftriaxone 
Plus Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by 
Neisseria gonorrhoeae 
Short Title:  Phase III, Comparator-Controlled, Efficacy and Safety Study of 
Gepotidacin in the Treatment of Uncomplicated Urogenital Gonorrhea; Efficacy of 
Antibacterial Gepotidacin Evaluated (EAGLE-1) 
Rationale: 
Gonorrhea is the second most prevalent bacterial sexually transmitted infection globally 
and remains an important clinical and public health problem throughout the world. A 
variety of antimicrobial agents have been used over the years for the treatment of 
gonorrhea; however, effective treatment options for gonorrhea have diminished rapidly 
because of the emergence and worldwide spread of antimicrobial resistance to many 
drugs previously used or considered first line. Gepotidacin is a first-in-class, novel 
triazaacenaphthylene antibacterial that has demonstrated in vitro activity against 
Neisseria gonorrhoeae (NG) with gepotidacin MIC90 values of 0.25 and 1 µg/mL for 
ciprofloxacin-susceptible and -resistant strains, respectively. In a Phase II study of 
urogenital gonorrhea caused by NG, microbiological success (bacterial eradication) was 
demonstrated for 97% and 95% of participants treated orally with single doses of 
1500 and 3000 mg gepotidacin, respectively. This Phase III study aims to evaluate oral 
gepotidacin compared to intramuscular (IM) ceftriaxone plus oral azithromycin, a 
currently recommended treatment regimen, for the treatment of uncomplicated urogenital 
infection caused by NG in adolescent and adult participants. 


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Objectives and Estimands/Endpoints: 
Objectives 
Endpoints 
Primary 
• 
To evaluate the efficacy of oral 
gepotidacin compared to IM ceftriaxone 
plus oral azithromycin to treat 
participants with uncomplicated 
urogenital gonorrhea caused by NG 
• 
Culture-confirmed bacterial eradication of 
NG from the urogenital body site (i.e., 
microbiological success) at the TOC 
(Day 4 to 8) Visit  
Secondary 
• 
To evaluate the efficacy of oral 
gepotidacin compared to IM ceftriaxone 
plus oral azithromycin to treat 
participants with rectal gonorrhea caused 
by NG 
• 
To evaluate the efficacy of oral 
gepotidacin compared to IM ceftriaxone 
plus oral azithromycin to treat 
participants with pharyngeal gonorrhea 
caused by NG 
• 
To evaluate the safety and tolerability of 
oral gepotidacin compared to IM 
ceftriaxone plus oral azithromycin 
• 
Culture-confirmed bacterial eradication of 
NG from the rectal body site (i.e., 
microbiological success) at the TOC 
(Day 4 to 8) Visit 
• 
Culture-confirmed bacterial eradication of 
NG from the pharyngeal body site (i.e., 
microbiological success) at the TOC 
(Day 4 to 8) Visit 
• 
Treatment-emergent adverse events and 
serious adverse events and change from 
baseline results for clinical laboratory 
tests and vital sign measurements 
Note: Exploratory objectives are described in the main protocol text. 
Estimands: 
The primary clinical question of interest is: What is the treatment effect on the culture-
confirmed bacterial eradication of NG from the urogenital body site (i.e., microbiological 
success) at the TOC (Day 4 to 8) Visit after treatment with oral gepotidacin compared to 
IM ceftriaxone plus oral azithromycin in participants with uncomplicated urogenital 
gonorrhea and have confirmed NG isolated from baseline culture of their urogenital 
specimen, regardless of treatment discontinuation for any reason.  
The primary estimand is described by the following attributes: 
• 
Population: Participants with uncomplicated urogenital gonorrhea caused by culture-
confirmed NG.  
• 
Treatment condition: Gepotidacin 2×3000 mg versus ceftriaxone 500 mg plus 
azithromycin 1 g, regardless of adherence. 
• 
Variable: Microbiological success: Participants with culture-confirmed bacterial 
eradication of NG from the urogenital body site (i.e., urogenital microbiological 
success) at the TOC (Day 4 to 8) Visit without the participant receiving other 
systemic antimicrobials before this visit. 


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• 
Summary measure: Difference in proportions (microbiological success rate in the 
gepotidacin treatment group - ceftriaxone plus azithromycin treatment group).  
• 
Intercurrent events: 
− Participants who receive systemic antimicrobials before the TOC Visit will be 
considered microbiological failures (composite strategy). 
− For study treatment discontinuation, the data will be analyzed as collected 
(treatment policy strategy). 
Components of estimands for all secondary endpoints are provided in Table 3.  
The rationale for a treatment policy intercurrent event strategy of study treatment 
discontinuation is that interest lies in the treatment effect irrespective of whether the full 
course of treatment was taken or not, this is reflective of how patients may be treated in 
clinical practice. 
The rationale for using a composite strategy for the intercurrent event of antimicrobial 
use is because usage could affect bacterial culture response; thus, a conservative 
approach has been adopted and if a participant receives systemic antimicrobials before 
the TOC Visit, the participant will be assumed to be a microbiological failure. Note: The 
intercurrent event of antimicrobial use is not applicable for the safety estimands. 
Overall Design: 
• 
BTZ116577 is a Phase III, open-label (sponsor-blinded), parallel-group, multicenter, 
comparator-controlled, noninferiority study in adolescent and adult participants 
comparing the efficacy and safety of oral gepotidacin to IM ceftriaxone plus oral 
azithromycin in the treatment of uncomplicated urogenital gonorrhea caused by NG. 
• 
Participants will be stratified by sex and sexual orientation combination and age; and 
will be randomly assigned to receive either oral gepotidacin or IM ceftriaxone plus 
oral azithromycin. 
• 
Appropriate safety and microbiological assessments will be conducted at the 
Baseline (Day 1) Visit and repeated at the TOC (Day 4 to 8) and Follow-up (Day 14 
to 21) Visits. 
• 
“Test-of-Cure” microbiological success will be defined by body site (i.e., urogenital 
and, as appropriate, pharyngeal and/or rectal) as culture-confirmed bacterial 
eradication of NG observed at the TOC (Day 4 to 8) Visit. 


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Number of Participants: 
Approximately 620 participants will be screened and randomized to achieve 
approximately 400 participants with culture-confirmed urogenital gonorrhea in the 
Microbiological Intent-to-Treat (micro-ITT) Population, for an estimated total of 
200 participants per treatment group in the micro-ITT Population. Enrollment will 
continue until the target number of participants in the micro-ITT Population has been 
reached. 
Treatment Groups and Duration: 
• 
Participants will receive 1 of the following treatments: 
− Gepotidacin: 3000 mg administered orally at the study site during the Baseline 
(Day 1) Visit followed by self-administration of a second oral 3000-mg dose as 
an outpatient 10 to 12 hours after the first dose; however, for participants who 
weigh <50 kg or have moderate renal impairment, the second dose should be 
taken approximately 12 hours after the first dose). (Note: Each dose should be 
taken after food consumption and with water to assist with tolerability.) 
− Ceftriaxone plus azithromycin: A single IM 500-mg dose of ceftriaxone plus a 
single oral 1-g dose of azithromycin administered at the study site during the 
Baseline (Day 1) Visit. (Note: Azithromycin should be taken after food 
consumption and with water.) 
• 
The duration of study participation is approximately 21 days with 3 planned study 
visits: 
− Baseline (Day 1) Visit 
− TOC (Day 4 to 8) Visit 
− Follow-up (Day 14 to 21) Visit 
Data Monitoring or Other Committee: Yes; an internal GSK Safety Review Team will 
monitor blinded safety data and an internal Microbiology Review Team will monitor 
blinded microbiological data instream. No external data monitoring review committees 
are planned for the study. 
 


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2. 
SCHEDULE OF ACTIVITIES 
Table 1 
Schedule of Activities 
Visita 
Baseline 
TOCb 
Follow-upc 
Early Withdrawal 
Study Day 
1 
4 to 8 
14 to 21 
NA 
Procedure 
Predose 
Postdose 
NA 
NA 
NA 
Written informed consent/assent 
X 
 
 
 
 
IRT – Screening module 
X 
 
 
 
 
Inclusion and exclusion criteria 
X 
 
 
 
 
Participant demography 
X 
 
 
 
 
Participant social and sexual historyd 
X 
 
 
 
 
Medical/surgical history 
X 
 
 
 
 
Diagnosis of presumptive uncomplicated urogenital gonorrhea 
X 
 
 
 
 
Bacteriology samplese 
X 
 
X 
X 
X 
NAAT assay samplesf 
X 
 
X 
X 
X 
Physical examination (including height and weight at Baseline only)g 
X 
 
X 
 
 
12-lead electrocardiogramh 
X 
 
 
 
 
Vital sign measurementsi 
X 
 
X 
 
 
Hematology, chemistry, and urinalysis 
X 
 
X 
 
 
Serology (hepatitis B and C and HIV)j 
X 
 
 
 
 
Urine pregnancy testk 
Xk 
 
X 
 
X 
Drug and alcohol screen 
X 
 
 
 
 
IRT – Randomization module 
X 
 
 
 
 
Administer oral gepotidacinl 
 
Xl 
 
 
 
Administer IM ceftriaxone plus oral azithromycinm 
 
Xm 
 
 
 
Sexual history since last visitd 
 
 
X 
X 
X 
Serious adverse eventsn 
X 
X 
X 
X 
X 
Adverse eventso 
 
X 
X 
X 
X 
Concomitant medication review 
X 
X 
X 
X 
X 
Schedule TOC and Follow-up Visits 
Xp,q 
 
Xq 
Xp 
 
Treatment for CT and/or Mgen infectionr 
 
 
X 
X 
X 
Genetic samples 
X 
 
 
 
 
CT=Chlamydia trachomatis; HIV=human immunodeficiency virus; IM=intramuscular; IRT; interactive response technology; Mgen=Mycoplasma genitalium; NA=not applicable; 
NAAT=nucleic acid amplification test; TOC=Test-of-Cure. 


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a. 
For all study visits, to minimize the amount of time that participants spend at the clinic, eConsent may be utilized and remote collection of study-related data may be obtained 
as described in the Study Reference Manual. Thus, some visit data may be collected through a combination of telemedicine and on-site visits. Collection of information via 
telemedicine will be performed only where local regulations permit.  
b. 
TOC (Day 4 to 8) Visit: Participants will be instructed to return to the study site within 3 to 7 days after study treatment administration. This visit may occur earlier if 
participants experience an adverse event. 
c. 
Participants will be instructed to return to the study site from Day 14 to 21 for a Follow-up Visit. The investigator and/or study site staff should make every effort to ensure the 
participant returns for this visit. If the participant is unable to return to the study site, the visit assessments may be completed via telephone, with the exception of 
assessments requiring sample collection for laboratory testing. 
d. 
Refer to the Study Reference Manual for information to collect for social and sexual history. 
e. 
See Table 2 for collection of bacteriology samples. Also refer to the laboratory manual. 
f. 
See Table 2 for collection of NAAT assay samples. Also refer to the laboratory manual.  
g. 
A complete physical examination will be performed at the Baseline Visit and a gonorrhea-focused examination will be performed at the TOC Visit (see Section 9.4.1). Height 
and weight will only be measured and recorded at the Baseline Visit (before dosing). 
h. 
See Section 6.2 for electrocardiogram exclusion criterion for participants aged ≥12 to <18 years. For additional details see Section 8.1.2 and Section 9.4.3.  
i. 
Take measurement of temperature, blood pressure, and pulse rate. See Section 9.4.2. 
j. 
If serology testing was performed within 3 months prior to the first dose of study treatment and results were positive, testing at Baseline is not required. If testing was 
performed within 3 months and any result was negative, testing at Baseline is required. 
k. 
For women of childbearing potential, a negative urine pregnancy test is sufficient for eligibility. See Appendix 6 for Baseline urine test sensitivity requirements and associated 
contraception requirements. 
l. 
During the Baseline Visit, participants randomly assigned to gepotidacin will receive their first oral dose (3000 mg) at the study site. Participants will self-administer their 
second dose (3000 mg) as an outpatient 10 to 12 hours after the first dose; however, for participants who weigh <50 kg or have moderate renal impairment, the second dose 
should be taken approximately 12 hours after the first dose). See Section 7.1. Each dose should be taken after food consumption and with water to assist with tolerability. 
Participants will be contacted to confirm that they took their second gepotidacin dose. See Section 7.6. 
m. During the Baseline Visit, participants randomly assigned to ceftriaxone plus azithromycin will receive a single IM dose of ceftriaxone (500 mg) plus a single oral dose of 
azithromycin (1 g). See Section 7.1. Azithromycin should be taken after food consumption and with water. 
n. 
Record serious adverse events from the time of consent/assent in order to fulfill international regulatory requirements. 
o. 
Record adverse events from the time of the first dose of study treatment. 
p. 
Confirm return day/time for the TOC and Follow-up Visits. 
q. 
Previsit reminder: Study site staff will contact the participant 24±4 hours before the respectively scheduled Baseline (if applicable), TOC, or Follow-up Visit. 
r. 
Participants who tested positive for CT and/or Mgen per NAAT results at the Baseline Visit should be treated per local standard of care at or after the TOC Visit or at the 
Follow-up Visit (if treatment has not already been initiated), as required, after all study procedures at the visit have been completed. 
s. 
Collect sample only if the participant has a signed consent/assent specific for this purpose. The Baseline Visit is the recommended time to collect the sample; however, it can 
be collected at any time during the study. 


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Table 2 
Collection of Bacteriology and NAAT Microbiological Specimens 
Visit 
Baseline 
TOCa 
Follow-up 
Early Withdrawal 
Study Day 
1 
4 to 8 
14 to 21 
NA 
Collection Type 
Anatomical Siteb – Organism  
Predose 
NA 
NA 
NA 
Bacteriology sample collectionb 
Urogenital – NGc  
X 
X 
 
X 
Pharyngeal – NGd 
X 
X 
Xe 
X 
Rectal – NGd 
X 
X 
 
X 
NAAT assay sample collectionf 
Urogenital – NG and CTg  
X 
Xh 
 
X 
Urogenital – Mgeng  
X 
 
Xi 
X 
Pharyngeal – NG and CTj 
X 
X 
Xk 
X 
Rectal – NG and CTj 
X 
X 
 
X 
CT=Chlamydia trachomatis; Mgen=Mycoplasma genitalium; NA=not applicable; NAAT=nucleic acid amplification test; NG=Neisseria gonorrhoeae; TOC=Test-of-Cure. 
a. 
Any participant that withdraws before TOC should have all bacteriology and NAAT assay collections performed as indicated at the TOC Visit. 
b. 
Multiple swab specimens and types may need to be obtained from each anatomical site; refer to the laboratory manual. 
c. 
Collect a pretreatment urogenital swab specimen from all participants for Gram stain (males and females), bacterial culture, and in vitro susceptibility testing at Baseline. At 
TOC, a urogenital swab specimen will be collected for Gram stain, bacterial culture, and in vitro susceptibility testing. Note: All urogenital swab specimens will be processed 
for Gram stain testing following inoculation of the culture plates. 
d. 
Pretreatment rectal and pharyngeal swab specimens for bacterial culture and in vitro susceptibility testing will be obtained from participants who are willing to provide such 
specimens, regardless of known exposure. At TOC, swab specimens will be collected from pharyngeal and/or rectal sites that were collected at Baseline for bacterial culture 
and in vitro susceptibility testing. Note: None of the rectal or pharyngeal swab specimens will be processed for Gram stain testing. 
e. 
At Follow-up, pharyngeal swab specimens will be obtained for bacterial culture and in vitro susceptibility testing from participants who had a positive NAAT assay for 
pharyngeal NG at both Baseline and TOC. Results from the NAAT assay will be available to the study sites by the Follow-up Visit.  
f. 
See the laboratory manual for local versus central laboratory details and the number and type of specimens to collect. 
g. 
Pretreatment baseline urogenital specimens will be obtained from all participants for detection of NG, Mgen, and CT by NAAT. At Baseline, while detection of NG and CT by 
NAAT may be performed using the same urogenital sample, 2 separate samples must be obtained (1 for the local laboratory and 1 for the central laboratory). 
h. 
Urogenital specimens will be obtained from all participants for detection of NG and CT by NAAT at the TOC Visit.  
i. 
At Follow-up, a urogenital specimen will be collected for the detection of Mgen only by NAAT from participants who had a positive NAAT assay for Mgen at Baseline. Results 
from the NAAT assay will be available to the study sites by the Follow-up Visit.  
j. 
Pretreatment baseline pharyngeal and rectal specimens for detection of NG and CT by NAAT will be obtained from participants who are willing to provide such specimens, 
regardless of known exposure. At TOC, a specimen will be collected from pharyngeal and/or rectal sites that were collected at Baseline.  
k. 
At Follow-up, a pharyngeal specimen will be collected for detection of NG and CT by NAAT from participants whose NAAT assay had the presence of nucleic acid for NG at 
both Baseline and TOC. NAAT assay results will be available to the study sites by the Follow-up Visit.  
 


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3. 
INTRODUCTION 
Gepotidacin (GSK2140944) is a novel, bactericidal, first-in-class triazaacenaphthylene 
antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action 
[Gibson, 2019; Bax, 2010] and equally and independently binds to 2 different type II 
topoisomerase enzymes [Oviatt, 2022]. 
This provides activity against most strains of Escherichia coli and Staphylococcus 
saprophyticus, including isolates resistant to current antibiotics [Biedenbach, 2016; 
Mushtaq, 2019]. Due to the equal and independent binding at both enzymes, mutations in 
both enzymes are needed to significantly affect gepotidacin susceptibility [Oviatt, 2022]. 
Gepotidacin has been evaluated in Phase II studies for the treatment of ABSSSIs, 
uncomplicated urogenital gonorrhea, and uncomplicated UTI. Phase III studies are 
ongoing to evaluate oral gepotidacin for the treatment of uncomplicated urogenital 
gonorrhea and uncomplicated UTI (acute cystitis). 
Gepotidacin selectively inhibits bacterial DNA replication by interacting in a unique way 
on the GyrA subunit of bacterial DNA gyrase and the ParC subunit of bacterial 
topoisomerase IV. This interaction appears to be highly specific to bacterial 
topoisomerases as evidenced by weak in vitro inhibition of human topoisomerase IIα, 
supporting the selective activity of gepotidacin against the bacterial target. The novel 
mode of action of this new class antibacterial affords in vitro activity against most target 
pathogens resistant to established antibacterials, including fluoroquinolones. 
3.1. 
Study Rationale 
This study is being conducted based on the need to identify new and effective antibiotic 
treatment options for gonorrhea as antimicrobial resistance continues to rise worldwide 
(see Section 3.2) and based on the results of an open-label, dose-ranging Phase II study of 
gepotidacin for the treatment of adults with uncomplicated urogenital gonorrhea caused 
by NG. 
Study BTZ116576 was a Phase II, randomized, multicenter, open-label, dose-ranging 
study evaluating the efficacy, safety, and tolerability of gepotidacin therapy in adult 
participants with uncomplicated urogenital gonorrhea caused by NG. Participants were 
administered single oral doses (1500 or 3000 mg) of gepotidacin on Day 1 with a 
Test-of-Cure (TOC) (Day 4 to 8) Visit. A total of 69 participants (1500 mg: 
30 participants; 3000 mg: 39 participants) were included in the Microbiologically 
Evaluable Population. The primary aim of the study was to provide evidence for 
95% bacterial eradication of urogenital NG in the Microbiologically Evaluable 
Population at the TOC Visit (cure rate) and to exclude the null hypothesis that the cure 
rate was 80% or less. Microbiological success was achieved by 97% and 95% of 
participants (lower 1-sided exact 95% confidence interval [CI] bound, 85.1% and 84.7%, 
respectively) in the 1500- and 3000-mg treatment groups, respectively. Microbiological 
success (bacterial eradication) was also evaluated for pharyngeal and rectal NG, with 
1 of the 2 participants with pharyngeal NG and all 3 participants with rectal NG 
achieving microbiological success. In Study BTZ116576, gepotidacin was active in vitro 


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against the 69 baseline urogenital NG isolates recovered, with a gepotidacin minimum 
inhibitory concentration (MIC) range of ≤0.06 to 1 µg/mL and 50th and 90th percentile 
minimum inhibitory concentration (MIC50 and MIC90) values of 0.12 and 0.5 µg/mL, 
respectively. Additional study results demonstrated that some baseline urogenital NG 
isolates were resistant to ciprofloxacin, penicillin, and/or tetracycline. 
This Phase III study (BTZ116577) aims to evaluate oral gepotidacin compared to 
intramuscular (IM) ceftriaxone plus oral azithromycin, a currently recommended 
treatment regimen, for the treatment of uncomplicated urogenital infection caused by NG 
in adolescent and adult participants. 
3.2. 
Background 
Gonorrhea is the second most prevalent bacterial sexually transmitted infection globally 
and remains an important clinical and public health problem throughout the world. In 
2012, an estimated 78 million cases of gonorrhea occurred among 15- to 49-year-olds 
worldwide with a global incidence rate of 19 per 1000 females and 24 per 1000 males 
[WHO, 2016]. Gonococcal infections following sexual and perinatal transmission are a 
major source of morbidity worldwide [Barry, 2009]. Infections can involve cervicitis, 
proctitis, urethritis, pelvic inflammatory disease, and pharyngitis. Complications include 
infertility, ectopic pregnancy, chronic pelvic pain, adverse outcomes of pregnancy, 
disseminated gonococcal infection, and increased susceptibility to and transmission of 
human immunodeficiency virus [Workowski, 2008; Barry, 2009]. 
A variety of antimicrobial agents have been used over the years for the treatment of 
gonorrhea; however, effective treatment options for gonorrhea have diminished rapidly 
because of the emergence and worldwide spread of antimicrobial resistance to many 
drugs previously used or considered first line, i.e., penicillins, narrow-spectrum 
cephalosporins, tetracyclines, macrolides, and fluoroquinolones [Workowski, 2008; 
Barry, 2009]. At the start of the present study, the recommended treatment for urogenital 
gonorrhea per the European Union, United States (Centers for Disease Control and 
Prevention [CDC]), and World Health Organization (WHO) guidelines is an IM injection 
of ceftriaxone combined with a single oral dose of azithromycin [Bignell, 2013; CDC, 
2015; WHO, 2016]. As of Dec 2020, the CDC now recommends an IM injection of 
ceftriaxone based on body weight and an oral regimen of doxycycline if chlamydia 
infection has not been ruled out [CDC, 2021]. While these guidelines may help delay the 
emergence of cephalosporin-resistant gonorrhea by using combination antibacterial 
therapy, they are not able to eliminate this impending threat. Therefore, drug-resistant 
NG has been labeled at a threat level of urgent by the CDC and as a high priority by 
WHO; both agencies have urged scientists and private sector drug developers to prioritize 
the identification and study of new, effective antibiotic treatment options for gonorrhea 
[CDC, 2019; CDC, 2015; WHO, 2017]. 


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Gepotidacin is a first-in-class, novel triazaacenaphthylene antibacterial that has 
demonstrated in vitro activity against NG with gepotidacin MIC90 values of 0.25 and 
1 µg/mL for ciprofloxacin-susceptible and -nonsusceptible strains, respectively (see 
Section 4.2.1.3 in the investigator’s brochure [IB]). In a Phase II study of uncomplicated 
urogenital gonorrhea caused by NG, microbiological success (bacterial eradication) was 
demonstrated for 97% and 95% of participants treated orally with single doses of 
1500 and 3000 mg gepotidacin, respectively. With its unique ability to selectively inhibit 
bacterial DNA replication by a means not utilized by any currently approved human 
therapeutic agent, gepotidacin warrants further study in order to address an unmet 
medical need by providing a new and effective oral treatment option for gonorrhea.  
A detailed description of the chemistry, pharmacology, efficacy, and safety of 
gepotidacin is provided in the IB. Details on the active comparator in this study, 
ceftriaxone plus azithromycin, may be found in locally approved prescribing information. 
3.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events (AEs) may be found in the IB for gepotidacin and in 
locally approved prescribing information for ceftriaxone and azithromycin. 
 


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3.3.1. 
Risk Assessment 
Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Gepotidacin (GSK2140944) 
Cardiovascular Effects 
Based on nonclinical data, cardiovascular 
effects were reversible increase in heart rate 
and blood pressure (dog and monkey); 
reversible 10 to 21 msec (4% to 9%) increase 
in QTc (monkey); and at the highest dose, a 
reversible 2 to 3 msec (6% to 8%) increase in 
QRS (monkey). 
Based on a thorough QTc clinical study, 
gepotidacin may cause mild, reversible heart 
rate effects and QT prolongation. 
In a thorough QTc study, infusion of gepotidacin 
at doses of 1000 and 1800 mg over 2 hours 
caused a mild increased heart rate effect of 
approximately 6 to 10 bpm and QT prolongation 
measured as ∆∆QTcF of 12 to 22 msec. The QT 
prolongation evolved during the infusion and was 
quickly reversed over 2 hours after the end of the 
infusion (see Section 5.2.6 and Section 6 of the 
IB). 
In Phase I and II studies, 
concentration-dependent QT prolongation has 
been observed during clinical trials with 
gepotidacin; however, this increase has not 
translated into medically significant QTc values or 
changes from baseline (QTcF >500 msec or 
change from baseline >60 msec) or 
cardiovascular safety concerns.  
In Phase I and II studies, gepotidacin did not have 
a clinically relevant effect on cardiac conduction 
(PR and QRS intervals). 
See Section 6.2 for excluded cardiac 
conditions. Close monitoring of clinical 
parameters and AEs (Section 2, Table 1) will 
be conducted, and treatment monitoring and 
evaluation criteria (Section 8.1.2) will be 
utilized to mitigate cardiovascular effects. 
Participants taking medications known to 
increase QT or potent CYP3A4 inhibitors will 
be excluded (Section 7.7.2). 
See also the Hepatic and Renal sections 
within this table below. 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Gastrointestinal Effects 
Based on nonclinical data, gastrointestinal 
effects were mild ulceration of the nonglandular 
mucosa and minimal erosion and/or mural 
inflammation of the glandular mucosa in 
stomach (rat, oral study); moderate cecal 
ulceration and minimal colonic erosion (rat, IV 
study); and vomiting (dog). 
Lower gastrointestinal effects (soft stools, 
flatulence, and diarrhea) are among the most 
common AEs reported in gepotidacin clinical 
studies. Nausea and vomiting AEs have also 
been commonly observed in gepotidacin 
clinical studies. 
See also the Acetylcholinesterase Inhibition 
section within this table below. 
Clostridium difficile-associated diarrhea has been 
observed in clinical trials with gepotidacin. 
See Section 6.2 for excluded medical 
conditions. Close monitoring of clinical 
parameters and AEs (Section 2, Table 1) will 
be conducted to mitigate and assess 
gastrointestinal effects.  
Suspected C. difficile infection will be 
managed according to a prespecified 
algorithm provided in Appendix 10. 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Acetylcholinesterase Inhibition 
In vitro testing showed gepotidacin to be a 
rapidly reversible inhibitor of 
acetylcholinesterase in the clinical plasma 
concentration range. 
Based on clinical data, caution should be used 
in participants who have a condition requiring 
treatment with anticholinergic medications or 
who have certain medical conditions that may 
be exacerbated by the acetylcholinesterase 
inhibition activity of gepotidacin. 
Increased cholinergic effects can potentially be 
associated with more severe symptoms including 
atrioventricular block, seizure/convulsions, 
bronchospasm, and vasovagal syncope. No 
causal relationship between these events and the 
use of gepotidacin has been established during 
clinical trials to date. 
Adverse events possibly consistent with 
acetylcholinesterase inhibition, including diarrhea, 
nausea, vomiting, gastrointestinal cramping and 
pain, dyspnea, bradycardia, lacrimation, 
salivation, dysarthria, and diaphoresis/sweating 
have been reported during clinical trials with 
gepotidacin.  
The majority of these AEs have been mild and 
transient and have been reported in clinical trials 
with comparable Cmax levels expected in this 
study. 
Participants who have medical conditions or 
require medications that may be impacted by 
inhibition of acetylcholinesterase will be 
excluded from participation in this study. See 
Section 6.2, for excluded medical conditions 
and Section 7.7.2, Prohibited Medications and 
Nondrug Therapies, for prohibited 
medications. 
Close monitoring of clinical parameters and 
AEs will be conducted to assess effects 
potentially related to acetylcholinesterase 
inhibition (Section 2, Table 1). 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Hepatic Effects 
In preclinical studies, increases in ALT, GLDH, 
alkaline phosphatase, and total bilirubin were 
observed in some rat studies of varying 
exposure. 
 
Elevations in ALT have occurred in a few 
participants with pre-existing hepatitis C infection, 
but none were felt related to study treatment. The 
type and pattern of elevation in liver 
transaminases observed has not been suggestive 
of an adverse effect of gepotidacin and none were 
considered related to study treatment. 
A substantial increase in Cmax and AUC and 
decrease in clearance was observed in volunteer 
participants with severe hepatic impairment. 
Participants with severe hepatic impairment 
are excluded from Phase III trials. See 
Section 6.2 for excluded medical conditions. 
Monitoring and stopping criteria liver events 
have been implemented. 
Renal Effects 
In preclinical trials, mild to moderate tubular 
degeneration was noted in the rat and 
proteinuria in the dog. Proteinuria was also 
observed in humans. 
No clinical evidence of renal toxicity has been 
seen in clinical trials to date.  
A substantial increase in Cmax and AUC and 
decrease in clearance was observed in severe 
renal impairment/ESRD participants not on 
hemodialysis and in ESRD participants requiring 
hemodialysis (note: gepotidacin may have been 
administered at any time other than when 
receiving dialysis). 
Participants with severe renal 
impairment/ESRD (including those who may 
require dialysis) are excluded from Phase III 
trials. See Section 6.2 for excluded medical 
conditions. Monitoring criteria have been 
implemented. 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Reproductive System Effects 
Preclinical studies demonstrated that 
gepotidacin was not genotoxic and no 
drug-related malformations were observed. 
Although positive in vitro findings for 
clastogenicity, consistent with a mechanism 
related to mammalian topoisomerase II 
inhibition were found, in vivo data from rat 
micronucleus and COMET assays suggest that 
gepotidacin does not pose a genotoxic hazard 
to humans. 
Gepotidacin effects on embryofetal 
development were limited to decreased fetal 
weights for male and female fetuses in rats and 
decreased fetal weights and increased fetal 
resorptions (fetal deaths) in mice, both at 
maternally toxic doses. These occurred at 
clinically relevant exposures (65 µg.h/mL in rat 
and 35 µg.h/mL in mouse). 
There are no data on the use of gepotidacin in 
pregnant women.  
Gepotidacin is not recommended in pregnant 
or nursing mothers. Pregnancy testing 
requirements in this study minimize the risk of 
exposure to a fetus. See Appendix 6 for 
contraceptive measures and for required 
pregnancy testing. 


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Other 
Ceftriaxone 
Intramuscular administration of ceftriaxone may 
be associated with local injection site reactions, 
including pain, warmth or induration, or 
tenderness. 
Some of the risks summarized for gepotidacin 
also apply to ceftriaxone, including the occurrence 
of gastrointestinal effects (diarrhea or loose 
stools) and the need to monitor for C. difficile-
associated diarrhea. Other adverse effects 
include hepatic (AST and ALT elevations) and 
hematologic (eosinophilia, thrombocytosis, and 
leukopenia). 
Additionally, ceftriaxone should not be 
reconstituted using diluents containing calcium, 
such as Ringer’s solution or Hartmann’s solution, 
because a precipitate can form.  
Refer to the locally approved ceftriaxone 
prescribing information for specific details relating 
to ceftriaxone. 
Close monitoring of clinical parameters and 
AEs (Section 2, Table 1) will be conducted, 
and treatment monitoring and evaluation 
criteria (Section 8.1.1) will be utilized to 
mitigate hepatic effects. 
Participants with a history of sensitivity to 
ceftriaxone, or components thereof, will not be 
allowed to enroll in the study (Section 6.2). 
Participant’s medical history will be carefully 
evaluated for a history of hypersensitivity. 
Suspected C. difficile infection will be 
managed according to a prespecified 
algorithm provided in Appendix 10. 
Precautions related to ceftriaxone solution 
preparation are included in Section 7.5 and 
summarized in detail in the Study Reference 
Manual.  


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Potential Risk of Clinical Significance 
Summary of Data/Rationale for Risk  
Mitigation Strategy 
Azithromycin 
Some of the risks summarized for gepotidacin 
also apply to azithromycin, including the 
occurrence of gastrointestinal effects (diarrhea or 
loose stools) and the need to monitor for 
C. difficile-associated diarrhea and prolongation of 
the QT interval.  
Azithromycin may also exacerbate muscle 
weakness in participants with myasthenia gravis. 
Other adverse effects include allergic and skin 
reactions and hepatotoxicity, which may be 
serious (including fatal).  
Close monitoring of clinical parameters and 
AEs (Section 2, Table 1) will be conducted. 
Suspected C. difficile infection will be 
managed according to a prespecified 
algorithm provided in Appendix 10. 
See Section 6.2 for excluded cardiac 
conditions. Monitoring and evaluation criteria 
(Section 8.1.2) will be utilized to mitigate 
cardiovascular effects. In addition, 
participants taking QT-prolonging drugs or 
strong CYP3A4 inhibitors will be excluded. 
Participants with myasthenia gravis will be 
excluded. 
Participants with a history of sensitivity to 
azithromycin, erythromycin, and any 
macrolide or ketolide drug will be excluded 
(Section 6.2). Participant’s medical history will 
be carefully evaluated for a history of 
hypersensitivity. Participants with a history of 
cholestatic jaundice or hepatic dysfunction 
associated with prior use of azithromycin will 
be excluded (Section 6.2). Treatment 
monitoring and evaluation criteria (Section 
8.1.1) will be utilized to mitigate hepatic 
effects. 
bpm=beats per minute; ABSSSI=acute bacterial skin and skin structure infection; AE=adverse event; ALT=alanine aminotransferase; AST=aspartate aminotransferase; AUC=area 
under the drug concentration-time curve; Cmax=maximum concentration; CYP3A4=cytochrome P450 enzyme 3A4; ECG=electrocardiogram; ESRD=end-stage renal disease; 
GLDH=glutamate dehydrogenase; IC50=inhibitory concentration inhibiting 50% of microbial isolates; IB=investigator’s brochure; IV=intravenous; ΔΔQTcF=placebo-corrected change 
from baseline in corrected QT interval using the Fridericia formula; QTc=corrected QT interval; QTcB=QT interval corrected for heart rate according to Bazett; QTcF=interval corrected 
for heart rate according to Fridericia.  


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3.3.2. 
Benefit Assessment 
Given the results of the previous Phase II study in adult participants with uncomplicated 
urogenital gonorrhea and the demonstrated in vitro activity of gepotidacin against NG, 
including ciprofloxacin-resistant strains (see Section 3.1 and Section 4.2.1.1 in the IB), as 
well as human safety data and the pharmacokinetic (PK) profile, it is anticipated that 
gepotidacin will benefit participants with uncomplicated urogenital gonorrhea.  
The active comparator in this study is ceftriaxone plus azithromycin, both of which are 
marketed antibiotics that have demonstrated effectiveness for eradication of NG and 
Chlamydia trachomatis (CT), respectively (refer to locally approved ceftriaxone and 
azithromycin prescribing information). Participants randomly assigned to this treatment 
group are also expected to experience treatment benefits. 
It is expected that gepotidacin will have a similar efficacy profile to ceftriaxone plus 
azithromycin and may have a better tolerability profile, as gepotidacin will be 
administered orally and ceftriaxone will be administered IM, possibly resulting in fewer 
treatment-related AEs associated with oral gepotidacin dose administration.  
Overall, all participants in this study will not only receive routine medical monitoring for 
uncomplicated urogenital gonorrhea, but they will also receive heightened monitoring, 
including detection and treatment of any co-occurring infections caused by CT or 
Mycoplasma genitalium (Mgen), to ensure safety when participating in a clinical study. 
3.3.3. 
Overall Benefit:Risk Conclusion 
The ability of NG to develop resistance to antimicrobials has complicated the 
management of treatment for gonorrhea, leading to an urgent need for new treatment 
options [CDC, 2015; WHO, 2016]. However, even in the face of increasing drug 
resistance to existing agents, few new antibiotics with novel mechanisms of action are 
being developed. Gepotidacin selectively inhibits bacterial DNA replication by a means 
not utilized by any currently approved human therapeutic agent. Clinical results from a 
Phase II study in adult participants showed that gepotidacin is an effective treatment for 
uncomplicated urogenital gonorrhea, including most ciprofloxacin-resistant strains. 
Gepotidacin, therefore, represents a potential new oral treatment option for gonorrhea and 
an opportunity to address an unmet medical need.  
None of the potential or identified risks seen to date in participants dosed with 
gepotidacin preclude further clinical development. Mitigation strategies have been 
implemented to promptly identify and appropriately address risks in order to protect 
participant safety and to better characterize the safety profile of the study treatments (see 
Section 3.3.1). Furthermore, an internal GSK Safety Review Team (SRT) will monitor 
blinded safety data instream. Careful safety monitoring should also identify any emerging 
safety issues for gepotidacin and contribute to the benefit-risk profile of ceftriaxone plus 
azithromycin. 
Taking into account the measures taken to minimize risk to participants participating in 
this study, the potential risks identified in association with gepotidacin and ceftriaxone 
plus azithromycin are justified by the anticipated benefits that may be afforded to 
participants with uncomplicated urogenital gonorrhea caused by NG. 


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4. 
OBJECTIVES AND ESTIMANDS/ENDPOINTS 
Objectives 
Endpoints 
Primary 
• 
To evaluate the efficacy of oral 
gepotidacin compared to IM ceftriaxone 
plus oral azithromycin to treat participants 
with uncomplicated urogenital gonorrhea 
caused by NG 
• 
Culture-confirmed bacterial eradication 
of NG from the urogenital body site (i.e., 
microbiological success) at the TOC 
(Day 4 to 8) Visit  
Secondary 
• 
To evaluate the efficacy of oral 
gepotidacin compared to IM ceftriaxone 
plus oral azithromycin to treat participants 
with rectal gonorrhea caused by NG 
• 
To evaluate the efficacy of oral 
gepotidacin compared to IM ceftriaxone 
plus oral azithromycin to treat participants 
with pharyngeal gonorrhea caused by NG 
• 
To evaluate the safety and tolerability of 
oral gepotidacin compared to IM 
ceftriaxone plus oral azithromycin 
• 
Culture-confirmed bacterial eradication 
of NG from the rectal body site (i.e., 
microbiological success) at the TOC 
(Day 4 to 8) Visit 
• 
Culture-confirmed bacterial eradication 
of NG from the pharyngeal body site 
(i.e., microbiological success) at the 
TOC (Day 4 to 8) Visit 
• 
Treatment-emergent AEs and serious 
AEs (SAEs) and change from baseline 
results for clinical laboratory tests and 
vital sign measurements 
Exploratory 
• 
To assess the clearance or persistence of 
NG nucleic acid (by nucleic acid 
amplification test [NAAT] assay) from 
urogenital specimens for oral gepotidacin 
compared to IM ceftriaxone plus oral 
azithromycin 
• 
Urogenital NG NAAT results at the TOC 
(Day 4 to 8) Visit 
• 
To assess the clearance or persistence of 
NG nucleic acid (NAAT assay) from 
pharyngeal specimens for oral 
gepotidacin compared to IM ceftriaxone 
plus oral azithromycin 
• 
Pharyngeal NG NAAT results at the 
TOC (Day 4 to 8) and Follow-up (Day 14 
to 21) Visits, where only participants 
who did not receive other systemic 
antimicrobials at or after the TOC (Day 4 
to 8) Visit will be evaluated at the 
Follow-up Visit 
• 
To assess the clearance or persistence of 
NG nucleic acid (NAAT assay) from rectal 
specimens for oral gepotidacin compared 
to IM ceftriaxone plus oral azithromycin 
• 
Rectal NG NAAT results at the TOC 
(Day 4 to 8) Visit 


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Objectives 
Endpoints 
• 
To assess the clearance or persistence of 
Mgen nucleic acid (by NAAT assay) from 
urogenital specimens for oral gepotidacin 
compared to IM ceftriaxone plus oral 
azithromycin 
• 
Urogenital Mgen NAAT results at the 
Follow-up (Day 14 to 21) Visit, where 
only participants who did not receive 
other systemic antimicrobials at or after 
the TOC (Day 4 to 8) Visit will be 
evaluated 
• 
To evaluate the microbiological 
characteristics and antimicrobial 
susceptibility profile of NG from 
urogenital, pharyngeal, or rectal 
specimens 
• 
Gram stain (urogenital specimens only), 
bacterial culture, and in vitro 
susceptibility test results from urogenital, 
pharyngeal, or rectal specimens at the 
Baseline (Day 1), TOC (Day 4 to 8), and 
Follow-up (Day 14 to 21) Visits, as data 
permit 
Estimands: 
The primary clinical question of interest is: What is the treatment effect on the 
culture-confirmed bacterial eradication of NG from the urogenital body site (i.e., 
microbiological success) at the TOC (Day 4 to 8) Visit after treatment with oral 
gepotidacin compared to IM ceftriaxone plus oral azithromycin in participants with 
uncomplicated urogenital gonorrhea and have confirmed NG isolated from baseline 
culture of their urogenital specimen, regardless of treatment discontinuation for any 
reason. 
Prespecified estimands with related attributes are presented in Table 3 for the primary 
and key secondary objectives. 
 


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Table 3 
Estimands 
Estimand 
Category  
Estimand 
Variable/Endpoint 
Population 
Treatment Condition 
Summary Measure 
Intercurrent Event Strategy 
Primary Objective: To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with uncomplicated 
urogenital gonorrhea caused by NG 
Primary  
Microbiological success: 
Participants with 
culture-confirmed bacterial 
eradication of NG from the 
urogenital body site (i.e., 
urogenital microbiological 
success) at the TOC 
(Day 4 to 8) Visit without 
the participant receiving 
other systemic 
antimicrobials 
Refer to Table 5 for further 
details on the endpoint 
definition, including the 
missing data strategy for 
participants who do not 
return for the TOC Visit 
Participants with 
uncomplicated 
urogenital gonorrhea 
caused by 
culture-confirmed 
NG 
Gepotidacin 2×3000 mg 
versus  
Ceftriaxone 500 mg plus 
azithromycin 1 g,  
regardless of adherence 
Difference in proportions  
(microbiological success 
rate in the gepotidacin 
treatment group - 
ceftriaxone plus 
azithromycin treatment 
group) 
Participants who receive 
systemic antimicrobials 
before the TOC Visit will be 
considered microbiological 
failures (composite strategy) 
For study treatment 
discontinuation, the data will 
be analyzed as collected 
(treatment policy strategy) 


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Estimand 
Category  
Estimand 
Variable/Endpoint 
Population 
Treatment Condition 
Summary Measure 
Intercurrent Event Strategy 
Secondary Objective: To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with rectal gonorrhea 
caused by NG 
Secondary 
Participants with 
culture-confirmed bacterial 
eradication of NG from the 
rectal body site (i.e., rectal 
microbiological success) at 
the TOC (Day 4 to 8) Visit 
without the participant 
receiving other systemic 
antimicrobials 
Refer to Table 5 for further 
details on the endpoint 
definition, including missing 
data strategy for 
participants who do not 
return for the TOC Visit 
Participants with 
uncomplicated 
urogenital and rectal 
gonorrhea caused 
by culture-confirmed 
NG 
Gepotidacin 2×3000 mg 
versus  
Ceftriaxone 500 mg plus 
azithromycin 1 g,  
regardless of adherence 
Difference in proportions  
(microbiological success 
rate in the gepotidacin 
treatment group - 
ceftriaxone plus 
azithromycin treatment 
group) 
Participants who receive 
systemic antimicrobials 
before the TOC Visit will be 
considered microbiological 
failures (composite strategy) 
For study treatment 
discontinuation, the data will 
be analyzed as collected 
(treatment policy strategy) 


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Estimand 
Category  
Estimand 
Variable/Endpoint 
Population 
Treatment Condition 
Summary Measure 
Intercurrent Event Strategy 
Secondary Objective: To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with pharyngeal 
gonorrhea caused by NG 
Secondary 
Participants with 
culture-confirmed bacterial 
eradication of NG from the 
pharyngeal body site (i.e., 
pharyngeal microbiological 
success) at the TOC (Day 
4 to 8) Visit without the 
participant receiving other 
systemic antimicrobials 
 
Refer to Table 5 for further 
details on the endpoint 
definition, including the 
missing data strategy for 
participants who do not 
return for the TOC Visit 
Participants with 
uncomplicated 
urogenital and 
pharyngeal 
gonorrhea caused 
by culture-confirmed 
NG 
Gepotidacin 2×3000 mg 
versus  
Ceftriaxone 500 mg plus 
azithromycin 1 g,  
regardless of adherence 
Difference in proportions  
(microbiological success 
rate in the gepotidacin 
treatment group - 
ceftriaxone plus 
azithromycin treatment 
group) 
Participants who receive 
systemic antimicrobials 
before the TOC Visit will be 
considered microbiological 
failures (composite strategy) 
For study treatment 
discontinuation, the data will 
be analyzed as collected 
(treatment policy strategy) 


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Estimand 
Category  
Estimand 
Variable/Endpoint 
Population 
Treatment Condition 
Summary Measure 
Intercurrent Event Strategy 
Secondary Objective: To evaluate the safety and tolerability of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin 
Secondary 
(Safety) 
Treatment-emergent AEs 
and serious AEs and 
change from baseline 
results for clinical 
laboratory tests and vital 
sign measurements 
Participants with 
uncomplicated 
urogenital gonorrhea 
Gepotidacin 2×3000 mg 
versus  
Ceftriaxone 500 mg plus 
azithromycin 1 g,  
regardless of adherence 
The proportions for 
treatment-emergent AEs 
and serious AEs will be 
produced for each arm 
separately. The means for 
change from baseline 
results (clinical laboratory 
results and vital sign 
measurements) will be 
produced for each arm 
separately. 
For study treatment 
discontinuation, the data will 
be analyzed as collected 
(treatment policy strategy) 
AE=adverse events; NG=Neisseria gonorrhoeae; TOC=Test-of-Cure. 
 


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The rationale for a treatment policy intercurrent event strategy of study treatment 
discontinuation is that interest lies in the treatment effect irrespective of whether the full 
course of treatment was taken or not, this is reflective of how patients may be treated in 
clinical practice. 
The rationale for using a composite strategy for the intercurrent event of antimicrobial 
use is because usage could affect bacterial culture response; thus, a conservative 
approach has been adopted and if a participant receives systemic antimicrobials before 
the TOC Visit, the participant will be assumed to be a microbiological failure. Note: The 
intercurrent event of antimicrobial use is not applicable for the safety estimands. 
5. 
STUDY DESIGN 
5.1. 
Overall Design 
• 
BTZ116577 is a Phase III, open-label (sponsor-blinded), parallel-group, multicenter, 
comparator-controlled, noninferiority study in adolescent and adult participants 
comparing the efficacy and safety of oral gepotidacin to IM ceftriaxone plus oral 
azithromycin in the treatment of uncomplicated urogenital gonorrhea caused by NG. 
• 
Participants will be stratified by sex and sexual orientation combination (men who 
have sex with men [MSM], men who have sex with women [MSW], or female) and 
age (<18 years, ≥18 to 65 years, or >65 years). The MSM category will include 
MSM and bisexual males (i.e., male participants who have sex with both males and 
females). Participants will be randomly assigned to receive 1 of the following 
treatments (see Section 7.1): 
− 
Gepotidacin: 3000 mg administered orally at the study site during the Baseline 
(Day 1) Visit followed by self-administration of a second oral 3000-mg dose as 
an outpatient 10 to 12 hours after the first dose; however, for participants who 
weigh <50 kg or have moderate renal impairment, the second dose should be 
taken approximately 12 hours after the first dose. (Note: Each dose should be 
taken after food consumption and with water to assist with tolerability.) 
− 
Ceftriaxone plus azithromycin: A single IM 500-mg dose of ceftriaxone plus a 
single oral 1-g dose of azithromycin administered at the study site during the 
Baseline (Day 1) Visit. (Note: Azithromycin should be taken after food 
consumption and with water.) 
• 
Appropriate safety and microbiological assessments will be conducted at the 
Baseline (Day 1) Visit and repeated at the TOC (Day 4 to 8) and Follow-up (Day 14 
to 21) Visits. 
• 
“Test-of-Cure” microbiological success will be defined by body site (i.e., urogenital 
and, as appropriate, pharyngeal and/or rectal) as culture-confirmed bacterial 
eradication of NG observed at the TOC (Day 4 to 8) Visit, which is 3 to 7 days 
posttreatment per Food and Drug Administration (FDA) guidance [DHHS, 2015]. 
• 
Participants may return to the study site before the TOC Visit due to AEs. 


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• 
Participants who test positive for a CT and/or Mgen infection per baseline NAAT 
results should be treated per local standard of care at or after the TOC Visit or at the 
Follow-up Visit (if treatment has not already been initiated), as required, after all 
study procedures at the visit have been completed (see Section 7.8). 
• 
Participants will be instructed to return to the study site anytime from Day 14 to 21 
for a Follow-up Visit. The investigator and/or study site staff should make every 
effort to ensure a participant returns for this visit. If it is determined that the 
participant is unable to return to the study site, the Follow-up Visit assessments may 
be completed via telephone, with the exception of assessments requiring sample 
collection for laboratory testing (see Table 1). 
• 
The duration of study participation is approximately 21 days with 3 planned study 
visits (see Section 9 for study visit details): 
− 
Baseline (Day 1) Visit 
− 
TOC (Day 4 to 8) Visit 
− 
Follow-up (Day 14 to 21) Visit 
A study design schematic is depicted in Figure 1. 
Refer to Appendix 11 for details regarding allowed revisions to study conduct and/or 
monitoring due to coronavirus disease (COVID-19). For all study visits, to minimize the 
amount of time that participants spend at the clinic, eConsent may be utilized and remote 
collection of study-related data may be obtained as described in the Study Reference 
Manual (SRM). Thus, some visit data may be collected through a combination of 
telemedicine and on-site visits. Collection of information via telemedicine will be 
performed only where local regulations permit. 


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Figure 1 
Study Design Schematic 
  
a. 
Refer to Inclusion Criterion #2 for details regarding urogenital gonococcal infection eligibility requirements. 
b. 
Stratification will be performed before randomization to ensure that treatment groups are balanced with regard to sex and sexual orientation combination and age. 
c. 
Study treatment will be administered under open-label conditions. All doses of oral study treatment should always be taken after food consumption and with water. 
d. 
Participants randomly assigned to gepotidacin will self-administer their second dose (3000 mg) as an outpatient 10 to 12 hours after the first dose; however, for participants who 
weigh <50 kg or have moderate renal impairment, the second dose should be taken approximately 12 hours after the first dose. 
e. 
Participants will return to the study site anytime from Day 14 to 21 for a Follow-up Visit. The investigator and/or study site staff should make every effort to ensure a participant 
returns for this visit. If it is determined that a participant is unable to return to the study site, the Follow-up Visit assessments may be completed via telephone, with the exception of 
assessments requiring sample collection for laboratory testing. 


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5.2. 
Number of Participants 
Approximately 620 participants will be screened and randomized to achieve 
approximately 400 participants with culture-confirmed urogenital gonorrhea in the 
Microbiological Intent-to-Treat (micro-ITT) Population, for an estimated total of 
200 participants per treatment group in the micro-ITT Population. Enrollment will 
continue until the target number of participants in the micro-ITT Population has been 
reached. 
5.3. 
Participant and Study Completion 
A participant is considered to have completed study treatment if he or she has taken all 
doses of the randomly assigned study treatment and completed the TOC Visit. A 
participant is considered to have completed the study if he or she has completed all study 
visits including the Follow-up Visit. 
The end of the study is defined as the date of the last visit of the last participant in the 
study. 
5.4. 
Scientific Rationale for Study Design 
The study design follows the FDA guidance for industry for developing drug treatments 
for uncomplicated gonorrhea [DHHS, 2015] and the European Medicines Agency (EMA) 
guideline on the evaluation of medicinal products indicated for treatment of bacterial 
infections [EMA, 2011]. 
The selected gepotidacin dose in this study (oral 3000-mg dose taken twice, with the 
second dose administered 10 to 12 hours after the first dose) was informed by the safety 
and efficacy results in the Phase II study, where single doses of 1500 and 3000 mg 
gepotidacin were efficacious against NG with gepotidacin MICs <1 µg/mL, including 
isolates resistant to ciprofloxacin (see Section 3.1). A comparison of gepotidacin MICs 
and the corresponding gepotidacin dose against NG demonstrated 100% microbiological 
success rate in both treatment groups for participants with baseline urogenital NG isolates 
with gepotidacin MICs ≤0.5 µg/mL. There were no unexpected safety signals at either 
dose in this study. As further described in Section 5.5, based on PK modeling, 
gepotidacin will be administered as 2 single oral 3000-mg doses, with 10 to 12 hours 
between doses, to provide higher daily systemic exposures that allow coverage of NG 
isolates with higher gepotidacin MIC values, which are likely to be observed in this 
global Phase III study, and reduce the risk of resistance emergence.  
Both adult and adolescent (≥12 to <18 years) eligible participants will be enrolled in this 
open-label (sponsor-blinded) study. Adolescent participants will only be enrolled at study 
sites where investigators have experience in this population and if allowed per the study 
site’s institutional ethic committees and local country/national guidelines and enrollment 
will be contingent upon such approvals. Adolescent assent forms and adult consent forms 
will be developed with oversight from local governing institutional review boards 
(IRBs)/independent ethics committees (IECs) (see Appendix 3). Randomization by sex 
and sexual orientation combination (MSM, MSW, or females) and age will be employed 
in this study. The effectiveness of gepotidacin is not expected to be different for the 


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participants in the stratification categories, but the randomization has been planned such 
that the treatment groups are balanced within each category. 
Given the method of study treatment administration (oral gepotidacin versus IM 
ceftriaxone plus oral azithromycin) blinding of the study was not feasible. A 
double-blind, double-dummy design would require all participants randomized to oral 
gepotidacin to receive a placebo IM injection, which is considered unnecessary because 
the primary endpoint is based on objective microbiological laboratory assessments rather 
than subjective clinical assessments. 
Ceftriaxone plus azithromycin was chosen as the comparator based on the recommended 
treatment regimen for uncomplicated gonorrhea by authoritative bodies. At the time of 
study start, both the CDC and WHO recommend a dual antibiotic regimen consisting of a 
single IM 250-mg dose of ceftriaxone and a single oral 1-g dose of azithromycin 
[CDC, 2015; WHO, 2016], while in Europe and Australia the recommended dose of 
ceftriaxone is a single IM 500-mg dose and either a single oral 2-g (Europe) or 1-g 
(Australia) dose of azithromycin [Bignell, 2013; ASHA, 2016]. As of Dec 2020, the CDC 
now recommends an IM injection of ceftriaxone based on body weight (500-mg IM if 
<150 kg and 1-g IM if ≥150 kg) and an oral regimen of doxycycline if chlamydia 
infection has not been ruled out [CDC, 2021]. For this study, a single IM 500mg- dose of 
ceftriaxone with a single oral 1-g dose of azithromycin has been chosen (for dose 
justification see Section 5.5). 
In this study, participants who test positive for CT and/or Mgen infection per baseline 
NAAT results should be treated per local standard of care at or after the TOC Visit or at 
the Follow-up Visit, as required, after all study procedures at the visit have been 
completed. Treatment with alternate antibiotic therapy for these co-infections is needed, 
as gepotidacin and ceftriaxone are not active in vitro against CT, not all participants will 
receive azithromycin study treatment (an effective treatment for CT), and the study 
treatment regimen may be insufficient for treatment of Mgen infection. At study entry, 
any participant suspected or confirmed to have a CT infection will not be allowed to 
enroll in the study if, per the investigator’s judgement, standard-of-care treatment for this 
infection cannot be safely postponed until the TOC Visit.  
Participants meeting eligibility criteria will be treated prior to the availability of culture 
data to confirm infection. Culture-confirmed bacterial eradication of NG will be assessed 
3 to 7 days after the initial treatment per FDA guidelines [DHHS, 2015]. Problems in 
studies of gonococcal infection include lower culture-confirmed pathogen recovery rates 
from NG cultures in certain patient populations and the risk for participants to not return 
for the TOC Visit. In order to maximize the efficiency of this study while minimizing 
discomfort and inconvenience to participants consenting to this protocol, an internal GSK 
SRT will monitor blinded safety data instream, while an internal Microbiology Review 
Team will monitor blinded pathogen identification and susceptibility data instream.  


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5.5. 
Dose Justification 
In the Phase II study, both single oral doses of 1500 and 3000 mg gepotidacin were ≥95% 
efficacious (bacterial eradication) against urogenital NG with no unexpected safety 
signals at either dose. A total of 3 participants failed therapy at the urogenital body site 
(all with a baseline gepotidacin MIC of 1 μg/mL, which was among the highest MIC for 
gepotidacin), and analysis of the posttreatment cultures identified 2 isolates that had 
become resistant to gepotidacin (TOC gepotidacin MICs ≥32 μg/mL). Further analysis 
revealed that both isolates also had a pre-existing D86N polymorphism in the 
topoisomerase IV gene at Baseline. Following treatment, both isolates showed a second 
mutation, an A92T substitution in the DNA gyrase enzyme, which resulted in reduced 
susceptibility to gepotidacin. Of the 8 participants in the study with D86N-positive 
baseline urogenital NG isolates, 5 were microbiological successes (bacterial eradication), 
including 2 that were infected with baseline organisms with the higher gepotidacin MIC 
of 1 μg/mL. These data suggest that the 3000-mg single dose may provide close to an 
effective exposure and that this genotype may be overcome with appropriate dosing. 
In the current study, gepotidacin will be administered as 2 oral 3000-mg doses. The two 
3000-mg doses, administered 10 to 12 hours apart, compared with the single 3000-mg 
dose used in the Phase II study, is expected to provide 2-fold higher systemic exposures 
that allow coverage of NG isolates with higher gepotidacin MIC values, which are likely 
to be observed in this global Phase III study, and also to reduce the risk of resistance 
emergence. 
Previous studies with antibacterials have shown that attaining a target exposure that 
correlates with bacterial reduction endpoints in preclinical models is predictive of good 
clinical outcome in participants with bacterial infections [Ambrose, 2007]. However, due 
to lack of validated preclinical models for NG, the PK/pharmacodynamic (PD) parameter 
and magnitude predictive of gepotidacin efficacy has not been established in preclinical 
models for this infection or pathogen. In the Phase II study, the bacterial cure rate was 
100% when the free drug area under the concentration-time curve/MIC (fAUC/MIC) was 
approximately 48 or higher and the free mean time above the MIC (fT>MIC) was ≥42% 
(10 hours) for NG isolates with gepotidacin MICs up to 0.5 µg/mL. Based on PK 
modeling, including PK data in adults and adolescents (Study 209611), the dosing 
strategy of 2 gepotidacin 3000-mg doses (administered 10 to 12 hours apart) is expected 
to limit the occurrence of maximum plasma exposures ≥14 μg/mL, which is necessary 
from a safety perspective due to corrected QT interval (QTc) increases and 
acetylcholinesterase inhibition. This dosing strategy also supports an fAUC/MIC of 
40 with an fT>MIC of 58% to 63% (14 to 15 hours), which will maximize the probability 
for efficacy against NG isolates with gepotidacin MICs up to 1 μg/mL. A set of duplicate 
10-day hollow fiber infection model studies was also completed using a NG isolate with a 
gepotidacin MIC of 1 μg/mL and a D86N mutation in ParC to determine if the exposure 
achieved by 2 gepotidacin 3000-mg doses (administered 8 or 12 hours apart) prevented 
amplification of a resistant subpopulation when a pre-existing single step mutation was 
already present. An inverted-U shaped function described the relationship between drug 
resistance amplification and gepotidacin dose with total daily gepotidacin doses 
≥4500 mg (including the 2 gepotidacin 3000-mg doses [administered either 8 or 12 hours 
apart]) preventing resistance amplification to gepotidacin for NG in the hollow fiber 


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infection model. Therefore, 2 gepotidacin 3000-mg doses (administered 8 or 12 hours 
apart) are expected to prevent amplification of resistance against NG isolates with 
gepotidacin MICs up to 1 μg/mL. However, it should be noted, any emergence of 
resistance to gepotidacin is not expected to limit or affect standard-of-care treatment for 
gonorrhea or a participant’s future treatment options in this study. 
At the start of this study, both the CDC and WHO recommend a dual antibiotic regimen 
that includes a single 250-mg IM ceftriaxone dose plus a single 1-g oral dose of 
azithromycin for the treatment of uncomplicated gonococcal infections [CDC, 2015; 
WHO, 2016]. The CDC now recommends an IM injection of ceftriaxone based on body 
weight and an oral regimen of doxycycline only if chlamydia infection has not been ruled 
out [CDC, 2021]. The selected ceftriaxone dose in this study is 500 mg IM. This higher 
ceftriaxone dose was selected because this dose allows for higher systemic exposures, 
which are predicted to offer additional coverage of NG isolates with higher ceftriaxone 
MIC values, should the prevalence of such isolates increase and be observed in this 
global Phase III study. A single 500-mg IM dose of ceftriaxone is within the prescribing 
limits, which states the total daily dose for ceftriaxone should not exceed 4000 mg, and is 
consistent with treatment guidance for Europe and from the Australian regulatory 
authority [Bignell, 2013; ASHA, 2016]. The selected azithromycin dose in this study is 
1 gm administered orally. The azithromycin dose is in alignment with the CDC, WHO, 
and Australian uncomplicated gonorrhea treatment recommendations [CDC, 2015; 
WHO, 2016; ASHA, 2016]. Lastly, with approximately 99% efficacy [CDC, 2021], the 
dual-therapy comparator arm of 500 mg ceftriaxone plus a single 1 g dose of 
azithromycin is expected to be at least as efficacious as 500 mg ceftriaxone monotherapy. 


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6. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
6.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age and Weight 
1. The participant is ≥12 years at the time of signing the informed consent/assent and 
has a body weight >45 kg.  
Note: Although participants as young as 12 years may enroll in the study, study sites 
must follow their institutional ethics committee and local country/national regulatory 
guidelines and enrollment will be contingent upon such approvals regarding the 
allowed lower age limit for clinical study participants. 
Type of Participant and Disease Characteristics 
2. The participant has clinical suspicion of a urogenital gonococcal infection (which 
can include sexual contact within the past 14 days with a partner who has a 
confirmed gonococcal infection) with or without pharyngeal and/or rectal 
gonococcal infection and has 1 of the following:  
− 
male participants with purulent yellow, green, or white urethral discharge or 
female participants with abnormal cervical or vaginal mucopurulent discharge 
upon physical examination 
OR 
− 
a prior positive culture for NG from up to 5 days before Screening (as long as 
the participant has not received any treatment for this infection), or 
− 
a Gram or equivalent stain (urogenital specimens only) positive or presumptive 
for intracellular diplococci from up to 5 days before Screening (as long as the 
participant has not received any treatment for this infection), or  
− 
a prior positive NAAT assay for NG from up to 7 days before Screening (as long 
as the participant has not received any treatment for this infection). 
Note:  A urogenital specimen will be taken from all participants (males and females) 
for NG culture at the Baseline Visit; however, these results will not be used to 
determine participant eligibility for enrollment in the study. The culture results will 
be used to identify the primary analysis population. 
3. The participant must be willing to abstain from anal, oral, and vaginal sexual 
intercourse or use condoms for all forms of intercourse from the Baseline Visit 
through the TOC Visit. 


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Sex 
4. Male or female and must have his or her original urogenital anatomy at birth 
a. Male participants: 
A male participant must agree to use contraception as detailed in Appendix 6 of this 
protocol from the Baseline Visit through completion of the TOC Visit. 
b. Female participants:  
A female participant is eligible to participate if she is a woman of childbearing 
potential (WOCBP) who is not pregnant as confirmed by a high sensitivity urine 
pregnancy text at Baseline (Day 1) regardless of current or prior contraception 
use or abstinence, is not breastfeeding, or is not a WOCBP. Note:  Pregnancy 
testing requirements, contraceptive guidance, and WOCBP definitions are provided 
in Appendix 6. 
Informed Consent 
5. The participant is capable of giving signed informed consent/assent as described in 
Appendix 3, which includes compliance with the requirements and restrictions listed 
in the informed consent form (ICF)/assent form and in this protocol. 
6.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions and History 
1. The participant is a male with a current diagnosis of epididymitis and/or orchitis at 
the time of the Baseline Visit. 
2. The participant is suspected or confirmed to have a CT infection and per the 
investigator’s judgement standard-of-care treatment for this infection cannot be 
safely postponed until the TOC Visit. 
3. The participant has a body mass index ≥40 kg/m2 or has a body mass index 
≥35.0 kg/m2 and is experiencing obesity-related health conditions such as 
uncontrolled high blood pressure or uncontrolled diabetes. 
4. The participant has a history of sensitivity to the study treatments, or components 
thereof, or a history of a drug (including erythromycin and any macrolide or ketolide 
drug) or other allergy that, in the opinion of the investigator or medical monitor, 
contraindicates his or her participation. 
5. The participant is immunocompromised or has altered immune defenses that may 
predispose the participant to a higher risk of treatment failure and/or complications 
(e.g., participants with uncontrolled diabetes, renal transplant recipients, participants 
with clinically significant persistent granulocytopenia [absolute neutrophil count 
<1000/µL], and participants receiving immunosuppressive therapy, including 
corticosteroid therapy [>40 mg/day prednisolone or equivalent for >1 week, 
≥20 mg/day prednisolone or equivalent for >2 weeks, or prednisolone or equivalent 


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≥10 mg/day for >6 weeks]). Participants with a known CD4 count of <200 cells/mm3 
should not be enrolled. 
Note: Participants taking pre-exposure prophylactics for human immunodeficiency 
virus (HIV) are allowed to enroll. HIV-infected participants are allowed to enroll, as 
long as their CD4 count is ≥200 cells/mm3. Use of strong cytochrome P450 enzyme 
3A4 (CYP3A4) inhibitors during the study is prohibited (see Exclusion 
Criterion 15). 
6. The participant has any of the following: 
− 
Medical condition that requires medication that may be impacted by inhibition 
of acetylcholinesterase, such as: 
− Poorly controlled asthma or chronic obstructive pulmonary disease at the 
Baseline Visit and, in the opinion of the investigator, not stable on current 
therapy 
− 
Acute severe pain, uncontrolled with conventional medical management 
− 
Active peptic ulcer disease 
− 
Parkinson disease 
− 
Myasthenia gravis 
− A history of seizure disorder requiring medications for control (this does not 
include a history of childhood febrile seizures) 
OR  
− Any surgical or medical condition (active or chronic) that may interfere with 
drug absorption, distribution, metabolism, or excretion of the study treatment 
(e.g., ileostomy or malabsorption syndrome). 
7. The participant has known anuria, oliguria, or severe impairment of renal function 
(creatinine clearance <30 mL/min or clinically significant elevated serum creatinine 
as determined by the investigator). 
8. The participant, in the judgment of the investigator, would not be able or willing to 
comply with the protocol or complete study follow-up. 
9. The participant has a serious underlying disease that could be imminently life 
threatening, or the participant is unlikely to survive for the duration of the study 
period. 
Cardiac Exclusions 
10. The participant has congenital long QT syndrome or known prolongation of QTc. 
11. The participant has uncompensated heart failure. 
12. The participant has severe left ventricular hypertrophy. 
13. The participant has a family history of QT prolongation or sudden death. 
14. The participant has a recent history of vasovagal syncope or episodes of 
symptomatic bradycardia or bradyarrhythmia within the last 12 months. 


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15. The participant is taking QT-prolonging drugs or drugs known to increase the risk of 
torsades de pointes (TdP) per the www.crediblemeds.org “Known Risk of TdP” 
category at the time of his or her Baseline Visit, which cannot be safely discontinued 
from the Baseline Visit to the TOC Visit; or the participant is taking a strong 
CYP3A4 inhibitor.  
Cardiac ECG Exclusions 
16. For any participant ≥12 to <18 years, the participant has an abnormal ECG reading. 
17. The participant has a QTc >450 msec or a QTc >480 msec for participants with 
bundle-branch block. 
Note:   
− 
The QTc is the QT interval corrected for heart rate according to either Bazett’s 
formula (QTcB), or Fridericia’s (QTcF) formula, and/or another method. It is 
either machine read or manually overread.  
− 
The specific formula used to determine eligibility and discontinuation for an 
individual participant should be determined prior to initiation of the study. In 
other words, several different formulas cannot be used to calculate the QTc for 
an individual participant and then the lowest QTc value used to include or 
discontinue the participant from the trial. 
18. The participant has a documented or recent history of uncorrected hypokalemia 
within the past 3 months.  
Hepatic Exclusions 
19. The participant has a known history of cholestatic jaundice or hepatic dysfunction 
associated with prior use of azithromycin. 
20. The participant has a known alanine aminotransferase (ALT) value >2 × upper limit 
of normal (ULN). 
21. The participant has a known bilirubin value >1.5 × ULN (isolated bilirubin >1.5 × 
ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%). 
22. The participant has a current or chronic history of liver disease, or known hepatic or 
biliary abnormalities (with the exception of Gilbert’s syndrome or asymptomatic 
gallstones), including symptomatic viral hepatitis or moderate-to-severe liver 
insufficiency (Child Pugh class B or C).  
Note:  Participants with asymptomatic viral hepatitis are eligible for study 
participation. 
Prior/Concurrent Clinical Study Experience Exclusions 
23. The participant has been previously randomized in this study or has previously been 
treated with gepotidacin. 
24. The participant has participated in a clinical trial and has received an investigational 
product within 30 days or 5 half-lives, whichever is longer. 


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Gonococcal Infection Exclusions 
25. The participant has any of the following gonococcal infections that require a 
different dose or duration of treatment: 
− 
Suspected or confirmed pelvic inflammatory disease 
− 
Suspected or confirmed gonococcal arthritis 
− 
Suspected or confirmed gonococcal conjunctivitis 
− 
Suspected or confirmed gonococcal endocarditis 
− 
Other evidence of disseminated gonococcal infection 
Prior Antibiotic/Antifungal Use and Concomitant Medication Exclusions 
26. The participant has received any antibacterial therapy for the treatment of a 
gonococcal infection within 14 days before the Baseline Visit. 
27. The participant has received any systemic, topical, or intravaginal antibiotics or any 
systemic antifungals within 7 days before the Baseline Visit. 
28. The participant must not use St John’s wort or ergot derivatives from within 14 days 
before the Baseline Visit through the TOC Visit. 
6.3. 
Lifestyle Restrictions 
Participants will be instructed to abstain from sexual activity from the Baseline Visit 
through the TOC Visit to prevent possible re-infection with NG. If a participant refuses to 
abstain and is sexually active, male participants as well as male partners of female 
participants, of both childbearing and nonchildbearing potential, must use a male condom 
during intercourse from the Baseline Visit through completion of the TOC Visit. Details 
for contraception requirements are included in Appendix 6. 
6.3.1. 
Meals and Dietary Restrictions 
Gepotidacin and azithromycin should be taken with food (a meal or snack) (see 
Section 7.1). 
6.4. 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized. Participants who are screen failures are not allowed 
to be rescreened for the same infection episode; however, participants who were screen 
failures for an earlier infection episode may be newly screened for a second infection 
episode ≥4 weeks later and participate in the study if they meet all of the inclusion and 
exclusion criteria. A minimal set of screen failure information is required to ensure 
transparent reporting of screen failure participants to meet the Consolidated Standards of 
Reporting Trials (CONSORT) publishing requirements and to respond to queries from 
regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any SAEs. 


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7. 
TREATMENTS 
All doses of oral study treatment should always be taken after food consumption and with 
water. Study treatment is defined as any investigational treatments or marketed products 
intended to be administered to a study participant according to the study protocol. 
7.1. 
Treatments Administered 
Study Treatment 
Name: 
Gepotidacin 
Ceftriaxone 
Azithromycina 
Dosage 
Formulation: 
Tablets containing 
gepotidacin and inactive 
formulation excipients 
Sterile powder for 
reconstitution with 
appropriate diluent 
Tabletsa 
Unit Dose 
Strengths/ 
Dosage Levels: 
4 × 750-mg tablets 
500-mg equivalent 
2 × 500-mg tabletsa 
Route of 
Administration: 
Oral 
IM 
Oral 
Dosing 
Instructions: 
Administer first oral dose 
at the study site. 
Participant 
self-administers the 
second dose as an 
outpatient 10 to 12 hours 
after the first dose; 
however, for participants 
who weigh <50 kg or 
have moderate renal 
impairment, the second 
dose should be taken 
approximately 12 hours 
after the first dose 
Dose 1: 3000 mg – 
4 tablets 
Dose 2: 3000 mg – 
4 tablets 
Each dose should be 
taken after food 
consumption and with 
water. 
Administer one 500-mg 
IM dose at the study site 
(volume administered will 
be dependent on the 
amount of diluentb added 
and resulting 
concentration; see Study 
Reference Manual). 
Administer one 1-gm 
oral dose at the study 
site. 
Dose should be taken 
after food consumption 
and with water. 


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Study Treatment 
Name: 
Gepotidacin 
Ceftriaxone 
Azithromycina 
Packaging and 
Labeling: 
Gepotidacin tablets will 
be provided in bottles. 
Each bottle will be 
labeled as required per 
country requirement. 
Ceftriaxone will be 
provided by PPD and 
labeled as required per 
country requirement. 
Azithromycin tabletsa 
will be provided by PPD 
and labeled as required 
per country 
requirement. 
Manufacturer: 
May be sourced locally 
or centrally within 
individual countries but 
will be supplied by PPD 
and labeled as per the 
regulatory requirements 
in all participating 
countries. 
May be sourced locally 
or centrally within 
individual countries but 
will be supplied by PPD 
and labeled as per the 
regulatory requirements 
in all participating 
countries. 
IM=intramuscular. 
a. 
The total oral dose of azithromycin must be 1 gm. Based on locally or centrally sourced available supplies 
and tablet/capsule strengths, the number of tablet/capsules may be adjusted to reach the 1-gm dose of 
azithromycin. 
b. Study sites will be responsible for procurement of diluent and injection supplies. 
The labeling, distribution, procurement, and/or drug returns for comparator investigative 
products were supported by Almac US, Almac UK, PPD Athlone (Germany and Spain), 
Flinders (Australia), World Courier Mexico, Clinigen (Australia, EMEA, and US), 
Bionical LTDA (UK), and Oncomedic (Mexico). 
7.2. 
Dose Modification 
The study design does not allow for dose modifications.  
7.3. 
Method of Treatment Assignment 
Participants will be stratified by sex and sexual orientation combination (MSM, MSW, or 
females) and age (<18 years, ≥18 to 65 years, or >65 years) to ensure that treatment 
groups are balanced within each category. The MSM category will include MSM and 
bisexual males (i.e., male participants who have sex with both males and females). 
Within each stratum, participants will be centrally randomized in a 1:1 ratio to either 
gepotidacin or ceftriaxone plus azithromycin using an interactive response technology 
(IRT) in accordance with the randomization schedule generated by or under the direction 
of GSK’s Clinical Statistics. Before the study is initiated, information and directions for 
the IRT will be provided to each study site.  
Each participant scheduled to receive study treatment will receive a randomization 
number at the time of randomization. This randomization number will be used to identify 
the participant and indicate the treatment to be administered to that participant. 
For those participants randomly assigned to gepotidacin, the first dose will be 
administered at the study site during the Baseline Visit and the second dose will be 
dispensed to participants during this visit for self-administration 10 to 12 hours after the 
CCI


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first dose (see Section 7.1). Participants randomly assigned to ceftriaxone plus 
azithromycin will be administered a single IM dose of ceftriaxone plus a single oral dose 
of azithromycin during the Baseline Visit. 
Returned gepotidacin should not be re-dispensed to other participants. 
7.4. 
Blinding 
This is an open-label (sponsor-blinded) randomized study. The specific treatment to be 
taken by a participant will be assigned using an IRT using central randomization. The 
study site will contact the IRT prior to the start of study treatment administration for each 
participant. The study site will record the treatment assignment on the applicable 
electronic case report form (eCRF), if required. Potential bias will be reduced by the use 
of central randomization. 
The GSK SRT, which will monitor safety data instream, will remain blinded to 
participant treatment assignment throughout the study (see Appendix 3). A Microbiology 
Review Team will monitor blinded pathogen identification and susceptibility data 
instream as well as the number of participants eligible for the micro-ITT Population. 
Blinded monitoring of pathogens will be conducted, to determine whether end-of-study 
targets are likely to be achieved. Provision will be made for a limited degree of 
unblinding of a minority of participant sample data should this be viewed as appropriate 
for planning closure of trial enrollment. Procedures will be described in a separate 
microbiology sample monitoring plan, and no impact on trial integrity is expected. 
7.5. 
Preparation/Handling/Storage/Accountability 
No special preparation of gepotidacin or azithromycin is required. 
A pharmacist or other qualified professional will prepare the ceftriaxone solution using a 
fixed volume of an appropriate diluent to reconstitute the ceftriaxone powder. Full details 
of the methods and materials required for ceftriaxone solution preparation are provided in 
the SRM. 
The following considerations must be made with regard to study treatment preparation, 
handling, storage, and accountability in this study: 
1. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study treatment received and any discrepancies 
are reported and resolved before use of the study treatment. 
2. Only participants enrolled in the study may receive study treatment and only 
authorized study site staff may supply or administer study treatment. All study 
treatments must be stored in a secure, environmentally controlled, and monitored 
(manual or automated) area in accordance with the labeled storage conditions with 
access limited to the investigator and authorized study site staff. 
3. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study treatment accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 


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4. Further guidance and information for the final disposition of unused study treatment 
are provided in the SRM. 
Under normal conditions of handling and administration, study treatment is not expected 
to pose significant safety risks to the study site staff. For ceftriaxone solution, take 
adequate precautions to avoid direct eye or skin contact and the generation of aerosols or 
mists. In the case of unintentional occupational exposure, notify the monitor, medical 
monitor, and/or GSK study contact. 
A Material Safety Data Sheet or equivalent document describing occupational hazards 
and recommended handling precautions either will be provided to the investigator, where 
this is required by local laws, or is available upon request from GSK. 
7.6. 
Treatment Compliance 
• 
When the individual dose for a participant is prepared from a bulk supply, the 
preparation of the dose will be confirmed by a second member of the study site staff. 
• 
Participants dosed at the study site will receive study treatment (oral dose of 
gepotidacin or single IM dose of ceftriaxone plus an oral dose of azithromycin) 
directly from the investigator or designee, under medical supervision. The date and 
time of each dose administered in the study site will be recorded in the source 
documents and reported in the eCRF. The dose of study treatment and study 
participant identification will be confirmed at the time of dosing by a member of the 
study site staff other than the person administering the study treatment. 
• 
Participants will self-administer the second oral dose of gepotidacin as an outpatient 
(see Section 7.1). Compliance with gepotidacin will be assessed by contacting the 
participant via telephone, email, or text message. The participants should confirm 
that the second dose was taken. Study site staff will also query the participant during 
the TOC Visit and document whether the second dose was taken. A record of the 
number of gepotidacin tablets dispensed to each participant must be recorded and 
reconciled with study treatment and compliance records. The date and time of each 
dose will also be recorded in the eCRF. 
7.7. 
Concomitant Therapy 
Any medication or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving within 30 days prior 
to the Baseline Visit or receives during the study must be recorded in the eCRF. In 
addition, any antibiotic use within 6 months prior to the Baseline Visit or during the study 
must be recorded in the eCRF. The concomitant therapy name must be recorded in the 
eCRF along with the following: 
• 
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. 


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7.7.1. 
Permitted Medications and Nondrug Therapies 
Participants testing positive for CT and/or Mgen per NAAT results at the Baseline Visit 
will be permitted to receive local standard of care at or after the TOC Visit or at the 
Follow-up Visit (if treatment has not already been initiated), as required, after all study 
procedures at the visit have been completed. Note: If at Baseline a participant is 
suspected or confirmed to have a CT infection and per the investigator’s judgement 
standard-of-care treatment for this infection cannot be safely postponed until the TOC 
Visit, the participant should not be enrolled in the study (see Section 6.2).  
The use of H1 antihistaminics not associated with QT prolongation is allowed (e.g., 
loratadine, cetirizine, ebastine, and fexofenadine). Use of pre-exposure prophylaxis for 
HIV is allowed. The use of nonsystemic antifungals (e.g., topical, intravaginal) is allowed 
throughout the study. Please also refer to Appendix 9. 
A list of permitted medications commonly used for nausea, vomiting, pain, and diarrhea 
per investigator discretion is provided in Appendix 9. 
A further detailed list of medications will be provided in the SRM. 
7.7.2. 
Prohibited Medications and Nondrug Therapies 
At the time of enrollment and/or during the study, the participant is prohibited from use 
of the following medications and nondrug therapies: 
• 
An investigational product within 30 days or 5 half-lives, whichever is longer, of 
Baseline Visit. 
• 
Any antibacterial therapy for the treatment of a gonococcal infection within 14 days 
before the Baseline Visit. 
• 
Any systemic, topical, or intravaginal antibiotics or any systemic antifungals within 
7 days before the Baseline Visit. 
• 
Immunosuppressive therapy, including corticosteroid therapy (>40 mg/day 
prednisolone or equivalent for >1 week, ≥20 mg/day prednisolone or equivalent for 
>2 weeks; or prednisolone or equivalent ≥10 mg/day for >6 weeks). 
• 
With the exception of azithromycin study treatment, QT-prolonging drugs or drugs 
with known TdP risk, per the www.crediblemeds.org “Known Risk of TdP” 
category, at the time of their Baseline Visit, which cannot be safely discontinued 
from the Baseline Visit to the TOC Visit. Details regarding website access are 
provided in the SRM; additional guidance is provided in Appendix 9. Of note, 
ondansetron is not allowed from the Baseline Visit to the TOC Visit due to its known 
TdP risk. Alternative antiemetics that are permitted per investigator discretion are 
listed in Appendix 9. 
Note: Crediblemeds.org categorizes drugs into 4 categories. The only category for 
exclusion in this study is the “Known Risk of TdP” category; participants taking 
drugs that meet criteria of other categories are NOT excluded from participation. 


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• 
St John’s wort or other strong CYP3A4 inhibitors within 14 days before the Baseline 
Visit through the TOC Visit (a list of strong CYP3A4 inhibitors is provided in the 
SRM). 
• 
Ergot derivatives from within 14 days before the Baseline Visit through the TOC 
Visit. 
Due to the gepotidacin’s property of acetylcholinesterase inhibition, the concomitant use 
of succinylcholine or other nondepolarizing paralytic agents is also prohibited. Caution 
should be used in participants who have a condition requiring medication that may 
exacerbate the inhibition of acetylcholinesterase, or neuromuscular blocking agents. 
7.8. 
Treatment After the End of the Study 
Participants testing positive for CT and/or Mgen per NAAT results at the Baseline Visit 
should be treated per local standard of care at or after the TOC or at Follow-up Visit (if 
treatment has not already been initiated), as required, after all study procedures at the 
visit have been completed. Treatment with alternate antibiotic therapy for these 
co-infections is needed, as gepotidacin and ceftriaxone are not active in vitro against CT, 
not all participants will receive azithromycin study treatment (an effective treatment for 
CT), and the study treatment regimen may be insufficient for treatment of Mgen 
infection. Note: If at Baseline a participant is suspected or confirmed to have a CT 
infection and per the investigator’s judgement standard-of-care treatment for this 
infection cannot be safely postponed until the TOC Visit, the participant should not be 
enrolled in the study (see Section 6.2).  
Participants with culture-confirmed bacterial persistence of urogenital and, as 
appropriate, pharyngeal and/or rectal NG at the TOC Visit should receive appropriate 
alternative therapy per the investigator’s choice. 
Participants will not receive any additional treatment for urogenital, pharyngeal, and/or 
rectal NG from GSK after they discontinue or complete the study (i.e., after the 
Follow-up Visit). However, the investigator is responsible for ensuring that consideration 
has been given to the poststudy care of the participant’s medical condition, whether or 
not GSK is providing specific poststudy treatment. 


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8. 
DISCONTINUATION CRITERIA 
8.1. 
Discontinuation of Study Treatment 
Participants may voluntarily discontinue study treatment at any time. The investigator 
may also, at his or her discretion, discontinue the participant from study treatment at any 
time and initiate appropriate alternative therapy. 
Reasons for study treatment discontinuation may include the following: 
• 
Adverse event 
• 
Protocol deviation 
• 
Termination of the study by GSK 
• 
Investigator discretion 
The reason for study treatment discontinuation will be recorded in the eCRF. Participants 
who discontinue study treatment for the reasons above will not be considered withdrawn 
from the study and should return to the study site to complete the TOC and Follow-up 
Visits (see Table 1). 
8.1.1. 
Liver Chemistry Evaluation Criteria 
Liver chemistry stopping and increased monitoring criteria have been designed to 
assure participant safety and evaluate liver event etiology. 
The stopping criteria for discontinuing dosing of study treatment due to liver chemistry 
parameters have limited application in this study, as study treatment is administered as 
2 oral doses of gepotidacin over a 24-hour period starting on Day 1 or as a single dose IM 
dose of ceftriaxone plus an oral dose of azithromycin on Day 1. However, if participants 
are found to have values consistent with the usual stopping parameters, it is appropriate 
to institute evaluation and monitoring criteria according to standard GSK criteria. 
Therefore, liver function tests should be evaluated according to stopping criteria and 
laboratory evaluation instituted if defined parameters are reached.  
Phase III liver chemistry evaluation criteria are presented in Table 4. 


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Table 4 
Liver Chemistry Evaluation Criteria 
Liver Chemistry Evaluation Criteria – Liver Event 
ALT Absolute 
ALT ≥8 × ULN 
ALT Increase 
ALT ≥5 x ULN but <8 x ULN persists for ≥2 weeks 
ALT ≥3 x ULN but <5 x ULN persists for ≥4 weeks 
Bilirubin 
ALT ≥3 × ULN and bilirubin ≥2 × ULN (>35% direct bilirubin) 
INR 
ALT ≥3 × ULN and INR >1.5, if INR measured 
Cannot Monitor 
ALT ≥5 x ULN but <8 x ULN and cannot be monitored weekly for ≥2 
weeks 
ALT ≥3 x ULN but <5 x ULN and cannot be monitored weekly for ≥4 
weeks 
Symptomatic 
ALT ≥3 × ULN associated with symptoms (new or worsening) believed to 
be related to liver injury or hypersensitivity 
ALT=alanine aminotransferase; INR=international normalized ratio; ULN=upper limit of normal. 
Liver safety required actions and follow-up assessments section can be found in 
Appendix 8. 
8.1.2. 
QTc Stopping Criteria 
• 
This protocol only requires an ECG evaluation at the Baseline Visit. Should further 
ECG monitoring or evaluation be needed for an individual participant, per 
investigator discretion, the following should be considered: 
• 
Further monitoring and/or evaluation should be considered in any participant who 
meets either of the bulleted criteria below: 
− 
QTc >500 msec OR uncorrected QT >600 msec 
− 
Change from baseline of QTc >60 msec 
For participants with underlying bundle-branch block, follow the evaluation criteria listed 
below: 
Baseline QTc With Bundle-Branch Block 
Criteria for Further Evaluation and 
Monitoring of QTc With Bundle-Branch 
Block 
<450 msec 
>500 msec 
450 to 480 msec 
≥530 msec 


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• 
The same QT correction formula must be used for each individual participant to 
determine eligibility for the study and whether further evaluation and/or monitoring 
are necessary. This formula may not be changed or substituted once the participant 
has been enrolled. (Note: Ideally, all ECGs for a participant should be performed 
with the same ECG machine.) 
− For example, if a participant is eligible for the protocol based on QTcB, then 
QTcB must be used for discontinuation of this individual participant as well. 
− Once the QT correction formula has been chosen for a participant’s eligibility, 
the same formula must continue to be used for that participant for all QTc data 
being collected for data analysis. Safety ECGs and other nonprotocol-specified 
ECGs are an exception. 
• 
The QTc should be based on averaged QTc values of triplicate ECGs obtained over a 
brief (e.g., 5- to 10-minute) recording period. 
8.1.3. 
Gastrointestinal Evaluation Criteria 
If a participant meets the clinical criteria outlined in Appendix 10, Clostridium difficile 
toxin detection should be conducted and the specific eCRF page completed. C. difficile 
infection or colitis is considered an AE of special interest (Section 9.2.5). 
8.2. 
Withdrawal From the Study 
• 
A participant may withdraw from the study at any time at his or her own request or 
may be withdrawn at any time at the discretion of the investigator for safety, 
behavioral, compliance, or administrative reasons. 
• 
Reasons for study withdrawal include: 
− 
Participant lost to follow-up 
− 
Participant withdrew consent 
− 
Termination of the study by GSK 
− 
Investigator discretion 
• 
If the participant withdraws consent for disclosure of future information, the sponsor 
may retain and continue to use any data collected before such a withdrawal of 
consent. 
• 
If a participant withdraws from the study, he or she may request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records. 
• 
Participants who withdraw from the study should be encouraged to return for the 
TOC and/or Follow-up Visits. Refer to Table 1 for data to be collected at these visits. 
• 
The reason for participant withdrawal will be recorded in the eCRF. Participants who 
were randomly assigned to gepotidacin should return all unused study treatment. 


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8.3. 
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 study site for a 
required study visit: 
• 
The study 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 or not 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 or she will be considered to 
have withdrawn from the study with a primary reason of lost to follow-up.  
9. 
STUDY ASSESSMENTS AND PROCEDURES 
• 
Study procedures and their timing are summarized in Table 1. 
• 
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 treatment (only applicable to participants randomly assigned to 
gepotidacin). 
• 
Adherence to the study design requirements, including those specified in Table 1, is 
essential and required for study conduct. 
• 
All baseline 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 (e.g., 
blood count) and obtained before signing of ICF may be utilized for screening or 
baseline purposes provided the procedure met the protocol-specified criteria and was 
performed within the time frame defined in Table 1. 
• 
The maximum amount of blood collected from each participant over the duration of 
the study, including any extra assessments that may be required, will not exceed 
150 mL. 
• 
Repeat or unscheduled samples may be taken for safety reasons or for technical 
issues with the samples. 


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The study will comprise the following 3 planned study visits: 
Note: For all study visits, to minimize the amount of time that participants spend at 
the clinic, eConsent may be utilized and remote collection of study-related data may 
be obtained as described in the SRM. Thus, some visit data may be collected through 
a combination of telemedicine and on-site visits. Collection of information via 
telemedicine will be performed only where local regulations permit. 
• 
Baseline (Day 1) Visit: The Baseline Visit will be performed before dosing on 
Day 1. Assessments will be performed as shown in Table 1, including the following: 
− 
If applicable, the Baseline Visit will be preceded by a documented reminder 
contact from the study site to the participant 24±4 hours before the scheduled 
appointment time per the method (e.g., text message, telephone call, e-mail) 
confirmed with the study site staff. 
− 
Demographic data such as year of birth, sex, sexual orientation, race, and 
ethnicity will be recorded in the participant’s eCRF. The collection of sex, 
sexual orientation, race, and ethnicity data is necessary to assess and monitor the 
diversity of the trial participants, and to determine if the trial participants are 
truly representative of the impacted population. The year of birth is collected to 
stratify the population. 
− 
The participant’s medical/surgical history will be obtained by interviewing the 
participant and/or the participant's legally authorized representative and/or 
review of the participant’s medical records. Any pre-existing conditions, signs 
and/or symptoms present prior to the first dose of study treatment will be 
recorded in the eCRF. 
− 
Pretreatment baseline specimens for microbiological testing will be collected as 
described in Section 9.1 and Table 2. 
− 
Following completion of all pretreatment assessments, eligible participants will 
be randomly assigned to treatment as described in Section 7.3. 
− 
The first oral gepotidacin dose (3000 mg) or the IM ceftriaxone dose (500 mg) 
plus the oral azithromycin dose (1 g) will be administered at the study site. Oral 
study treatment (gepotidacin and azithromycin) should be taken after food 
consumption and with water to assist with tolerability. After dose 
administration, Day 1 posttreatment assessments will be performed, as shown in 
Table 1. Any AEs or clinically significant changes should be followed 
accordingly. 
− 
Participants randomly assigned to gepotidacin will self-administer the second 
3000-mg oral dose as an outpatient 10 to 12 hours after the first dose; however, 
for participants who weigh <50 kg or have moderate renal impairment, the 
second dose should be taken approximately 12 hours after the first dose. 
Gepotidacin study treatment should be taken after food consumption and with 
water to assist with tolerability. Note: The second dose may occur on Day 1 or 
Day 2, depending on the time at which the first dose was taken. Participants 
randomly assigned to gepotidacin will be contacted to confirm that they took 
their second gepotidacin dose (see Section 7.6). 


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− 
The TOC and Follow-up Visits should be scheduled before the participant 
leaves the study site on Day 1 (as indicated in Table 1); the planned return 
day/time should be at the convenience of the participant and also the availability 
of the study site staff. 
• 
TOC (Day 4 to 8) Visit: Participants will be instructed to return to the study site 3 to 
7 days following study treatment administration at Baseline in order to complete the 
TOC Visit. Assessments will be performed as shown in Table 1, including the 
following: 
− 
The TOC Visit will be preceded by a documented reminder contact from the 
study site to the participant 24±4 hours before the scheduled appointment time 
per the method (e.g., text message, telephone call, e-mail) confirmed with the 
study site staff prior to departing the study site on Day 1. 
− 
Specimens for microbiological testing will be collected as described in 
Section 9.1 and Table 2. 
− 
Participants may return to the study site before the scheduled TOC Visit due to 
AEs.  
− 
Participants testing positive for a CT and/or Mgen infection per baseline NAAT 
results should be treated, as required, per local standard of care at the TOC Visit 
only after completion of all visit procedures or at any point after the TOC Visit. 
− 
Participants with culture-confirmed bacterial persistence of urogenital and, as 
appropriate, pharyngeal and/or rectal NG should receive appropriate alternative 
therapy per the investigator’s choice either on or after the TOC Visit, based on 
availability of results. 
• 
Follow-up (Day 14 to 21) Visit: Participants will be instructed to return to the study 
site 14 to 21 days following study treatment administration at Baseline in order to 
complete the Follow-up Visit. Assessments will be performed as shown in Table 1, 
including the following: 
− 
The Follow-up Visit will be preceded by a documented reminder contact from 
the study site to the participant 24±4 hours before the scheduled appointment 
time per the method (e.g., text message, telephone call, e-mail) confirmed with 
the study site staff prior to departing the study site on Day 1. 
− 
The investigator and/or study site staff should make every effort to ensure a 
participant returns for this visit. If it is determined that the participant is unable 
to return to the study site, the Follow-up Visit assessments may be completed 
via telephone, with the exception of assessments requiring sample collection for 
laboratory testing. 
− 
Specimens for microbiological testing will be collected as described in 
Section 9.1 and Table 2. 
− 
Participants may return to the study site before the scheduled Follow-up Visit 
due to AEs or if they feel they are not responding to any alternative therapy 
started after the TOC Visit. 


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− 
Participants testing positive for a CT and/or Mgen infection per baseline NAAT 
results should be treated, as required, per local standard of care (if treatment has 
not already been initiated) only after completion of all Follow-up Visit 
procedures. 
9.1. 
Efficacy Assessments 
Microbiological efficacy laboratory assessments were performed at PPD Global Clinical 
Laboratory and JMI Laboratories. Addresses for the central laboratories, as well as all 
local laboratories, are provided in the List of Clinical Laboratories Used for Human 
Biological Sample Analysis, which will be stored in the trial master file. 
9.1.1. 
Bacteriology Samples for Culture 
Multiple swab specimens and types may need to be obtained from each anatomical site; 
refer to the laboratory manual. See Table 2 for collection of bacteriology samples. 
At the Baseline Visit, a pretreatment urogenital swab specimen must be obtained from all 
participants for Gram stain (male and females) and bacteriological culture for NG. 
Pretreatment pharyngeal and rectal swab specimens will also be obtained from 
participants who are willing to provide such specimens, regardless of known exposure, 
for bacteriological culture for NG.  
At the TOC Visit, specimens will be obtained for Gram stain (urogenital specimens only) 
and bacteriological culture for NG only from all body sites collected at Baseline.  
At the Follow-up Visit, only pharyngeal swab specimens will be obtained for 
bacteriological culture for NG from participants who had a positive NAAT assay for 
pharyngeal NG at both Baseline and TOC. 
Gram stain and bacteriological cultures will be performed at a designated laboratory(ies). 
Confirmation of identification and susceptibility testing by agar dilution will be 
conducted at a designated laboratory(ies) for all isolates of NG recovered at all visits 
from all body sites. Instructions for sample collection, processing, and shipment are 
provided in the SRM and the laboratory manual. Laboratories should follow the 
Microbiology Procedures section of the laboratory manual to minimize potential 
contamination of the specimens or isolates. 
Only those participants who have NG confirmed by a designated laboratory(ies) from 
their baseline bacteriology specimen will be evaluated for microbiological outcome and 
response. The microbiological outcome and response to the study treatment will be 
determined programatically at GSK before breaking of the study blind. (Note: The 
sponsor is blinded to participant treatment assignment; see Section 7.4.) 
The microbiological outcome is determined by comparing the baseline culture results to 
the respective culture results at each subsequent visit. The corresponding microbiological 
response (success or failure) “by participant” will then be assigned, as shown in Table 5. 


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Table 5 
Determining Microbiological Outcome and Response at the TOC 
Visit 
Defining Criteria 
Microbiological 
Outcome 
Microbiological 
Response 
Culture-confirmed elimination of baseline NG 
pathogen from a bacteriology sample taken at 
the TOC Visit, without the participant 
receiving other systemic antimicrobials before 
this visit 
Bacterial eradication 
Microbiological 
success 
Culture-confirmed persistence of baseline NG 
pathogen from a bacteriology sample taken at 
the TOC Visit, without the participant 
receiving other systemic antimicrobials before 
this visit 
Bacterial persistence 
Microbiological failure 
1) A determination of the TOC NG pathogen 
microbiological outcome cannot be made 
(e.g., no bacteriology sample taken for 
culture, sample lost, visit did not occur) 
2) The participant received other systemic 
antimicrobials before the TOC Visit 
Unable to determine 
Microbiological failure 
NG=Neisseria gonorrhoeae; TOC=Test-of-Cure. 
Note: A bacteriological specimen refers to either a urogenital, pharyngeal, or rectal sample obtained for 
bacteriological culture. Microbiological outcomes are determined on a per-pathogen and per-specimen source 
basis. 
9.1.2. 
NAAT Assay 
Refer to the laboratory manual for local versus central laboratory details and the number 
and type of specimens to collect for NAAT assay. See Table 2 for collection of NAAT 
assay samples. 
Pretreatment urogenital specimens will be obtained from all participants for NAAT assay 
to detect the presence of NG, Mgen, and CT nucleic acids at the Baseline Visit. 
Urogenital specimens will also be obtained from all participants for NAAT assay to 
detect the presence of NG and CT nucleic acids at the TOC Visit. At the Follow-up Visit, 
a urogenital specimen for NAAT assay will be collected for detection of Mgen only from 
participants who had a positive NAAT assay for Mgen at Baseline. 
In addition, pretreatment baseline pharyngeal and rectal specimens for NAAT assay for 
detection of NG and CT will be obtained from participants who are willing to provide 
such specimens, regardless of known exposure. Specimens will also be collected for 
NAAT assay for detection of NG and CT at the TOC Visit from all body sites collected at 
the Baseline Visit. At the Follow-up Visit, a pharyngeal specimen for NAAT assay will 
be collected for detection of NG and CT from participants whose NAAT assay had the 
presence of nucleic acid for NG at both Baseline and TOC.  


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The NAAT assay will be performed at a designated laboratory(ies). Participants testing 
positive for CT or Mgen nucleic acid by NAAT assay at the Baseline Visit should be 
treated per local standard of care at or after the TOC Visit or at the Follow-up Visit (if 
treatment has not already been initiated), as required, after all study procedures for the 
visit have been completed.  
Only those participants who have NG or Mgen nucleic acid detected from their baseline 
NAAT specimen will be evaluated for NAAT outcome and response. The NAAT 
outcome and response to study treatment will be determined by an algorithm at GSK 
before breaking of the study blind (Note: Sponsor is blinded to participant treatment 
assignment; see Section 7.4). 
For the exploratory objectives, the NAAT outcome is determined by comparing the 
baseline NAAT result with the respective NAAT result at each subsequent visit. The 
corresponding NAAT response (success or failure) “by participant” will then be assigned, 
as shown in Table 6 and Table 7. 
Table 6 
Determining NAAT Outcome and Response at the Test-of-Cure Visit 
(NG Only) 
Defining Criteria 
NAAT Outcome 
NAAT Response  
Clearance of baseline pathogen nucleic acid 
from a specimen taken at the TOC Visit, without 
the participant receiving other systemic 
antimicrobials before this visit 
Nucleic acid 
clearance 
NAAT success 
Persistence of baseline pathogen nucleic acid 
from a specimen taken at the TOC Visit, without 
the participant receiving other systemic 
antimicrobials before this visit 
Nucleic acid 
persistence 
NAAT failurea 
1) A determination of the nucleic acid 
outcome from a specimen taken at the 
TOC Visit cannot be made (e.g., no 
sample taken, sample lost, visit did not 
occur) 
2) The participant received other systemic 
antimicrobials before the TOC Visit 
Unable to determine 
NAAT failurea 
NAAT=nucleic acid amplification test; NG=Neisseria gonorrhoeae; TOC = Test-of-Cure. 
Note: Specimen refers to either a urogenital, pharyngeal, or rectal specimen obtained for NAAT. The NAAT 
outcomes are determined on a per-pathogen basis.  
a. 
Participants who are a “NAAT failure” at the TOC Visit assessment yet are not switched to other systemic 
antimicrobials are evaluable at subsequent time points. 


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Table 7 
Determining NAAT Outcome and Response at the Follow-Up Visit 
(Pharyngeal NG and Mgen Only) 
Defining Criteria 
NAAT Outcome 
NAAT Response  
Clearance of baseline pathogen nucleic acid 
from a specimen taken at the Follow-up Visit, 
without the participant receiving other systemic 
antimicrobials before this visit 
Nucleic acid 
clearance 
NAAT success 
Persistence of baseline pathogen nucleic acid 
from a specimen taken at the Follow-up Visit, 
without the participant receiving other systemic 
antimicrobials before this visit 
Nucleic acid 
persistence 
NAAT failure 
A determination of the nucleic acid outcome 
from a specimen taken at the Follow-up Visit 
cannot be made (e.g., no sample taken, sample 
lost, visit did not occur) 
Note: Any participants who received other 
systemic antimicrobials before the Follow-up 
Visit will not be evaluated for NAAT outcome or 
response at the Follow-up Visit 
Unable to determine 
NAAT failure 
Mgen=Mycoplasma genitalium; NAAT=nucleic acid amplification test; NG=Neisseria gonorrhoeae. 
Note: Specimen refers to either a urogenital or pharyngeal specimen obtained for NAAT. The NAAT outcomes are 
determined on a per-pathogen basis and will only be conducted if both the Baseline (NG and Mgen) and TOC 
(NG only) NAAT assay showed the presence of nucleic acid for the respective pathogen and specimen.  
9.2. 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 4. 
The investigator and any designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study treatment or the study, 
or that caused the participant to discontinue the study treatment or from the study (see 
Section 8). PPD was responsible for the safety oversight for this study. 
9.2.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All SAEs will be collected from the signing of the ICF until the Follow-up Visit at 
the time points specified in Table 1 (Section 2).  
• 
All AEs will be collected from the start of treatment until the Follow-up Visit at the 
time points specified in Table 1 (Section 2). 
• 
Medical occurrences that begin before the start of study treatment but after obtaining 
informed consent will be recorded on the medical history/current medical conditions 
section of the eCRF and not the AE section. 
• 
All SAEs will be recorded and reported to the sponsor or designee immediately and 
under no circumstances should this exceed 24 hours, as indicated in Appendix 4. The 


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investigator will submit any updated SAE data to the sponsor within 24 hours of it 
being available. 
• 
Investigators are not obligated to actively seek AEs or SAEs in former study 
participants. However, if the investigator learns of any SAE, including a death, at 
any time after a participant has been discharged from the study, and he or she 
considers the event to be reasonably related to the study treatment or study 
participation, the investigator must promptly notify the sponsor. 
• 
The method of recording, evaluating, and assessing causality of AEs and SAEs and 
the procedures for completing and transmitting SAE reports are provided in 
Appendix 4. 
9.2.2. 
Method of Detecting AEs and SAEs 
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 occurrence.  
9.2.3. 
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 and nonserious AEs of special interest 
(as defined in Section 9.2.5) will be followed until the event is resolved, stabilized, 
otherwise explained, or the participant is lost to follow-up (as defined in Section 8.3). 
Further information on follow-up procedures is given in Appendix 4. 
9.2.4. 
Regulatory Reporting Requirements for SAEs 
• 
Prompt notification by the investigator to the sponsor of an SAE is essential so that 
legal obligations and ethical responsibilities towards the safety of participants and 
the safety of a study treatment 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 treatment under clinical 
investigation. The sponsor will comply with country-specific regulatory 
requirements relating to safety reporting to the regulatory authority, IRBs/IECs, and 
investigators. 
• 
Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary. 
• 
An investigator who receives an investigator safety report describing an SAE or 
other specific safety information (e.g., summary or listing of SAEs) from the sponsor 
will review and then file it along with the IB and will notify the IRB/IEC, if 
appropriate according to local requirements. 


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9.2.5. 
Adverse Events of Special Interest 
Predefined AEs of special interest for this study are cardiovascular (CV) events, 
gastrointestinal events, C. difficile infection or colitis events, and AEs related to 
acetylcholinesterase inhibition (see Section 3.3.1), which will be identified by a 
prespecified list of coded terms or determined by algorithm, as described in the reporting 
and analysis plan (RAP). Additional details are provided in Appendix 4. 
C. difficile specimens were analyzed at IHMA, Inc. Addresses for the central laboratories, 
as well as all local laboratories, are provided in the List of Clinical Laboratories Used for 
Human Biological Sample Analysis, which will be stored in the trial master file. 
9.2.6. 
Cardiovascular and Death Events 
For any CV events detailed in Appendix 4 and all deaths, whether or not they are 
considered SAEs, specific CV and death sections of the eCRF will be required to be 
completed. These sections include questions regarding CV (including sudden cardiac 
death) and non-CV death.  
The CV eCRFs are presented as queries in response to reporting of certain CV Medical 
Dictionary for Regulatory Activities (MedDRA) terms. The CV information should be 
recorded in the specific CV section of the eCRF within 1 week of receipt of a CV event 
data query prompting its completion. 
The death eCRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within 1 week 
of when the death is reported. 
9.2.7. 
Pregnancy 
• 
Details of all pregnancies in female participants will be collected after the start of 
study treatment and through the Follow-up Visit. 
• 
If a pregnancy is reported, the investigator should inform GSK/PPD within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in 
Appendix 6. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
9.3. 
Treatment of Overdose 
In the ceftriaxone plus azithromycin treatment group, only 1 dose of ceftriaxone and 
1 dose of azithromycin are administered during the study, and both are administered at 
the study site. Although 2 doses of gepotidacin will be administered in the study, 
participants will not have access to more than the required gepotidacin dose at each 
dosing time point. At the Baseline Visit, the first gepotidacin dose is administered at the 
study site and the study site staff will dispense to the participant only the number of 
tablets required for the second dose (self-administered as an outpatient 10 to 12 hours 
after the first dose). Therefore, overdoses of either study treatment are not anticipated in 
this study.  


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There is no specific antidote for overdose with a bacterial topoisomerase inhibitor. In the 
event of a suspected overdose, it is recommended that the appropriate supportive clinical 
care should be instituted, as dictated by the participant’s clinical status. 
There is no specific antidote for an overdose of ceftriaxone or azithromycin. Treatment of 
an overdose should be symptomatic (refer to the locally approved ceftriaxone and 
azithromycin prescribing information). 
9.4. 
Safety Assessments 
Planned time points for all safety assessments are provided in Table 1. 
9.4.1. 
Physical Examinations 
• 
A complete physical examination will be performed at the Baseline Visit and a 
gonorrhea-focused physical examination will be performed at the TOC Visit. At 
Baseline, the complete physical examination will include assessments of the 
respiratory, CV, abdominal, gastrointestinal, and urogenital systems, as well as 
pharyngeal and rectal examinations with collections of microbiology specimen(s) as 
appropriate (see Section 9.1). Height and weight will only be measured and recorded 
at the Baseline Visit (before dosing). The gonorrhea-focused physical examination at 
the TOC visit will include urogenital systems, as well as pharyngeal and rectal 
examinations with collections of microbiology specimen(s) as appropriate (see 
Section 9.1). 
• 
Investigators should pay special attention to clinical signs related to previous serious 
illnesses. 
• 
Clinically significant changes from baseline or clinically significant new clinical 
signs will be reported as AEs. 
9.4.2. 
Vital Signs 
• 
Vital signs will be measured at the time points indicated in Table 1. 
• 
Vital signs will be measured in a semi-supine position after 5 minutes rest and will 
include temperature, systolic and diastolic blood pressure, and pulse rate. 
− Vital sign measurements should be obtained before any blood draws scheduled 
on the same assessment day. 
− Clinically significant changes from baseline will be reported as AEs. 


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9.4.3. 
Electrocardiograms 
• 
Triplicate 12-lead ECGs (over an approximate 5- to 10-minute period) will be 
performed at the Baseline Visit using an ECG machine that automatically calculates 
the heart rate and measures PR, QRS, QT, and QTc intervals. Refer to Section 8.1.2 
for QTc withdrawal criteria and additional QTc readings that may be necessary. 
• 
This protocol only requires an ECG evaluation at the Baseline Visit. Ideally, ECGs 
will be obtained before any vital sign measurements or blood draws scheduled on the 
same assessment day; however, sites may perform procedures in an order per their 
standard of care, as long as participants return to a resting state prior to the start of 
the ECG collections. Subsequent ECGs only need to be triplicate if the initial one is 
prolonged. 
• 
If clinically significant changes occur during the study, they will be reported as AEs. 
• 
Equipment provided qualified ECG machines and supportive maintenance during the 
study to sites that required provision.  
9.4.4. 
Clinical Safety Laboratory Assessments 
• 
Refer to Appendix 2 for the list of clinical laboratory tests to be performed and to 
Table 1 for the timing and frequency.  
• 
The investigator must review the laboratory report, document this review, and record 
any clinically relevant 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 should be repeated until the values return to normal or 
baseline or are no longer considered significantly abnormal by the investigator or 
medical monitor.  
• 
If such values do not return to normal or baseline within a period of time judged 
reasonable by the investigator, the etiology should be identified and the sponsor 
notified. 
• 
All protocol-required laboratory assessments, as defined in Appendix 2, must be 
conducted in accordance with the laboratory manual and Table 1.  
• 
All safety laboratory tests will be performed at PPD Global Clinical Laboratory. 
Addresses for the central laboratories, as well as all local laboratories, are provided 
in the List of Clinical Laboratories Used for Human Biological Sample Analysis, 
which is stored in the trial master file. 


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9.5. 
Pharmacokinetics 
No PK samples will be collected in this study except as potentially required for liver 
safety follow-up assessments as described in Appendix 8. Any PK samples will be 
performed by PPD Bioanalytical Lab. 
9.6. 
Pharmacodynamics 
Microbiological assessments will include the determination of gepotidacin MICs and 
other antibacterial MICs for urogenital, pharyngeal, and rectal NG isolates in this study. 
The MIC values will be used in the PD analysis. 
9.7. 
Genetics 
A 6-mL blood sample for DNA isolation will be collected from participants who have 
consented to participate in the genetics analysis component of the study. Participation is 
optional. Participants who do not wish to participate in the genetic research may still 
participate in the study. 
In the event of DNA extraction failure, a replacement genetic blood sample may be 
requested from the participant. Signed informed consent will be required to obtain a 
replacement sample unless it was included in the original consent. 
Details on processes for collection and shipment and destruction of these samples can be 
found in Appendix 7. 
9.8. 
Biomarkers 
Biomarkers are not evaluated in this study. 
9.9. 
Health Economics or Medical Resource Utilization and 
Health Economics 
Health economics/medical resource utilization and health economics parameters are not 
evaluated in this study. 


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10. 
STATISTICAL CONSIDERATIONS 
Full details of all data handling conventions and statistical analyses conducted for this 
study will be provided in the RAP. 
10.1. 
Statistical Hypothesis 
The study is designed to demonstrate that gepotidacin administered orally is noninferior 
compared to ceftriaxone plus azithromycin on the primary efficacy endpoint of 
culture-confirmed eradication of NG from the urogenital body site (i.e., microbiological 
success) at the TOC Visit. 
The following are null and alternative hypotheses for the primary analysis of the 
microbiological success rates at the prespecified noninferiority margin of -10%: 
H0: Microbiological success rate of gepotidacin – Microbiological success rate of 
ceftriaxone plus azithromycin ≤-10.0% 
H1: Microbiological success rate of gepotidacin – Microbiological success rate of 
ceftriaxone plus azithromycin >-10.0% 
Gepotidacin will be declared noninferior to treatment with ceftriaxone plus azithromycin 
if the lower limit of the 2-sided 95% CI for the difference between the microbiological 
success rate of gepotidacin and ceftriaxone plus azithromycin at the TOC Visit is 
above -10.0%. Superiority of gepotidacin will be declared if the lower end of the CI is 
above 0%. 
The difference in the microbiological success rate between the 2 treatment groups and the 
corresponding CI will be computed using the Miettinen and Nurminen method 
[Miettinen, 1985]. 
10.2. 
Sample Size Determination 
10.2.1. 
Justification of Sample Size 
Approximately 400 participants will be needed for the primary analysis population (i.e., 
the micro-ITT Population, as defined in Section 10.3) to demonstrate efficacy of 
gepotidacin in this study.  
A conservative estimate of a 90% microbiological success rate has been assumed for 
ceftriaxone 500 mg IM plus azithromycin 1 g orally. Participants not returning for TOC 
will be considered a microbiological failure in this study. 


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Assuming a 90% microbiological success rate of ceftriaxone plus azithromycin and the 
same value for the actual success rate of gepotidacin, a sample size of 400 urogenital 
microbiological evaluable participants (200 participants in each treatment) will provide 
approximately 91% power to demonstrate noninferiority of gepotidacin and ceftriaxone 
plus azithromycin in adolescents and adults with uncomplicated gonorrhea caused by NG 
with a 0.025 one-sided significance level and a -10% noninferiority margin.  
Approximately 620 participants will be enrolled and randomized 1:1 to gepotidacin and 
ceftriaxone plus azithromycin in order to identify approximately 400 participants that 
meet the definition of the micro-ITT Population.  
10.2.2. 
Sample Size Sensitivity 
Sensitivity of the sample size has been explored considering various microbiological 
success rates. The assumed reference microbiological success rate affects the power for a 
target number of participants in the study. Table 8 shows the power with the target 
number of participants in this clinical trial under different assumptions of the 
microbiological success rate.  
Table 8 
Power of the Study for the Target Microbiological Intent-to-Treat 
Population at Various Microbiological Success Rates 
Microbiological 
Success Rate of 
Ceftriaxone Plus 
Azithromycin 
Microbiological 
Success Rate of 
Gepotidacin 
Total Number of 
Participants in 
the Primary 
Analysis 
Number of 
Participants in the 
Primary Analysis in 
Each Treatment Group 
Power 
92% 
92% 
400 
200 
95% 
90% 
90% 
400 
200 
91% 
89% 
89% 
400 
200 
89% 
88% 
88% 
400 
200 
86% 
87% 
87% 
400 
400 
84% 
The power of the study will remain above 84% if the true microbiological success rate in 
the 2 treatment groups is the same and 87% or higher. 


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10.3. 
Populations for Analyses 
For purposes of analysis, the following key populations are defined: 
Population 
Description 
Screened Population 
All participants who were screened for eligibility. 
Intent-to-Treat (ITT) 
Population 
All participants randomly assigned to study treatment.  
Participants will be analyzed according to their randomized study 
treatment arm. 
Microbiological ITT 
(micro-ITT) Population 
All participants randomly assigned to study treatment who 
receive at least 1 dose of study treatment and have confirmed 
NG isolated that is ceftriaxone-susceptible from baseline culture 
of their urogenital specimen. 
Participants will be analyzed according to their randomized study 
treatment arm. 
This is the primary analysis population. 
Micro-ITT Rectal 
Population 
Participants who meet the definition of the micro-ITT Population 
and have confirmed NG isolated that is ceftriaxone-susceptible 
from baseline culture of their rectal specimen. 
Participants will be analyzed according to their randomized study 
treatment arm. 
Micro-ITT Pharyngeal 
Population 
Participants who meet the definition of the micro-ITT Population 
and have confirmed NG isolated that is ceftriaxone-susceptible 
from baseline culture of their pharyngeal specimen. 
Participants will be analyzed according to their randomized study 
treatment arm. 
Microbiologically Evaluable 
(ME) Population 
Participants who meet the definition of the micro-ITT Population 
and follow important components of the study (i.e., [1] receive all 
planned doses as randomized and actual treatment is the same 
as randomized, [2] have a urogenital specimen collected at the 
TOC Visit, with available culture results, [3] have not taken any 
other systemic antibiotic prior to the TOC Visit, unless it was 
taken for the current infection, and [4] have no major deviation 
that prevents evaluation of efficacy). 
Participants will be analyzed according to their randomized study 
treatment arm. 
Safety Population 
All participants who receive at least 1 dose of study treatment.  
Participants will be analyzed according to their actual treatment 
received. 
 Mgen=Mycoplasma genitalium; NG=Neisseria gonorrhoeae; TOC=Test-of-Cure. 


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10.4. 
Statistical Analyses 
10.4.1. 
General Considerations 
Any additional analysis populations or supplemental analyses will be detailed in the 
RAP. Any additional analyses or outputs needed as a result of COVID-19 on the study 
will be detailed in the RAP. 
10.4.2. 
Efficacy Analyses 
Endpoint 
Statistical Analysis Methods 
Primary 
The primary analysis will be performed using the micro-ITT Population. 
• The primary efficacy endpoint is culture-confirmed bacterial eradication 
of NG from the urogenital body site (i.e., microbiological success) at the 
TOC (Day 4 to 8) Visit. For this analysis, participants who do not return 
for the TOC (Day 4 to 8) Visit will be treated as failures. 
• The number and percentage of participants with culture-confirmed 
bacterial eradication of NG from the urogenital body site (i.e., 
microbiological success) will be summarized, along with 95% CIs, at the 
TOC (Day 4 to 8) Visit by treatment group. 
• The difference in microbiological success rates between gepotidacin and 
ceftriaxone plus azithromycin for culture-confirmed bacterial eradication 
of urogenital NG at the TOC Visit will be summarized, along with 95% 
CIs. 
• Gepotidacin will be declared noninferior to treatment with ceftriaxone plus 
azithromycin if the lower limit of the 2-sided 95% CI for the difference 
between the microbiological success rate of gepotidacin and ceftriaxone 
plus azithromycin at the TOC Visit is above -10.0%. Superiority of 
gepotidacin will be declared if the lower end of the CI is above 0%. The 
Miettinen and Nurminen method will be used for the analysis adjusting for 
treatment and stratification factors of sex and sexual orientation 
combination (i.e., MSM, MSW, or female). 
• A further supplementary analysis on the primary endpoint may be 
performed based on the Microbiologically Evaluable Population. 
Additional sensitivity analysis, if warranted, will be described in the RAP.  
• The microbiological success in each treatment group along with the 
difference in microbiological success rates for culture-confirmed bacterial 
eradication of urogenital NG at the TOC Visit between gepotidacin and 
ceftriaxone plus azithromycin will be summarized (along with 95% CI) by 
subgroups based on sex and sexual orientation combination (MSM, 
MSW, or female). Further analyses may be performed based on the 
observed differences between the treatment groups in these subgroups; 
additional details will be provided in the RAP. 


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Endpoint 
Statistical Analysis Methods 
Secondary 
Secondary analyses will be performed using the micro-ITT Population subset 
to only include participants with confirmed NG isolated from baseline culture 
of their rectal/pharyngeal specimen, respectively, unless otherwise specified. 
• The microbiological success rates for culture-confirmed bacterial 
eradication of rectal NG at the TOC Visit will be summarized by 
treatment group and sex and sexual orientation combination. 
• The microbiological success rates for culture-confirmed bacterial 
eradication of pharyngeal NG at the TOC Visit will be summarized by 
treatment group and sex and sexual orientation combination. 
• Additional details will be provided in the RAP. 
Exploratory 
• 
Gram stain (urogenital specimens only), bacterial culture, and in vitro 
susceptibility test results and NAAT results at the Baseline, TOC (Day 4 
to 8), and Follow-up (Day 14 to 21) Visits will be summarized as data 
permit. 
• 
Details regarding exploratory analyses, including additional exploratory 
analyses not defined in the protocol, will be described in the RAP. 
PPD, in conjunction with GSK, will perform the analysis of the primary and secondary 
endpoints. 
10.4.3. 
Safety Analyses 
All safety analyses will be performed on the Safety Population. The severity of AEs and 
SAEs will be determined by the investigator according to the US National Institute of 
Allergy and Infectious Diseases Division of Microbiology and Infectious Diseases 
(DMID) criteria for adult toxicity assessment [DMID, 2007a], with the exception of 
serum creatinine adolescent laboratory data, which will be assessed using pediatric 
toxicity criteria [DMID, 2007b] (Appendix 5). All reported AEs will be coded using 
MedDRA and summarized by system organ class and preferred terms. 


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Endpoint 
Statistical Analysis Methods 
Secondary 
• 
The number and percentage of treatment-emergent AEs, study treatment 
related AEs, deaths, SAEs, and AEs leading to study treatment or study 
withdrawal will be provided. 
• 
Treatment-emergent AEs will be summarized by severity. 
• 
Change from baseline over time in laboratory parameters and vital signs 
will be summarized with descriptive statistics. 
• 
The frequency of laboratory abnormality events along with the shift from 
baseline to the worst-case postbaseline value will be provided. Abnormal 
liver chemistry results will be determined using increases above the upper 
limit of normal. Changes from baseline values will be summarized with 
descriptive statistics. 
• 
The severity of specified AEs and laboratory abnormalities will be graded 
according to the modified DMID toxicity grading system (Appendix 5). 
Data will be tabulated and reported by absolute grade for Grades 3 and 
higher and shift tables, as appropriate. 
• 
Adverse events of special interest will include CV, gastrointestinal, and 
C. difficile infection or colitis events. In addition, AEs associated with 
acetylcholinesterase inhibition are also considered special interest. As 
described in the RAP, manual and programmatic reviews of AEs/preferred 
terms will be used to assess these events. 
• 
Baseline ECG results will be provided in a listing. 
10.4.4. 
Other Analyses 
Pharmacodynamic analysis will be performed to examine the potential relationship 
between MIC values for the treatment/isolate pairings in this study and microbiological 
response at the TOC Visit. The full details will be described in the RAP. 
10.5. 
Interim Analysis 
No interim analysis is planned for this study. 
10.6. 
Data Monitoring Committee or Other Review Board 
An internal GSK Safety Review Team will monitor blinded safety data and an internal 
Microbiology Review Team will monitor blinded microbiological data instream. No 
external data monitoring review committees are planned for the study. For details on 
these internal review teams, refer to Appendix 3. 


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11. 
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Pharmacokinetics–pharmacodynamics of antimicrobial therapy: it's not just for mice 
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Australian Sexual Health Alliance (ASHA). Australian STI management guidelines for 
use in primary care: gonorrhoea. http://www.sti.guidelines.org.au/sexually-transmissible-
infections/gonorrhoea. Last updated June 2016. Accessed 05-Apr-2017. 
Barry PM, Klausner JD. The use of cephalosporins for gonorrhea: the impending problem 
of resistance. Expert Opin Pharmacother. 2009;10(4):555-77. 
Bax BD, Chan PF, Eggleston DS, et al. Type IIA topisomerase inhibition by a new class 
of antibacterial agents. Nature. 2010;466(7309:935-40. 
Biedenbach DJ, Bouchillon SK, Hackel M et al. In vitro activity of gepotidacin, a novel 
triazaacenaphthylene bacterial topoisomerase inhibitor, against a broad spectrum of 
bacterial pathogens. Antimicrob Agents Chemother. 2016;60(30):1918-23. 
Bignell C, Unemo M; European STI Guidelines Editorial Board. 2012 European 
guideline on the diagnosis and treatment of gonorrhoeae in adults. Int J STD AIDS. 
2013;24(2):85-92. 
Centers for Disease Control and Prevention (CDC). Antibiotic resistance threats in the 
United States, 2019. https://www.cdc.gov/drugresistance/pdf/threats-report/2019-ar-
threats-report-508.pdf. Accessed 01-Aug-2021. 
Centers for Disease Control and Prevention (CDC). Morbidity and Mortality Weekly 
Report (MMWR): Neisseria gonorrhoeae Antimicrobial Susceptibility Surveillance — 
The Gonococcal Isolate Surveillance Project, 27 Sites, United States, 2014. 
https://www.cdc.gov/mmwr/volumes/65/ss/ss6507a1.htm?s_cid=ss6507_w. Last updated 
15-Jul-2016. Accessed 14-Mar-2017. 
Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases 
treatment guidelines, 2015. MMWR Recomm Rep 2015;64(No. RR-3):1-137. 
https://www.cdc.gov/mmwr/preview/mmwrhtml/rr6403a1.htm. Accessed 03-Dec-2021. 
Centers for Disease Control and Prevention (CDC). Sexually transmitted diseases 
treatment guidelines, 2021. https://www.cdc.gov/std/treatment-guidelines/gonorrhea-
adults.htm#:~:text=Although%20clinical%20data%20confirm%20that%20a%20single%
20injection,necessary%20for%20isolates%20with%20elevated%20MICs%20%28880%2
C%20881%29. Last updated 09-Nov-2021. Accessed 17-Nov-2021. 
European Medicine Agency (EMA). Guideline on the evaluation of medicinal products 
indicated for treatment of bacterial infections. CPMP/EWP/558/95 rev 2. 15-Dec-2011. 


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Gibson EG, Bax B, Chan PF, et al. Mechanistic and structural basis for the actions of 
antibacterial gepotidacin against staphylococcus aureus gyrase. ACS Infect Dis. 
2019;5(4):570-81. 
Mushtaq S, Vickers A, Sadouki Z, et al. In vitro activities of gepotidacin, a novel 
triazaacenaphthylene and topoisomerase IV DNA gyrase inhibitor, against 
Gram-negative bacteria and Staphylococcus saprophyticus, poster P1849. 2019. Abstr 
29th ECCMID, Amsterdam, The Netherlands. 
Miettinen, O.S., and M.M. Nurminen. 1985. “Comparative Analysis of Two Rates. 
Statistics in Medicine, 213-226.  
Oviatt A, Huang J, Mattern K, et al. Biochemical and genetic evidence that gepotidacin 
demonstrates well-balanced dual targeting against DNA gyrase and topoisomerase IV in 
Escherichia coli, poster L0178. 2022. Abstr 32nd ECCMID, Lisbon, Portugal. 
US Department of Health and Human Services, DHHS, Food and Drug Administration, 
Center for Drug Evaluation and Research, Clinical/Antimicrobial. Guidance for industry. 
Uncomplicated gonorrhea: developing drugs for treatment. 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM401620.pdf. Last updated August 2015. Accessed 05-Apr-2016. 
US National Institute for Allergy and Infectious Disease Division of Microbiology and 
Infectious Disease. Division of Microbiology and Infectious Disease (DMID) Adult 
Toxicity Table. Draft. https://www.niaid.nih.gov/sites/default/files/dmidadulttox.pdf. 
Last updated November 2007a. Accessed 10-Mar-2017. 
US National Institute for Allergy and Infectious Diseases, Division of Microbiology and 
Infectious Diseases. Division of Microbiology and Infectious Diseases (DMID) Pediatric 
Toxicity Table. Draft. https://www.niaid.nih.gov/sites/default/files/dmidpedtox.pdf. Last 
updated November 2007b. Accessed 10-Mar-2017. 
Workowski KA, Berman SM, Douglas JM Jr. Emerging antimicrobial resistance in 
Neisseria gonorrhoeae: urgent need to strengthen prevention strategies. Ann Intern Med. 
2008;148(8):606-13. 
World Health Organization (WHO). Global priority list of antibiotic-resistant bacteria to 
guide research, discovery, and development of new antibiotics. 2017. 
http://www.who.int/medicines/publications/WHO-PPL-Short_Summary_25Feb-
ET_NM_WHO.pdf?ua=1. Accessed 12-Apr-2017. 
World Health Organization (WHO). WHO guidelines for the treatment of Neisseria 
gonorrhoeae. 2016. http://apps.who.int/iris/bitstream/10665/246114/1/9789241549691-
eng.pdf?ua=1. Accessed 14-Mar-2017. 


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12. 
APPENDICES 
12.1. 
Appendix 1: Abbreviations and Trademarks 
AE 
adverse event 
ALT 
alanine aminotransferase 
CDC 
Centers for Disease Control and Prevention  
CI 
confidence interval  
CONSORT 
Consolidated Standards of Reporting Trials  
COVID-19 
coronavirus disease 
CRF 
case report form 
CT 
Chlamydia trachomatis 
CV 
cardiovascular  
CYP3A4 
cytochrome P450 enzyme 3A4 
DMID 
Division of Microbiology and Infectious Diseases 
EAGLE 
Efficacy of Antibacterial Gepotidacin Evaluated 
ECG 
Electrocardiogram 
eCRF 
electronic case report form  
EMA 
European Medicines Agency  
EU 
European Union 
fAUC 
free drug area under the concentration-time curve 
FDA 
Food and Drug Administration  
fT>MIC 
free mean time above the minimum inhibitory 
concentration 
FU 
Follow-up 
GCP 
Good Clinical Practice 
HIV 
human immunodeficiency virus 


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IB 
investigator’s brochure  
ICF 
informed consent form  
ICH 
International Council on Harmonisation 
IEC 
independent ethics committee 
IM 
intramuscular  
IRB 
institutional review board 
IRT 
interactive response technology  
ITT 
Intent-to-Treat  
IV 
intravenous  
Kg 
Kilogram 
M 
Meter 
ME 
Microbiologically Evaluable 
MedDRA 
Medical Dictionary for Regulatory Activities  
Mg 
Milligram 
Mgen 
Mycoplasma genitalium 
MIC 
minimum inhibitory concentration  
MIC50 
50th percentile minimum inhibitory concentration 
MIC90 
90th percentile minimum inhibitory concentration 
micro-ITT 
Microbiological Intent-to-Treat  
Min 
Minute 
mL 
Milliliter 
Mm 
Millimeter 
Msec 
Millisecond 
MSM 
men who have sex with men 
MSW 
men who have sex with women 


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NAAT  
nucleic acid amplification test  
NG 
Neisseria gonorrhoeae 
PD 
Pharmacodynamic 
PK 
pharmacokinetic  
QTc 
corrected QT interval 
QTcB 
QT interval corrected for heart rate according to Bazett 
QTcF 
QT interval corrected for heart rate according to 
Fridericia  
RAP 
reporting and analysis plan  
SAE 
serious adverse event 
SRM 
Study Reference Manual  
SRT 
Safety Review Team 
TdP 
torsades de pointes  
TOC 
Test-of-Cure  
µg 
Microgram 
ULN 
upper limit of normal 
WHO 
World Health Organization  
WOCBP 
woman of childbearing potential  
Trademark Information 
Trademarks of the GSK 
 group of companies 
 
Trademarks not owned by the GSK 
group of companies 
NONE 
 
FIRST RESPONSE 
 
 
MedDRA 


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12.2. 
Appendix 2: Clinical Laboratory Tests 
• 
The tests detailed in Table 9 will be performed by the central laboratory.  
− Local laboratory results are only required in the event that the central laboratory 
results are not available in time for response evaluation. If a local sample is 
required, it is important that the sample for central analysis is obtained at the 
same time. 
• 
Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 6 of the protocol. 
• 
Additional tests may be performed at any time during the study as determined 
necessary by the investigator or required by local regulations. 


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Table 9 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet count  
RBC Indices: 
MCV 
MCH 
WBC Count With 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
RBC count 
Hemoglobin 
Hematocrit 
Clinical 
Chemistrya 
Blood urea 
nitrogen 
Potassium 
AST/SGOT 
Total and direct 
bilirubin 
Creatinine 
Sodium 
ALT/SGPT 
Total protein 
Glucose, 
nonfasting 
Calcium 
Alkaline 
phosphatase 
Albumin 
Chloride 
Magnesium 
 
 
Routine 
Urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, and ketones by dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
Other 
Screening 
Tests 
• 
Serum or urine alcohol and drug screen (to include at minimum: 
amphetamines, barbiturates, cocaine, opiates, cannabinoids, and 
benzodiazepines) 
• 
Urine hCG pregnancy test (as needed for women of childbearing 
potential)b 
• 
Serology (HBsAg, hepatitis C virus antibody, and HIV). If serology 
testing was performed within 3 months prior to the first dose of study 
treatment and results were positive, testing at Baseline is not required. 
If testing was performed within 3 months and any result was negative, 
testing at Baseline is required. 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; eCRF=electronic case report form; 
HBsAg=hepatitis B surface antigen; hCG=human chorionic gonadotropin; HIV=human immunodeficiency 
virus; MCH=mean corpuscular hemoglobin; MCV=mean corpuscular volume; RBC=red blood cell; 
SGOT=serum glutamic-oxaloacetic transaminase; SGPT=serum glutamic-pyruvic transaminase; WBC=while 
blood cell. 
a. 
Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 8.1.1 and Appendix 8. All events of ALT ≥3 × upper limit of normal 
(ULN) and bilirubin ≥2 × ULN (>35% direct bilirubin) or ALT ≥3 × ULN and international normalized ratio 
(INR) >1.5, if INR measured, which may indicate severe liver injury (possible Hy’s Law), must be reported as 
a serious adverse event. 
b. 
See Appendix 6 for urine test requirement details. Local urine testing will be standard for the protocol unless 
serum testing is required by local regulation or the Institutional Review Board/Independent Ethics Committee. 


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12.3. 
Appendix 3: Study Governance Considerations 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with: 
− 
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 International Council on Harmonisation (ICH) Good Clinical 
Practice (GCP) Guidelines 
− 
Applicable laws and regulations 
− The protocol, protocol amendments, informed consent form (ICF)/assent 
form/eConsent (if applicable), investigator’s brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an institutional 
review board/independent ethics committee (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 are 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 serious adverse events (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 Code of Federal Regulations (CFR), ICH guidelines, the 
IRB/IEC, European regulation 536/2014 for clinical studies (if applicable), and 
all other applicable local regulations 
*Note:  In countries where the responsibility to perform these submissions and 
notifications resides with the sponsor rather than the investigator, GSK or their 
designee PPD (as described in the applicable powers of attorney) will take these 
responsibilities. 
Financial 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 
course of the study and for 1 year after completion of the study. 


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Informed Consent/Assent Process 
• 
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 should advise their sexual partner of their infection; 
this will be discussed with participants as part of the informed consent process and 
will be documented in the medical chart by the study site staff. 
• 
Participants must be informed that their participation is voluntary. Participants or 
their legally authorized representative will be required to sign a statement of 
informed consent and/or eConsent (if applicable) 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 and/or 
eConsent (if applicable) was obtained before the participant was enrolled in the study 
and the date informed consent was obtained. The authorized person obtaining the 
informed consent must also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s)/eConsent 
during their participation in the study.  
• 
A copy of the ICF(s)/eConsent must be provided to the participant or the 
participant’s legally authorized representative.  
− Adolescent participants should be asked for their written assent or eConsent (if 
appliable) to participate in the study. 
− As applicable, the IRB/IEC will be consulted before assent form development for 
guidance around age-appropriate groupings and any specific IRB/IEC 
requirements or local laws for conducting and documenting assent. 
Participants who are rescreened are required to sign a new ICF or provide eConsent (if 
applicable). 
Study Conduct Materials and Support 
The following vendors will be used to support study conduct, translations, participant 
recruitment, stipends, and transportation: 
Vendor Name 
Vendor Service 
Medable 
Telemedicine and teleconsent provider 
Proforma ProClinix 
Central advertising/printing/patient recruitment materials 
Signant Health 
Patient Texting Service 
Transperfect 
Translations (including labels & patient cards) 
TAKSEE 
Patient Transportation in Spain 
SERMES 
Patient Reimbursement in Spain  
Jumo Health 
Study Website 


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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. 
• 
GSK will ensure protection of the personal data of the investigator and site staff 
which is collected within the framework of and for the purpose of the study. 
• 
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 and as described in 
the ICF. 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. 
Committees Structure 
To protect the safety interests of participants, an internal GSK Safety Review Team will 
review blinded safety data instream on a regular basis throughout study conduct. Data 
reviewers will include but are not limited to the following participants: medical monitor, 
safety team lead, statistician, clinical team lead, and data quality lead. 
An internal Microbiology Review Team will monitor blinded pathogen identification and 
susceptibility data instream. 
No external data monitoring review committees are planned for the study. 
Provision will be made for a limited degree of unblinding of a minority of participant 
sample data should this be viewed as appropriate for planning closure of trial enrollment. 
Procedures will be described in a separate microbiology sample monitoring plan. 
Written documentation regarding key decisions made by the review teams/committee will 
be promptly distributed to participating investigators and IRB/IECs. 
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. 
• 
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 
study site data. In this case, a coordinating investigator will be designated by mutual 
agreement. 


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• 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
Dissemination of Clinical Study Data 
• 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov and/or GSK Clinical Study Register in compliance with 
applicable regulations/GSK policy. GSK will aim to register protocol summaries 
prior to study start and target results summaries submission within 12 months of the 
primary/study completion date. Where external regulations require earlier disclosure, 
GSK will follow those timelines. 
• 
Where required by regulation, summaries will also be posted on applicable national 
or regional clinical study registers. 
− 
Where required by applicable regulatory requirements, an investigator signatory 
will be identified for the approval of the clinical study report, and will be 
provided reasonable access to statistical tables, figures, and relevant reports. 
GSK will also provide the investigator with the full summary of the study 
results, including a summary of study results understandable to laypersons. The 
investigator is encouraged to share the plain language summary with the study 
participants, as appropriate. The full study report will be made available upon 
request, after decision on marketing authorization by regulatory authorities. 
• 
GSK will provide the investigator with the randomization codes and participant-level 
line listings for their site only after completion of the full statistical analysis. 
• 
GSK intends to make anonymized participant-level data from this study available to 
external researchers for scientific analyses or to conduct further research that can 
help advance medical science or improve patient care. This helps ensure the data 
provided by study participants are used to maximum effect in the creation of 
knowledge and understanding. 
Data Quality Assurance 
• 
All participant data relating to the study will be recorded on printed case report 
forms (CRFs) or electronic CRFs (eCRFs) unless transmitted to the sponsor or 
designee electronically (e.g., 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.  
• 
The investigator must permit study-related monitoring, audits, IRB/IEC review, and 
regulatory agency inspections and provide direct access to source data documents.  
• 
Monitoring details describing strategy, including definition of study critical data 
items and processes (e.g., 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. 


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• 
The sponsor or designee is responsible for the data management of this study 
including quality checking of the data. Detailed information about study data 
collection and management process can be found in the Data Validation Manual. 
• 
Document review of financial disclosures, site staff changes, and a list of 
investigators was also supported by Tata Consulting Services. 
• 
The sponsor assumes accountability for actions delegated to other individuals (e.g., 
contract research organizations). 
• 
Study monitors will perform ongoing source data verification to confirm that data 
entered into the eCRF by authorized study 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, pertaining to the conduct of this 
study must be retained by the investigator for 25 years from the issue of the final 
clinical study report/equivalent summary 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. 
− The Electronic Data Capture system was provided by Medidata Rave. 
Source Documents 
• 
Source documents provide evidence for the existence of the participant and 
substantiate the integrity of the data collected. Source documents are filed at the 
investigator’s site. 
• 
Data reported on the CRF 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. 
• 
Definition of what constitutes source data can be found in the Study Reference 
Manual. 
− The investigator must maintain accurate documentation (source data) that 
supports the information entered in the eCRF. 
− The sponsor or designee will perform monitoring 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. 


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− Copies of documents are shared with external third parties contracted by 
GSK/PPD for review by a central reader mechanism (e.g. endpoint adjudication 
committee; expert reader). The non-exhaustive list of documents shared to 
inform the central reader may include, discharge summaries, imaging reports, 
ECG reports etc. Participant names or any information which would make the 
participant identifiable or is not essential for the central reader mechanism will 
be redacted by the investigator sites prior to transfer. Details of the list of 
documents and the redaction procedure are provided in the site manual or 
equivalent. These documents will be used by the third party solely for the 
purpose indicated within this protocol. 
Study and Site Closure 
GSK or its designee reserves the right to close the study site or terminate the study at any 
time for any reason at the sole discretion of GSK. 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 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 treatment development 
• 
Total number of participants included earlier than expected 
If the study is prematurely terminated or temporarily suspended, the sponsor shall 
promptly inform the investigators, the IECs/IRBs, the regulatory authorities, and any 
contract research organization(s) used in the study of the reason for termination or 
temporary suspension, as specified by the applicable regulatory requirements. The 
investigator shall promptly inform the participant and should assure appropriate 
participant therapy and/or follow-up. 


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12.4. 
Appendix 4: Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
Definition of Adverse Event 
Adverse Event Definition 
• 
An adverse event (AE) is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study treatment, whether or not considered related 
to the study treatment. 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study treatment. 
• 
A treatment-emergent AE is an event that emerges during treatment having been absent 
pretreatment or worsens relative to the pretreatment state. 
 
Events Meeting the AE Definition  
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other 
safety assessments (e.g., electrocardiograms, radiological scans, vital signs 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not related to 
progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase 
in frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even though it 
may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/serious AE (SAE) unless it is an intentional overdose taken with possible 
suicidal/self-harming intent. Such overdoses should be reported regardless of sequelae. 
• 
“Lack of efficacy” or “failure of expected pharmacological action” per se will not be 
reported as an AE or SAE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will 
be reported as AE or SAE if they fulfill the definition of an AE or SAE.  
 


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Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments which are associated with the underlying disease, unless judged by the 
investigator to be more severe than expected for the participant’s condition. 
• 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the participant’s 
condition. 
• 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition that leads 
to the procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
 
Definition of an SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
An SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life threatening 
The term “life threatening” in the definition of “serious” refers to an event in which the 
participant was at risk of death at the time of the event. It does not refer to an event, which 
hypothetically might have caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for observation 
and/or treatment that would not have been appropriate in the physician’s office or 
outpatient setting. Complications that occur during hospitalization are AE. If a complication 
prolongs hospitalization or fulfills any other serious criteria, the event is serious. When in 
doubt as to whether “hospitalization” occurred or was necessary, the AE should be 
considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from 
baseline is not considered an AE. 


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An SAE is defined as any untoward medical occurrence that, at any dose: 
d. Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal 
life functions. 
• 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and 
accidental trauma (e.g., sprained ankle), which may interfere with or prevent everyday life 
functions but do not constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be 
immediately life-threatening or result in death or hospitalization but may jeopardize the 
participant or may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the above definition. These events should usually be considered 
serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions 
that do not result in hospitalization, or development of drug dependency or drug abuse. 
Cardiovascular Adverse Events of Special Interest and Cases of Clostridium Difficile 
Investigators will be required to fill out the specific event page of the electronic case 
report form (eCRF) for the following cardiovascular AEs and SAEs, and for cases of 
Clostridium difficile: 
Cardiovascular Events: 
• 
Myocardial infarction/unstable angina 
• 
Congestive heart failure 
• 
Arrhythmias 
• 
Valvulopathy 
• 
Pulmonary hypertension 
• 
Cerebrovascular events/stroke and transient ischemic attack 
• 
Peripheral arterial thromboembolism 
• 
Deep venous thrombosis/pulmonary embolism 
• 
Revascularization 


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Recording AEs and SAEs 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory, and diagnostics reports) related 
to the event. 
• 
The investigator will then record all relevant AE/SAE information in the eCRF. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s medical 
records to GSK/PPD in lieu of completion of the GSK/PPD AE/SAE eCRF page. 
• 
There may be instances when copies of medical records for certain cases are requested 
by GSK. In this case, all participant identifiers, with the exception of the participant 
number, will be redacted on the copies of the medical records before submission to GSK. 
• 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
• 
The severity of AEs and SAEs will be determined by the investigator according to the US 
National Institute of Allergy and Infectious Diseases Division of Microbiology and 
Infectious Diseases criteria for adult toxicity assessment [DMID, 2007a], with the 
exception of serum creatinine adolescent laboratory data, which will be assessed using 
pediatric toxicity criteria [DMID, 2007b] (Appendix 5). 
An event is defined as “serious” when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe. 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study treatment and each 
occurrence of each AE/SAE. 
• 
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk 
factors, as well as the temporal relationship of the event to study treatment administration, 
will be considered and investigated. 
• 
The investigator will also consult the investigator’s brochure and/or product information, for 
marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK/PPD. However, it is very important that 


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AE and SAE Recording 
the investigator always make an assessment of causality for every event before the 
initial transmission of the SAE data to GSK/PPD. 
• 
The investigator may change his/her opinion of causality in light of follow-up information 
and send an SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
Follow-up of AE and SAE 
• 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by GSK to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
• 
If a participant dies during participation in the study or during a recognized follow-up 
period, the investigator will provide GSK with a copy of any postmortem findings including 
histopathology. 
• 
New or updated information will be recorded in the originally completed eCRF. 
• 
The investigator will submit any updated SAE data to GSK/PPD within 24 hours of receipt 
of the information. 
Reporting of SAE to GSK/PPD 
SAE Reporting to GSK/PPD via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAE to GSK/PPD will be the electronic data 
collection tool. 
• 
The study site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
The investigator or medically qualified subinvestigator must show evidence within the 
eCRF (e.g., check review box, signature, etc) of review and verification of the relationship 
of each SAE to study treatment/study participation (causality) within 72 hours of SAE entry 
into the eCRF. 
• 
After the study is completed at a given study site, the electronic data collection tool will be 
taken off-line to prevent the entry of new data or changes to existing data. 
• 
If a study site receives a report of a new SAE from a study participant or receives updated 
data on a previously reported SAE after the electronic data collection tool has been taken 
off-line, then the study site can report this information to the medical monitor or SAE 
coordinator by telephone. 
• 
Contacts for SAE reporting can be found in the Study Reference Manual. 


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12.5. 
Appendix 5: Division of Microbiology and Infectious 
Diseases Adult Toxicity Tables for Adverse Event 
Assessment 
ESTIMATING SEVERITY GRADE: For abnormalities NOT found elsewhere in the 
Toxicity Tables, use the scale below to estimate grade of severity: 
GRADE 1 
Mild 
Transient or mild discomfort (<48 hours); no medical 
intervention/therapy required 
GRADE 2 
Moderate 
Mild to moderate limitation in activity – some assistance 
may be needed; no or minimal medical 
intervention/therapy required 
GRADE 3 
Severe 
Marked limitation in activity, some assistance usually 
required; medical intervention/therapy required, 
hospitalizations possible 
GRADE 4 
Life-
threatening 
Extreme limitation in activity, significant assistance 
required; significant medical intervention/therapy required, 
hospitalization or hospice care probable 
SERIOUS OR LIFE-THREATENING AEs: ANY clinical event deemed by the 
investigator to be serious or life-threatening should be considered a Grade 4 event. 
Clinical events considered to be serious or life-threatening include, but are not limited to: 
seizures, coma, tetany, diabetic ketoacidosis, disseminated intravascular coagulation, 
diffuse petechiae, paralysis, acute psychosis, and severe depression. 
COMMENTS REGARDING THE USE OF THESE TABLES 
• 
Standardized and commonly used toxicity tables (Division of AIDS, National Cancer 
Institute’s Common Toxicity Criteria, and World Health Organization) have been 
adapted for use by the Division of Microbiology and Infectious Diseases (DAIDS) 
and modified to better meet the needs of participants in Division of Microbiology 
and Infectious Diseases (DMID) trials. 
• For parameters not included in the following Toxicity Tables, study sites should refer 
to the “Guide for Estimating Severity Grade” located above. 
• Criteria are generally grouped by body system. 
Some protocols may have additional protocol specific grading criteria, which will 
supersede the use of these tables for specified criteria. 
Note: Adult DMID toxicity criteria will be applied for all laboratory parameters, with the 
exception of serum creatinine adolescent laboratory data, which will be assessed using 
pediatric DMID toxicity criteria. The DMID pediatric toxicity table may be accessed at 
https://www.niaid.nih.gov/sites/default/files/dmidpedtox.pdf. 
 


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HEMATOLOGY 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin 
9.5 to 10.5 gm/dL 
8.0 to 9.4 gm/dL 
6.5 to 7.9 gm/dL 
<6.5 gm/dL 
Absolute Neutrophil Count 
1000 to 1500 /mm3 
750 to 999 /mm3` 
500 to 749 /mm3 
<500 /mm3 
Platelets 
75,000 to 99,999 /mm3 
50,000 to 74,999 /mm3 
20,000 to 49,999 /mm3 
<20,000 /mm3 
White Blood Cells 
11,000 to 13,000 /mm3 
13,000 to 15,000 /mm3 
15,000 to 30,000 /mm3 
>30,000 or <1000 /mm3 
% Polymorphonuclear Leukocytes + 
Band Cells 
>80% 
90 to 95% 
>95% 
N/A 
Abnormal Fibrinogen 
Low: 100 to 200 mg/dL 
High: 400 to 600 mg/dL 
Low: <100 mg/dL 
High: >600 mg/dL 
Low: <50 mg/dL 
High: N/A 
Fibrinogen associated with gross bleeding 
or with disseminated coagulation 
Fibrin Split Product 
20 to 40 mcg/mL 
41 to 50 mcg/mL 
51 to 60 mcg/dL 
>60 mcg/dL 
Prothrombin Time (PT) 
1.01 to 1.25 x ULN 
1.26 to 1.5 x ULN 
1.51 to 3.0 x ULN 
>3 x ULN 
Activated Partial Thromboplastin (APTT) 
1.01 to 1.66 x ULN 
1.67 to 2.33 x ULN 
2.34 to 3 x ULN 
>3 x ULN 
Methemoglobin 
5.0 to 9.9% 
10.0 to 14.9% 
15.0 to 19.9% 
>20% 
N/A=not applicable; ULN=upper limit of normal.  


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CHEMISTRIES 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hyponatremia 
130 to 135 mEq/L 
123 to 129 mEq/L 
116 to 122 mEq/L 
<116 mEq/L or abnormal sodium with 
mental status changes or seizures 
Hypernatremia 
146 to 150 mEq/L 
151 to 157 mEq/L 
158 to 165 mEq/L 
>165 mEq/L or abnormal sodium with 
mental status changes or seizures 
Hypokalemia 
3.0 to 3.4 mEq/L 
2.5 to 2.9 mEq/L 
2.0 to 2.4 mEq/L or intensive 
replacement therapy of 
hospitalization required 
<2.0 mEq/L or abnormal potassium with 
paresis, ileus, or life-threatening 
arrhythmia 
Hyperkalemia 
5.6 to 6.0 mEq/L 
6.1 to 6.5 mEq/L 
6.6 to 7.0 mEq/L 
>7.0 mEq/L or abnormal potassium with 
life-threatening arrhythmia 
Hypoglycemia 
55 to 64 mg/dL 
40 to 54 mg/dL 
30 to 39 mg/dL 
<30 mg/dL or abnormal glucose with 
mental status changes or coma 
Hyperglycemia 
(nonfasting and no prior 
diabetes) 
116 to 160 mg/dL 
161 to 250 mg/dL 
251 to 500 mg/dL 
>500 mg/dL or abnormal glucose with 
ketoacidosis or seizures 
Hypocalcemia 
(corrected for albumin) 
8.4 to 7.8 mg/dL 
7.7 to 7.0 mg/dL 
6.9 to 6.1 mg/dL 
<6.1 mg/dL or abnormal calcium with 
life-threatening arrhythmia or tetany 
Hypercalcemia 
(corrected for albumin) 
10.6 to 11.5 mg/dL 
11.6 to 12.5 mg/dL 
12.6 to 13.5 mg/dL 
>13.5 mg/dL or abnormal calcium with 
life-threatening arrhythmia 
Hypomagnesemia 
1.4 to 1.2 mEq/L 
1.1 to 0.9 mEq/L 
0.8 to 0.6 mEq/L 
<0.6 mEq/L or abnormal magnesium with 
life-threatening arrhythmia 
Hypophosphatemia 
2.0 to 2.4 mg/dL 
1.5 to 1.9 mg/dL or 
replacement Rx required 
1.0 to 1.4 mg/dL 
intensive therapy or hospitalization 
required 
<1.0 mg/dL or abnormal phosphate with 
life-threatening arrhythmia 
Hyperbilirubinemia (when 
accompanied by any increase in 
other liver function test) 
1.1 to <1.25 x ULN 
1.25 to <1.5 x ULN 
1.5 to 1.75 x ULN 
>1.75 x ULN 
Hyperbilirubinemia (when other 
liver function tests are in the 
normal range) 
1.1 to <1.5 x ULN 
1.5 to <2.0 x ULN 
2.0 to 3.0 x ULN 
>3.0 x ULN 
Blood urea nitrogen  
1.25 to 2.5 x ULN 
2.6 to 5 x ULN 
5.1 to 10 x ULN 
>10 x ULN 
Hyperuricemia (uric acid) 
7.5 to 10.0 mg/dL 
10.1 to 12.0 mg/dL 
12.1 to 15.0 mg/dL 
>15.0 mg/dL 
Creatinine 
1.1 to 1.5 x ULN 
1.6 to 3.0 x ULN 
3.1 to 6.0 x ULN 
>6 x ULN or dialysis required 
Rx=therapy; ULN=upper limit of normal. 


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ENZYMES 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Aspartate aminotransferase (AST) 
1.1 to <2.0 x ULN 
2.0 to <3.0 x ULN 
3.0 to 8.0 x ULN 
>8.0 x ULN 
Alanine aminotransferase (ALT) 
1.1 to <2.0 x ULN 
2.0 to <3.0 x ULN 
3.0 to 8.0 x ULN 
>8.0 x ULN 
Gamma to glutamyl transferase (GGT) 
1.1 to <2.0 x ULN 
2.0 to <3.0 x ULN 
3.0 to 8.0 x ULN 
>8.0 x ULN 
Alkaline Phosphatase 
1.1 to <2.0 x ULN 
2.0 to <3.0 x ULN 
3.0 to 8.0 x ULN 
>8.0 x ULN 
Amylase 
1.1 to 1.5 x ULN 
1.6 to 2.0 x ULN 
2.1 to 5.0 x ULN 
>5.1 x ULN 
Lipase 
1.1 to 1.5 x ULN 
1.6 to 2.0 x ULN 
2.1 to 5.0 x ULN 
>5.1 x ULN 
ULN=upper limit of normal. 
 
URINALYSIS 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Proteinuria 
1+ or 
200 mg to 1 gm loss/day 
2 to 3+ or 
1 to 2 gm loss/day 
4+ or 
2 to 3.5 gm loss/day 
Nephrotic syndrome or 
>3.5 gm loss/day 
Hematuria 
Microscopic only 
<10 RBC/HPF 
Gross, no clots 
>10 RBC/HPF 
Gross, with or without clots, 
or red blood cells casts 
Obstructive or  
required transfusion 
HPF=high powered field; RBC=red blood cells. 


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CARDIOVASCULAR 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Cardiac rhythm 
N/A 
Asymptomatic, transient signs, no 
Rx required 
Recurrent/persistent; symptomatic 
Rx required 
Unstable dysrhythmia; 
hospitalization and treatment 
required 
Hypertension 
Transient increase >20 mm/Hg; 
no treatment  
Recurrent, chronic increase 
>20 mm/Hg; 
treatment required  
Acute treatment required; 
outpatient treatment or 
hospitalization possible  
End organ damage or 
hospitalization required  
Hypotension 
Transient orthostatic hypotension 
with heart rate increased by 
<20 beat/min or decreased by 
<10 mmHg systolic BP. 
No treatment required 
Symptoms due to orthostatic 
hypotension or BP decreased by 
<20 mmHg systolic; correctable 
with oral fluid treatment 
Requires IV fluids; 
no hospitalization required 
Mean arterial pressure 
<60 mmHg or end organ damage 
or shock; 
requires hospitalization and 
vasopressor treatment 
Pericarditis 
Minimal effusion 
Mild/moderate asymptomatic 
effusion, no treatment 
Symptomatic effusion; pain; EKG 
changes 
Tamponade; pericardiocentesis 
or surgery required 
Hemorrhage, Blood Loss 
Microscopic/occult 
Mild, no transfusion 
Gross blood loss;  
1 to 2 units transfused 
Massive blood loss; >3 units 
transfused 
BP=blood pressure; IV=intravenous; EKG=electrocardiogram; N/A=not applicable; Rx=therapy. 
 
RESPIRATORY 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Cough 
Transient; no treatment 
Persistent cough; treatment responsive 
Paroxysmal cough; uncontrolled with 
treatment 
N/A 
Bronchospasm, 
Acute 
Transient; no treatment; 
FEV1 70 to 80% of peak flow 
Requires treatment; normalizes with 
bronchodilator; FEV1 50 to 70% of peak 
flow 
No normalization with bronchodilator; FEV1 25 
to 50% of peak flow; or retractions present 
Cyanosis: FEV1 <25% of 
peak flow; or intubation 
necessary 
Dyspnea 
Dyspnea on exertion 
Dyspnea with normal activity 
Dyspnea at rest 
Dyspnea requiring oxygen 
therapy 
FEV1=forced expiratory volume in 1 second; N/A=not applicable. 


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GASTROINTESTINAL 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Nausea 
Mild or transient; maintains 
reasonable intake 
Moderate discomfort; intake 
decreased significantly; some 
activity limited 
No significant intake; requires IV fluids 
Hospitalization required 
Vomiting 
1 episode in 24 hours 
2 to 5 episodes in 24 hours 
>6 episodes in 24 hours or needing IV 
fluids 
Physiologic consequences requiring 
hospitalization or requiring parenteral 
nutrition 
Constipation 
Requiring stool softener or 
dietary modification 
Requiring laxatives 
Obstipation requiring manual evacuation 
or enema 
Obstruction or toxic megacolon 
Diarrhea 
Mild or transient; 3 to 
4 loose stools/day or mild 
diarrhea lasting <1 week 
Moderate or persistent; 5 to 
7 loose stools/day or diarrhea 
lasting >1 week 
>7 loose stools/day or bloody diarrhea; 
or orthostatic hypotension or electrolyte 
imbalance or >2L IV fluids required 
Hypotensive shock or physiologic 
consequences requiring hospitalization 
Oral discomfort/ 
Dysphagia 
Mild discomfort; no 
difficulty swallowing 
Some limits on eating/drinking 
Eating/talking very limited; unable to 
swallow solid foods 
Unable to drink fluids; requires IV fluids 
IV=intravenous. 
 
NEUROLOGICAL 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Neuro-Cerebellar 
Slight incoordination 
dysdiadochokinesis 
Intention tremor, dysmetria, 
slurred speech; nystagmus 
Locomotor ataxia 
Incapacitated 
Psychiatric 
Mild anxiety or depression 
Moderate anxiety or depression; 
therapy required; change in 
normal routine 
Severe mood changes requiring therapy; 
or suicidal ideation; or aggressive 
ideation 
Acute psychosis requiring 
hospitalization; or suicidal 
gesture/attempt or 
hallucinations 
Muscle strength 
Subjective weakness; no objective 
symptoms/signs 
Mild objective signs/symptoms; no 
decrease in function 
Objective weakness; function limited 
Paralysis 
Paresthesia 
(burning, tingling, etc.) 
Mild discomfort; no treatment 
required 
Moderate discomfort; 
non- narcotic analgesia required 
Severe discomfort; or narcotic analgesia 
required with symptomatic improvement 
Incapacitating; or not 
responsive to narcotic analgesia 
Neurosensory 
Mild impairment in sensation 
(decreased sensation, e.g., 
vibratory, pinprick, hot/cold in 
great toes) in focal area or 
symmetrical distribution; or 
Moderate impairment (moderately 
decreased sensation, e.g., 
vibratory, pinprick, hot/cold to 
ankles) and/or joint position or 
Severe impairment (decreased or loss of 
sensation to knees or wrists) or loss of 
sensation of at least moderate degree in 
multiple different body areas (i.e., upper 
and lower extremities) 
Sensory loss involves limbs and 
trunk; paralysis; or seizures 


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change in taste, smell, vision, 
and/or hearing 
mild impairment that is not 
symmetrical 
MUSCULOSKELETAL 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Arthralgia 
(joint pain) 
Mild pain not interfering with function 
Moderate pain, analgesics and/or pain 
interfering with function but not with ADL 
Severe paid; pain and/or analgesics 
interfering with ADL 
Disabling pain 
Arthritis 
Mild pain with inflammation, erythema or 
joint swelling, but not interfering with 
function 
Moderate pain with inflammation, erythema or 
joint swelling; interfering with function but not 
with ADL 
Severe pain with inflammation, 
erythema or joint swelling, and 
interfering with ADL 
Permanent and/or 
disabling joint 
destruction 
Myalgia 
Myalgia with no limitation of activity 
Muscle tenderness (at other than injection site) 
or with moderate impairment of activity 
Severe muscle tenderness with marked 
impairment of activity 
Frank myonecrosis 
ADL=activities of daily living. 
 
SKIN 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Mucocutaneous 
Erythema; pruritus 
Diffuse, maculo papular rash, dry 
desquamation   
Vesiculation or moist 
desquamation or ulceration 
Exfoliative dermatitis, mucous membrane 
involvement or erythema, multiforme or suspected 
Stevens-Johnson or necrosis requiring surgery 
Induration 
<15 mm 
15 to 30 mm 
>30 mm 
N/A 
Erythema 
<15 mm 
15 to 30 mm 
>30 mm 
N/A 
Edema 
<15 mm 
15 to 30 mm 
>30 mm 
N/A 
Rash at injection site 
<15 mm 
15 to 30 mm 
>30 mm 
N/A 
Pruritus 
Slight itching at injection site 
Moderate itching at injection 
extremity 
Itching over entire body 
N/A 
N/A=not applicable. 


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SYSTEMIC 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Allergic reaction 
Pruritus without rash 
Localized urticarial 
Generalized urticarial; angioedema 
Anaphylaxis 
Headache 
Mild, no treatment required 
Transient, moderate; treatment 
required 
Severe; responds to initial narcotic 
therapy 
Intractable; requires 
repeated narcotic therapy 
Fever: oral 
37.7 to 38.5°C or 100.0 to 101.5°F 
38.6 to 39.5°C or 101.6 to 102.9°F 
39.6 to 40.5°C or 103 to 105°F 
>40°C or >105°F 
Fatigue 
Normal activity reduced <48 hours 
Normal activity decreased 25 to 50%; 
>48 hours 
Normal activity decreased >50%; 
cannot work 
Unable to care for self 
 


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12.6. 
Appendix 6: Contraceptive Guidance and Collection of 
Pregnancy Information 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with ONE of the following: 
− 
Documented hysterectomy 
− 
Documented bilateral salpingectomy 
− 
Documented bilateral oophorectomy 
Note:  Documentation can come from the study site personnel’s review of 
participant’s medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
− 
A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high follicle-stimulating hormone (FSH) level in 
the postmenopausal range may be used to confirm a postmenopausal state in 
women not using hormonal contraception or hormonal replacement therapy 
(HRT). However, in the absence of 12 months of amenorrhea, a single FSH 
measurement is insufficient.  
− 
Females on HRT and whose menopausal status is in doubt will be required to 
use 1 of the nonhormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to 
allow confirmation of postmenopausal status before study enrollment. 
Pregnancy Testing 
• 
WOCBP should only be included after a confirmed menstrual period and a negative 
urine pregnancy test.  
• 
Pregnancy testing will be performed at Baseline (Day 1) before study treatment 
administration. The urine pregnancy test at Baseline will determine study 
contraception and abstinence requirements as follows: 
− Pregnancy testing at Baseline (Day 1) should be performed using the urine test 
kit provided to the study site (FIRST RESPONSE Early Result Pregnancy Test 
with a high sensitivity of ≤6.3 mIU/mL). Participants with a negative urine 
pregnancy test result from this test kit may be included in the study with no 
pretreatment contraception or abstinence requirements. 
Note:  ONLY if the study-specific pregnancy kit provided to the study site is 
unavailable, a standard urine pregnancy test with a sensitivity of 25 mIU/mL may be 
used as an exception. A participant with a negative urine pregnancy test result from 


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the standard test may be included in the study only if the participant has used a 
highly effective contraception method as described in Table 10 or has practiced 
abstinence from penile/vaginal intercourse for at least 14 days before receiving study 
treatment.  
• 
A pregnancy test will also be performed at the Test-of-Cure (Day 4 to 8) Visit.  
• 
Pregnancy testing will be performed whenever a menstrual cycle is missed or when 
pregnancy is otherwise suspected. 
• 
Urine pregnancy test kits were provided by PPD except for sites in Australia where 
urine pregnancy test kits were provided by Flinders and Zuellig Pharma. 
Contraception Guidance – Male and Female Participants 
See the section directly above regarding pregnancy testing for female participants at 
Baseline (Day 1) and associated pretreatment contraception and abstinence requirements. 
Female participants of childbearing potential who enter the study using contraception 
must continue to do so throughout the study.  
For male and female participants, the only contraception requirement from the Baseline 
Visit through the TOC Visit is abstinence or the use of a male condom during intercourse. 
As described in Section 6.3, all participants will be instructed to abstain from sexual 
activity from the Baseline Visit through the TOC Visit to prevent possible re-infection 
with NG. If a participant refuses to abstain and is sexually active, male participants as 
well as male partners of female participants, of both childbearing and nonchildbearing 
potential, must use a male condom during intercourse from the Baseline Visit through 
completion of the TOC Visit. 
Table 10 
Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependenta 
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulationb 
• 
oral 
• 
intravaginal  
• 
transdermal  
Progestogen-only hormonal contraception associated with inhibition of ovulationb 
• 
injectable  
Highly Effective Methods That Are User Independent  
• 
implantable progestogen-only hormonal contraception associated with inhibition of ovulationb 
• 
intrauterine device (IUD) 
• 
intrauterine hormone-releasing system (IUS) 
• 
bilateral tubal occlusion 


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Vasectomized partner  
(A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used. Note: Male 
partners of female participants, of both childbearing and nonchildbearing potential, must use a 
male condom during intercourse from the Baseline Visit through completion of the TOC Visit.)  
Sexual abstinence  
(Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the participant.)  
WOCBP=woman of childbearing potential. 
a. 
Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants in clinical studies.  
b. 
Hormonal contraception may be susceptible to interaction with the study treatment, which may reduce the efficacy 
of the contraceptive method. 
Collection of Pregnancy Information 
Female participants who become pregnant 
• 
Investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study.  
• 
Information will be recorded on the appropriate form and submitted to GSK/PPD 
within 24 hours of learning of a participant’s pregnancy.  
• 
Participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on participant and neonate, which will 
be forwarded to GSK. 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 procedure.  
• 
While pregnancy itself is not considered to be an adverse event (AE) or serious AE 
(SAE), any pregnancy complication or elective termination of a pregnancy for 
medical reasons 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 SAE occurring as a result of a poststudy pregnancy that is considered 
reasonably related to the study treatment by the investigator will be reported to GSK 
as described in Appendix 4. 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.  
Any female participant who becomes pregnant while participating will discontinue study 
treatment. 


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12.7. 
Appendix 7: Genetics 
USE/ANALYSIS OF DNA 
• 
Genetic variation may impact a participant’s response to therapy, susceptibility, 
severity and progression of disease. Variable response to therapy may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and 
excretion; mechanism of action of the drug; disease etiology; and/or molecular 
subtype of the disease being treated. Therefore, where local regulations and 
institutional review board/independent ethics committee allow, a blood sample will 
be collected for DNA analysis. 
• 
DNA samples will be used for research related to gepotidacin or urogenital 
gonorrhea and related diseases. They may also be used to develop tests/assays 
including diagnostic tests) related to gepotidacin and urogenital gonorrhea. Genetic 
research may consist of the analysis of 1 or more candidate genes or the analysis of 
genetic markers throughout the genome (or analysis of the entire genome) (as 
appropriate). 
• 
DNA samples will be analyzed if it is hypothesized that this may help further 
understand the clinical data.  
• 
The samples may be analyzed as part of a multi-study assessment of genetic factors 
involved in the response to gepotidacin or study treatments of this class. The results 
of genetic analyses may be reported in the clinical study report or in a separate study 
summary. 
• 
The sponsor will store the DNA samples in a secure storage space with adequate 
measures to protect confidentiality.  
• 
The samples will be retained while research on gepotidacin (or study treatments of 
this class) or urogenital gonorrhea continues but no longer than 15 years after the last 
participant’s last visit or other period as per local requirements. 


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12.8. 
Appendix 8: Liver Safety: Required Actions and Follow-up 
Assessments  
Phase III liver chemistry stopping and increased monitoring criteria have been 
designed to assure participant safety and evaluate liver event etiology. 
The stopping criteria for discontinuing dosing of study treatment due to liver chemistry 
parameters have limited application in this study, as study treatment is only administered 
as 2 doses of gepotidacin over a 24-hour period starting on Day 1 or as a single 
intramuscular dose of ceftriaxone plus an oral dose of azithromycin on Day 1. However, 
if participants are found to have values consistent with the usual stopping parameters, it is 
appropriate to institute evaluation and monitoring criteria according to standard GSK 
criteria. Therefore, if defined parameters are reached, liver function tests should be 
evaluated as shown in the table below, which is in keeping with the liver stopping 
criteria, and laboratory evaluation should be instituted. 
Phase III liver chemistry evaluation criteria and required follow-up assessments  
Liver Chemistry Evaluation Criteria – Liver Event 
ALT Absolute 
ALT ≥8 x ULN 
ALT Increase 
ALT ≥5 x ULN but <8 x ULN persists for ≥2 weeks 
ALT ≥3 x ULN but <5 x ULN persists for ≥4 weeks 
Bilirubina,b 
ALT ≥3 x ULN and bilirubin ≥2 x ULN (>35% direct bilirubin)  
INRb 
ALT ≥3 x ULN and INR>1.5, if INR measured 
Cannot 
Monitor 
ALT ≥5 x ULN but <8 x ULN and cannot be monitored weekly for ≥2 weeks 
ALT ≥3 x ULN but <5 x ULN and cannot be monitored weekly for ≥4 weeks 
Symptomaticc 
ALT ≥3 x ULN associated with symptoms (new or worsening) believed to be 
related to liver injury or hypersensitivity 
Required Actions and Follow-up Assessments  
Actions 
Follow-Up Assessments 
• 
Report the event to GSK within 24 hours 
• 
Complete the liver event eCRF and 
complete an SAE data collection tool if the 
event also meets the criteria for an SAEb 
• 
Perform liver event follow-up assessments  
• 
Monitor the participant until liver chemistries 
resolve, stabilize, or return to within 
baseline (see MONITORING below) 
• 
Viral hepatitis serologyd 
• 
Obtain INR and recheck with each 
liver chemistry assessment until the 
transaminases values show downward 
trend 
• 
Only in those with underlying chronic 
hepatitis B at study entry (identified by 
positive hepatitis B surface antigen), 


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Liver Chemistry Evaluation Criteria – Liver Event 
MONITORING: 
For bilirubin or INR criteria:  
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow-up assessments within 
24 hours 
• 
Monitor participants twice weekly until liver 
chemistries resolve, stabilize, or return to 
within baseline 
• 
A specialist or hepatology consultation is 
recommended 
For All other criteria:  
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, bilirubin) and perform 
liver event follow-up assessments within 
24 to 72 hours  
• 
Monitor participants weekly until liver 
chemistries resolve, stabilize, or return to 
within baseline 
quantitative hepatitis B DNA, and 
hepatitis delta antibodye 
• 
Obtain blood sample for PK analysis, 
within 24 hours after last dosef 
• 
Serum creatine phosphokinase and 
lactate dehydrogenase 
• 
Fractionate bilirubin, if total bilirubin 
≥2 x ULN 
• 
Obtain complete blood count with 
differential to assess eosinophilia 
• 
Record the appearance or worsening 
of clinical symptoms of liver injury, or 
hypersensitivity, on the AE report form 
• 
Record use of concomitant 
medications on the concomitant 
medications report form including 
acetaminophen, herbal remedies, 
other over-the-counter medications 
• 
Record alcohol use on the liver event 
alcohol intake eCRF page 
For bilirubin or INR criteria: 
• 
Antinuclear antibody, antismooth 
muscle antibody, type 1 anti-liver 
kidney microsomal antibodies, and 
quantitative total immunoglobulin G 
(IgG or gamma globulins). 
• 
Serum acetaminophen adduct HPLC 
assay (quantifies potential 
acetaminophen contribution to liver 
injury in participants with definite or 
likely acetaminophen use in the 
preceding week [James, 2009]). 
NOTE: not required in China.  
• 
Liver imaging (ultrasound, magnetic 
resonance, or computed tomography) 
and/or liver biopsy to evaluate liver 
disease; complete Liver Imaging 
and/or liver biopsy eCRFs. 
AE=adverse event; ALT=alanine aminotransferase; AST=aspartate aminotransferase; eCRF=electronic case report 
form; HPLC=high-performance liquid chromatography; IgM=immunoglobulin M; INR=international normalized 
ratio; PK=pharmacokinetic; SAE=serious adverse event; ULN=upper limit of normal. 


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a. 
Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study treatment for that participant if ALT ≥ 3 x ULN and bilirubin ≥ 2 x ULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record presence of detectable urinary 
bilirubin on dipstick, indicating direct bilirubin elevations and suggesting liver injury.  
b. 
All events of ALT ≥ 3 x ULN and bilirubin ≥ 2 x ULN (>35% direct bilirubin) or ALT ≥ 3 x ULN and INR >1.5, if INR 
measured which may indicate severe liver injury (possible “Hy’s Law”), must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis); INR measurement is not required and the threshold value stated 
will not apply to participants receiving anticoagulants. 
c. 
New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or believed to be related to hypersensitivity (such as fever, rash or 
eosinophilia). 
d. 
Includes: hepatitis A immunoglobulin M (IgM) antibody; hepatitis B surface antigen, and hepatitis B core antibody 
(IgM); hepatitis C RNA; cytomegalovirus IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if 
unavailable, obtain heterophile antibody or monospot testing); hepatitis E IgM antibody  
e. 
If hepatitis delta antibody assay cannot be performed, it can be replaced with a polymerase chain reaction of 
hepatitis D RNA virus (where needed) [Le Gal, 2005]. 
f. 
The PK sample may not be required for participants known to be receiving placebo or non-GSK comparator 
treatments. Record the date/time of the PK blood sample draw and the date/time of the last dose of study 
treatment prior to PK blood sample draw on the eCRF. If the date or time of the last dose is unclear, provide the 
participant’s best approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot 
be collected in the time period indicated above, do not obtain a PK sample. Instructions for sample handling and 
shipping are in the Study Reference Manual. 
Phase III liver chemistry increased monitoring criteria  
Liver Chemistry Increased Monitoring Criteria – Liver Monitoring Event 
Criteria 
Actions 
ALT ≥5 x ULN and <8 x ULN and 
bilirubin <2 x ULN without symptoms 
believed to be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 2 weeks. 
OR 
ALT ≥3 x ULN and <5 x ULN and 
bilirubin <2 x ULN without symptoms 
believed to be related to liver injury or 
hypersensitivity, and who can be 
monitored weekly for 4 weeks. 
• 
Notify the GSK medical monitor within 24 
hours of learning of the abnormality to discuss 
participant safety.  
• 
Participant can continue study treatment. 
• 
Participant must return weekly for repeat liver 
chemistries (ALT, AST, alkaline phosphatase, 
bilirubin) until they resolve, stabilize or return to 
within baseline. 
• 
If at any time participant meets the liver 
chemistry stopping criteria, proceed as 
described above. 
• 
If ALT decreases from ALT ≥5 x ULN and 
<8 x ULN to ≥3 x ULN but <5 x ULN, continue to 
monitor liver chemistries weekly.  
• 
If, after 4 weeks of monitoring, ALT <3 x ULN 
and bilirubin <2 x ULN, monitor participants 
twice monthly until liver chemistries normalize or 
return to within baseline. 
ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of normal. 


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References 
James LP, Letzig L, Simpson PM, et al. Pharmacokinetics of acetaminophen-protein 
adducts in adults with acetaminophen overdose and acute liver failure. Drug Metab 
Dispos 2009;37:1779-1784. 
Le Gal F, Gordien E, Affolabi D, et al. Quantification of hepatitis delta virus RNA in 
serum by consensus real-time PCR indicates different patterns of virological response to 
interferon therapy in chronically infected patients. J Clin Microbiol. 2005;43:2363-2369.  


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12.9. 
Appendix 9: Additional Guidance on Permitted and 
Prohibited Medications and Crediblemeds.org 
For quick reference, a list of some common concomitant medications that are permitted 
for participants to take during the study for nausea, vomiting, pain, diarrhea, etc. per 
investigator discretion is provided below. A list of some of the commonly used 
medications that are prohibited is also provided in this appendix. Lastly, a topline 
overview of how to use crediblemeds.org is also provided. 
A further detailed list of medications will be provided in the Study Reference Manual. 
List of Concomitant Medications Permitted During the Study: 
Generic Namea 
Common Therapeutic Use(s) 
Dolasetron 
Nausea, vomiting 
Granisetron 
Nausea, vomiting 
Metoclopramide 
Nausea, vomiting 
Palonosetron 
Nausea, vomiting 
Promethazine 
Nausea, vomiting 
Tropisetron (Only on Non-US markets) 
Nausea, vomiting 
Acetaminophen or paracetamol 
Pain  
Tramadol 
Pain 
Hydrocodone ER 
Pain, severe 
Lidocaine (solution for intramuscular injection only) 
Anesthetic 
Loperamide 
Diarrhea 
Cetirizine 
Antihistamine (H1) 
Ebastine 
Antihistamine (H1) 
Fexofenadine 
Antihistamine (H1) 
Loratadine 
Antihistamine (H1) 
Clotrimazole 
Antifungal – topical, nonsystemic 
only 
Tolnaftate 
Antifungal – topical, nonsystemic 
only 
Ketoconazole 
Antifungal – topical, nonsystemic 
only 
Tenofovir and emtricitabine 
Pre-exposure prophylaxis for HIV 
ER=extended release; HIV=human immunodeficiency virus; US=United States. 
a. 
Check within each local country to assess if other generic names apply. 
Note: See also Section 7.7.1 for other permitted medications. 


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List of Concomitant Medications Prohibited During the Study: 
Generic Namea 
Common Therapeutic Use(s) 
Ondansetron 
Nausea, vomiting 
Other investigational products 
Various 
Systemic antibiotics (e.g., ciprofloxacin, 
amoxicillin/clavulanate, cephalexin, doxycycline) 
Antibiotic – all systemic 
Topical and intravaginal antibiotics (e.g., clindamycin, 
Neomycin, polymyxin, clotrimazole, tolnaftate, ketoconazole, 
metronidazole) 
Antibiotic – all topical and 
intravaginal 
Systemic antifungals (e.g., itraconazole, fluconazole) 
Antifungal – all systemic 
Prednisolone or equivalent (refer to Section 7.7.2 for details) 
Immunosuppressive therapy 
Strong CYP3A4 inhibitors 
See Study Reference Manual 
St John’s wort 
Herbal, various 
Succinylcholine and other nondepolarizing paralytic agents 
Muscle relaxation, muscle paralysis 
CYP3A4=cytochrome P450 enzyme 3A4. 
a. 
Check within each local country to assess if other generic names apply. 
Note: See also Section 7.7.2 for other prohibited medications. 
Crediblemeds.org Instructions 
Instructions for accessing www.crediblemeds.org and searching for an exclusionary drug 
due to its “Known Risk of Torsades de Pointes (TdP)” category are summarized below.  
To access www.crediblemeds.org, copy and paste this link into the internet search bar: 
https://www.crediblemeds.org/ 
On the main home page, there are 3 search options available. Choose the first option to 
search for 1 drug at a time. Free registration is required by the website.  
 


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Choosing that option brings you to a screen that allows for you to enter a generic or brand 
drug name and choose Search. If it has a Known risk of TdP (i.e., is a prohibited 
exclusionary medication), it will show a red triangle with an exclamation point as shown 
here: 
 
Always check the www.crediblemeds.org website for the most up-to-date information on 
drugs with a Known Risk of TdP for participant safety. 


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12.10. 
Appendix 10: Clostridium Difficile Testing Procedure and 
Algorithm 
 
CRA = clinical research associate (PPD site monitor); SRM = Study Reference Manual 
Note:  This algorithm is subject to investigator discretion when the clinical 
presentation and time course of diarrhea (e.g., during or within 12 hours immediately 
after dosing) do not fit the Clostridium difficile associated diarrhea definition; 
consideration should be given to diarrhea occurring in this early time frame to be 
suggestive of a cholinergic effect. 


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12.11. 
Appendix 11: COVID-19 Protocol Information 
12.11.1. 
Overall Rationale for this Appendix 
The COVID-19 pandemic may impact the conduct of clinical studies. Challenges may 
arise from quarantines, site closures, travel limitations, interruptions to the supply chain 
for the investigational product or other considerations if site personnel or study 
participants become infected with COVID-19. These challenges may lead to difficulties 
in meeting protocol-specified procedures.  
This appendix outlines measures that may be applicable for any study site impacted by 
the COVID-19 pandemic. The purpose of the appendix is to provide information on the 
measures to be taken to protect participants’ safety, welfare and rights, and promote data 
integrity. These measures are expected to be temporary and study sites will be notified of 
any change to these allowances as the COVID-19 pandemic evolves. 
12.11.2. 
Study Procedures During the COVID-19 Pandemic 
During the special circumstances caused by the current COVID-19 pandemic, sites 
should consider specific public health guidance, the impact of any travel restrictions 
implemented by local/regional health authorities and local institutions, and individual 
benefit/risk when making enrollment and treatment decisions for study participants. 
Every effort should be made to adhere to protocol-specified assessments for participants 
on study treatment, including follow-up assessments; however, when not possible, for the 
duration of these special circumstances, the following measures may be implemented: 
• 
For all study visits, to minimize the amount of time that participants spend at the 
clinic, eConsent may be utilized and remote collection of study-related data may be 
obtained as described in the Study Reference Manual. Thus, some visit data may be 
collected through a combination of telemedicine and on-site visits. Collection of 
information via telemedicine will be performed only where local regulations permit. 
• 
Clinical investigators should document in site/participant/source files how 
restrictions related to COVID-19 led to changes in study conduct, the duration of 
those changes, and indicate which trial participants were impacted and how those 
trial participants were impacted (as per the current local COVID-19 related 
regulatory guidance).  
• 
Missing protocol-required data/visits due to COVID-19 should be noted in 
site/participant/source files and recorded as a COVID-19 protocol deviation.  


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Specifically for data management and monitoring the following will apply: 
• 
If on-site monitoring is no longer permitted, GSK/PPD will consider remote Source 
Data Verification/Source Document Review (SDV/SDR) where permitted by the 
clinical site/institution. Remote SDV/SDR will be proposed to study sites to meet a 
participant and/or critical quality need, e.g., to assess participant safety or to ensure 
data integrity. In case of remote SDV/SDR, GSK/PPD will work with the site to 
ensure participant privacy.  
• 
eCRF/CRF Final or Interim Sign-Off Process: The principal investigator is 
responsible for ensuring that the data within the eCRF casebook and any other data 
sources utilized during the study for each study participant is complete and 
consistent with source documents throughout the study (ICH GCP 4.9.1 4.9.2). The 
principal investigator may sign/re-sign the eCRF from any computer/location by 
accessing the validated system using his/her unique eCRF log-in credentials. The 
principal investigator may delegate this activity to another medically qualified and 
trained subinvestigator and this must be documented on the Delegation of 
Responsibilities Log. It is recommended that the principal investigator identifies a 
subinvestigator as a back-up for eCRF signatures and that appropriate training on the 
protocol and eCRF requirements is provided and documented.  
• 
Essential Document Sign-Off Process: If an investigator is unable to print and sign 
essential documents such as Protocol/Amendment signature page then e-mail 
approval can be accepted by replying to the relevant e-mail that is sent by GSK/PPD. 


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12.12. 
Appendix 12: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents. 
Amendment 2 16 December 2022 
This global amendment is considered to be non-substantial. 
Overall rationale for the current Amendment:  
This global amendment increased the total enrollment sample size; revised and added key 
populations for analyses to support the planned efficacy analyses per the current reporting 
and analysis plan; and removed the covariate age at Baseline from the primary efficacy 
analyses. The amendment includes minor updates to gepotidacin introductory and risk 
text for consistency with the current investigator’s brochure, and revised 
crediblemeds.org instructions for consistency with the current website. The amendment 
also includes minor administrative and wording edits and editorial text additions per the 
current protocol template. 
List of main changes in the protocol and their rationale: 
Section # and Name 
Description of Change 
Brief Rationale 
Synopsis 
5.2 Number of 
Participants 
10.2.1 Justification of 
Sample Size 
Increased the total number of 
enrolled participants from 
approximately 600 to 
approximately 620. 
Based on the microbiological 
evaluability rate, the total sample 
size was increased to ensure the 
number of participants in the 
micro-ITT Population was 
reached.  
10.3 Populations for 
Analyses 
The key populations for analyses 
have been updated and added. 
Revisions were made to support 
the planned efficacy analyses 
per the current reporting and 
analysis plan. 
10.4.2 Efficacy 
Analyses 
Excluded the covariate “Age at 
Baseline” from the primary 
efficacy analyses. Of note, there is 
no change to the randomization 
stratification. 
Based on current enrollment 
projections, there will be an 
insufficient number of 
participants in the <18 and 
>65 years age categories in 
each treatment group at the end 
of the study; thus, the sample 
size in those categories will not 
be sufficient to support the 
primary analysis. 
Section 3 Introduction 
 
Updated gepotidacin text based 
on the investigator’s brochure. 
Revised for consistency with the 
investigator’s brochure. 


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Section # and Name 
Description of Change 
Brief Rationale 
Section 3.3.1 Risk 
Assessment 
Minor text updates were made to 
the QTcF, 
acetylcholinesterase-inhibition, 
and reproduction sections for 
gepotidacin. 
Revised for clarification and 
consistency with current 
investigator’s brochure. 
Section 9 Study 
Assessments and 
Procedures 
The demographic data that is 
collected at the Baseline Visit was 
clarified and rationale text was 
added. 
Information was added per the 
current GSK protocol template. 
12.3 Appendix 3: 
Study Governance 
Considerations 
Clarified that redaction of source 
documents will be performed by 
study sites before documents are 
shared with outside vendors. 
Study Conduct Materials and 
Support subsection was added. 
Information was added per the 
current GSK protocol template. 
12.4 Appendix 4: 
Adverse Events 
Definitions and 
Procedures for 
Recording, 
Evaluating, Follow-up, 
and Reporting 
Definition of a treatment-emergent 
adverse event was added. 
Information was added per the 
current GSK protocol template. 
12.9 Appendix 9: 
Additional Guidance 
on Permitted and 
Prohibited 
Medications and 
Crediblemeds.org 
Updated the text and picture to 
indicate free registration is now 
required. 
Revised for consistency with the 
current website. 
Throughout 
Vendor information was added.  
Information was added per the 
current GSK protocol template. 
Throughout 
Minor editorial and document 
formatting revisions, including the 
addition of text per the current 
protocol template. 
Minor, therefore, have not been 
summarized. Updated text added 
per the current GSK protocol 
template provided further 
clarification of the original text. 
Amendment 1 14 December 2021 
This global amendment was considered to be non-substantial. 
Overall Rationale for the Amendment:  
This global amendment revised the primary analysis to be performed using the Miettinen 
and Nurminen method instead of the Cochran-Mantel-Haenszel method; added estimand 


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text; indicated study operational allowances with regard to COVID-19; incorporated past 
administrative and site notification letters; provided minor clarifications to the 
microbiology and NAAT defining criteria in the response and outcomes tables; indicated 
the total enrollment population will be approximately 600 participants; added micro-ITT 
subpopulations for participants with NG isolated in their rectal/pharyngeal specimen; and 
incorporated updates per the most recent safety and PK data known for gepotidacin, 
which included removal of P-glycoprotein inducers from the prohibited medications. 
Minor clarifications were also made throughout the protocol including, but not limited to, 
the Schedule of Activities table, inclusion and exclusion criteria, primary and secondary 
objectives, randomization stratification text, and adverse events of special interest. The 
amendment also includes additional minor administrative and wording edits. 
Summary of changes table of previous amendments: 
Section # and Name 
Description of Change 
Brief Rationale 
Synopsis 
4 Objectives and 
Estimands/Endpoints 
Table 3 Estimands 
Added estimands for the primary 
and secondary objectives and 
endpoints 
To meet current ICH guidelines 
on estimands 
Synopsis 
5.1 Overall Design 
Figure 1 Study Design 
Schematic 
5.4 Scientific 
Rationale for Study 
Design 
7.3 Method of 
Treatment 
Assignment 
10.4.2 Efficacy 
Analyses 
Updated text to clarify that 
participants will be stratified by 
“sex and sexual orientation 
combination” and age 
Text clarification as the 
stratification factor of “gender” 
(i.e., male/female) was 
inadvertently being used 
interchangeably for sex 
characteristics that are 
biologically defined. To avoid 
confusion, the term “sex” will be 
used from this point forward. 
Synopsis 
4 Objectives and 
Estimands/Endpoints 
Removed the analysis population 
(i.e., micro-ITT) from the primary 
and secondary objectives  
Not a requirement in the 
objectives text and the analysis 
populations are further described 
in Section 10 of the protocol 
Synopsis 
5.2 Number of 
Participants 
10.2.1 Justification of 
Sample Size 
Revised the target number of 
randomized participants to 
approximately 600 
To reflect currently known safety 
database requirements for 
regulatory authorities 


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Section # and Name 
Description of Change 
Brief Rationale 
2 Schedule of 
Activities (Table 1) 
Divided the “Interactive response 
technology” row into 2 separate 
rows specific for the screening 
and randomization modules; 
removed the “Randomization” row 
accordingly 
To align with how the interactive 
response is being used at study 
sites and to more closely follow 
the expected order of procedures 
2 Schedule of 
Activities (Table 1) 
5.1 Overall Study 
Design 
9 Study Assessments 
and Procedures 
Appendix 3 Study 
Governance 
Considerations 
Appendix 11 
COVID-19 Protocol 
Information 
Added text and table footnotes to 
allow for eConsent, telemedicine 
study-related data collection, 
collection of visit data as a 
combination of telemedicine and 
on-site visits, remote source data 
verification, and eCRF sign-off 
flexibility for investigators 
To support ongoing study 
conduct from safety and 
operational perspectives during 
the COVID-19 pandemic 
Synopsis 
3.3.3 Overall 
Benefit:Risk 
Conclusion 
5.4 Scientific 
Rationale for Study 
Design 
10.6 Data Monitoring 
Committee or Other 
Review Board 
Appendix 3 Study 
Governance 
Considerations 
Clarified only internal review 
teams will monitor study data 
during the study and that no 
external data monitoring 
committee is planned 
Text clarification 


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Section # and Name 
Description of Change 
Brief Rationale 
2 Schedule of 
Activities (Table 2) 
9.1.2 NAAT Assay 
Clarified that any specimens 
collected for NG NAAT assay at 
the central laboratory for NG 
would also be assayed for CT per 
standard laboratory procedures 
Incorporation of Protocol 
Administration Letter 4 dated 
06-MAY-2020, which addressed 
that CT can cause infection at all 
3 body sites (urogenital, rectal, 
pharyngeal) that are being 
evaluated in this study. Thus, 
when NAAT samples are 
submitted for NG testing, they 
are also routinely tested for CT 
and results are reported for both 
pathogens. 
2 Schedule of 
Activities (Table 2) 
9.1.2 NAAT Assay 
Clarified text and table footnotes 
for the NAAT assay at the 
Follow-up Visit to specify 
pathogens be tested and to refer 
to presence of nucleic acid 
instead of a positive result 
Text clarifications 
3.2 Background 
5.4 Scientific 
Rationale for Study 
Design 
5.5 Dose Justification 
Included text regarding the US 
CDC current standard of care 
treatment recommendations for 
gonococcal infection. Per FDA 
communications, no changes to 
the comparator arm are 
warranted. 
Incorporation of the Site 
Notification Letter dated 
26-JAN-2021 (sent to US-only 
sites), which described the most 
recent US CDC 
recommendations for treatment 
of gonococcal infection 
3.3.1 Risk 
Assessment 
Minor text clarifications for 
gepotidacin (clinical QTc effects, 
added relevant exposures for 
nonclinical embryofetal effects, 
etc.). Note, the risk benefit 
assessment for the study did not 
change. 
Consistency with currently 
known safety and PK data for 
gepotidacin 


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Section # and Name 
Description of Change 
Brief Rationale 
3.3.1 Risk 
Assessment 
6.2 Exclusion Criteria 
#15 
7.7.2 Prohibited 
Medications and 
Nondrug Therapies 
Appendix 9 Additional 
Guidance on 
Permitted and 
Prohibited 
Medications and 
Crediblemeds.org 
Removed exclusion for strong 
P-glycoprotein inhibitors 
Consistency with currently 
known PK data for gepotidacin 
6.1 Inclusion Criteria 
#2 
Figure 1 Study Design 
Schematic 
Revised the criterion to further 
describe what would be 
considered clinical suspicion of a 
urogenital gonococcal infection 
based on investigator feedback  
Incorporation of Protocol 
Administration Letter 2 dated 
30-SEP-2019, which provided 
additional details for expected 
clinical presentation of urogenital 
gonococcal infection 
6.1 Inclusion Criteria 
#4b 
Revised the criterion to state there 
was no requirement for 
contraception use or abstinence 
within 14 days of study entry in 
WOCBP who have a negative 
high sensitivity urine pregnancy 
test result 
Incorporation of Protocol 
Administration Letter 2 dated 
30-SEP-2019, which streamlined 
the criterion text for clarification 
and consistency with Appendix 6  
6.2 Exclusion Criteria 
#3 and #5 
Edited to include “uncontrolled” 
before high blood pressure and 
diabetes 
Text clarification 
6.2 Exclusion Criteria 
#17  
Added details to the exclusion 
criterion note for ECG exclusion 
To support consistency in ECG 
measurements 
7.7 Concomitant 
Therapy 
Clarified that any antibiotic use 
within 6 months of the Baseline 
Visit should be recorded 
To support the study analysis 
9 Study Assessments 
and Procedures 
Removed the requirement for 
participants to remain at the site 
for approximately 30 minutes after 
dosing at the Baseline Visit; 
however, retained text indicating 
that posttreatment assessments 
still need to be completed 
To support site flexibility for 
study conduct  


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Section # and Name 
Description of Change 
Brief Rationale 
9.1.1 Bacteriology 
6Samples for Culture 
Minor text clarifications were 
added to the defining criteria in 
the outcome and response 
Table 5  
Clarification to support the 
planned statistical analyses and 
programming details 
9.1.2 NAAT Assay 
Minor text clarifications were 
added to the defining criteria in 
the outcome and response Table 
6 and Table 7  
Clarification to support the 
planned statistical analyses and 
programming details 
10.2.1 Justification of 
Sample Size 
Clarified the significance level is a 
0.025 one-sided significance level 
rather than a 0.05 two-sided 
significance level, noted the 
estimated power was approximate 
in Table 8, and clarified that no 
treatment difference is assumed 
Text clarifications 
10.2.2 Sample Size 
Sensitivity 
Revised the percentage of power 
in Table 8 for the 92% and 88% 
success rate rows by a single 
digit; removed unnecessary text; 
and clarified that no treatment 
difference is assumed  
Minor text update for consistency 
in rounding the numbers and text 
clarifications 
10.1 Statistical 
Hypothesis 
10.4.2 Efficacy 
Analysis 
Revised the primary analysis to be 
performed using the Miettinen and 
Nurminen method instead of the 
Cochran-Mantel-Haenszel method 
and expanded text to state there 
would be 9 total subgroups based 
on the randomization stratification 
variables  
Consistency with the reporting 
and analysis plan 
10.3 Populations for 
Analyses 
10.4.2 Efficacy 
Analysis 
Added micro-ITT subpopulations 
for participants who have NG 
isolated from the 
rectal/pharyngeal specimen 
To support the planned analysis 
10.5 Interim Analysis 
Clarification that no interim 
analysis is planned 
Text clarification 
Appendix 2 Clinical 
Laboratory Tests 
Added magnesium to the 
laboratory assessments 
Consistency with the chemistry 
laboratory panel that will be 
conducted in the study 


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Section # and Name 
Description of Change 
Brief Rationale 
Appendix 3 Study 
Governance 
Considerations 
Clarified that study participants 
should advise their sexual 
partners of their infection status 
and that it should be documented 
in the medical chart per study site 
staff 
Incorporation of Protocol 
Administration Letter 1 dated 
22-JUL-2019, which supports 
notification of NG infection status 
to sexual partners of study 
participants 
Appendix 3 Study 
Governance 
Considerations 
Clarified that, in countries where 
certain responsibilities reside with 
the sponsor instead of the 
investigator, GSK or its designee 
will be responsible for those 
activities  
To support site feasibility 
Throughout 
Updated the second dose window 
for gepotidacin to 10 to 12 hours 
after the first dose; the original 
second dose window was 6 to 
12 hours 
Incorporation of Protocol 
Administration Letter 3 dated 
12-FEB-2020, which narrowed 
the second dose window for 
gepotidacin for safety reasons 
and to support uniformity in study 
conduct and subsequent data 
analysis. Note: There is no 
evidence this impacts efficacy. 
Throughout 
Updated text to state Clostridium 
difficile and acetylcholinesterase 
inhibition events are considered 
adverse events of special interest 
To support the planned safety 
analysis 
Throughout 
Minor editorial and document 
formatting revisions 
Minor, therefore, have not been 
summarized 
 

SAP_001.pdf: 
 
CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
BTZ116577 
 
1 
Division 
: Worldwide Development 
Information Type 
: Reporting and Analysis Plan (RAP) 
 
Title 
: Reporting and Analysis Plan for A Phase III, Randomized, 
Multicenter, Open-Label Study in Adolescent and Adult 
Participants Comparing the Efficacy and Safety of 
Gepotidacin to Ceftriaxone Plus Azithromycin in the 
Treatment of Uncomplicated Urogenital Gonorrhea Caused 
by Neisseria gonorrhoeae 
Compound Number  : GSK2140944 
Effective Date  
: 13 Oct 2023 
 
Description: 
• 
The purpose of this RAP is to describe the planned analyses and output to be 
included in the Clinical Study Report for Protocol BTZ116577. 
• 
This RAP is intended to describe the full analyses required for the study. 
• 
This RAP will be provided to the study team members to convey the content of 
the Statistical Analysis Complete (SAC) deliverable. 
 
RAP Author(s): 
Approver 
Date 
Approval 
Method 
Refer to 
Signature 
Signature 
Biostatistician II (Biostatistics, PPD) 
 
Copyright 2023 the GlaxoSmithKline group of companies. All rights reserved. 
Unauthorized copying or use of this information is prohibited. 
 
PPD


 
CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
BTZ116577 
 
2 
RAP Team Approvals: 
Approver 
Date 
Approval 
Method 
 
11 Oct 2023 
Email 
Manager Statistics (Clinical Statistics) 
(Clinical Statistics) 
12 Oct 2023 
Email 
4 Oct 2023 
Email 
Principal Programmer (Clinical Programming) 
4 Oct 2023 
Email 
4 Oct 2023 
Email 
4 Oct 2023 
Email 
Clinical Development Manager 
9 Oct 2023 
Email 
 
 
SERM 
11 Oct 2023 
Email 
4 Oct 2023 
Email 
(SERM) 
(Infectious Diseases 
Research Unit) 
5 Oct 2023 
Email 
Scientific Investigator (Infectious Diseases 
Research Unit) 
5 Oct 2023 
Email 
 Clinical Pharmacology Modeling 
Simulation 
11 Oct 2023 
Email 
Clinical Statistics and Clinical Programming Line Approvals: 
Approver 
Date 
Approval 
Method 
Refer to 
Signature 
Signature 
Statistics (Clinical Statistics) 
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD


 
CONFIDENTIAL 
The GlaxoSmithKline group of companies 
 
BTZ116577 
 
3 
 
Refer to 
Signature 
Signature 
Programming Leader (Clinical Programming) 
PPD


 
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BTZ116577 
 
4 
TABLE OF CONTENTS 
PAGE 
1. 
INTRODUCTION ...................................................................................................... 7 
2. 
SUMMARY OF KEY PROTOCOL INFORMATION ................................................ 10 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan .......................... 10 
2.2. 
Study Objective(s) and Estimand(s) / Endpoint(s) ....................................... 11 
2.2.1. 
Estimands .................................................................................... 12 
2.3. 
Study Design .............................................................................................. 17 
2.4. 
Statistical Hypotheses /Statistical Analyses ................................................ 18 
3. 
PLANNED ANALYSES .......................................................................................... 20 
3.1. 
Interim Analyses ......................................................................................... 20 
3.2. 
Final Analyses ............................................................................................ 20 
4. 
ANALYSIS POPULATIONS ................................................................................... 20 
4.1. 
Protocol Deviations ..................................................................................... 24 
5. 
CONSIDERATIONS FOR DATA ANALYSIS AND DATA HANDLING 
CONVENTIONS ..................................................................................................... 25 
5.1. 
Study Treatment & Sub-group Display Descriptors ..................................... 25 
5.2. 
Baseline Definitions .................................................................................... 25 
5.3. 
Multicenter Studies ..................................................................................... 25 
5.4. 
Examination of Covariates, Other Strata and Subgroups ............................ 25 
5.4.1. 
Strata and Other Covariates ........................................................ 25 
5.4.2. 
Examination of Subgroups ........................................................... 27 
5.5. 
Multiple Comparisons and Multiplicity ......................................................... 29 
5.6. 
Analysis Visits ............................................................................................. 29 
5.7. 
Other Considerations for Data Analyses and Data Handling 
Conventions ................................................................................................ 30 
6. 
STUDY POPULATION ANALYSES ....................................................................... 31 
6.1. 
Overview of Planned Study Population Analyses ........................................ 31 
6.1.1. 
Disposition and Withdrawals ........................................................ 31 
6.1.2. 
Demographic and Baseline Disease Characteristics .................... 31 
6.1.3. 
Prior and Concomitant Medications ............................................. 32 
6.1.4. 
Medical History and Current Medical Conditions .......................... 33 
6.1.5. 
Treatment Exposure .................................................................... 33 
7. 
EFFICACY ANALYSES .......................................................................................... 34 
7.1. 
Primary Efficacy Analyses .......................................................................... 34 
7.1.1. 
Endpoint / Variables ..................................................................... 34 
7.1.2. 
Summary Measure ...................................................................... 35 
7.1.3. 
Population of Interest ................................................................... 35 
7.1.4. 
Strategy for Intercurrent Events ................................................... 36 
7.1.5. 
Treatment Condition .................................................................... 36 
7.1.6. 
Statistical Analyses / Methods ..................................................... 36 
7.2. 
Secondary Efficacy Analyses ...................................................................... 45 
7.2.1. 
Endpoint / Variables ..................................................................... 45 
7.2.2. 
Summary Measure ...................................................................... 45 


 
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BTZ116577 
 
5 
7.2.3. 
Population of Interest ................................................................... 45 
7.2.4. 
Strategy for Intercurrent Events ................................................... 46 
7.2.5. 
Treatment Condition .................................................................... 46 
7.2.6. 
Statistical Analyses / Methods ..................................................... 46 
7.3. 
Exploratory Efficacy Analyses ..................................................................... 48 
7.3.1. 
Endpoint / Variables/Analysis ....................................................... 48 
7.3.2. 
Analysis Population of Interest ..................................................... 53 
7.3.3. 
Statistical Analyses / Methods ..................................................... 53 
8. 
SAFETY ANALYSES ............................................................................................. 55 
8.1. 
Adverse Events Analyses ........................................................................... 55 
8.2. 
Adverse Events of Special Interest Analyses .............................................. 56 
8.2.1. 
Clostridium difficile AESI .............................................................. 56 
8.2.2. 
Cardiovascular and Gastrointestinal Adverse Events ................... 56 
8.2.3. 
Acetylcholinesterase-Inhibition Adverse Events ........................... 56 
8.3. 
Clinical Laboratory Analyses ....................................................................... 57 
8.4. 
Vital Signs and ECG ................................................................................... 59 
8.5. 
Classification and analysis of safety signals ................................................ 60 
8.5.1. 
Multiplicity Adjustment ................................................................. 60 
8.5.2. 
Quantitative Screening for Identification of Potential ARs ............ 60 
8.5.3. 
Qualitative Causality Assessment ................................................ 62 
9. 
ADDITIONAL ANALYSES DUE TO THE COVID-19 PANDEMIC ........................... 63 
9.1. 
Study Population ......................................................................................... 63 
9.1.1. 
Participant Disposition ................................................................. 63 
9.1.2. 
Protocol Deviations ...................................................................... 63 
9.2. 
Safety ......................................................................................................... 63 
10. BENEFIT/RISK ....................................................................................................... 64 
11. REFERENCES ....................................................................................................... 65 
12. APPENDICES ........................................................................................................ 66 
12.1. 
Appendix 1: Schedule of Activities .............................................................. 66 
12.1.1. 
Protocol Defined Schedule of Events ........................................... 66 
12.2. 
Appendix 2: Study Phases and Treatment Emergent Adverse 
Events ........................................................................................................ 70 
12.2.1. 
Study Phases .............................................................................. 70 
12.2.1. 
Treatment Emergent Flag for Adverse Events ............................. 70 
12.3. 
Appendix 3: Data Display Standards & Handling Conventions .................... 71 
12.3.1. 
Reporting Process ....................................................................... 71 
12.3.2. 
Reporting Standards .................................................................... 71 
12.4. 
Appendix 4: Derived and Transformed Data ............................................... 73 
12.4.1. 
General ........................................................................................ 73 
12.4.2. 
Efficacy ........................................................................................ 73 
12.4.3. 
Safety .......................................................................................... 82 
12.5. 
Appendix 5: Reporting Standards for Missing Data ..................................... 87 
12.5.1. 
Premature Withdrawals ................................................................ 87 
12.5.2. 
Handling of Missing Data ............................................................. 87 
12.6. 
Appendix 6: Values of Potential Clinical Importance ................................... 89 
12.6.1. 
ECG ............................................................................................. 89 
12.6.2. 
Vital Signs .................................................................................... 89 


 
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BTZ116577 
 
6 
12.7. 
Appendix 7: Division of Microbiology and Infectious Diseases 
Toxicity Tables for Adverse Event Assessment........................................... 90 
12.7.1. 
Laboratory Values ........................................................................ 90 
12.8. 
Appendix 8: Abbreviations & Trademarks ................................................... 94 
12.8.1. 
Abbreviations ............................................................................... 94 
12.8.2. 
Trademarks ................................................................................. 95 
12.9. 
Appendix 9: List of Data Displays ............................................................... 96 
12.9.1. 
Data Display Numbering .............................................................. 96 
12.9.2. 
Mock Example Shell Referencing ................................................ 96 
12.9.3. 
Deliverables ................................................................................. 96 
12.9.4. 
Study Population Tables .............................................................. 97 
12.9.5. 
Study Population Figures ........................................................... 101 
12.9.6. 
Efficacy Tables .......................................................................... 101 
12.9.7. 
Efficacy Figures ......................................................................... 125 
12.9.8. 
Safety Tables ............................................................................. 127 
12.9.9. 
Safety Figures ........................................................................... 133 
12.9.10. ICH and Non-ICH Listings .......................................................... 135 
 


 
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BTZ116577 
 
7 
1. 
INTRODUCTION 
The purpose of this reporting and analysis plan (RAP) is to describe the analyses to be 
included in the Clinical Study Report for study BTZ116577. 
Revision Chronology: 
Version 
Date 
Original 
05 Oct 2022 
Amendment No. 1 
16 Mar 2023 
Updates include: 
• 
Minor formatting and typographical updates. 
• 
Alignment with changes in Protocol Amendment 2: 
o Increased the total number of enrolled participants from approximately 600 to 
approximately 620 (Section 2.3). 
o Primary analysis population (Micro ITT) updated with ceftriaxone susceptibility 
evaluated using EUCAST breakpoints (Section 4). 
• 
Clarified primary and secondary efficacy estimands variable/endpoint attribute to state that for 
microbiological success participant must not receive other systemic antimicrobials prior to the 
TOC assessment (Section 2.2.1). 
• 
Clarified text on declaration of superiority (Section 2.4). 
• 
Clarified that all Microbiologically Evaluable analysis populations include the condition that 
actual treatment is the same as randomized (Section 4). 
• 
Added Micro-ITT CLSI Analysis Population (Section 4) for the sensitivity analysis for the primary 
analysis including isolates identified as resistant by EUCAST but susceptible by CLSI (Section 
7.1.6.2). 
• 
Removed references to Lu K., Guo H. Multiple imputation analysis of Miettinen-Nurminen 
interval for difference in proportions, Pharmaceutical Statistics. 2021;1–13 as this method will 
not be used (Section 7.1.6.1, Section 7.1.6.2 and Section 11). 
• 
Updated confidence interval methods for pooled estimates (after using Rubin’s rules) to Wald-
type confidence intervals for both the multiple-imputation and tipping point sensitivity analyses 
(Section 7.1.6.2). 
• 
Clarified that there will be no multiplicity adjustment or formal hypothesis testing of secondary or 
exploratory endpoints, but that confidence intervals may be included for descriptive purposes 
(Section 7.2.6 and Section 7.3.3). 
• 
Added Adverse Reactions analyses (Section 8.5). 
• 
Clarified efficacy analyses for Benefit/Risk (Section 10). 
• 
Clarification on “Out of stability” isolates for the Keepers file (Section 12.4.2). 
• 
Clarification on the calculation of MIC50 and MIC90 (Section 12.4.2). 
• 
Removed imputation rules for laboratory parameter character values (Section 12.4.3). 
• 
Removal of laboratory values not relevant to this study (Section 12.7). 
• 
Added note regarding All Analyses Complete (AAC) (Section 12.9.3). 
Amendment No. 2 
13 Oct 2023 
Updates Include: 
• 
Minor formatting and typographical updates throughout. 
• 
Added a note for clarification that “systemic antimicrobials before the TOC Visit” in the 
intercurrent event strategy for the efficacy estimands in Table refers to "other systemic 
antimicrobials” i.e., excluding the investigational product (Section 2.2.1). 
• 
For the Micro-ITT population, ceftriaxone susceptibility determination has been changed to CLSI 
from EUCAST guidelines in order to meet regulatory submission requirements (Section 4). 
Additionally: 


 
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BTZ116577 
 
8 
o Micro-ITT CLSI population amended to Micro-ITT EU population (Section 4). 
o References to EUCAST in primary analysis updated to CLSI (Section 7.1). 
o Sensitivity analysis for the primary analysis changed from being based on Micro-ITT 
CLSI to Micro-ITT EU population (Section 7.1.6.2) and corresponding text relating to 
determination of ceftriaxone susceptibility by disk diffusion (CLSI guidelines) added. 
o Provision added for the reproduction of any summaries or listings using populations 
based on CLSI guidelines to be repeated on the equivalent population but using 
EUCAST guidelines for the determination of ceftriaxone susceptibility (Section 4 and 
Section 7). 
• 
Added clarification that the Micro-ITT population will be used for Study Population summaries as 
well as Efficacy summaries (Section 4). 
• 
Added clarification that for participants with more than 1 NG isolate recovered at baseline from 
the same body site, all of the isolates must be susceptible to ceftriaxone for that participant to be 
included in the Micro-ITT populations (Section 4). 
• 
Added clarification on the handling of out of stability NG negative samples at the TOC visit for 
the purposes of Microbiologically Evaluable populations (Section 4). 
• 
Added clarification that final determination of population inclusion will be performed after final 
data extraction and that two pre-specified criteria for ME populations will be applied on 
unblinded data (Section 4). 
• 
Added clarification that the Micro-ITT CAPA population may be defined, and corresponding 
supplementary analysis be conducted, if one or more sites/investigators had a CAPA that 
stipulates that a supplementary analysis should be conducted, as agreed by a GSK 
multidisciplinary team (Section 4 and Section 7.1.6.3). 
• 
Summary of randomized versus actual pooled strata added (Section 5.4.1). 
• 
Clarified that any medication or vaccine that the participant is receiving within 6 months prior to 
the Baseline Visit or receives during the study will be recorded (Section 6.1.3). 
• 
Added instructions on how to handle estimation of risk differences and CIs when 100% (or 0%) 
success rates are observed in both treatment arms (Section 7). 
• 
Updated denominator for bacterial eradication rate equation to correctly reflect the population of 
interest (Section 7.1.2). 
• 
Clarified that the overall test for homogeneity will use the combined pooled strata levels (Section 
7.1.6.1). 
• 
Added summaries for further granularity of reasons for microbiological failure and on the use of 
systemic antibiotics (Section 7.1.6.1). 
• 
Clarified that ‘randomized’ treatment group will be used in the multiple imputation sensitivity 
analysis logistic regression model (Section 7.1.6.2). 
• 
Added instructions on the handling of dominant pathogens in the multiple imputation analysis 
and updated text on MIC grouping for clarity (Section 7.1.6.2). 
• 
Added provision for repeating MI and tipping point sensitivity analyses, if data warrant, with all 
missing microbiological response data imputed, irrespective of the reason for missingness 
(Section 7.1.6.2). 
• 
Clarified that for the tipping point sensitivity analysis, CIs will be displayed for the risk difference 
but not for the proportion of successes within each treatment arm as not required (Section 
7.1.6.2). 
• 
Added provision for repeating MI and tipping point analyses with a higher number of 
imputations, should results be considered sensitive to the random number seed and/or number 
of imputations (Section 7.1.6.2). 
• 
Added instructions for handling MI / tipping point analyses in situations where between 
imputation variance is zero (Section 7.1.6.2). 
• 
Added provision for additional sensitivity analyses if data warrant repeating the primary analysis 
(Micro-ITT) and Micro-ITT EU sensitivity analyses but excluding participants whose ceftriaxone 


 
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BTZ116577 
 
9 
susceptibility was determined by disk diffusion (Section 7.1.6.2). 
• 
Added analyses of phenotypes and genotypes within subgroups (Section 7.1.6.5). 
• 
Clarified that some summaries will be presented at the isolate level, so that participants with 
multiple isolates may enter a descriptive summary more than once. However, when point 
estimates and confidence intervals are presented, results will be presented at the participant-
level (Section 7.1.6.5). 
• 
Updated disk diffusion summary statistics to include median and standard deviation but not 
include the mode and add that results will not be displayed if <10 isolates (Section 7.3.1.2). 
• 
Added that the relatedness of pre- and post-baseline isolates (e.g., as it relates to 4-fold 
increases and/or microbiological failures) will be described in a stand-alone report, if needed 
(Section 7.3.1.3). 
• 
Added that analyses of reduction in susceptibility may be repeated for study treatments by 
phenotypic and genotypic subgroups (Section 7.3.1.3). 
• 
Clarified that the relatedness of pre- and post-baseline isolates (e.g., as it relates to 4-fold 
increases and/or microbiological failures) will be described in a stand-alone report, if needed 
(Section 7.3.1.3). 
• 
Updated NAAT FU analyses (Pharyngeal NG and Urogenital Mgen) of microbiological response 
to be unadjusted since it is anticipated that there will be insufficient observations to adequately 
perform an adjusted analysis (Section 7.3.1.5). 
• 
Added clarification that both CLSI and EUCAST versions of the Micro Review Aid will be created 
(Section 7.3.1.6). 
• 
Added non-serious drug-related AEs to AE types to be summarised (Section 8.1) 
• 
Added Cockroft-Gault formula for determination of renal impairment by baseline CrCL (Section 
8.3). 
• 
Clarified that Adverse Reactions will be reported in the regulatory submission but are not 
required as part of the CSR (Section 8.5). 
• 
Updated Benefit-Risk analysis to additionally include incidence of any AE (Section 10). 
• 
Updated references (Section 11). 
• 
Added data-handling instructions relating to extra NAAT specimens i.e., where both urine and 
swab specimen are taken for the central laboratory urogenital NAAT at the same visit/timepoint 
(Section 12.4.2). 
• 
Added further clarification on the Keepers file process (Section 12.4.2). 
• 
Added clarification on the determination and handling of Out-of-Stability samples (Section 
12.4.2). 
• 
Updated instructions on handling laboratory values with non-detectable levels reported in the 
data base (Section 12.4.3). 
• 
Updated output numbering, titles and programming notes in list of data displays as required and 
included additional summaries added in this RAP update (Appendix 9, Section 12.9). 
 


 
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2. 
SUMMARY OF KEY PROTOCOL INFORMATION 
This Phase III study (BTZ116577) aims to evaluate the efficacy and safety of oral 
gepotidacin compared to intramuscular (IM) ceftriaxone plus oral azithromycin, a 
currently recommended treatment regimen, for the treatment of uncomplicated urogenital 
gonorrhea (GC) caused by Neisseria gonorrhoeae (NG). 
 
2.1. 
Changes to the Protocol Defined Statistical Analysis Plan 
There were no changes to the planned statistical analyses specified in protocol 
amendment 3 (GSK Document Number: TMF-16433266, Dated 10 Aug 2023). 
Additional analysis sets to those described in the protocol are given in Section 4. 
 


 
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2.2. 
Study Objective(s) and Estimand(s) / Endpoint(s) 
Objectives 
Endpoints 
Primary 
Primary 
To evaluate the efficacy of oral gepotidacin 
compared to IM ceftriaxone plus oral 
azithromycin to treat participants with 
uncomplicated urogenital gonorrhea 
caused by Neisseria gonorrhoeae (NG) 
Culture-confirmed bacterial eradication of NG from the 
urogenital body site (i.e., microbiological success) at the TOC 
(Day 4 to 8) Visit 
Secondary 
Secondary 
To evaluate the efficacy of oral gepotidacin 
compared to IM ceftriaxone plus oral 
azithromycin to treat participants with 
rectal gonorrhea caused by NG  
Culture-confirmed bacterial eradication of NG from the rectal 
body site (i.e., microbiological success) at the TOC (Day 4 to 
8) Visit 
To evaluate the efficacy of oral gepotidacin 
compared to IM ceftriaxone plus oral 
azithromycin to treat participants with 
pharyngeal gonorrhea caused by NG  
Culture-confirmed bacterial eradication of NG from the 
pharyngeal body site (i.e., microbiological success) at the 
TOC (Day 4 to 8) Visit 
To evaluate the safety and tolerability of 
oral gepotidacin compared to IM 
ceftriaxone plus oral azithromycin 
Treatment-emergent adverse events (AEs) and serious AEs 
(SAEs) and change from baseline results for clinical laboratory 
tests and vital sign measurements 
Exploratory 
Exploratory 
To assess the clearance or persistence of 
NG nucleic acid (by nucleic acid 
amplification test [NAAT] assay) from 
urogenital specimens for oral gepotidacin 
compared to IM ceftriaxone plus oral 
azithromycin 
Urogenital NG NAAT results at the TOC (Day 4 to 8) Visit 
To assess the clearance or persistence of 
NG nucleic acid (NAAT assay) from 
pharyngeal specimens for oral gepotidacin 
compared to IM ceftriaxone plus oral 
azithromycin 
Pharyngeal NG NAAT results at the TOC (Day 4 to 8) and 
Follow-up (Day 14 to 21) Visits, where only participants who 
did not receive other systemic antimicrobials at or after the 
TOC (Day 4 to 8) Visit will be evaluated at the Follow-up Visit 
To assess the clearance or persistence of 
NG nucleic acid (NAAT assay) from rectal 
specimens for oral gepotidacin compared 
to IM ceftriaxone plus oral azithromycin 
Rectal NG NAAT results at the TOC (Day 4 to 8) Visit 
To assess the clearance or persistence of 
Mycoplasma genitalium (Mgen) nucleic 
acid (by NAAT assay) from urogenital 
specimens for oral gepotidacin compared 
to IM ceftriaxone plus oral azithromycin 
Urogenital Mgen NAAT results at the Follow-up (Day 14 to 21) 
Visit, where only participants who did not receive other 
systemic antimicrobials at or after the TOC (Day 4 to 8) Visit 
will be evaluated 
To evaluate the microbiological 
characteristics and antimicrobial 
susceptibility profile of NG from urogenital, 
pharyngeal, or rectal specimens 
Gram stain (urogenital specimens only), bacterial culture, and 
in vitro susceptibility test results from urogenital, pharyngeal, 
or rectal specimens at the Baseline (Day 1), TOC (Day 4 to 8), 
and Follow-up (Day 14 to 21), as data permits 
 


 
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12 
2.2.1. 
Estimands 
The primary clinical question of interest is: What is the treatment effect on the 
culture-confirmed bacterial eradication of NG from the urogenital body site (i.e., 
microbiological success) at the TOC (Day 4 to 8) Visit after treatment with oral 
gepotidacin compared to IM ceftriaxone plus oral azithromycin in participants with 
uncomplicated urogenital gonorrhea and have confirmed NG isolated from baseline 
culture of their urogenital specimen, regardless of treatment discontinuation for any 
reason. 
 
Prespecified estimands with related attributes are presented in Table 1 for the primary 
and secondary objectives.


 
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BTZ116577 
 
13 
Table 1 
Estimands 
Estimand 
Category  
Estimand 
Variable/Endpoint 
Population 
Treatment Condition 
Summary Measure 
Intercurrent Event Strategy 
Primary Objective: To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with uncomplicated 
urogenital gonorrhea caused by NG 
Primary  
Microbiological success: 
Participants with culture 
confirmed bacterial 
eradication of NG from the 
urogenital body site (i.e., 
urogenital microbiological 
success) at the TOC 
(Day 4 to 8) Visit without 
the participant receiving 
other systemic 
antimicrobials prior to the 
TOC assessment. 
Refer to Table 2 for further 
details on the endpoint 
definition, including the 
missing data strategy for 
participants who do not 
return for the TOC Visit 
Participants with 
uncomplicated 
urogenital gonorrhea 
caused by culture 
confirmed NG 
Gepotidacin 2×3000 mg 
versus  
Ceftriaxone 500 mg plus 
azithromycin 1 g,  
regardless of adherence 
Difference in proportions  
(microbiological success 
rate in the gepotidacin 
treatment group - 
ceftriaxone plus 
azithromycin treatment 
group) 
Participants who receive 
systemic antimicrobials before 
the TOC Visit will be 
considered microbiological 
failures (composite strategy) 
For study treatment 
discontinuation, the data will 
be analyzed as collected 
(treatment policy strategy) 


 
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Estimand 
Category  
Estimand 
Variable/Endpoint 
Population 
Treatment Condition 
Summary Measure 
Intercurrent Event Strategy 
Secondary Objective: To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with rectal gonorrhea 
caused by NG in the Micro ITT Population 
Secondary 
Participants with culture-
confirmed bacterial 
eradication of NG from the 
rectal body site (i.e., rectal 
microbiological success) at 
the TOC (Day 4 to 8) Visit 
without the participant 
receiving other systemic 
antimicrobials prior to the 
TOC assessment. 
Refer to Table 2 for further 
details on the endpoint 
definition, including missing 
data strategy for 
participants who do not 
return for the TOC Visit 
Participants with 
uncomplicated 
urogenital and rectal 
gonorrhea caused 
by culture-confirmed 
NG 
Gepotidacin 2×3000 mg 
versus  
Ceftriaxone 500 mg plus 
azithromycin 1 g,  
regardless of adherence 
Difference in proportions  
(microbiological success 
rate in the gepotidacin 
treatment group - 
ceftriaxone plus 
azithromycin treatment 
group) 
Participants who receive 
systemic antimicrobials before 
the TOC Visit will be 
considered microbiological 
failures (composite strategy) 
For study treatment 
discontinuation, the data will 
be analyzed as collected 
(treatment policy strategy) 


 
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Estimand 
Category  
Estimand 
Variable/Endpoint 
Population 
Treatment Condition 
Summary Measure 
Intercurrent Event Strategy 
Secondary Objective: To evaluate the efficacy of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin to treat participants with pharyngeal 
gonorrhea caused by NG 
Secondary 
Participants with culture-
confirmed bacterial 
eradication of NG from the 
pharyngeal body site (i.e., 
pharyngeal microbiological 
success) at the TOC (Day 
4 to 8) Visit without the 
participant receiving other 
systemic antimicrobials 
prior to the TOC 
assessment. 
 
Refer to Table 2 for further 
details on the endpoint 
definition, including the 
missing data strategy for 
participants who do not 
return for the TOC Visit 
Participants with 
uncomplicated 
urogenital and 
pharyngeal 
gonorrhea caused 
by culture-confirmed 
NG 
Gepotidacin 2×3000 mg 
versus  
Ceftriaxone 500 mg plus 
azithromycin 1 g,  
regardless of adherence 
Difference in proportions  
(microbiological success 
rate in the gepotidacin 
treatment group - 
ceftriaxone plus 
azithromycin treatment 
group) 
Participants who receive 
systemic antimicrobials before 
the TOC Visit will be 
considered microbiological 
failures (composite strategy) 
For study treatment 
discontinuation, the data will 
be analyzed as collected 
(treatment policy strategy) 


 
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Estimand 
Category  
Estimand 
Variable/Endpoint 
Population 
Treatment Condition 
Summary Measure 
Intercurrent Event Strategy 
Secondary Objective: To evaluate the safety and tolerability of oral gepotidacin compared to IM ceftriaxone plus oral azithromycin 
Secondary 
(Safety) 
Treatment-emergent AEs 
and serious AEs and 
change from baseline 
results for clinical 
laboratory tests and vital 
sign measurements 
Participants with 
uncomplicated 
urogenital gonorrhea 
Gepotidacin 2×3000 mg 
versus  
Ceftriaxone 500 mg plus 
azithromycin 1 g,  
regardless of adherence 
The proportions for 
treatment-emergent AEs 
and serious AEs will be 
produced for each arm 
separately. The means for 
change from baseline 
results (clinical laboratory 
results and vital sign 
measurements) will be 
produced for each arm 
separately. 
For study treatment 
discontinuation, the data will 
be analyzed as collected 
(treatment policy strategy) 
1. AE=adverse events; NG=Neisseria gonorrhoeae; TOC=Test-of-Cure. Note that “systemic antimicrobials before the TOC Visit” refers to "other systemic antimicrobials” i.e., 
excluding the investigational product (see Table 2). 
 


 
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Rationale for estimands: 
The rationale for a treatment policy intercurrent event strategy of study treatment 
discontinuation is that interest lies in the treatment effect irrespective of whether the full 
course of treatment was taken or not, this is reflective of how patients may be treated in 
clinical practice. 
The rationale for using a composite strategy for the intercurrent event of antimicrobial 
use is because usage could affect bacterial culture response; thus, a conservative 
approach has been adopted and if a participant receives systemic antimicrobials before 
the TOC Visit, the participant will be assumed to be a microbiological failure. Note: The 
intercurrent event of antimicrobial use is not applicable for the safety estimands. 
2.3. 
Study Design 
Overview of Study Design and Key Features 
The study design schematic is shown in Figure 1. 
 
Figure 1 Study Design Schematic 
 
 
a. 
Refer to Inclusion Criterion #2 in protocol amendment 3 for details regarding urogenital gonococcal infection 
eligibility requirements. 
b. 
Stratification will be performed before randomization to ensure that treatment groups are balanced with regard 
to sex, sexual orientation and age. 
c. 
Study treatment will be administered under open-label conditions. All doses of oral study treatment should 
always be taken after food consumption and with water. 
d. 
Participants randomly assigned to gepotidacin will self-administer their second dose (3000 mg) as an 
outpatient 10 to 12 hours after the first dose; however, for participants who weigh <50 kg or have moderate 
renal impairment, the second dose should be taken approximately 12 hours after the first dose. 
e. 
Participants will return to the study site anytime from Day 14 to 21 for a Follow-up Visit. The investigator and/or 
study site staff should make every effort to ensure a participant returns for this visit. If it is determined that a 
participant is unable to return to the study site, the Follow-up Visit assessments may be completed via 
telephone, with the exception of assessments requiring sample collection for laboratory testing. 


 
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Overview of Study Design and Key Features 
Design 
Features 
• 
Phase III, randomized, multicenter, open-label (sponsor-blinded), comparator-
controlled, noninferiority study 
• 
The study duration is approximately 21 days with 3 planned study visits: 
• 
Baseline (Day 1) Visit 
• 
TOC (Day 4 to 8) Visit 
• 
Follow-up (Day 14 to 21) Visit 
• 
The study will screen and randomize approximately 620 participants to obtain 
approximately 400 participants with culture-confirmed urogenital gonorrhea in the 
Micro-ITT Population, for an estimated total of 200 participants per treatment group 
in the Micro-ITT Population. Enrollment will continue until the target number of 
participants in the Micro-ITT Population has been reached. 
Dosing 
• 
Participants will receive 1 of the following study treatments: 
• 
Gepotidacin: 3000 mg administered orally at the study site during the Baseline 
(Day 1) Visit followed by self-administration of a second oral 3000-mg dose as 
an outpatient 10 to 12 hours after the first dose. 
• 
Ceftriaxone plus azithromycin: A single IM 500-mg dose of ceftriaxone plus a 
single oral 1-g dose of azithromycin administered at the study site during the 
Baseline (Day 1) Visit. 
Time & 
Events 
• 
Refer to Appendix 1: Schedule of Activities 
Treatment 
Assignment 
• 
Participants will be stratified by sex and sexual orientation (men who have sex with 
men [MSM], men who have sex with women [MSW], or female) and age (<18 years, 
≥18 to 65 years, or >65 years). The MSM category will include MSM and bisexual 
males (i.e., male participants who have sex with both males and females) and 
participants ≥12 years will be included in the study. Eligible participants will be 
randomly assigned in a 1:1 ratio to receive 1 of the study treatments (gepotidacin or 
ceftriaxone plus azithromycin) with dosing as described above. 
Interim 
Analysis 
• 
No interim analyses are planned for this study. 
2.4. 
Statistical Hypotheses /Statistical Analyses 
The study is designed to demonstrate that gepotidacin administered orally is noninferior 
compared to ceftriaxone plus azithromycin on the primary efficacy endpoint of culture-
confirmed eradication of NG from the urogenital body site (i.e., microbiological success) 
at the TOC visit. 
The following are null and alternative hypotheses for the primary analysis of the 
microbiological success rate at the prespecified noninferiority margin of -10%: 
H0: Microbiological success rate of gepotidacin – Microbiological success rate of 
ceftriaxone plus azithromycin ≤ -10.0% 
H1: Microbiological success rate of gepotidacin – Microbiological success rate of 
ceftriaxone plus azithromycin > -10.0% 
Gepotidacin will be declared noninferior to treatment with ceftriaxone plus azithromycin 
if the lower limit of the 2-sided 95% confidence interval (CI) for the difference between 
the microbiological success rate of gepotidacin and ceftriaxone plus azithromycin at the 
TOC visit is above -10.0%. 


 
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If noninferiority is declared between gepotidacin and ceftriaxone plus azithromycin, then 
superiority will be tested using the following null and alternative hypothesis: 
 
H0: Microbiological success rate of gepotidacin – Microbiological success rate of 
ceftriaxone plus azithromycin ≤ 0% 
H1: Microbiological success rate of gepotidacin – Microbiological success rate of 
ceftriaxone plus azithromycin > 0% 
 
Superiority of gepotidacin will be declared if the lower end of the 2-sided 95% CI is 
above 0%. Testing for superiority using 2.5% level of significance will occur if 
noninferiority is achieved and one-sided p-value will be calculated.   
 
The difference in microbiological success rate between the 2 treatment groups and the 
corresponding CI will be computed using the Miettinen and Nurminen (MN) method 
(Miettinen, 1985) stratified by sex and sexual orientation (men who have sex with men 
[MSM], men who have sex with women [MSW], or female) combination. In the event 
that any participants are mis-stratified, for the primary efficacy analysis, the actual sex 
and sexual orientation collected in eCRF will be used to create actual pooled 
stratification. A sensitivity analysis of the primary efficacy analysis will also be 
conducted from the pooled stratification as randomized (Section 7.1.6.2). 


 
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3. 
PLANNED ANALYSES 
3.1. 
Interim Analyses 
No formal interim analyses are planned. 
3.2. 
Final Analyses 
The final planned primary analyses will be performed after the completion of the 
following sequential steps: 
1. All participants have completed the study as defined in the protocol at the FU visit. 
2. All protocol deviations captured and categorized, and analysis populations defined. 
3. All final database cleaning and data lock activities completed by data management. 
4. All criteria for the unblinding of participant randomization codes have been 
achieved. 
5. All randomization codes have been distributed per standard operating procedures. 
6. All access to unblinded data prior to the final DBF will be restricted in accordance 
with the Master Blinding Plan. 
4. 
ANALYSIS POPULATIONS 
Population 
Definition / Criteria 
Analyses Evaluated 
Screened Population 
• 
All participants who were screened for eligibility. 
• 
Study Population 
Intent-to-Treat (ITT) 
Population 
• 
All participants randomly assigned to study 
treatment.  
• 
Participants will be analyzed according to their 
randomized treatment arm  
• 
Study Population 
• 
Efficacy 
Microbiological ITT 
(Micro-ITT) 
Population 
• 
All participants randomly assigned to study treatment 
who receive at least 1 dose of study treatment and 
have confirmed NG isolated that is ceftriaxone-
susceptible (based on CLSI breakpoints) from 
baseline culture of their urogenital specimen. 
• 
Participants will be analyzed according to their 
randomized study treatment arm. 
• 
This is the primary analysis population. 
• 
Study Population 
• 
Efficacy 
Microbiological ITT 
FDA (Micro-ITT 
FDA) Population 
• 
All participants randomly assigned to study treatment 
who receive at least 1 dose of study treatment and 
have confirmed NG isolated that is ceftriaxone-
susceptible (based on CLSI breakpoints) from 
baseline culture of their urogenital specimen plus 
participants who have missing susceptibility and NG 
isolated at the local laboratory, identified using a 
recognized method. 
• 
Participants will be analyzed according to their 
randomized study treatment arm. 
• 
Study Population 
 


 
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Population 
Definition / Criteria 
Analyses Evaluated 
Microbiological ITT 
EU (Micro-ITT EU) 
Population 
• 
All participants who meet the definition of the Micro-
ITT population and any participants randomly 
assigned to study treatment who receive at least 1 
dose of study treatment and have confirmed NG 
isolated that is ceftriaxone-susceptible (based on 
EUCAST breakpoints) from baseline culture of their 
urogenital specimen. 
• 
Participants will be analyzed according to their 
randomized study treatment arm. 
• 
Efficacy 
Micro-ITT Rectal 
Population 
• 
Participants who meet the definition of the Micro-ITT 
Population and have confirmed NG isolated that is 
ceftriaxone susceptible from baseline culture of their 
rectal specimen.  
• 
Participants will be analyzed according to their 
randomized study treatment. 
• 
Efficacy 
Micro-ITT 
Pharyngeal 
Population 
• 
Participants who meet the definition of the Micro-ITT 
Population and have confirmed NG isolated that is 
ceftriaxone susceptible from baseline culture of their 
pharyngeal specimen. 
• 
Participants will be analyzed according to their 
randomized study treatment. 
• 
Efficacy 
Microbiologically 
Evaluable (ME) 
Population 
• 
Participants who meet the definition of the Micro-ITT 
Population and follow important components of the 
study (i.e., (1) receive all planned doses as 
randomized and actual treatment is the same as 
randomized, (2) have a urogenital specimen 
collected at the TOC Visit, with available culture 
results, (3) have not taken any other systemic 
antibiotic prior to TOC, unless it was taken for the 
current infection, and (4) have no major deviation 
that prevents evaluation of efficacy).  
• 
Participants will be analyzed according to their 
randomized treatment arm. 
• 
Efficacy 
Microbiologically 
Evaluable (ME) 
Rectal Population 
• 
Participants who meet the definition of the Micro-ITT 
Rectal Population and follow important components 
of the study (i.e., (1) receive all planned doses as 
randomized and actual treatment is the same as 
randomized, (2) have a Rectal specimen collected at 
the TOC Visit, with available culture results, (3) have 
not taken any other systemic antibiotic prior to TOC, 
unless it was taken for the current infection, and (4) 
have no major deviation that prevents evaluation of 
efficacy).  
• 
Participants will be analyzed according to their 
randomized treatment arm. 
• 
Efficacy 
Microbiologically 
Evaluable (ME) 
Pharyngeal 
Population 
• 
Participants who meet the definition of the Micro-ITT 
Pharyngeal Population and follow important 
components of the study (i.e., (1) receive all planned 
doses as randomized and actual treatment is the 
same as randomized, (2) have a Pharyngeal 
• 
Efficacy 


 
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Population 
Definition / Criteria 
Analyses Evaluated 
specimen collected at the TOC Visit, with available 
culture results, (3) have not taken any other systemic 
antibiotic prior to TOC, unless it was taken for the 
current infection, and (4) have no major deviation 
that prevents evaluation of efficacy). 
• 
Participants will be analyzed according to their 
randomized treatment arm. 
ME NAAT TOC 
Population 
• 
Participants who meet the definition of the Micro-ITT 
and follow important components of the study and 
were NG NAAT positive at baseline (i.e., (1) receive 
all planned doses as randomized and actual 
treatment is the same as randomized, (2) have a 
Urogenital NAAT specimen collected at the TOC 
Visit, with available NAAT results, (3) have not taken 
any other systemic antibiotic prior to TOC, unless it 
was taken for the current infection, and (4) have no 
major deviation that prevents evaluation of efficacy).  
• 
Participants will be analyzed according to their 
randomized treatment arm. 
• 
Efficacy 
ME NAAT TOC 
Rectal Population 
• 
Participants who meet the definition of the Micro-ITT 
Rectal Population and follow important components 
of the study and were NG NAAT positive for Rectal 
specimen at baseline (i.e., (1) receive all planned 
doses as randomized and actual treatment is the 
same as randomized, (2) have a Rectal NAAT 
specimen collected at the TOC Visit, with available 
NAAT results, (3) have not taken any other systemic 
antibiotic prior to TOC, unless it was taken for the 
current infection, and (4) have no major deviation 
that prevents evaluation of efficacy).  
• 
Participants will be analyzed according to their 
randomized treatment arm. 
• 
Efficacy 
ME NAAT TOC 
Pharyngeal 
Population 
• 
Participants who meet the definition of the Micro-ITT 
Pharyngeal Population and follow important 
components of the study and were NG NAAT 
positive for Pharyngeal specimen at baseline (i.e., (1) 
receive all planned doses as randomized and actual 
treatment is the same as randomized, (2) have a 
Pharyngeal NAAT specimen collected at the TOC 
Visit, with available NAAT results, (3) have not taken 
any other systemic antibiotic prior to TOC, unless it 
was taken for the current infection, and (4) have no 
major deviation that prevents evaluation of efficacy).  
• 
Participants will be analyzed according to their 
randomized treatment arm. 
• 
Efficacy 
ME NAAT FU Mgen 
Population 
• 
Participants who meet the definition of the Micro-ITT 
and follow important components of the study and 
were Mgen (urogenital) NAAT positive at baseline 
(i.e., (1) receive all planned doses as randomized 
and actual treatment is the same as randomized, (2) 
have Mgen (urogenital) NAAT specimen collected at 
• 
Efficacy 


 
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Population 
Definition / Criteria 
Analyses Evaluated 
the FU Visit, with available NAAT results, (3) have 
not taken any other systemic antibiotic prior to FU, 
unless it was taken for the current infection, and (4) 
have no major deviation that prevents evaluation of 
efficacy).  
• 
Participants will be analyzed according to their 
randomized treatment arm. 
ME NAAT FU 
Pharyngeal 
Population 
• 
Participants who meet the definition of the Micro-ITT 
Pharyngeal Population and follow important 
components of the study and were NG (pharyngeal) 
NAAT positive at baseline and TOC (i.e., (1) receive 
all planned doses as randomized and actual 
treatment is the same as randomized, (2) have a NG 
(pharyngeal) NAAT specimen collected at the FU 
Visit, with available NAAT results, (3) have not taken 
any other systemic antibiotic prior to FU, unless it 
was taken for the current infection, and (4) have no 
major deviation that prevents evaluation of efficacy).  
• 
Participants will be analyzed according to their 
randomized treatment arm. 
• 
Efficacy 
Safety Population 
• 
All participants who receive at least 1 dose of study 
treatment.  
• 
Participants will be analyzed according to their actual 
treatment received 
• 
Safety 
1. NAAT = Nucleic Acid Amplification Test. 
2. Refer to Appendix 9: List of Data Displays. 
3. Note: 
• 
The Micro-ITT populations are based on culture confirmed NG isolates at the central laboratory. 
Ceftriaxone susceptibility will be evaluated by applying CLSI MIC breakpoints to results from 
ceftriaxone agar dilution testing (or EUCAST MIC breakpoints in the case of the Micro-ITT EU 
population). If an agar dilution value is not available for ceftriaxone, CLSI disk diffusion breakpoints 
will be applied to results from ceftriaxone disk diffusion testing for the Micro-ITT populations 
(including Micro-ITT EU). The ceftriaxone MIC breakpoints for N. gonorrhoeae currently differ 
between CLSI and EUCAST, if isolates are identified with different interpretations applying the 
EUCAST breakpoints as compared to CLSI, any populations/subjects/isolates impacted by the 
difference in breakpoints will be described in the text as narratives and additional sensitivity 
analyses for the primary endpoint may be performed (Section 7.1.6.2). Further, any summaries and 
listings presented on CLSI-based populations may be repeated on EUCAST-based equivalent 
populations, as required (see Section 7). 
• 
The term “ME Population” is used to refer to all ME Populations and the term “NAAT Population” is 
used to refer to all NAAT populations. 
• 
Micro-ITT FDA population will be used for listings only and not summaries. 
• 
If more than 1 NG isolate is recovered at baseline from the same participant and body site, all of 
the isolates must be susceptible to ceftriaxone for the participant to be included in the 
corresponding Micro-ITT populations. 
• 
If a participant has an out-of-stability urogenital sample at the TOC visit which is NG negative then 
that participant is not considered as having ‘available culture results’ for the purposes of ME 
Population criterion 2: “have a urogenital specimen collected at the TOC Visit, with available 
culture results”. The same rule will be applied to the other ME populations for the corresponding 
body sites. 


 
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Inclusion into the ITT and Safety Population will be determined programmatically from 
eCRF data. 
Inclusion criteria for the Micro-ITT/Micro-ITT Rectal/Micro-ITT Pharyngeal, ME 
Populations, and NAAT Populations will be determined programmatically and through 
manual review conducted by the Sponsor. The Sponsor will be blinded to treatment 
assignment and may review the data concurrent with conduct of the study. Final 
determination of population inclusion will be performed after final extraction and prior to 
unblinding. Exclusion from ME Populations related to receipt of incorrect study drug and 
related to receipt of other systemic antimicrobials not for the current infection (see e.g., 
ME Population criteria 1 and 3) will be determined programmatically on unblinded data 
using the prespecified criteria in Section 4. 
In the event that one or more investigators/sites receive a corrective and preventative 
action (CAPA) that stipulates a supplementary analysis should be conducted excluding 
them as agreed by a multidisciplinary GSK team prior to unblinding, a supplementary 
analysis will be performed. A flag will be included to identify subjects enrolled by those 
investigators/sites. This will enable further subpopulations to be defined for the primary 
analysis population (Micro-ITT). These sub populations (micro-ITT [CAPA]) may be 
defined which will consist of all subjects in the micro-ITT population excluding subjects 
from those investigative sites (e.g., micro-ITT (CAPA)). 
 
4.1. 
Protocol Deviations 
Important protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, participant management or participant assessment) will be 
summarized and listed. In addition, important deviations which result in exclusion from 
analysis populations will be listed. 
Protocol deviations will be tracked by the study team throughout the conduct of the study 
in accordance with the Protocol Deviation Management Plan, entitled Study Deviation 
Rules Document. 
o Data will be reviewed prior to unblinding and locking the database to define all 
analysis populations, and thus ensure all important deviations and deviations 
which may lead to exclusion from the analysis are captured and categorized in the 
protocol deviations dataset. 
o This dataset will be the basis for the summaries and listings of important protocol 
deviations. 
A separate listing of all inclusion/exclusion criteria deviations will also be provided. This 
listing will be based on data as recorded on the inclusion/exclusion page of the electronic 
case report form (eCRF). 


 
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5. 
CONSIDERATIONS FOR DATA ANALYSIS AND DATA 
HANDLING CONVENTIONS 
5.1. 
Study Treatment & Sub-group Display Descriptors 
Treatment Group Descriptions  
Data Displays for Reporting  
Description 
Order in TFL 
Gepotidacin 2x 3000 mg  
1 
Ceftriaxone 500 mg plus azithromycin 1 g 
2 
Note: Total across treatment groups will be presented for study population, safety, and selected 
microbiology displays. 
Whilst the scientific formatting requirements for bacterial nomenclature is for genus and species names to 
be italicized, with first letter of genus upper case, and rest of the genus and species name in lower case, 
system limitations have resulted in the lack of italicization in TFL outputs. 
5.2. 
Baseline Definitions 
For all endpoints (except as noted in baseline definitions) the baseline value will be the 
latest pre-dose assessment with a non-missing value (or randomization date for 
participants who are randomized but did not receive treatment), including those from 
unscheduled visits. If time is not collected, Day 1 assessments are assumed to be taken 
prior to first dose and used as baseline. Unless otherwise stated, if baseline data is 
missing, then change from baseline calculations will not be performed and will be set to 
missing. 
5.3. 
Multicenter Studies 
In this multicenter global study, enrollment will be presented by investigative site, 
country, and region for descriptive summaries. Data from all sites will be combined for 
statistical analyses; analyses will not be adjusted by site. 
5.4. 
Examination of Covariates, Other Strata and Subgroups 
In the case of a difference between the stratification assigned at the time of randomization 
and the data collected in the eCRF: 
• subgroups will be summarized based on the actual subgroup to which the 
participant belongs, 
• covariate adjustment will be based on the actual strata for primary analysis. 
5.4.1. 
Strata and Other Covariates 
The list of covariates and other strata may be used in descriptive summaries and 
statistical analyses, some of which may also be used for subgroup analyses. Additional 
covariates and other strata of clinical interest may also be considered. 


 
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• 
If the number of participants is small within a category of a covariate or strata, 
then the covariate/strata categories may be further refined prior to unblinding the trial. 
• 
If the category cannot be refined further, then the covariate may be included as a 
continuous measure. 
 
Participants will be randomized to a treatment arm using stratification by sex and sexual 
orientation (men who have sex with men [MSM], men who have sex with women 
[MSW], or female) and age (<18 years, ≥18 to 65 years, or >65 years). The MSM 
category will include MSM and bisexual males (i.e., male participants who have sex with 
both males and females). 
 
Summaries of participants for whom the randomized and actual strata differ, quantifying 
the number of participants whose strata differ between the primary analysis (adjusting for 
actual pooled strata) and the relevant sensitivity analysis (adjusting for pooled strata as 
randomized, Section 7.1.6.2) will be provided. 
 
Randomized Stratification 
Factor 
Randomized Stratification Level 
Age Category 
<18 years 
 
≥18 to 65 years 
 
>65 years 
Sex and Sexual Orientation 
Men who have sex with men (and females) (MSM) 
 
Men who have sex with women (MSW) 
 
Female 


 
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The stratification combinations are as follows: 
Randomized Stratification 
Value 
Randomized Stratification Description 
1 
<18 years, MSM 
2 
<18 years, MSW 
3 
<18 years, Female 
4 
≥18 to 65 years, MSM 
5 
≥18 to 65 years, MSW 
6 
≥18 to 65 years, Female 
7 
>65 years, MSM 
8 
>65 years, MSW 
9 
>65 years, Female 
For primary analysis, stratification values (after combining the three age strata) are 
defined as follows: 
Stratification Value 
Stratification Description 
1 
MSM 
2 
MSW 
3 
Female 
Other covariates considered in statistical analyses (for logistic regression used in multiple 
imputation): 
Covariates 
Randomized treatment 
Sex and sexual orientation (MSM, MSW, or female) 
Interaction term between treatment and MIC (gepotidacin or ceftriaxone plus azithromycin) for 
randomized treatment 
Site (Sites with <10 participants in the Micro-ITT Population may be combined prior to unblinding) 
5.4.2. 
Examination of Subgroups 
Subgroup analyses will be performed using the following categories for the efficacy 
analyses. Treatment group differences will be displayed for subgroups with ≥10 
participants across both treatment groups. Additional subgroups of clinical interest may 
also be considered. If the number of participants is small within a subgroup, then the 
subgroup categories may be refined prior to unblinding the trial. 
 


 
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Subgroup 
Categories 
Age category 
<18 years, ≥18 to 65 years, or >65 years 
Sex and sexual orientation 
Male (MSM, MSW), or Female 
Stratification combinations 
as defined in Section 5.4.1 (for above mentioned age and sex and 
sexual orientation categories) 
Ethnicity 
Hispanic, not Hispanic 
Race 
White, Black or African American, Asian, American Indian or Alaskan 
Native, Native Hawaiian or other Pacific Islander, Multiple 
Region 
Americas (United States and Mexico), Europe: (Germany, Spain, and 
United Kingdom), Asia-Pacific: Australia  
Country 
United States, Mexico, Germany, Spain, United Kingdom and Australia  
FDA Region  
United States regions:  
• Northeast: Connecticut, Maine, Massachusetts, New Hampshire, New 
Jersey, New York, Pennsylvania, Rhode Island, Vermont  
• South: Alabama, Arkansas, Delaware, District of Columbia, Florida, 
Georgia, Kentucky, Louisiana, Maryland, Mississippi, North Carolina, 
Oklahoma, South Carolina, Tennessee, Texas, Virginia, West Virginia 
• Midwest: Ohio, Michigan, Indiana, Illinois, Wisconsin, Minnesota, 
Iowa, Missouri, North Dakota, South Dakota, Nebraska, Kansas 
• West: Arizona, California, Colorado, Idaho, Montana, Nevada, New 
Mexico, Oregon, Utah, Washington, Wyoming 
• Pacific: Alaska, Hawaii (Not applicable) 
 
 
Baseline BMI Category 
•<25 kg/m2 
•≥25-<30 kg/m2 
•≥30 kg/m2 
Phenotypic and genotypic 
subcategories 
as defined in Section 7.1.6.5 
Number of sexual partners 
1-5, 6-10, 11-15, greater than 15 (for primary endpoint only) 
Recreational drug use 
Yes, No (for primary endpoint only) 
Co-infections 
With or without co-infection with Chlamydia trachomatis and/or 
Mycoplasma genitalium (for primary endpoint only) 
Multiple Body Sites 
With or without infections at multiple body sites (for primary endpoint 
only) 
Renal impairment 
Creatinine clearance <30 mL/min, ≥30 to 59 mL/min, ≥60 to 89 
mL/min, ≥90 mL/min (for primary endpoint only) 
HIV Status 
HIV positive, HIV negative (for primary endpoint only) 
 
 


 
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The following subgroups will be explored for the safety analyses: 
Subgroup 
Categories 
Age category 
<18 years, ≥18 to 64 years, ≥65 to 74 years, ≥ 75 years 
Sex 
Male or Female 
Race 
White, Black or African American, Asian, American Indian or Alaskan 
Native, Native Hawaiian or other Pacific Islander, Multiple 
Region 
Americas (United States and Mexico), Europe: (Germany, Spain, and 
United Kingdom), Asia-Pacific: Australia 
Renal impairment 
Creatinine clearance <30 mL/min, ≥30 to 59 mL/min, ≥60 to 89 
mL/min, ≥90 mL/min 
HIV Status 
HIV positive, HIV negative 
If the number of participants is small (i.e., <10 participants) within a subgroup, then the 
subgroup categories may be refined prior to unblinding the trial. 
5.5. 
Multiple Comparisons and Multiplicity 
The primary comparison of interest is the comparison between oral gepotidacin to IM 
ceftriaxone plus oral azithromycin for the primary endpoint of urogenital microbiological 
success in the Micro-ITT population. This analysis will be adjusted for stratification 
factors at randomization that are defined in Section 5.4.1. The issue of multiple 
comparisons in the primary analysis will be addressed via a hierarchical testing strategy 
(Fixed-Sequence Method, FDA 2022), that is, the noninferiority of gepotidacin to 
treatment with ceftriaxone plus azithromycin must first be achieved before subsequently 
testing for superiority as described in Section 2.4. The statistical analyses of all other 
efficacy endpoints will be descriptive in nature, and therefore, will not be subject to 
multiplicity adjustments. 
5.6. 
Analysis Visits 
Due to participants potentially returning outside the protocol scheduled visit window, 
analysis visit windows will be defined for by-visit summaries and analysis purposes as 
illustrated in the table below. Data not reported by-visit, including adverse events and 
concomitant medications, will not employ analysis visits. Analysis visit labels will be 
assigned to each post-baseline record (including records from unscheduled and early 
termination visits) based on the corresponding study day (relative to first study treatment 
or randomization if not treated). For post-baseline records collected outside the analysis 
visit window, a blank analysis visit label will be assigned. For example, a record 
collected at study Day 11 will not be utilized in any analyses conducted at the TOC or FU 
scheduled visit. Descriptive summaries that are shown for “any assessment post baseline” 
e.g., maximum/minimum/ worst case post baseline, will use all assessments irrespective 
of whether they fall in an analysis visit window. There are no scheduled FU assessments 
for Urogenital (except Mgen participants) or rectal body site, but it is possible that any 
unscheduled assessment or a late TOC fall into this FU window and in that case FU visit 
will not be presented in summaries but in listings it will be included. 


 
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Scheduled Post-
baseline Visit 
Protocol Window 
Target Day 
Analysis Visit 
Window (Days) 
Test-of-Cure 
4 to 8 
6 
4 to 10 
Follow-up 
14 to 21 
18 
13 to 24 
If multiple records exist within the same analysis visit window, then the record occurring 
closest to the target day will be utilized in all analyses and analysis population 
determinations. If multiple records are equally close to the target day, then the later 
record will be utilized. If multiple records occur on the same day and time is not 
collected, then the record with the larger Study Data Tabulation Model (SDTM) record 
sequence number will be utilized in all analyses. All protocol scheduled assessments 
(including unscheduled and early termination visits) will be presented in subject listings. 
Both the nominal and analysis visit will be presented in listings. 
5.7. 
Other Considerations for Data Analyses and Data Handling 
Conventions 
Other considerations for data analyses and data handling conventions are outlined in the 
appendices: 
Section 
Component 
12.1 
Appendix 1: Schedule of Activities 
12.2 
Appendix 2: Study Phases and Treatment Emergent Adverse Events 
12.3 
Appendix 3: Data Display Standards & Handling Conventions 
12.4 
Appendix 4: Derived and Transformed Data 
12.5 
Appendix 5: Reporting Standards for Missing Data  
12.6 
Appendix 6: Values of Potential Clinical Importance 
12.7 
Appendix 7: Division of Microbiology and Infectious Diseases Toxicity Tables for 
Adverse Event Assessment 
12.8 
Appendix 8: Abbreviations & Trademarks 
12.9 
Appendix 9: List of Data Displays 
 


 
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6. 
STUDY POPULATION ANALYSES 
6.1. 
Overview of Planned Study Population Analyses 
The study population analyses will be based on the ITT population and the primary 
analysis population (Micro-ITT), unless otherwise specified. 
Study population analyses including analyses of participant’s disposition, protocol 
deviations, demographic and baseline characteristics, prior and concomitant medications, 
and exposure and treatment compliance will be based on GSK Core Data Standards. 
Baseline disease characteristics including baseline NG recovery rate (including body site 
of recovery), substance use, and past and current medical conditions will be summarized. 
Baseline ECG results will be provided in listings. Social sexual history will be 
summarized and provided in listings.  
Details of the planned displays are presented in Appendix 9. 
6.1.1. 
Disposition and Withdrawals 
A summary of the number of participants included in each of the analysis populations 
defined in Section 4 will be provided. A listing and summary of participants excluded 
from each analysis population will be provided. 
The number and percentage of participants enrolled by country and site will be 
summarized for each treatment group and overall for the ITT Population. 
Participant disposition will be tabulated for each study treatment and for all participants 
combined with the number and percentage of participants who complete the study, 
prematurely withdraw, and the reason for study withdrawal for ITT and Micro-ITT 
Populations. A listing of the reasons for study withdrawal will be provided. A separate 
listing of the reasons for treatment discontinuation will also be provided. 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomized. Participants who are screen failures are not allowed 
to be rescreened for the same infection episode; however, participants who were screen 
failures for an earlier infection episode may be newly screened for a second infection 
episode ≥4 weeks later and participate in the study if they meet all the inclusion and 
exclusion criteria. Any participant who was originally a screen failure, but is then 
enrolled after a new screening, will be counted once as a screen failure (for the earlier 
episode) and once as enrolled (for the second episode). Summary and listing of reasons 
for screen failures will be produced. 
6.1.2. 
Demographic and Baseline Disease Characteristics 
Demographic characteristics such as age, sex, race, ethnicity, childbearing potential, 
height, weight, and body mass index (BMI) will be summarized and tabulated by 
treatment and for all participants in ITT and Micro-ITT Populations. Descriptive statistics 
will be presented for age, height, weight, and BMI. Frequency counts and percentages 
will be presented for age category (<18 years, ≥18 to 65 years, >65 years as well as 12-


 
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17, 18-64, 65-84, ≥85), sex, ethnicity, renal impairment category and childbearing 
potential. Age is computed as integer part of (First Dose Date - JUN30 of Collected Birth 
Year + 1)/365.25; when first dose date is missing, the informed consent date is used. 
Individual participant demographics (including baseline renal impairment) will be 
presented in listings. 
Race and racial combinations will be summarized and listed as reported using the five 
high level categories (American Indian or Alaskan Native, Asian, Black or African 
American, Native Hawaiian or other Pacific Islander, White, Multiple). In addition, the 
nine standard race categories collected on the Integrated Data Standards Library (IDSL) 
eCRF along with categories for mixed race will be summarized and listed. Baseline renal 
impairment will be summarized and included in a listing. 
Baseline disease characteristics will be summarized including pre-treatment NG, CT, and 
Mgen NAAT assay results and presence of white blood cells (WBCs), epithelial cells and 
bacteria in urogenital bacteriological specimens evaluated by Gram stain. Separately, the 
overall recovery rate of NG by culture will be summarized by specimen source 
(urogenital, pharyngeal, and rectal), sex and sexual orientation, and age. The concordance 
of presumptive diagnosis of NG at baseline visit and NAAT test on samples collected 
from baseline visit with central lab identification will be summarized, respectively. Data 
will be listed and summarized using frequency counts and percentages. Serology 
including HIV, Hepatitis B, and Hepatitis C will also be summarized. 
 
Substance use such as smoking history, cigarettes per day, alcohol consumption, alcohol 
weekly use, caffeine consumption, and average caffeinated servings per day will also be 
summarized in ITT and Micro-ITT Populations and listed. 
Social sexual history at baseline will be summarized for ITT and Micro-ITT Populations 
and will be listed. Social sexual history at the TOC visit, since last visit will also be listed 
separately. 
6.1.3. 
Prior and Concomitant Medications 
Any medication or vaccine (including over the counter or prescription medicines, 
vitamins, and/or herbal supplements) that the participant is receiving within 6 months 
prior to the Baseline Visit or receives during the study will be recorded. Prior and 
concomitant medications will be coded using GSK Drug coding dictionary, summarized, 
and listed using generic term, verbatim text, and indication. Separate summaries of prior 
and concomitant medications will show the number and percentage of participants in the 
ITT and Micro-ITT Populations taking each prior and concomitant medications and 
corresponding Anatomical Therapeutic Chemical (ATC) classification Level 1 
information. The number and percentage of participants with prior and concomitant 
antibiotic medications will be presented. The summary of prior medications will include 
a separate summary of prior antibiotic medications. The summary of concomitant 
medications will display separate summaries for systemic concomitant medications, non-
systemic concomitant medications, systemic antibiotics taken for the disease under study, 
systemic antibiotics taken for another disease/condition and prohibited (non-antibiotic) 
medications. Prohibited concomitant medications are listed in Protocol Appendix 9.  


 
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A concomitant medication is considered systemic if the route is oral, subcutaneous, 
intramuscular, intravenous, or rectal. 
All prior and concomitant medications, as well as prior and concomitant antibiotic 
medications for NG, will be provided in separate listings. Listing of Concomitant 
Antibiotic Therapies for Chlamydia trachomatis or Mycoplasma genitalium after TOC 
Visit also will be provided. 
6.1.4. 
Medical History and Current Medical Conditions 
Past (medical history) and current medical conditions will be summarized and displayed 
by the number and percentage of participants for each body system for ITT and Micro-
ITT Populations. They will also be displayed in the listings.  
6.1.5. 
Treatment Exposure 
All eligible participants will be randomized to receive two doses of gepotidacin (the first 
dose administered at the investigational site and the second dose self-administered up to 
12 hours later) or a single dose of ceftriaxone plus azithromycin administered at the 
investigational site. Therefore, exposure duration will not be calculated in this study. A 
listing of treatment exposure will be provided. A separate listing for gepotidacin 
compliance will be provided. 
 


 
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7. 
EFFICACY ANALYSES 
Note: For any analyses of binary outcomes discussed in this section for which a risk 
difference will be estimated, if 100% (or 0%) success rates are observed in both treatment 
arms then a constant of 1E-10 will be added to each zero cell in the resultant contingency 
table to overcome software limitations and enable determination of the risk difference 
and two-sided 95% CI. 
The ceftriaxone MIC breakpoints for N. gonorrhoeae currently differ between CLSI and 
EUCAST, if isolates are identified with different interpretations applying the EUCAST 
breakpoints as compared to CLSI, then any summaries or listings on CLSI-based 
populations may be repeated on corresponding EUCAST-based populations.  
7.1. 
Primary Efficacy Analyses 
The primary clinical question of interest is: What is the treatment effect on the culture-
confirmed bacterial eradication of NG from the urogenital body site (i.e., microbiological 
success) at the TOC (Day 4 to 8) Visit after treatment with oral gepotidacin compared to 
IM ceftriaxone plus oral azithromycin in participants with uncomplicated urogenital 
gonorrhea and have confirmed NG isolated from baseline culture of their urogenital 
specimen, regardless of treatment discontinuation for any reason. For clarification this 
population are also required to be ceftriaxone susceptible. Further details on the primary 
estimand are given in Section 2.2. 
7.1.1. 
Endpoint / Variables 
The primary efficacy endpoint is culture-confirmed bacterial eradication of NG from the 
urogenital body site (i.e., microbiological success) at the TOC visit. 
• Only those participants who have central laboratory confirmed NG from culture of 
their baseline bacteriology specimen will be evaluated for microbiological outcome 
and response. Ceftriaxone susceptibility will be evaluated by applying CLSI MIC 
breakpoints to results from ceftriaxone agar dilution testing. If an agar dilution value 
is not available for ceftriaxone, CLSI disk diffusion breakpoints will be applied to 
results from ceftriaxone disk diffusion testing. The microbiological outcome and 
response to study treatment will be determined by prespecified programmed 
algorithm for each participant (see Table 2). 
• The microbiological outcome is determined by comparing the baseline culture results 
to the respective culture results at the TOC visit. The corresponding microbiological 
response (success or failure) “by participant” is then assigned. The criteria of 
microbiological participant level outcome and response is shown in Table 2. 
• Participant level microbiological success refers to participants who have been deemed 
a “microbiological success” based on their microbiological response. All other 
participants are deemed “microbiological failures” for participant level 
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Table 2 
Microbiological Outcome and Response at the Test-of-Cure Visit 
Defining Criteria 
Microbiological 
Outcome 
Microbiological 
Response 
Culture-confirmed elimination of baseline pathogen 
(NG) from a bacteriology sample taken at the TOC 
visit without the participant receiving other systemic 
antimicrobials before this visit 
Bacterial eradication 
Microbiological success 
Culture-confirmed persistence of baseline NG 
pathogen from a bacteriology sample taken at the 
TOC visit without the participant receiving other 
systemic antimicrobials before this visit 
Bacterial persistence 
Microbiological failure 
1) A determination of the TOC NG pathogen 
microbiological outcome cannot be made (e.g., no 
bacteriological sample taken for culture, sample 
lost, visit did not occur etc.) 
2) The participant received other systemic 
antimicrobials before the TOC visit 
Unable to determine 
Microbiological failure 
1. TOC=Test-of-Cure. 
2. Note: A bacteriological specimen refers to a urogenital specimen obtained for bacteriological culture.  
3. Note: If the TOC bacteriological specimen is out of stability and the result is Bacterial eradication, then 
microbiological outcome will be categorized as ‘Unable to determine’ and if the TOC bacteriological 
specimen is out of stability and result is Bacterial persistence then microbiological outcome will be 
characterized as Bacterial persistence (see Section 12.4.2 for further details). 
4. Note: If two different strains of Neisseria gonorrhoeae are identified from the baseline urogenital culture 
sample and at the TOC one is eradicated and the other persists, the participant outcome is Bacterial 
Persistence and response is Microbiological failure. 
7.1.2. 
Summary Measure 
The culture-confirmed bacterial eradication rate (i.e., microbiological success rate) for 
NG from the urogenital site at the TOC visit will be summarized for the gepotidacin and 
ceftriaxone plus azithromycin treatment arms. The bacterial eradication rate is calculated 
as:  
𝑅𝑅𝑅𝑅𝑅𝑅𝑅𝑅= 𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑖𝑖𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐𝑐 𝑤𝑤𝑤𝑤𝑤𝑤ℎ 𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢𝑢 𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚 𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠𝑠 𝑎𝑎𝑎𝑎 𝑇𝑇𝑇𝑇𝑇𝑇 𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉𝑉
𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁𝑁 𝑜𝑜𝑜𝑜 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑓𝑓𝑓𝑓𝑓𝑓𝑓𝑓 𝑡𝑡ℎ𝑒𝑒 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑜𝑜𝑜𝑜 𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖𝑖
 × 100%   
The summary measure will be the difference in bacterial eradication rate (i.e., 
microbiological success rate) between the treatment arms (gepotidacin - ceftriaxone plus 
azithromycin) at TOC visit. The adjusted estimates of the difference in microbiological 
success rate for the two treatment groups (gepotidacin – ceftriaxone plus azithromycin) 
will be calculated and summarized with 2-sided 95% CI based on a stratified analysis 
using Miettinen and Nurminen (MN) method (see Section 7.1.6.1).  
 
7.1.3. 
Population of Interest 
The primary population of interest is participants with uncomplicated urogenital 
gonorrhea caused by culture-confirmed NG (Neisseria gonorrhoeae). For clarification 


 
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this population are also required to be ceftriaxone susceptible. The primary analysis of 
the primary efficacy endpoint will therefore be performed using the urogenital culture 
confirmed Micro-ITT Population. 
7.1.4. 
Strategy for Intercurrent Events 
There are two kinds of ICE: 
o Study treatment discontinuation (due to any reason) – treatment policy 
strategy (the occurrence of the ICE is considered irrelevant in defining the 
treatment effect of interest). 
o Use of systemic antimicrobials - composite strategy. This intercurrent event is 
captured through the definitions of microbiological response (see Section 
7.1.1 ) and will be counted as microbiological failures. 
If a participant experiences both ICE, then a composite strategy (assigning 
microbiological response as a failure) will be used from the point that the relevant 
systemic antimicrobial was taken. 
7.1.5. 
Treatment Condition 
Gepotidacin 2×3000 mg versus Ceftriaxone 500 mg plus azithromycin 1 g, regardless of 
adherence. 
7.1.6. 
Statistical Analyses / Methods 
7.1.6.1. 
Statistical Methodology Specification 
The primary efficacy endpoint is culture-confirmed bacterial eradication (microbiological 
success) of NG from the urogenital body site at the TOC visit.  
Microbiological success rate and Exact Clopper-Pearson confidence interval (CI) in each 
treatment group will be calculated. For the statistical analysis, three strata (subgroups) 
will be formed according to the combinations of levels of the sex and sexual orientation 
(MSM, MSW, Female) at baseline. For age strata, due to few participants in <18 years 
and >65 years age categories, the categories <18 years, ≥18 to 65 years and >65 years 
will be combined for primary statistical analysis, thereby removing the age effect from 
the analysis. If a participant is mis-stratified, then the actual pooled strata collected in the 
eCRF will be used in the analysis instead of the randomized pooled strata, unless 
specified. The effect of this stratification is to provide statistical control over these 
potentially important prognostic variables. 
The adjusted estimates of the difference in microbiological success rate for the two 
treatment groups (gepotidacin – ceftriaxone plus azithromycin) will be calculated and 
summarized with 2-sided 95% CI based on a stratified analysis using Miettinen and 
Nurminen (MN) method.  
The Miettinen-Nurminen (score) confidence limits for the treatment difference 
[Miettinen, 1985] are computed (SAS PROC FREQ [SAS, 2018] uses iterative 
computation for this). Stratum based point estimates and variances can be estimated from 


 
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these CIs. The MN estimate of the common risk difference and variance is computed by 
combining the point estimates and variances from the individual pooled strata using MN 
weights. The estimate uses inverse variance stratum weights to produce MN confidence 
limits for the stratum risk differences. The mathematics and algorithm of MN method can 
be found in the SAS procedure guide under “Summary Score Estimate of the Common 
Risk Difference” [SAS, 2018].  
This MN method is the primary estimator of the primary efficacy endpoint and will 
statistically test the null hypothesis contained in Section 2.4. Gepotidacin will be declared 
noninferior to treatment with ceftriaxone plus azithromycin if the lower limit of the 2-
sided 95% confidence interval (CI) for the difference between the microbiological 
success rate of gepotidacin and ceftriaxone plus azithromycin at the TOC visit is above -
10.0%. Superiority of gepotidacin will be declared if the lower end of the 2-sided 95% CI 
is above 0%. Testing for superiority using 2.5% level of significance will occur if 
noninferiority is achieved and one-sided p-value will be calculated.  
The number and percentage of participants with culture-confirmed bacterial eradication 
of NG from the body site will be summarized at the TOC visit by treatment group along 
with the 95% Exact (Clopper-Pearson) CIs. 
Microbiological response and microbiological outcome (success, failure, and reason for 
failure) of NG at the TOC visit will be summarized. Additional summaries providing 
further granularity into reasons for microbiological failure, including summaries of 
participants whose microbiological outcome was unable to determine, and further details 
on use of systemic antibiotics prior to assessments, differentiating use for the disease 
under study or for other conditions, may be provided. 
Supportive analyses will be performed to enable the assessment of the homogeneity of 
the treatment difference across analysis strata used in the primary analysis. 
The weighted least squares chi-squared statistic of [Fleiss, 1981] will be used to test for 
one-way homogeneity of the treatment difference across the levels of the strata used for 
the primary analysis. The overall test for homogeneity will use the combined pooled 
strata levels. Additional tests for homogeneity of the treatment difference across the 
levels of each pooled strata will be performed, with each pooled strata considered 
separately. Following Lui and Kelly [Lui , 2000], ½ will be added to each cell in any 
stratum (pooled) for which the stratum-specific success rate estimates of either 
gepotidacin or ceftriaxone plus azithromycin are zero or one, and tests will be one-sided. 
Tests of homogeneity will be assessed at the one-sided 10% level of significance.  
For each stratum, the percent of participants with microbiological successes by treatment 
group and unadjusted difference in percent between treatment groups with corresponding 
two-sided 95% CI using MN method will be reported. In addition, the p-value from the 
overall test of homogeneity will be reported. 
7.1.6.2. 
Sensitivity Analyses 
Sensitivity analyses will be performed to investigate the robustness of the primary 
efficacy results for the primary estimand. Treatment group differences will be displayed 
for subgroups with ≥10 participants across both treatment groups, see Section 5.4.2 for 


 
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definition of subgroups. The following sensitivity analyses will be performed in the 
Micro-ITT Population at the TOC visit. 
1) An analysis of microbiological response at TOC unadjusted for the stratification 
factors. Unadjusted difference in proportions between treatment groups 
(gepotidacin – ceftriaxone plus azithromycin), and corresponding two-sided 95% 
CI using MN method (adjusting for treatment only) will be presented. 
2) An analysis of microbiological response at TOC adjusted for the stratification 
factors based on the randomization stratum the participant was randomized to 
(instead of the actual stratum the participant should be assigned to). Difference in 
the proportion of microbiological responders between each treatment group 
adjusted by MN weights (using randomized stratification) will be presented along 
with two-sided 95% CIs (using MN method adjusting for treatment and pooled 
strata as randomized). 
3) A sensitivity estimator for the primary estimand will be determined by dealing 
with missing values of the microbiological response at TOC per the following: 
• If the entire visit, bacteriology samples were missed due to COVID-19 
then the missing value will be assessed using multiple imputation under a 
missing at random assumption 
• If the bacteriology sample was taken but a result is not available for the 
sample for any reason, then the missed value will be assessed using 
multiple imputation under a missing at random assumption 
• All other missing data will be assumed to be a failure 
The rationale for this strategy is that it may be reasonable to assume that missing 
data due to either COVID-19 or due to microbiology samples which were taken 
but not able to be processed will not have been impacted by the treatment the 
patient received or their response to treatment. Microbiology samples may be 
missing for reasons due to COVID-19 (e.g., out of stability samples arriving at the 
local lab due to extended shipping times or lack of couriers to pick up the samples 
within agreed timeframes). But they may also be missing, for example, due to 
sample packing or mis-labelling issues at the site. In all cases a missing at random 
multiple imputation will be performed irrespective of the reason the sample is 
missing. All other missing data will be considered as a failure (i.e., non-
responders), consistent with the primary analysis. Multiple imputations will be 
implemented with the following steps: 
Step 1: Microbiological response will be imputed by multiple imputation using 
logistic regression models under a missing at random assumption in the Micro-
ITT population. The number of imputations will be 1,000 and SEED= 116577. 
The variables used in the imputation model will include: 
• Sex and sexual orientation (MSM, MSW, or female) 
• Randomized Treatment group 
• 
Interaction term between treatment and MIC (gepotidacin or ceftriaxone 
plus azithromycin) for randomized treatment. If needed, this may be 
refined prior to unblinding. Note: Baseline pathogen (N. gonorrhoeae 


 
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isolate) will be determined by GSK Microbiology prior to unblinding and 
will include separate holistic reviews to: 
o identify dominant isolate for participants with more than one N. 
gonorrhoeae isolate at Baseline. This selection will be completed 
for all participants with more than one N. gonorrhoeae isolate at 
Baseline in the micro-ITT Population, regardless of missing data 
and will be based on gepotidacin or ceftriaxone and azithromycin 
MIC value (and phenotypic profile if required) and will identify 
the dominant N. gonorrhoeae isolate for gepotidacin and for 
ceftriaxone/azithromycin treatment groups as these may differ. 
This will be documented prior to unblinding.  Post unblinding, the 
dominant N. gonorrhoeae isolate for the randomized treatment will 
be used and the corresponding Baseline N. gonorrhoeae MICs will 
be used in the analysis. 
o Group MICs (gepotidacin or ceftriaxone and/or azithromycin) by 
randomized treatment which may be based on Baseline N. 
gonorrhoeae isolate. This will be documented prior to unblinding. 
• Site (Sites with <10 participants in the Micro-ITT Population may be 
combined prior to unblinding)  
 
Any subjects that have a missing value for one or more variables listed above will 
be excluded from the relevant imputation model(s). While logistic regression will 
be used for the imputation model, the stratified MN statistic will be used for the 
analysis of each imputed dataset. 
 
Step 2: Step 1 will produce 1,000 imputed datasets with complete data. For each 
dataset, participants microbiological response will then be derived using the 
imputed and non-missing data per Section 7.1.1. We will estimate the proportion 
of success in each treatment group and its standard error using the sample 
estimates, and the difference in the proportion of success between the two 
treatment groups and its standard error using the MN method weighted on actual 
pooled strata as in the primary efficacy analysis for each imputed dataset 
separately.  All estimated quantities (proportion of success in each treatment 
group, difference between two groups, and their associated standard errors) will 
be saved for step 3.  
Note: the number of imputations may be increased if required following model 
checking to ensure results are not sensitive to the random number seed and/or 
number of imputations. 
 
Step 3:  The estimated quantities in Step 2 will be combined across the imputed 
datasets using Rubin’s rules to provide pooled estimates for the success rate in 
each treatment group and for the difference in the proportion of successes 
between the two treatment groups. The 95% (Wald) CIs will be calculated for the 
proportions of successes in each arm as well as for the risk difference between the 
two treatment groups. Testing for superiority may occur if noninferiority is 
achieved. A one-sided p-value will be calculated. 


 
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40 
If there is zero between imputation variance, e.g., if there are no missing data to impute, 
then the methods described in Step 2 will be applied to a single instance of the complete 
data set and it will not be necessary to combine estimated quantities in Step 3. Note that if 
the extent of missing data is considered sufficiently high, this analysis may be repeated 
with all missing microbiological responses at TOC, i.e. irrespective of the reason for 
missingness, and assessed using multiple imputation logistic regression. Prior to 
unblinding a review with GSK Microbiology will determine appropriate groupings of 
MICs (gepotidacin and ceftriaxone plus azithromycin) for the purposes of this analysis. 
 
4) A tipping point analysis may be performed for the primary endpoint in the Micro-
ITT population to assess the impact of failure imputation of missing data on the 
microbiological response at TOC. The scope of missing data will be consistent 
with the multiple imputation analyses, specifically, if the entire TOC Visit, 
microbiology samples were missed due to COVID-19 pandemic, then the missed 
value will be imputed under the MAR assumption. If the TOC microbiology 
sample was taken but a result is not available for the sample for any reason, then 
the missed value will also be imputed under the MAR assumption. All other 
missing data will be considered as a failure (i.e., non-responders) per the primary 
analysis.  The tipping point analysis will vary assumptions on the proportion of 
participants achieving success in the two treatment groups. For each combination 
of assumed success rates in the two treatment groups, the number of additional 
participants achieving success among subjects with missing microbiological 
response will be imputed by drawing from a binomial distribution.  
o A grid of paired values will be established, ranging from 0 to 1 in 
steps of 0.025, establishing the assumed response rates for each 
treatment group in participants with missing microbiological 
response. 
o For each pair of assumed response rates corresponding to treatment 
group, (𝜃𝜃𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺
(𝑖𝑖)
, 𝜃𝜃𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎ℎ𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟
(𝑗𝑗)
), repeat the 
following steps 100 times: 
o Sample additional responders among participants with 
missing responses by drawing from a binomial distribution, 
using the assumed response rate assigned to each treatment 
group. Sampling will be completed separately by treatment,   
 
𝑟𝑟𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺,
𝑎𝑎
 ~ Binomial (𝑛𝑛𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺
𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚
, 𝜃𝜃𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺
(𝑖𝑖)
), 
𝑟𝑟𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎ℎ𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟 
𝑎𝑎
 ~ 
  Binomial (𝑛𝑛𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎ℎ𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟
𝑚𝑚𝑚𝑚𝑚𝑚𝑚𝑚
, 𝜃𝜃𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑎𝑎𝑧𝑧𝑧𝑧𝑧𝑧ℎ𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟
(𝑗𝑗)
) 
 
o The proportion of success in each treatment group and the 
difference in the proportion of success between two treatment 
groups as well as the respective associated standard errors will be 
computed. Standard error of the risk difference estimate will be 
calculated using the MN method weighted on actual strata. 


 
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41 
o Using Rubin’s rules we will combine the estimated quantities (success rate 
in each treatment group, difference in proportions between two groups, 
and their standard errors). The calculations for pooled estimates will be 
implemented using SAS PROC MIANALYZE. 95% (Wald) CIs for the 
risk difference between the two treatment groups will be presented. The 
noninferiority conclusion will be drawn if lower limit of the 2-sided 95% 
confidence interval (CI) is above -10.0%. Testing for superiority may 
occur if noninferiority is achieved and one-sided p-values will be 
calculated. 
o The process described above will be repeated for each pair of assumed 
response rates, (𝜃𝜃𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺𝐺
(𝑖𝑖)
, 𝜃𝜃𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶 𝑝𝑝𝑝𝑝𝑝𝑝𝑝𝑝 𝑎𝑎𝑎𝑎𝑎𝑎𝑎𝑎ℎ𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟𝑟
(𝑗𝑗)
). 
o Visual representations of treatment difference and noninferiority 
decisions will be produced using a colored heatmap illustrating the 
gradual change of treatment difference. Colored borders will be 
used to highlight the microbiological response rates that resulted in 
noninferiority. 
If for a pair of assumed response rates there is zero between imputation variance, e.g., if 
there are no missing data to impute, then the methods described above for calculating the 
proportion of successes, risk difference and associated standard errors, will be applied to 
a single instance of the complete data set and it will not be necessary to combine 
estimated quantities across imputations. Note also that tipping point analysis may be 
repeated with a greater number of imputations (if necessary over a smaller, refined grid 
range), if tipping points are considered to be sensitive to the random number seed and/or 
number of imputations. Furthermore, if the extent of missing data is considered 
sufficiently high, tipping point analysis may be repeated, imputing all missing 
microbiological responses at TOC, irrespective of the reason for missingness, using 
random draws from a binomial distribution as described above. 
5) Primary analysis is based on Micro-ITT population using CLSI breakpoints. The 
ceftriaxone MIC breakpoints for N. gonorrhoeae currently differ between CLSI 
and EUCAST, if isolates are identified with different interpretations applying the 
EUCAST breakpoints as compared to CLSI, a sensitivity analysis of primary 
endpoint will be produced on a population defined based on EUCAST 
breakpoints (Micro-ITT EU). Ceftriaxone susceptibility will be evaluated by 
applying EUCAST MIC breakpoints to results from ceftriaxone agar dilution 
testing. If an agar dilution value is not available for ceftriaxone, CLSI disk 
diffusion breakpoints will be applied to results from ceftriaxone disk diffusion 
testing. The number and percentage of participants with culture-confirmed 
bacterial eradication of NG from the body site will be summarized at the TOC 
visit by treatment group along with the 95% Exact (Clopper-Pearson) CIs. The 
adjusted estimates of the difference in microbiological success rate for the two 
treatment groups (gepotidacin – ceftriaxone plus azithromycin) will be calculated 
and summarized with 2-sided 95% CI based on a stratified analysis (pooled strata) 
using Miettinen and Nurminen (MN) method. Non-inferiority and superiority will 
be tested as stated in Section 2.4. 


 
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42 
Note that if data warrant, this analysis may be repeated on the Micro-ITT and Micro-ITT 
EU populations, but excluding participants whose ceftriaxone susceptibility is determined 
by disk diffusion. 
7.1.6.3. 
Supplementary Analyses 
Supplementary analysis of the primary efficacy endpoint will be performed on the 
Microbiologically Evaluable (ME) Population with all other details as per Section 
7.1.6.1.  
In the event that one or more investigators/sites receive a CAPA that stipulates a 
supplementary analysis should be conducted excluding them as agreed by a 
multidisciplinary GSK team prior to unblinding, a supplementary analysis will be 
performed. A flag will be included to identify subjects enrolled by those 
investigators/sites. This will enable further subpopulations to be defined for the primary 
analysis population (Micro-ITT). These subpopulations (micro-ITT [CAPA]) may be 
defined which will consist of all subjects in the micro-ITT population excluding subjects 
from those investigative sites. The methods described for the primary analysis (Section 
7.1.6.1) may then be repeated on the newly defined analysis population(s). 
7.1.6.4. 
Subgroup Analyses 
Subgroup analyses will be performed for the microbiological success rate at the TOC 
visit in Micro ITT and ME population. Microbiological success rate and Exact Clopper-
Pearson confidence interval in each treatment group at each level will be calculated.  
Unadjusted difference in microbiological success rate will be included and summarized 
with 2-sided 95% CI using MN method (adjustment will not be performed). For each 
specific subgroup, if there are not enough participants (i.e., <10 participants across 
treatment groups), treatment difference in microbiological success rate and CI will not be 
derived. A forest plot showing the results for the subgroup analyses of microbiological 
success rate will be presented. 
See Section 5.4.2 for definition of subgroups. 
7.1.6.5. 
NG Phenotype and Genotype Subgroups 
• NG isolated at Baseline will be categorized as listed below. The necessity of these 
categories will depend on the phenotypes that are recovered. Any present in 10 or 
more participants across treatment groups will be summarized separately. 
• Summaries of participant-level microbiological success, failure, and reasons for 
failure at the TOC (including phenotypic and genotypic subcategories) overall and by 
subgroup including by sex and sexual orientation (men who have sex with men 
[MSM], men who have sex with women [MSW], or female) and age (<18 years, ≥18 
to 65 years, or >65 years), geographic region, including country and FDA region) will 
be presented by phenotypic and genotypic subcategories (Note: FDA region for CLSI 
summaries only). Phenotypic and genotypic subcategory analysis for subgroups as 
described above will also be conducted for tables showing microbiology summary 
and frequency MIC and disk diffusion data. Note: these analyses will be conducted 
for the urogenital body site and, if required, pharyngeal and rectal body sites. 


 
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o Neisseria gonorrhoeae (NG) [Clinical & Laboratory Standards Institute 
(CLSI) Tables and Listings] 
 Azithromycin-nonsusceptible NG 
 Ciprofloxacin Intermediate NG 
 Ciprofloxacin-resistant NG 
 Extended spectrum cephalosporin (ESC)-nonsusceptible NG 
• Cefixime-nonsusceptible NG 
• Ceftriaxone-nonsusceptible NG 
 Tetracycline-resistant NG 
 β-lactamase positive NG 
 Susceptible to all tested drugs NG 
 Penicillin/Ciprofloxacin and tetracycline -resistant NG 
 Multidrug-resistant (MDR)a NG 
 Extensively drug-resistantb (XDR) NG 
 
aMultidrug-resistant (MDR) NG: [Resistant or nonsusceptible to at least one of the 
following CFM, AXO or SPT plus resistant or non-susceptible to 2 or more of the 
following antibiotics (CIP, AZM or PEN)] 
bExtensively drug-resistant (XDR) NG: [Resistant or nonsusceptible to two or more of 
the following antibiotics (CFM, AXO or SPT) plus resistant or non-susceptible to all 3 of 
the following antibiotics (CIP, AZM or PEN)]- if isolate meets XDR criteria MDR flag is 
not added. 
 
o Neisseria gonorrhoeae (NG) [European Committee on Antimicrobial 
Susceptibility Testing (EUCAST) Tables and Listings] 
 Azithromycina (No NG EUCAST Breakpoints) 
 Ciprofloxacin Intermediate NG 
 Ciprofloxacin-resistant NG 
 Extended spectrum cephalosporin (ESC)-resistant NG 
• Cefixime-resistant NG 
• Ceftriaxone-resistant NG  
 Tetracycline-resistant NG  
 β-lactamase positive NG 
 Susceptible to all tested drugs NG 
 Penicillinb/Ciprofloxacin and Tetracycline -resistant NG 
 Multidrug-resistant (MDR)c NG 
 Extensively drug-resistantd (XDR) NG 
 
aGiven that there are no EUCAST azithromycin breakpoints for NG, EUCAST has 
provided guidance for defining azithromycin resistance for the definition of the 
MDR/XDR category. When applying EUCAST guidelines, a NG isolate with an 
azithromycin MIC of >1 ug/mL is considered resistant for the sole purpose of 
determining azithromycin resistance for the MDR/XDR definition. However, 


 
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azithromycin interpretations are not reported in any BTZ116577 tables, listings or figures 
that apply EUCAST guidelines. 
bGiven that there are no EUCAST penicillin breakpoints for NG, EUCAST has provided 
guidance for defining penicillin resistance for the definition of the MDR/XDR category. 
When applying EUCAST guidelines, a NG isolate with a penicillin MIC of >1 ug/mL or 
a positive Beta-lactamase test is considered resistant for the sole purpose of determining 
penicillin resistance for the MDR/XDR definition. However, penicillin interpretations are 
not reported in any BTZ116577 tables, listings or figures that apply EUCAST guidelines. 
cMultidrug-resistant (MDR) NG: [Resistant to at least one of the following CIX, CTR or 
SPE plus resistant to 2 or more of the following antibiotics (CIP, AZI or PEN)] 
dExtensively drug-resistant (XDR) NG: [Resistant to two or more of the following 
antibiotics (CIX, CTR or SPE) plus resistant to all 3 of the following antibiotics (CIP, 
AZI or PEN)]- if isolate meets XDR criteria MDR flag is not added. 
 
Subcategories for all significant (n≥10 across treatment groups) drug combinations that 
comprise MDR/ extensively-drug resistant (XDR) will be analyzed (i.e., 
tetracycline/ciprofloxacin resistant, penicillin/tetracycline/ciprofloxacin resistant). Note: 
Some categories may be removed, or new categories added based on final data. Key 
subcategories with n<10 across treatment groups may be displayed. The Microbiology 
Team will provide advice on the exact list once data is final and before unblinding. 
• The main focus will be ciprofloxacin-resistant, azithromycin-nonsusceptible, ESC- 
nonsusceptible and MDR NG isolates. These categories will be determined 
phenotypically based on results from antimicrobial susceptibility testing. Other drug-
resistant phenotypes may also be summarized if present in 10 or more participants 
across treatment groups depending on a final decision from the Microbiology Team. 
Other drug-resistant phenotypes may include but are not limited to: XDR, 
ciprofloxacin non-susceptible, or resistance to other drug combinations (i.e., 
tetracycline/ciprofloxacin, penicillin/tetracycline/ciprofloxacin). 
o A NG isolate will be defined as MDR if it is reported as resistant or 
nonsusceptible to: 
 At least 1 of the antibiotic classes currently generally recommended 
for treatment (ESCs [oral and injectable ones are considered 
separately] and spectinomycin) and 
 ≥2 of the of the following: ciprofloxacin, azithromycin or penicillin 
o A NG isolate will be defined as XDR if it is reported as resistant or 
nonsusceptible to: 
 ≥2 of the antibiotic classes currently generally recommended for 
treatment (ESCs [oral and injectable ones are considered separately] 
and spectinomycin) and 
 All 3 of the following: ciprofloxacin, azithromycin, or penicillin. 
(Note: if isolate meets XDR criteria MDR flag is not added.) 
• All NG isolates will also undergo genetic characterization to test for the presence of 
various resistance mechanisms (e.g., quinolone-resistant determining region 


 
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mutations). Other drug-resistant genotypes may also be summarized if present 
depending on a final decision from the Microbiology Team. 
• Phenotype and genotype results will appear in summary tables, listings, and figures as 
subsets in blocks. Note that if a participant has multiple NG isolated at baseline, all 
isolates may be presented separately if applicable for the summary section. For 
summaries where a point estimate and confidence interval are presented, analyses will 
be conducted at the participant-level (i.e., participant with multiple isolates at baseline 
is counted once). 
• GSK microbiologists will give the detailed list of applicable phenotypes and 
genotypes once microbiology data becomes available. 
7.2. 
Secondary Efficacy Analyses 
The secondary clinical questions of interest are: What is the treatment effect on each of 
the secondary efficacy endpoints after treatment with two doses of gepotidacin 3000 mg, 
10-12 hours apart, compared to a single IM 500-mg dose of ceftriaxone plus a single oral 
1-g dose of azithromycin in participants with uncomplicated gonorrhea at the body site of 
interest (rectal/pharyngeal) who have a confirmed NG isolated from baseline culture of 
their body site (rectal/pharyngeal) specimen. For clarification this population are also 
required to be ceftriaxone susceptible. Receipt of systemic antimicrobials impacts the 
endpoint definition. Further details of the estimands for secondary efficacy endpoints are 
given in Section 2.2. The statistical analyses of all secondary efficacy endpoints will be 
descriptive in nature, and therefore, will not be subject to multiplicity adjustments. 
7.2.1. 
Endpoint / Variables 
• A secondary efficacy endpoint is culture-confirmed bacterial eradication of NG from 
the rectal body site (i.e., microbiological success) at the TOC visit. 
• A secondary efficacy endpoint is culture-confirmed bacterial eradication of NG from 
the pharyngeal body site (i.e., microbiological success) at the TOC visit. 
For definition and derivation, please refer to Section 7.1.1 Endpoint / Variables. The 
microbiological outcome and response to study treatment (for the rectal and pharyngeal 
body sites) will be determined for each participant by the same algorithm described in 
Table 1 Table 2 for the urogenital body site. 
7.2.2. 
Summary Measure 
The summary measure for the secondary analyses will be the difference in culture-
confirmed bacterial eradication rates for NG between gepotidacin and ceftriaxone plus 
azithromycin. A similar method to that described in Section 7.1.2 will be used for 
determining the summary measure for the secondary endpoints, with replacement of 
urogenital by rectal or pharyngeal, as applicable. 
7.2.3. 
Population of Interest  
The secondary population of interest is male and female participants with uncomplicated 
urogenital and rectal or pharyngeal (depending on the endpoint) gonorrhea caused by 
Neisseria gonorrhoeae. The secondary analyses of the secondary efficacy endpoints will 


 
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therefore be performed using the Micro-ITT Rectal Population and the Micro-ITT 
Pharyngeal Population. 
7.2.4. 
Strategy for Intercurrent Events 
For details of the estimand strategy for intercurrent events see Section 2.1 and Section 
2.2.1. 
7.2.5. 
Treatment Condition  
Gepotidacin 2×3000 mg versus Ceftriaxone 500 mg plus azithromycin 1 g, regardless of 
adherence. 
7.2.6. 
Statistical Analyses / Methods 
7.2.6.1. 
Statistical Methodology Specification 
There will be no multiplicity adjustment for the testing of the secondary endpoints. No 
formal hypothesis testing will be performed; 95% CIs may be included but only for 
descriptive purposes. Microbiological response and microbiological outcome for NG 
from pharyngeal or rectal body sites will be summarized using the Micro-ITT Rectal, 
Micro-ITT Pharyngeal, ME Rectal and ME Pharyngeal populations for respective body 
sites. The number and percentage of participants with culture-confirmed bacterial 
eradication of NG from the rectal body site will be summarized at the TOC visit by 
treatment group. The corresponding 95% Exact (Clopper-Pearson) CIs will be 
summarized for each treatment group. The same analysis will also be presented for the 
pharyngeal body site. The unadjusted difference in microbiological success rate for the 
two treatments (gepotidacin – ceftriaxone plus azithromycin) will be calculated and 
summarized along with its 2-sided 95% CI using MN method (adjustment for strata will 
not be performed). 
Participants who do not return for the TOC visit (or have missing data at TOC for any 
other reason) will be treated as failures. Participants who withdraw from the study prior 
to TOC will be considered not achieving success for the microbiological response and 
will be imputed as failures. 
7.2.6.2. 
Subgroup Analyses 
Subgroup analysis for rectal or pharyngeal NG body sites will be done for 
microbiological response at the TOC visit for sex and sexual orientation, age, and 
ethnicity. Other subgroups (e.g., phenotypic, and genotypic subgroups) defined in Section 
5.4.2 will also be analyzed, as appropriate. Continuous data will be summarized using 
number of subjects, mean, standard deviation, median, minimum and maximum and 
categorical data will be presented using counts and percentages in subgroup analysis. 
Unadjusted difference in microbiological success rate and summarized with 2-sided 95% 
CI using MN method will be included (adjustment will not be performed). For each 
specific subgroup, if there are not enough participants (i.e., <10 participants across 
treatment groups), the corresponding analyses will not be performed. 


 
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Analysis/Endpoint Description 
Visit 
Population 
Subgroup 
Microbiological Response of 
Rectal NG 
TOC 
Micro-ITT Rectal 
Sex and Sexual 
Orientation 
 
TOC 
Micro-ITT Rectal 
Age 
 
TOC 
Micro-ITT Rectal 
Ethnicity 
 
TOC 
Micro-ITT Rectal 
Other subgroup 
categories defined in 
Section 5.4.2 & Section 
7.1.6.5 
 
TOC 
ME Rectal 
Sex and Sexual 
Orientation 
 
TOC 
ME Rectal 
Age 
 
TOC 
ME Rectal 
Ethnicity 
 
TOC 
ME Rectal 
Other subgroup 
categories defined in 
Section 5.4.2 & Section 
7.1.6.5 
Microbiological Response of 
Pharyngeal NG 
TOC 
Micro-ITT Pharyngeal 
Sex and Sexual 
Orientation 
 
TOC 
Micro-ITT Pharyngeal 
Age 
 
TOC 
Micro-ITT Pharyngeal 
Ethnicity 
 
TOC 
Micro-ITT Pharyngeal 
Other subgroup 
categories defined in 
Section 5.4.2 & Section 
7.1.6.5 
 
TOC 
ME Pharyngeal 
Sex and Sexual 
Orientation 
 
TOC 
ME Pharyngeal 
Age 
 
TOC 
ME Pharyngeal 
Ethnicity 
 
TOC 
ME Pharyngeal 
Other subgroup 
categories defined in 
Section 5.4.2 & Section 
7.1.6.5 


 
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7.3. 
Exploratory Efficacy Analyses 
There will be no multiplicity adjustment for the testing of the exploratory endpoints. No 
formal hypothesis testing will be performed; 95% CIs may be included but only for 
descriptive purposes. The details of data displays being presented are in Appendix 9. 
7.3.1. 
Endpoint / Variables/Analysis 
7.3.1.1. 
 Gram stain (urogenital only) results at Baseline and TOC visits 
o Variables: Gram stain results (WBCs, epithelial cells, and bacteria) from 
urogenital specimens 
o Analysis: The endpoints will be summarized at the Baseline and TOC visits using 
counts and percentages for ITT Population. A listing of Gram stain results will be 
provided. 
7.3.1.2. 
In vitro antibacterial susceptibility testing results for NG from 
urogenital, pharyngeal, or rectal body sites at Baseline, TOC, and FU 
visits  
o Variables: minimum inhibitory concentrations (MICs) and respective 
interpretations 
o Analysis: For antimicrobial susceptibility, results and interpretation from testing 
for all NG isolates against gepotidacin and other antimicrobials will be 
summarized by visit, region, country, FDA region, Sex and Sexual Orientation 
and NG phenotype and genotype subgroups (including phenotypic and genotypic 
subcategory analysis for subgroups including age, sex and sexual orientation, 
region, country and FDA region) and antimicrobials tested, for each body site 
urogenital, rectal and pharyngeal based on respective populations; Micro-ITT, 
Micro-ITT Rectal, Micro-ITT Pharyngeal, ME, ME Rectal and ME Pharyngeal 
populations (Note: FDA region only for CLSI summaries). For participants with 
multiple NG isolates from the same body site at the same visit, unique NG 
isolate(s) will be selected for analysis as described in Appendix 4 (“keepers 
data”). For summaries, a participant may be counted multiple times if there are 
multiple unique NG isolates at baseline for the participant. Percent susceptibility 
(based on interpretations of susceptible, intermediate, resistant, or nonsusceptible) 
will be summarized where available. Susceptibility interpretations based on 
Clinical and Laboratory Standards Institute guidelines (CLSI) and EUCAST will 
be presented separately. 
The overall frequency distribution of minimum inhibitory concentrations (MICs) 
and the minimum, maximum, 50th percentile (MIC50), and 90th percentile 
(MIC90) for MIC will be presented. MIC50 and MIC90 refer to the corresponding 
antimicrobial concentrations required to inhibit 50% and 90% of the isolates 
obtained, respectively. MIC50 and MIC90 will not be reported if less than 10 
isolates are obtained. Details of the MIC50 and MIC90 calculations are presented in 
Appendix 4. The overall frequency distribution of the disk diffusion zone 
diameters and the mean, median, standard deviation, minimum and maximum 


 
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49 
disk diffusion zone diameters will be presented. The mean, median and standard 
deviation will not be reported if less than 10 isolates are obtained. 
Analyses will be performed to examine the potential relationship between MIC 
values for the treatment/isolate pairings and microbiological success at the TOC 
visit. Similar analyses will be performed based on the disk diffusion results. A 
listing of the susceptibility results as well as a listing of gepotidacin MIC and disk 
diffusion results including the microbiological outcomes and responses will be 
provided. 
 
7.3.1.3. 
Reduction in susceptibility to gepotidacin 
o Variables: reduced susceptibility, defined as a post-baseline N. gonorrhoeae isolate 
with a confirmed ≥ 4-fold increase in MIC result when compared with the baseline 
MIC of the corresponding N. gonorrhoeae isolate from the same participant. 
o Analysis: Reduction in susceptibility to gepotidacin will be evaluated by comparing 
the baseline gepotidacin MIC value based on agar dilution with the value obtained 
post-baseline. Post-baseline isolates from the same participant and body site with a 
confirmed ≥ 4-fold increase in gepotidacin MIC is considered to have developed a 
reduction in susceptibility to gepotidacin. The relatedness of pre- and post-baseline 
isolates (e.g., as it relates to 4-fold increases and/or microbiological failures) will be 
described in a stand-alone report, if needed. The number and percentage of 
participants who develop reduction in susceptibility to gepotidacin will be 
summarized by visit and body site for ITT population. Similar development of 
resistance analysis will be conducted for the study comparators ceftriaxone and 
azithromycin. Analysis of reduction in susceptibility may be repeated for study 
treatments by phenotypic and genotypic subgroups (CLSI and EUCAST). 
 
7.3.1.4. 
Beta-Lactamase Production  
o Variables: Beta-lactamase production (Positive/Negative)  
o Analysis: Beta-lactamase production by specimen source (urogenital, 
pharyngeal, and rectal) will be summarized by visit for Micro-ITT, Micro-ITT 
Rectal, Micro-ITT Pharyngeal Population. A listing for beta-lactamase 
production will be provided. 
7.3.1.5. 
NAAT outcome and response  
• 
Variables: NAAT outcome and response will be determined by pathogen (NG or 
Mgen), body site (as applicable), for the TOC and FU visits as follows: 
o Those participants who have NG detected from their baseline NAAT 
specimen (urogenital, pharyngeal, rectal) will be evaluated for NAAT 
outcome and response at TOC visit for urogenital, pharyngeal, rectal 
respectively. For baseline pharyngeal NG confirmed participants, NAAT 
specimen will be evaluated at follow up visit as well if both the baseline and 
TOC pharyngeal NAATs were positive. Participants who have Mgen nucleic 
acid detected from their baseline NAAT specimen will be evaluated for Mgen 
NAAT outcome and response at follow up visit. The NAAT outcome and 


 
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response to study treatment will be determined by prespecified programmed 
algorithm for each participant (see Table 3). 
o The NAAT outcome will be determined by comparing the baseline NAAT 
result with the respective NAAT result at each subsequent visit. The 
corresponding NAAT response (success or failure) by participant will then be 
assigned. The criteria for determining NAAT outcome and response are 
shown in Table 3 and Table 4. 
o Participants who are a NAAT failure at the TOC visit but have not switched to 
other systemic antimicrobials with activity against NG are evaluable at FU 
visit (applicable to pharyngeal NG only). 
o Participants who received other systemic antimicrobials on or after the TOC 
visit will be categorized as Unable to determine for NAAT outcome or 
response at the FU visit. 
Table 3 
NAAT Outcome and Response at the TOC Visit (NG Only) 
Defining Criteria 
NAAT 
Outcome 
NAAT 
Response 
Clearance of baseline pathogen nucleic acid from a 
specimen taken at the TOC visit, without the 
participant receiving other systemic antimicrobials 
before this visit 
Nucleic acid clearance 
NAAT success 
Persistence of baseline pathogen nucleic acid from 
a specimen taken at the TOC visit, without the 
participant receiving other systemic antimicrobials 
before this visit 
Nucleic acid persistence 
NAAT failurea 
1) A determination of the nucleic acid outcome from 
a specimen taken at the TOC visit cannot be made 
(e.g., no sample taken, 
sample lost, visit did not occur) 
2) The participant received other systemic 
antimicrobials before the TOC visit 
Unable to determine 
NAAT failurea 
NAAT=Nucleic Acid Amplification Test; NG=Neisseria gonorrhoeae; TOC = Test-of-Cure. 
Note: Specimen refers to either a urogenital, pharyngeal, or rectal specimen obtained for NAAT. The NAAT 
outcomes are determined on a per-pathogen and per-specimen source basis. 
a. Participants who are a “NAAT failure” at the TOC visit assessment yet are not switched to other 
systemic antimicrobials are evaluable at subsequent time points. 


 
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Table 4 
NAAT Outcome and Response at the FU Visit (Pharyngeal NG and 
Urogenital Mgen Only) 
Defining Criteria 
Microbiological 
Outcome 
Microbiological 
Response 
Clearance of baseline pathogen nucleic acid from 
a specimen taken at the FU visit, without the 
participant receiving other systemic antimicrobials 
before this visit 
Nucleic acid clearance 
NAAT success 
Persistence of baseline pathogen nucleic acid 
from a specimen taken at the FU visit, without the 
participant receiving other systemic antimicrobials 
before this visit 
Nucleic acid persistence 
NAAT failure 
A determination of the nucleic acid outcome from 
a specimen taken at the Follow-up Visit cannot be 
made (e.g., no sample taken, sample lost, visit did 
not occur) 
Note: Any participants who received other 
systemic antimicrobials before the Follow-up Visit 
will not be evaluated for NAAT outcome or 
response at the Follow-up Visit  
Unable to determine 
NAAT failure 
Mgen=Mycoplasma genitalium; NAAT=Nucleic Acid Amplification Test; NG=Neisseria gonorrhoeae. 
Note: Specimen refers to either a urogenital or pharyngeal specimen obtained for NAAT. The NAAT 
outcomes are determined on a per-pathogen and per-specimen source basis and will only be conducted 
if either the Baseline (NG or Mgen) and TOC (NG only) NAAT assay showed the presence of nucleic acid 
for the respective pathogen and specimen. 
Note: Participants who are a “NAAT failure” at the TOC visit assessment yet are not switched to other 
systemic antimicrobials are evaluable at subsequent time points. 
 
o Analyses: NAAT results (outcome and response) will be summarized by visit for 
each body site as indicated in the table below. Summaries for NAAT outcome at 
the TOC visit will be based on the 95% Exact (Clopper-Pearson) CIs for each 
treatment group. For urogenital body site at the TOC visit, the adjusted (adjusting 
for actual pooled strata of sex and sexual orientation) estimates of the difference 
in NAAT success rate for the two treatments (gepotidacin – ceftriaxone plus 
azithromycin) with 2-sided 95% CI using MN method. For the body sites 
pharyngeal and rectal, unadjusted estimates of difference in NAAT success rate 
for the two treatments and CIs will be presented. Analyses based on the FU visit 
(Pharyngeal NG and Urogenital Mgen) will also use this unadjusted approach 
since it is anticipated that there will be insufficient observations to adequately 
perform an adjusted analysis. A listing of NAAT results will also be provided. 
NG phenotype and genotype results will appear in summary tables, listings, and 
figures. Summary by strata and stratification combinations defined in Section 
5.4.1. will also be reported. For each stratum, the percent of participants with 
NAAT successes by treatment group and unadjusted difference in percent 
between treatment groups with corresponding two-sided 95% CI using MN 
method will be reported. Treatment group differences will be displayed for 
subgroups with ≥10 participants across both treatment groups. The table below 
outlines planned analyses for NAAT outcome and response: 


 
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Analysis/Endpoint 
Description 
Visit Body site 
Population 
Subgroup 
NAAT outcome 
and response rate 
for NG 
TOC Urogenital 
Rectal 
Pharyngeal 
micro-ITT,  
micro-ITT Rectal,  
micro-ITT Pharyngeal 
 
 
TOC Urogenital 
Rectal 
Pharyngeal 
micro-ITT,  
micro-ITT Rectal,  
micro-ITT Pharyngeal 
Subgroup categories defined 
in Section 5.4.2 
Strata and Stratification 
combination defined in 
Section 5.4.1 
 
TOC Urogenital 
Rectal 
Pharyngeal 
ME, 
ME Rectal,  
ME Pharyngeal   
 
 
TOC Urogenital 
Rectal 
Pharyngeal 
ME,  
ME Rectal,  
ME Pharyngeal 
Subgroup categories defined 
in Section 5.4.2 
Strata and Stratification 
combination defined in 
Section 5.4.1 
 
TOC Urogenital 
Rectal 
Pharyngeal 
ME NAAT TOC,  
ME NAAT TOC Rectal,  
ME NAAT TOC 
Pharyngeal  
 
 
TOC Urogenital 
Rectal 
Pharyngeal 
ME NAAT TOC,  
ME NAAT TOC Rectal,  
ME NAAT TOC 
Pharyngeal 
Subgroup categories defined 
in Section 5.4.2 
Strata and Stratification 
combination defined in 
Section 5.4.1 


 
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Analysis/Endpoint 
Description 
Visit Body site 
Population 
Subgroup 
NAAT outcome 
and response rate 
for NG 
FU 
Pharyngeal 
micro-ITT Pharyngeal  
 
 
FU 
Pharyngeal 
ME NAAT FU Pharyngeal 
 
NAAT outcome 
and response rate 
for Mgen 
FU 
Urogenital 
micro-ITT 
 
 
FU 
Urogenital 
ME NAAT FU Mgen 
 
 
7.3.1.6. 
Additional Microbiology Data 
A microbiology database and “Micro Review Aid” (Excel) will be provided for the 
microbiology reviewer’s guide. All pathogen-level and participant-level microbiological 
outcome/response data, susceptibility tests results, susceptibility phenotypes, and 
genotype data (where available) will be combined and displayed together (CLSI and 
EUCAST).  
7.3.2. 
Analysis Population of Interest 
For details of the analysis populations used in each exploratory endpoint, see Section 
7.3.1. 
7.3.3. 
 Statistical Analyses / Methods 
There will be no multiplicity adjustment for the testing of the exploratory endpoints. No 
formal hypothesis testing will be performed; 95% CIs may be included but only for 
descriptive purposes. For more details of the analysis methods for each exploratory 
endpoints, see Section 7.3.1.   
7.3.3.1. 
Subgroup Analyses 
Subgroup analyses of certain exploratory endpoints will be performed at the relevant 
visits for the endpoint, which may include Baseline (BL), TOC, and FU. See Section 
5.4.2 for definition of subgroups and Section 7.3.1 for subgroup analysis planned for each 
endpoint. Subgroup analyses for NAAT outcome and response for NG will only be 
performed if the corresponding subgroup analysis is conducted in the corresponding 
primary and secondary endpoint analyses. Additional exploratory analyses may be 
presented as needed. 


 
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All subgroup analyses will follow the same layout/content of the overall population for 
each endpoint. For subgroup analyses, the summary table will be paginated by each level 
of the subgroup, and only the unadjusted difference in success rate will be presented. 


 
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8. 
SAFETY ANALYSES 
The safety analyses will be based on the Safety population, unless otherwise specified. 
8.1. 
Adverse Events Analyses 
All AEs will be collected from the start of treatment until the FU visit and all SAEs will 
be collected from the signing of the informed consent form until the FU visit based on the 
timepoints specified in Appendix 1. All reported AEs will be coded using Medical 
Dictionary for Regulatory Activities (MedDRA) and summarized by system organ class 
(SOC) and preferred term (PT). 
A treatment emergent AE (TEAE) is defined as an AE with start date/time after the first 
dose date/time of the study treatment. If the time part is missing, only dates will be 
considered. The number and percentage of TEAEs, study treatment-related AEs, non-
serious drug-related AEs, SAEs, and AEs leading to study treatment or study withdrawal 
will be provided. Any AE starting before the first dose date/time will not be included in 
any summary analyses but will be displayed in the listings. Therefore, only TEAEs will 
be included in summary tables with all AEs displayed in listings. 
The severity of AEs and SAEs will be determined by the investigator according to the US 
National Institute of Allergy and Infectious Diseases Division of Microbiology and 
Infectious Diseases (DMID) criteria for adult toxicity assessment, except for serum 
creatinine adolescent laboratory data, which will be assessed using DMID pediatric 
toxicity criteria. Adverse event severity is classified as mild (Grade 1), moderate (Grade 
2), severe (Grade 3), potentially life-threatening (Grade 4), or resulting in death (Grade 
5). Adverse events starting after the first dose of study treatment with a missing severity 
will be classified as severe. If a participant reports an AE more than once within the same 
SOC/PT, the AE with the worst-case severity will be used in the corresponding severity 
summaries. 
The relationship to study treatment, as indicated by the investigator, is classified as “not 
related” or “related”. Adverse events with a missing relationship to study treatment will 
be regarded as “related” to study treatment. If a participant reports the same AE more 
than once within an SOC/PT, the AE with the worst-case relationship to study treatment 
will be used in the corresponding relationship summaries. 
Adverse events analyses including the analysis of AEs, SAEs and other significant AEs 
will be based on GSK Core Data Standards. All AEs, study drug related AEs, SAEs, and 
AEs leading to discontinuation of study treatment or withdrawal from study will be 
provided in separate listings. The listings will capture the hierarchical relationship 
between SOC, PT, and verbatim term. 
In summary tables where AEs are presented by SOC, PT, and maximum grade, SOCs 
will be sorted in descending order of the total incidence then alphabetically, PTs will be 
sorted in descending order of the total incidence then alphabetically within the SOC. 
In addition, a summary of the number and percentage of participants with common AEs, 
defined as AEs with ≥1% incidence (before rounding) in any treatment group, will be 


 
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presented in descending order of total incidence by PT. The incidence of common AEs 
with relative risk and associated 95% CI (Wald method) will also be summarized in 
tables and presented graphically by treatment group. 
All deaths occurring any time from informed consent through study completions will be 
listed. Participant-specific details including date of death, cause of death, and whether the 
death was attributed to a cardiovascular procedure or surgery will be provided. 
For completely missing or partial missing AE start date or end date, imputation rules will 
be applied following Appendix 5. A listing of Clostridium difficile laboratory test results 
will be provided. The details of data displays are presented in Appendix 9. 
AE summaries will also be presented for subgroups defined for safety analysis in Section 
5.4.2.  
8.2. 
Adverse Events of Special Interest Analyses 
Cardiovascular (CV) AEs, gastrointestinal (GI) AEs, C. difficile AEs, and AEs related to 
Acetylcholinesterase Inhibition (AChE-I) as determined by algorithm will be considered 
AESIs. 
8.2.1. 
Clostridium difficile AESI 
C. difficile AESIs (PTs Clostridium difficile infection and Clostridium difficile colitis) 
will be included in the overall summary of AEs. C. difficile laboratory testing results are 
collected and recorded on distinct eCRF pages, which will be presented in a separate 
subject listing. 
8.2.2. 
Cardiovascular and Gastrointestinal Adverse Events 
Gastrointestinal AESIs are defined as AEs with a gastrointestinal SOC. Cardiovascular 
AESIs are defined as AEs with PTs that match the terms listed in Appendix 4 (Section 
12.4.3). 
For cardiovascular and gastrointestinal AESIs, the number and percentage of participants 
with an event will be summarized by PT and the maximum grade. In addition, the 
incidence of AEs of gastrointestinal effects and time to the first occurrence will be 
summarized. Graphical presentation of the cumulative distribution of time to the first 
gastrointestinal event occurrence will be provided via Kaplan-Meier curve (participants 
with no occurrence will be regarded as censored at the last day of the study). The details 
of data displays are presented in Appendix 9. 
8.2.3. 
Acetylcholinesterase-Inhibition Adverse Events 
Any reported AE listed in the table in Section 12.4.3 with a start time no later than 12 
hours after the last dose administered, as evaluated by the investigator as per the DMID 
grading criteria provided in in protocol Section 12.5 and Appendix 7, will be included in 
the programmatic identification of AChE-I related AESI. The list of preferred terms for 


 
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programming to be considered due to potential AChE-I is provided in Appendix 4 
(Section 12.4.3). 
Cumulative grade score of Acetylcholinesterase-Inhibition (AChE-I) will be calculated as 
the sum of the grade of each reported AE. This enables the number of AEs and the 
severity of each AE to be considered. The grading scale is defined as 
Cumulative Grade: 
0 
1 
2 
3 
4 
Cumulative Grade Score: 
0 
1 to 3 
4 to 6 
7 to 10 
>=11 
For instance, if a participant reports two AEs, one of Grade 1 and the other of Grade 3 
their cumulative grade score of 4 would result in cumulative grade 2. This will be 
calculated for All AChE-I events, non-GI AChE-I events and GI AChE-I events. 
Acetylcholinesterase inhibition AESIs will be listed and tabulated by SOC and preferred 
term and maximum grade. Non-GI AChE-I events will also be summarized. A separate 
table will summarize the AChE-I AESI by the number of events and unique preferred 
terms. In addition, time of onset (time from first dose to the onset of first event in hours), 
duration, and lag time (the time from last dose to the end date/time of the last event for 
subjects whose end date/time of the last event is after treatment end date/time) of AChE-I 
event will also be summarized and repeated for non-GI AChE-I and GI AChE-I events. 
AChE-I events with a start time less than 6 hours after the latest dose administered will 
also be flagged in listings. 
Graphical presentation via stacked bar charts of percentage of subjects in each AChE-I 
cumulative grade will be produced for All AChE-I events and non-GI AChE-I events 
separately. In addition, a forest plot of relative risk of AChE-I events between two 
treatment groups and its 95% Wald CI for each event will also be included. The details of 
the planned displays are provided in Appendix 9. 
8.3. 
Clinical Laboratory Analyses 
Laboratory evaluations including the analyses of chemistry laboratory tests, hematology 
laboratory tests, urinalysis, and liver function tests will be based on GSK Core Data 
Standards. 
For adults, laboratory abnormalities will be graded according to the modified DMID 
criteria [DMID, 2007a]. For adolescent participants over 12 years of age and less than 
18 years of age, the adult DMID will be applied for all laboratory parameters with the 
exception of serum creatinine, which will be programmatically graded according to the 
modified DMID criteria for pediatric participants [DMID, 2007b]. 
Summaries of change from baseline values over time for clinical chemistry and 
hematology tests will be provided in separate tables. The frequency of laboratory 
abnormality events along with the shift from baseline to the worst-case post baseline 
value will also be provided. 
 


 
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Abnormal liver chemistry results will be summarized by increasing folds above the upper 
limit of normal (ULN) including tests of interest and thresholds as follows: 
• ALT or AST > 3xULN and Total Bilirubin > 2xULN 
• ALT or AST > 3xULN and ALP < 2xULN and Total Bilirubin ≥ 2xULN 
• ALT or AST > 3xULN and Total Bilirubin > 1.5xULN 
• ALT or AST > 3xULN and INR > 1.5xULN 
• (ALT/ALT ULN)/(ALP/ALP ULN)) > 5 and ALT > 3xULN * 
• ALT or AST ≥ 20xULN 
• ALT or AST ≥ 10xULN 
• ALT or AST ≥ 8xULN 
• ALT or AST ≥ 5xULN 
• ALT or AST ≥ 3xULN 
• ALT ≥ 20xULN 
• ALT ≥ 10xULN 
• ALT ≥ 8xULN 
• ALT ≥ 5xULN 
• ALT ≥ 3xULN 
• AST ≥ 20xULN 
• AST ≥ 10xULN 
• AST ≥ 8xULN 
• AST ≥ 5xULN 
• AST ≥ 3xULN 
• Total Bilirubin > 2xULN 
• Total Bilirubin > 1.5xULN 
*: sign of hepatocellular injury, ALT and ALP values must occur on the same day. 
In addition, graphical summary of liver function test as described below will be 
presented. 
• Scatterplot of maximum post-baseline ALT against baseline ALT by treatment 
group 
• Scatterplot of maximum total bilirubin value post baseline against maximum post-
baseline ALT by treatment group 
• Participant profiles of ALT, AST, ALP and total bilirubin 
If liver events are reported in the study, listings of liver event assessment, liver biopsy 
details and liver imaging details will be provided. Urinalysis dipstick results will be 
summarized using categorical statistics. Clinical chemistry and hematology test results 
with toxicity grade 3 or higher will be listed in separate listings. Urinalysis data will be 
listed. 
Renal impairment will be evaluated by baseline creatinine clearance (CrCL) using the 
Cockcroft and Gault formula (1976)  


 
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𝐶𝐶𝐶𝐶𝐶𝐶𝐶𝐶 (𝑚𝑚𝑚𝑚/𝑚𝑚𝑚𝑚𝑚𝑚) = ൫(140 −𝐴𝐴𝐴𝐴𝐴𝐴) × 𝑊𝑊𝑊𝑊𝑊𝑊𝑊𝑊ℎ𝑡𝑡൯
72 × 𝑆𝑆𝑆𝑆𝑆𝑆
× 𝑐𝑐 
where: 
• 𝑆𝑆𝑆𝑆𝑆𝑆 is serum creatinine in (mg/dL), 
• 𝐴𝐴𝐴𝐴𝐴𝐴 is in years (actual at baseline). 
• 𝑊𝑊𝑊𝑊𝑊𝑊𝑊𝑊ℎ𝑡𝑡 is in kg (at baseline), 
• And where 𝑐𝑐 = 1 for males and 𝑐𝑐 = 0.85 for females. 
Severity of renal impairment will be categorized based on CrCL at baseline (rounded to 
the nearest integer): 
• Normal (≥90 mL/min) 
• Mild impairment (≥60 to 89 mL/min) 
• Moderate impairment (≥30 to 59 mL/min) 
• Severe impairment (<30 mL/min) 
 
The details of data displays are presented in Appendix 9. 
8.4. 
Vital Signs and ECG 
The analyses of non-laboratory safety test results including ECGs and vital signs will be 
based on GSK Core Data Standards, unless otherwise specified. Summary tables will be 
provided for vital signs change from baseline values, and worst post-baseline vital signs 
results relative to baseline results. Participants with missing baseline values are assumed 
to have within range baseline values. 
The arithmetic mean of the three recorded ECG measurements will be employed in all 
data summaries and participant listings. ECG measurements at baseline will be recorded, 
including heart rate, PR interval, QRS duration, QT interval, QRS axis and RR interval. 
When not entered directly on eCRF, corrected QT intervals will be calculated by Bazett’s 
formula: 
QTcB (msec ) =
𝑄𝑄𝑄𝑄
ඥRR/1000
 
and by Fridericia’s formula: 
QTcF (msec ) =
𝑄𝑄𝑄𝑄
ඥ𝑅𝑅𝑅𝑅/1000
3
 
depending on the availability of other measurements. ECGs may be collected after start 
of treatment, when medically warranted. In such cases, change from baseline in 
measurements will be derived. 


 
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Listings will be provided for baseline abnormal ECG findings, ECG values of potential 
clinical importance, and vital sign values of potential clinical importance. Details of the 
ECG values or vital signs of potential clinical importance are provided in Appendix 6 
The details of data displays are presented in Appendix 9. 
8.5. 
Classification and analysis of safety signals 
As per GSK Guidance document (VQD-REF-019393), “Adverse reactions” (ARs) are 
undesirable effects, reasonably associated with use of a product that may occur as part of 
the pharmacological action of the product or may be unpredictable in its occurrence.” 
Determining which AEs should be considered ARs is a two-step process: 
1) Identification of potential ARs using quantitative methodology, 
2) Qualitative evaluation of the potential ARs to determine if there is sufficient 
evidence of a causal association with the product (gepotidacin) to support 
inclusion in the label. 
This section details the quantitative screening methods to identify potential ARs and key 
data displays that support quantitative identification of potential ARs and qualitative 
causality assessments. ARs will be reported separately from the CSR within the 
regulatory submission to support the safety profile of Gepotidacin. 
8.5.1. 
Multiplicity Adjustment 
As screening for potential ARs is intended as an aid to medical judgment rather than to be 
used for decision making, no adjustment for multiplicity will be applied. 
8.5.2. 
Quantitative Screening for Identification of Potential ARs 
Frequentist approach to screen for potential ARs will be used. Specifically, the Crowe 
method [Crowe B, et al, 2013] will be applied for initial screening of the large number of 
adverse events to generate a “short list” of potential ARs. This method is based on three 
measures: 
• Absolute incidence rate (%) in control arm (ceftriaxone plus azithromycin), 
• Estimate of treatment effect (Relative Risk [RR]) relative to active control arm 
(ceftriaxone plus azithromycin), 
• An estimate of variability around the treatment effect (95% CI for RR). 
High Level Terms (HLTs) will be used to group adverse events and the screening for 
potential ARs will be conducted at HLT level. Quantitative screening criteria for 
potential ARs endorsed by the Safety Review Team (SRT) are displayed in the following 
table: 


 
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Criterion 
Absolute Incidence in 
ceftriaxone plus oral 
azithromycin 
HLT RR  
(Gepotidacin vs 
ceftriaxone plus 
azithromycin) 
95% CI for HLT RR* 
1 
No conditions 
No conditions 
Lower CI > 1 
2 
≥5% 
≥1.25 
No conditions 
3 
<5% 
≥1.50 
No conditions 
*95% CI for RRs determined using Wald method. 
For each criterion, it is necessary to have all the features described in the column 
headings in order for the event to be considered to have achieved that particular criterion. 
Events may meet more than one criterion. Events that meet at least one of the criteria are 
shortlisted as a potential AR. 
Based on 310 participants being exposed to Gepotidacin, there is a 90% chance of 
observing at least one particular adverse event if the true incidence rate of that adverse 
event is not below 0.75%. When the active control arm has zero events, the estimate of 
relative risk (RR) would be undefined and therefore cannot be evaluated using the 
quantitative screening criteria given above. The screening criteria in this case will be 
based on the minimum number of subjects with the event of interest in gepotidacin arm 
(vs 0 in ceftriaxone plus azithromycin arm). At least 3 participants with the AE of interest 
must be observed in the gepotidacin arm in order to be included in the “short list” of 
potential ARs. 
A summary table of treatment emergent adverse events by SOC, HLTs and PTs with 
incidence (%) for each treatment group, RR and the associated 95% CI will be generated. 
An additional table will be produced displaying only the adverse events meeting the pre-
specified quantitative screening criteria. 
The incidence of treatment emergent AEs at HLT level for each treatment group with 
relative risk (95% CI) will also be presented graphically. In addition to potential ARs 
identified using the screening criteria shown above, AESIs (specified in Section 8.2 will 
be automatically included in the “short list” of potential ARs. 
ARs listed in the Development Core Safety Information (DCSI) for gepotidacin will be 
re-assessed using data from this study to determine whether they should be carried 
forward as ARs based on the current supporting data. 
Extra care has been taken when considering labelled/known ARs, such as fungal 
infections and hepatobiliary disorders, for the active comparators, ceftriaxone and 
azithromycin. It is not known whether the investigational product, gepotidacin, may also 
cause the event known to be associated with the active comparator, and therefore 
quantitative criteria may not be met if the incidence of these ARs are similar for the 
investigational product, gepotidacin. 
The following AEs will automatically be included in the “short list” of potential ARs for 
further qualitative evaluation: 


 
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• QT Prolongation: It is a very rare serious event that has been observed in early 
phase gepotidacin studies and therefore needs further evaluation. It is identified 
using HLT “ECG investigations”. 
• Serious and severe adverse events: The incidence of serious and severe AEs is 
expected to be very low, and the qualitative assessment will be applied directly to 
these events without going through the quantitative screening process. 
• Fungal infections: It is a known AR for ceftriaxone plus azithromycin. It is 
identified using HLT “Fungal infections”. 
• Hepatobiliary disorders: It is a known AR for ceftriaxone plus azithromycin. It is 
identified using HLT “Hepatic and hepatobiliary disorders”.  
8.5.3. 
Qualitative Causality Assessment 
After identification of potential ARs using the quantitative method, qualitative evaluation 
of the potential ARs in the “short list” will be performed to determine if there is sufficient 
evidence of causal association with gepotidacin. The following data displays will be 
produced for each AE in the “short list” of potential ARs to support the qualitative 
causality assessments. 
• Summary of treatment emergent adverse events by SOC, HLT and PTs by 
subgroups (Consistency check between subgroups: Actual Age Category, Sex, 
Race, Renal Impairment Evaluated by Baseline CrCL, Geographic Region and 
HIV Status) 
• Incidence rate of treatment emergent AEs according to different attributes by 
treatment group (Consistency check in AE attribute: AEs related to study 
treatment, AEs leading to permanent discontinuation of study treatment, AE 
leading to dose reduction, AE leading to dose interruption/delay, SAEs related to 
study treatment, Fatal SAEs, and Fatal SAEs related to study treatment) 
• Summary of treatment emergent AEs by HLT and Maximum Grade (Consistency 
check in AE attribute) 
• Summary of Cumulative Incidence of Treatment Emergent Adverse Events 
(HLTs) by Time to First Occurrence (Temporal association) 
• Heatmap of RR for treatment emergent AE HLTs that meet the screening criteria 
by SOC (Consistency check in AE attribute: AEs, Drug-related AEs, SAEs, AEs 
leading to discontinuation of study treatment, and Grade 3 or Higher AEs) 
• Kaplan Meier Curve for Treatment Emergent Potential AR Event by Treatment 
(Temporal association)  
Additional data displays may be generated as needed to assist with further qualitative 
assessment of the potential ARs once the safety data is reviewed. The generated data 
displays may be useful in evaluating the likelihood of a causal association and the 
strength of causality by assessing the following factors: 
• Consistency across pre-defined subgroups, 
• Consistency according to clinically relevant attributes, 
• Temporal association. 
 
 


 
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9. 
ADDITIONAL ANALYSES DUE TO THE COVID-19 
PANDEMIC 
9.1. 
Study Population 
9.1.1. 
Participant Disposition 
A summary of recruitment by country and site, relative to COVID-19 pandemic measures 
will be produced. For details on the determination of phases of the COVID-19 pandemic 
measures see Appendix 2. A country level listing of the dates of the COVID-19 
Pandemic measures will be produced.  
9.1.2. 
Protocol Deviations 
An optional participant listing of significant protocol deviations related to COVID-19 
may be produced, however, these deviations will already be captured in the listing of all 
significant protocol deviations. Visits and assessments missed due to the COVID-19 
pandemic, together with visits conducted remotely, will be summarized in both a table 
and listed by participant. 
9.2. 
Safety 
COVID-19 assessments and symptom assessments for participants with COVID-19 AEs 
will be listed, which will include the clinical outcome of any COVID-19 AE. 
 
 


 
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10. 
BENEFIT/RISK 
Forest plots showing the treatment effect and confidence intervals related to benefits and 
risks of treatment with gepotidacin will be created. Benefits will be represented by risk 
differences and corresponding confidence intervals from the following analyses based on 
the Micro-ITT analysis population: 
• Microbiological outcome and response rate of urogenital Gonorrhea at the TOC 
Visit (primary analysis), 
• NAAT outcome and response rate of urogenital Gonorrhea at the TOC Visit 
(exploratory analysis). 
For these analyses, risk differences and 95% confidence intervals will be determined 
using the methods described in Section 7.1.6.1 and Section 7.3.1.5, respectively. 
Additionally, relative risks and corresponding 95% confidence intervals will be displayed 
for the following safety endpoints: incidence of AEs, SAEs and, separately, CV, GI, C. 
difficile, and AChE-I AESIs using the Safety analysis population. Confidence intervals 
for relative risks will be determined using the asymptotic Wald method.  


 
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11. 
REFERENCES 
Fleiss J.L. Statistical Methods for Rates and Proportions. 2nd ed. New York: John Wiley; 
1981. 
Cockcroft, D. W., & Gault, H. (1976). Prediction of creatinine clearance from serum 
creatinine. Nephron, 16(1), 31-41. 
Crowe B, Brueckner A, Beasley C, Kulkarni P. Current Practices, Challenges, and 
Statistical Issues with Product Safety Labeling. Statistics in Biopharmaceutical Research 
2013;5(3): 180-193. 
GlaxoSmithKline Document Number TMF-14342295 (Amendment 1 14-Dec-2021): A 
Phase III, Randomized, Multicenter, Open-Label Study in Adolescent and Adult 
Participants Comparing the Efficacy and Safety of Gepotidacin to Ceftriaxone Plus 
Azithromycin in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by 
Neisseria gonorrhoeae 
Lui K.J., Kelly C. A Revisit on Tests for Homogeneity of the Risk Difference, 
Biometrics, 2000;56:309-315. 
Miettinen, O.S., and M.M. Nurminen. 1985. “Comparative Analysis of Two Rates. 
“Statistics in Medicine 213-226. 
SAS Institute Inc. (2018), SAS/STAT User’s Guide, Version 15.1, Cary, NC: SAS 
Institute Inc. 
US Department of Health and Human Services, DHHS, Food and Drug Administration, 
Center for Drug Evaluation and Research, Clinical/Antimicrobial. Guidance for industry. 
Uncomplicated gonorrhea: developing drugs for treatment. 
http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guid
ances/UCM401620.pdf. Last updated August 2015. 
US National Institute for Allergy and Infectious Diseases, Division of Microbiology and 
Infectious Diseases. Division of Microbiology and Infectious Diseases (DMID) Adult 
Toxicity Table. Draft. https://www.niaid.nih.gov/sites/default/files/dmidadulttox.pdf. 
Last updated November 2007a. 
US National Institute for Allergy and Infectious Diseases, Division of Microbiology and 
Infectious Diseases. Division of Microbiology and Infectious Diseases (DMID) Pediatric 
Toxicity Table. Draft. https://www.niaid.nih.gov/sites/default/files/dmidpedtox.pdf. Last 
updated November 2007b. 
FDA (2022), Multiple Endpoints in Clinical Trials Guidance for Industry 
 


 
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12. 
APPENDICES 
12.1. 
Appendix 1: Schedule of Activities 
12.1.1. 
Protocol Defined Schedule of Events 
Table 5 
Schedule of Activities 
 


 
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CT=Chlamydia trachomatis; HIV=human immunodeficiency virus; IM=intramuscular; Mgen=Mycoplasma genitalium; NA=not applicable; NAAT=nucleic acid amplification test; 
TOC=Test-of-Cure. 
a. 
For all study visits, to minimize the amount of time that participants spend at the clinic, eConsent may be utilized and remote collection of study-related data may be obtained 
as described in the Study Reference Manual. Thus, some visit data may be collected through a combination of telemedicine and on-site visits. Collection of information via 
telemedicine will be performed only where local regulations permit. 
b. 
TOC (Day 4 to 8) Visit: Participants will be instructed to return to the study site within 3 to 7 days after study treatment administration. This visit may occur earlier if participants 
experience an adverse event. 
c. 
Participants will be instructed to return to the study site from Day 14 to 21 for a Follow-up Visit. The investigator and/or study site staff should make every effort to ensure the 
participant returns for this visit. If the participant is unable to return to the study site, the visit assessments may be completed via telephone, with the exception of assessments 
requiring sample collection for laboratory testing. 
d. 
Refer to the Study Reference Manual for information to collect for social and sexual history. 
e. 
See Table 6 for collection of bacteriology samples. Also refer to the laboratory manual. 
f. 
See Table 6 for collection of NAAT assay samples. Also refer to the laboratory manual. 
g. 
A complete physical examination will be performed at the Baseline Visit and a gonorrhea-focused examination will be performed at the TOC Visit (see Protocol Section 9.4.1). 
Height and weight will only be measured and recorded at the Baseline Visit (before dosing). 
h. 
See Protocol Section 6.2 for electrocardiogram exclusion criterion for participants aged ≥12 to <18 years. For additional details see Protocol Section 8.1.2 and Section 9.4.3.  
i. 
Take measurement of temperature, blood pressure, and pulse rate. See Protocol Section 9.4.2. 
j. 
If serology testing was performed within 3 months prior to the first dose of study treatment and results were positive, testing at Baseline is not required. If testing was performed 
within 3 months and any result was negative, testing at Baseline is required. 
k. 
For women of childbearing potential, a negative urine pregnancy test is sufficient for eligibility. See Protocol appendix 6 for Baseline urine test sensitivity requirements and 
associated contraception requirements. 
l. 
During the Baseline Visit, participants randomly assigned to gepotidacin will receive their first oral dose (3000 mg) at the study site. Participants will self-administer their second 
dose (3000 mg) as an outpatient 10 to 12 hours after the first dose; however, for participants who weigh <50 kg or have moderate renal impairment, the second dose should be 
taken approximately 12 hours after the first dose). See Protocol Section 7.1. Each dose should be taken after food consumption and with water to assist with tolerability. 
Participants will be contacted to confirm that they took their second gepotidacin dose. See Protocol Section 7.6. 
m. During the Baseline Visit, participants randomly assigned to ceftriaxone plus azithromycin will receive a single IM dose of ceftriaxone (500 mg) plus a single oral dose of 
azithromycin (1 g). See Protocol Section 7.1. Azithromycin should be taken after food consumption and with water. 
n. 
Record serious adverse events from the time of consent/assent in order to fulfill international regulatory requirements. 
o. 
Record adverse events from the time of the first dose of study treatment. 
p. 
Confirm return day/time for the TOC and Follow-up Visits. 
q. 
Previsit reminder: Study site staff will contact the participant 24±4 hours before the respectively scheduled Baseline (if applicable), TOC, or Follow-up Visit. 
r. 
Participants who tested positive for CT and/or Mgen per NAAT results at the Baseline Visit should be treated per local standard of care at or after the TOC Visit or at the 
Follow-up Visit (if treatment has not already been initiated), as required, after all study procedures at the visit have been completed. 
s. 
Collect sample only if the participant has a signed consent/assent specific for this purpose. The Baseline Visit is the recommended time to collect the sample; however, it can 
be collected at any time during the study. 


 
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Table 6 
Collection of Bacteriological Microbiological Specimens 
 
NA=not applicable; NG=Neisseria gonorrhoeae; TOC=Test-of-Cure. 
CT=Chlamydia trachomatis; Mgen=Mycoplasma genitalium; NA=not applicable; NAAT=nucleic acid amplification test; NG=Neisseria gonorrhoeae; TOC=Test-of-Cure. 
a. Any participant that withdraws before TOC should have all bacteriology and NAAT assay collections performed as indicated at the TOC Visit. 
b. Multiple swab specimens and types may need to be obtained from each anatomical site; refer to the laboratory manual. 
c. Collect a pretreatment urogenital swab specimen from all participants for Gram stain (males and females), bacterial culture, and in vitro susceptibility testing at Baseline. At TOC, 
a urogenital swab specimen will be collected for Gram stain, bacterial culture, and in vitro susceptibility testing. Note: All urogenital swab specimens will be processed for Gram 
stain testing following inoculation of the culture plates. 
d. Pretreatment rectal and pharyngeal swab specimens for bacterial culture and in vitro susceptibility testing will be obtained from participants who are willing to provide such 
specimens, regardless of known exposure. At TOC, swab specimens will be collected from pharyngeal and/or rectal sites that were collected at Baseline for bacterial culture and 
in vitro susceptibility testing. Note: None of the rectal or pharyngeal swab specimens will be processed for Gram stain testing. 
e. At Follow-up, pharyngeal swab specimens will be obtained for bacterial culture and in vitro susceptibility testing from participants who had a positive NAAT assay for pharyngeal 
NG at both Baseline and TOC. Results from the NAAT assay will be available to the study sites by the Follow-up Visit. 
f. See the laboratory manual for local versus central laboratory details and the number and type of specimens to collect. 
g. Pretreatment baseline urogenital specimens will be obtained from all participants for detection of NG, Mgen, and CT by NAAT. At Baseline, while detection of NG and CT by 
NAAT may be performed using the same urogenital sample, 2 separate samples must be obtained (1 for the local laboratory and 1 for the central laboratory). 
h. Urogenital specimens will be obtained from all participants for detection of NG and CT by NAAT at the TOC Visit. 
i. At Follow-up, a urogenital specimen will be collected for the detection of Mgen only by NAAT from participants who had a positive NAAT assay for Mgen at Baseline. Results from 
the NAAT assay will be available to the study sites by the Follow-up Visit. 
j. Pretreatment baseline pharyngeal and rectal specimens for detection of NG and CT by NAAT will be obtained from participants who are willing to provide such specimens, 
regardless of known exposure. At TOC, a specimen will be collected from pharyngeal and/or rectal sites that were collected at Baseline. 
k. At Follow-up, a pharyngeal specimen will be collected for detection of NG and CT by NAAT from participants whose NAAT assay had the presence of nucleic acid for NG at both 
Baseline and TOC. NAAT assay results will be available to the study sites by the Follow-up Visit. 


 
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Table 7 
BTZ116577 NAAT Overview by Body Site and Organism 
Body site 
Organism 
Baseline Visit 
TOC Visit 
F/U Visit 
Local Lab 
Central Lab 
Central Lab 
Central Lab 
Real Time 
Batch 
Real Time 
Batch 
Real Time 
Batch 
Urogenital 
NG/CT 
X 
X 
 
X 
 
 
MGen 
 
 
X 
 
 
Xb 
Pharyngeala 
NG/CT 
 
X 
 
X 
 
Xc 
 
Rectala 
NG/CT 
 
X 
 
X 
 
 
NG = N. gonorrhoeae; CT = C. trachomatis; MGen = M. genitalium; RT = real time (processed upon arrival); F/U=Follow-up. 
a. 
Optional (upon patient consent) 
b. 
Only if positive NAAT at baseline visit. MG NAATs will be run weekly by the central lab, so that baseline and results are back to the site in time for F/U. 
c. 
Only if positive NG NAAT at baseline and TOC visit. Sites will have baseline and TOC pharyngeal NAAT results back by F/U 
Note: Only central laboratory NAAT results will be used in the exploratory analysis, local lab NAAT is conducted to guide therapy at the TOC visit (Chlamydia trachomatis) 
 
 


 
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12.2. 
Appendix 2: Study Phases and Treatment Emergent 
Adverse Events 
12.2.1. 
Study Phases 
Assessments and events will be classified according to the time of occurrence relative to 
the start and end date of study treatment. 
Study Phase 
Definition 
Pre-Treatment  
Date/Time < Study Treatment Start Date/Time 
On-Treatment 
Study Treatment Start Date and Time < Date and Time ≤ Study Treatment Stop Date 
and Time 
Post-Treatment 
Date and Time > Study Treatment Stop Date and Time 
 
12.2.1.1. 
Study Phases for Concomitant Medication 
Study Phase 
Definition 
Prior 
If medication started prior to the first dose date (or randomized date if first dose date is 
missing) 
Concomitant 
If medication ended after the first dose date or is ongoing regardless of the start date 
(or randomized date if first dose date is missing) 
NOTES:  
• 
Please refer to Appendix 5: for handling of missing and partial dates for concomitant medication. Use the rules in 
this table if concomitant medication date is completely missing. 
• 
If a single medication taken on the same date as the first dose date, time will be used to determine if it’s prior or 
concomitant. If time is missing, it will be considered concomitant. 
12.2.1.2. 
Phases of COVID-19 Pandemic Measures 
Pandemic measures began in different countries at different times. A dataset containing 
the date when COVID-19 pandemic measures began, as determined by the GSK country 
Issue Management Teams will be used to determine the start date of pandemic measures 
within each country. A copy of this dataset will be taken at the time of DBF. 
12.2.1. 
Treatment Emergent Flag for Adverse Events 
Flag 
Definition 
Treatment 
Emergent 
• 
If AE onset date/time is on or after treatment start date/time. That is, study 
treatment start date/time ≤ AE start date/time. If time is missing, only date will 
be compared. 
NOTES:  
• 
All doses of study treatments administered within 24 hours. 
 
 


 
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12.3. 
Appendix 3: Data Display Standards & Handling 
Conventions 
12.3.1. 
Reporting Process 
Software 
• 
The currently supported versions of SAS software will be used. 
Analysis Datasets  
• 
Analysis datasets will be created according to CDISC standards (SDTM IG Version 3.2 & ADaM IG 
Version 1.0) 
• 
For creation of ADaM datasets (ADCM/ADAE), the same version of dictionary datasets will be 
implemented for conversion from SI to SDTM. 
Generation of RTF Files 
• 
RTF files will be generated for all reporting efforts described in the RAP. 
12.3.2. 
Reporting Standards 
General 
• 
The current GSK Integrated Data Standards Library (IDSL) will be applied for reporting, unless 
otherwise stated (IDSL Standards Location:  
https://spope.gsk.com/sites/IDSLLibrary/SitePages/Home.aspx): 
• 
4.03 to 4.23: General Principles 
• 
5.01 to 5.08: Principles Related to Data Listings 
• 
6.01 to 6.11: Principles Related to Summary Tables 
• 
7.01 to 7.13: Principles Related to Graphics  
• 
Do not include participant level listings in the main body of the GSK Clinical Study Report. All 
participant level listings should be located in the modular appendices as ICH or non-ICH listings 
Formats 
• 
GSK IDSL Statistical Principles (5.03, 6.06.3, & 6.09) for decimal places (DP’s) will be adopted for 
reporting of data based on the raw data collected, unless otherwise stated. 
• 
For efficacy outputs, both summaries and Statistical analysis outputs percentages will be presented 
with 1 dp. 
• 
Numeric data will be reported at the precision collected on the eCRF. 
• 
The reported precision from non eCRF sources will follow the IDSL statistical principles but may be 
adjusted to a clinically interpretable number of DP’s. 
Planned and Actual Time 
• 
Reporting for tables, figures and formal statistical analyses: 
• 
The impact of any major deviation from the planned assessment times and/or scheduled visit 
days on the analyses and interpretation of the results will be assessed as appropriate. 
• 
Reporting for Data Listings: 
• 
Planned and actual time relative to study drug dosing will be shown in listings (Refer to IDSL 
Statistical Principle 5.05.1). 
• 
Unscheduled or unplanned readings will be presented within the participant’s listings. 


 
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Unscheduled Visits 
• 
Unscheduled visits and Early withdrawal visits may be included in summary tables and/or figures as 
described in Section 5.6 on Analysis Visits and analyses such as “all post baseline”, “worst case post 
baseline”, and “max post baseline” etc.  All unscheduled visits and Early Withdrawal visits will be 
included in listings. 
Descriptive Summary Statistics 
Continuous Data 
Refer to IDSL Statistical Principle 6.06.1 
Categorical Data 
N, n, frequency, % 
Graphical Displays 
• 
Refer to IDSL Statistical Principles 7.01 to 7.13. 
 


 
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12.4. 
Appendix 4: Derived and Transformed Data 
12.4.1. 
General 
Multiple Measurements at One Analysis Time Point 
• 
Analysis visits will be created based on visit windows as described in Section 5.6. All assessments 
(including unscheduled and early termination visits) will be presented in participant listings. The 
arithmetic mean of the three recorded ECG measurements will be employed as described in Section 
8.4.  
• 
Participants having both High and Low values for Normal Ranges at any post-baseline visit for safety 
parameters will be counted in both the High and Low categories of “Any visit post-baseline” row of 
related summary tables. This will also be applicable to relevant Potential Clinical Importance 
summary tables. 
Study Day 
• 
Calculated as the number of days from Study Treatment Start Date (or Randomization Date if not 
dosed): 
• 
Ref Date = Missing→ Study Day = Missing  
• 
Ref Date < Study Treatment Start Date → Study Day = Ref Date – First Dose Date 
• 
Ref Date ≥ Study Treatment Start Date → Study Day = Ref Date – (First Dose Date) + 1 
12.4.2. 
Efficacy 
Microbiology Procedures 
• 
Microbiology data will be received from below sources 
• 
Local laboratory 
• 
Central laboratory 
• 
3rd party laboratory  
Local laboratory procedures: 
• 
A local laboratory will be utilized for processing of the specimen for Gram stain (urogenital 
specimen only), NG culture, and shipment of the presumptive NG isolates to the central 
laboratory. Presumptive identification of NG is based on the following: (1) growth of typical 
appearing colonies on a selective medium such as Thayer-Martin at 35 °C to 36.5 °C in 5% 
CO2, (2) a positive oxidase test, and (3) the observation of gram-negative diplococci in stained 
smears. 
 
 


 
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• 
Gram stain results (WBCs, epithelial cells, and bacteria) from urogenital specimens 
only will be reported as follows: 
 
 
Observed  
Report Terminology 
WBCs per 100x field  
0 
<1 
1-9 
10-25 
>25 
No cells seen 
Rare or occasional 
Few 
Moderate 
Many 
Epithelial cells per 100x field  
0 
<1 
1-9 
10-25 
>25 
No cells seen 
Rare or occasional 
Few 
Moderate 
Many 
Bacteria per 1000x field (oil 
immersion)  
0 
<1 
1-5 
6-30 
>30 
No organisms seen 
Rare or occasional 
Few 
Moderate 
Many 
 
Central laboratory procedures: 
• 
The central laboratory will conduct confirmatory identification of NG isolates, susceptibility 
testing (agar dilution will be conducted at a 3rd party laboratory) and storage. 
• 
All isolates received by the central laboratory will be identified to genus and species by 
matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-
TOF MS) and stored. If MALDI-TOF MS is not available, isolate identification will be 
performed based on colony morphology and Gram stain characteristics and the use of 
routine microbiology laboratory identification procedures. 
• 
Various methodologies may be used to identify each isolate to genus and species. If an 
isolate is not identified to genus and species by the first methodology used, a second 
attempt may be made to identify the isolate to genus and species using an alternate 
methodology.  
• 
If the isolate is still not identified to genus and species after using at least two 
methodologies, the best identification available will be reported e.g. 
Pseudomonas species. 
• 
Susceptibility testing, as outlined below will be performed on all NG isolates from all body sites 
including duplicate isolates recovered from the same participant: 
• 
MIC testing will be conducted on all NG isolates as follows:  
• 
Agar dilution: ranges for the antimicrobial agents to be tested are shown 
below. Isolates displaying MIC results higher than the last concentration 
tested for any given agent (i.e., off-scale high) will be re-tested at the end of 
the trial using a higher dilution range in an attempt to get on-scale values for 
all isolates; however,  the highest concentration will be set at 512 µg/mL for 
tetracycline and spectinomycin, at 16 µg/mL for ceftriaxone and cefixime, and 
at 256 µg/mL for all remaining drugs. 
a. Gepotidacin (0.06 – 32 µg/mL) 
b. Ceftriaxone (0.002 – 0.5 µg/mL)  
c. Ciprofloxacin (0.0005 – 32 µg/mL) 
d. Azithromycin (0.03 – 16 µg/mL)  
e. Cefixime (0.002 – 0.5 µg/mL) 
f. 
Penicillin (0.06 – 16 µg/mL) 


 
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g. Tetracycline (0.12 – 64 µg/mL) 
h. Spectinomycin (4 – 256 µg/mL) 
i. 
Gentamicin (1 – 32 µg/mL) 
• 
Gradient diffusion results will also be generated for all NG isolates for 
susceptibility to gepotidacin only. 
• 
MIC results will be reported according to Clinical and Laboratory Standards Institute 
(CLSI) guidelines.
 
 
The concentration (in micrograms per milliliter) and the 
interpretation code (S=susceptible, I=intermediate, R=resistant, NS=nonsusceptible) 
will be reported for the minimum inhibitory concentration (MIC) values. Where no CLSI 
or EUCAST interpretation is available, only the MIC will be reported. 
• 
Gradient Diffusion MICs and Interpretation 
• 
Being a fully quantitative MIC method, gradient diffusion enables the 
laboratory to report the exact MIC value together with the interpretive 
category. Gradient diffusion strips generate MIC values from a continuous 
scale and can give results in-between conventional two-fold dilutions i.e. half 
dilutions. A gradient diffusion MIC value which falls between standard two-fold 
dilutions must be rounded up to the next upper two-fold value before 
categorization. Example: Benzylpenicillin MIC (ug/mL) breakpoints for 
Streptococcus pneumoniae 
o S: <=0.06 
o I: 0.12-1 
o R: 2 
• 
A gradient diffusion MIC of 1 ug/mL is reported as intermediate (I) while 1.5 is 
rounded up to 2 ug/mL and the category reported as resistant (R). 
• 
When growth occurs along the entire strip i.e. no inhibition ellipse is seen, 
report the MIC as ≥ the highest value on the MIC scale. When the inhibition 
ellipse is below the strip (does not intersect the strip), report the MIC < the 
lowest value on the MIC scale. 
• 
MIC Reporting Concentrations 
• 
When serial two-fold dilution MICs are being prepared and tested, the actual 
dilution scheme is, e.g.: 16, 8, 4, 2, 1, 0.5, 0.25, 0.125, 0.0625, 0.03125, 
0.015625, 0.0078125 ug/ml, etc. 
• 
For convenience only, it was decided to use the following values for reporting 
purpose (reporting format):16, 8, 4, 2, 1, 0.5, 0.25, 0.12, 0.06, 0.03, 0.015, 
0.008, 0.004, 0.002 ug/mL, etc. The values that appear in the tables are 
equivalent to the actual values tested, e.g., 0.12 ug/mL = 0.125 ug/mL; 0.015 
ug/mL = 0.015625 ug/mL. 
• 
Any values contain '<', '<=', '>=', '>' will be counted in its separate categories. 
However, when calculating the minimum, maximum, MIC50, MIC90, a small 
amount will be added or subtracted in order to impute the corresponding 
numeric value for calculation. For example,  
o '<0.06' will be imputed as 0.06-0.001; 
o '>256' will be imputed as 256+0.001. 
o '>=32' will be imputed as 32. 
• 
But for reporting, they will still be presented in original format if they happen to 
be those summary statistics. 
• 
Disk diffusion will be conducted on all NG isolates as follows: 
CCI


 
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Compound 
Organisms 
Gepotidacina 
All NG isolates 
Ceftriaxone 
All NG isolates 
Azithromycin 
All NG isolates 
a Two manufacturers (Becton Dickinson and MAST) 
 
• 
Disk diffusion results will be reported according to approved microbiology standards (e.g. CLSI 
or EUCAST, note that there are currently no EUCAST disk diffusion interpretive criteria for N. 
gonorrhoeae). The zone size will be recorded and reported in millimeters along with the 
interpretation code (S=susceptible, I=intermediate, R=resistant, NS=nonsusceptible) for disk 
diffusion results. Where no interpretation is available, only zone diameters will be recorded. 
• 
Urogenital, pharyngeal, and rectal specimens for NAAT will be collected from all participants at 
designated visits (refer to Table 6) and processed as outlined below at the central laboratory: 
• 
Detection of NG and CT (Positive or Negative) 
• 
Detection of Mgen and five macrolide resistance markers (Detected or Not Detected) 
• 
Detection of ciprofloxacin resistance markers in NG (Detected or Not Detected) 
• 
Detection of gepotidacin resistance markers in NG (Detected or Not Detected) 
• 
Testing for Beta-lactamase production will be performed on all NG isolates. Results will be 
reported as β-lactamase positive or β-lactamase negative. 
• 
Susceptibility data will be included in PPD GCL data transfers to PPD clinical and therefore 
available for PPD Biostatistics and PPD clinical programing for inclusion in analysis database. 
• 
The data from two or more N. gonorrhoeae isolates reported from the same patient from the 
same body site at the same visit will be reviewed by the study microbiologist and the algorithm 
in the ‘keepers data” process below applied to determine if the isolates are the same or different 
strains (see microbiological “Keepers” process below). 
Microbiological Data Procedures 
• 
JMI isolate genotype data is derived from isolate whole genome sequencing and other genomic 
assays as requested by GSK and will be performed by JMI when a minimum of 20 isolates are 
available but not more frequent on a monthly basis (testing may be conducted more frequently 
near the end of the study). Genotype data therefore will be available no sooner than 1-2 months 
after isolate receipt. 
• 
JMI isolate genotypic data will be sent to PPD GCL and included in PPD GCL data transfers to 
PPD clinical and therefore available for PPD Biostatistics and PPD clinical programming for 
inclusion in analysis database. 
 


 
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Keepers Process 
Scenario #1: Keepers 
• 
All cases will be identified within the central laboratory dataset where two or more pathogens of 
the same genus and species have been identified for the same participant at the same visit from 
the same body site. An excel file containing a list of these pathogens and the associated MIC 
results for each isolate will be provided to the study microbiologist. (Note: There may be 
instances where the comment “Out of stability” appears for an isolate.  It will be isolate number 
2.  If the time to receipt of the isolate is markedly longer than the 1st isolate, select the 1st 
isolate that tested closer to the visit date to maintain in the analysis set.)  The microbiologist will 
review the list and determine if the isolates are the same or different strains of the identified 
pathogen based on a predefined algorithm: 
• 
If there is a ≥4-fold difference in MIC to three or more antibiotic classes, then the applicable 
isolates will be considered different strains and each of the applicable different isolates will be 
used in the analysis regardless of susceptibility interpretations (Note: agar dilution MIC will be 
used in this analysis, not the gradient diffusion MIC). 
• 
If two or more NG isolates from the same visit and same sample type and there is a ≥4-fold 
difference in MIC to two antibiotic classes, and if at least one isolate has different breakpoint 
interpretations to both antibiotic classes (e.g. susceptible and resistant or non-susceptible), the 
applicable isolates will be considered different strains and each of the applicable different 
isolates will be analyzed. 
• 
NOTE: In certain instances, should there be two or more NG that DO NOT have a ≥4-fold 
difference in MIC to two antibiotic classes but at least one isolate has a different breakpoint 
interpretation (e.g. susceptible and resistant) for an antimicrobial of epidemiological or study 
importance [i.e. ceftriaxone, cefixime, azithromycin, gepotidacin (presumptive breakpoints 
applied)], the applicable isolates will be considered different strains and each of the applicable 
NG isolates will be analyzed. 
• 
In some cases, molecular results may be used to determine if two or more N. gonorrhoeae 
isolates are the same or different strains. 
• 
If none of the criteria for determining the isolates as different are met, only one isolate will 
be kept for analysis based on a pre-defined algorithm. 
• 
The microbiologist will add a flag to the list to indicate which of the duplicate records to keep 
(flag = >0; e.g. 1, 2). All records with this flag will be kept in the SDTM/ADaM datasets, and 
those records that are deemed to be duplicates (flag = 0) will be removed from the final 
analyses. 
 
Isolates other than Neisseria gonorrhoeae will receive a 'Keepers' designation of 'NA' to 
signify that the Keepers process does not apply for isolates other than Neisseria 
gonorrhoeae. 
• 
Should an NG isolate be recovered from post-baseline visits of participants with more than 
one NG recovered from the baseline visit, each baseline NG will be presented alongside 
participant-level microbiological outcome. The relatedness of pre- and post-baseline 
isolates as it relates to microbiological failure will be described in a stand-alone report. 
Phenotype and Genotype Subcategory Flagging 
• 
A summary for the number of participants for each distinct phenotype and genotype isolated at 
Baseline by body site will be produced for the microbiologist. 
• 
The microbiologist will review that summary to flag those phenotype and genotype 
subcategories to be reported in the TLFs. 
Fold Change 


 
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• 
Fold change will be used to describe how much the MIC for gepotidacin changes between Baseline 
Visit and subsequent visits). Fold change analysis will also be conducted for study comparators 
azithromycin and ceftriaxone. 
• 
Fold change will be calculated (in doubling dilutions) as the ratio of the MIC at the subsequent visit to 
the MIC at the Baseline Visit.  However, ratio of 1 will be reported as 0-fold. Ratio less than 1 will be 
reported in reciprocal with negative sign (e.g. ratio of 0.5 will be reported as -2-fold). Below are some 
examples: 
Baseline MIC (mcg/mL)  
Post-baseline MIC (mcg/mL)  
Fold-change 
1 
1 
0-fold 
1 
2 
2-fold 
1 
4 
4-fold 
1 
8 
8-fold 
1 
16 
16-fold 
1 
0.5 
- 2-fold 
1 
0.25 
- 4-fold 
1 
>32 
>/=64-fold 
1 
>/=32 
>/=32-fold 
1 
<0.125 
>/= - 16-fold 
1 
</=0.125 
>/= - 8-fold 
MIC50 and MIC90 
• 
MIC50 and MIC90 refer to the corresponding concentrations required to inhibit 50% and 90% of the 
strains tested, respectively. The MIC50 is the dilution which includes the 50th percentile (similar for 
MIC90). The 50th and 90th percentiles will be determined by tabulation of the cumulative percentage of 
MICs: the MIC50 is the first value for which the cumulative percentage is >=50% and the MIC90 is the 
first value for which the cumulative percentage is >=90%. They will only be reported if sample size is 
larger or equal to 10 (otherwise reported as ‘NC’). 
• 
MIC ranges to be tested in this protocol (in ug/mL): 
Gepotidacin Gradient 
Strip 
<0.015; 0.015, 0.03; 0.06; 0.12; 0.25; 0.5; 1; 2; 4; 8; 16; 32; 64; 128; >=256 
Gepotidacin (JMI) 
<=0.06; 0.12; 0.25; 0.5; 1; 2; 4; 8; 16; 32; >32; 64; 128; 256; >256 
Ceftriaxone (JMI) 
<=0.002; 0.004; 0.008; 0.015; 0.03; 0.06; 0.12; 0.25; 0.5; >0.5; 1; 2; 4; 8; 16; >16 
Cefixime (JMI) 
<=0.002; 0.004; 0.008; 0.015; 0.03; 0.06; 0.12; 0.25; 0.5; >0.5; 1; 2; 4; 8; 16; >16 
Azithromycin (JMI) 
<=0.03; 0.06; 0.12; 0.25; 0.5; 1; 2; 4; 8; 16; >16; 32; 64; 128; 256; >256 
Ciprofloxacin (JMI) 
<=0.0005; 0.001; 0.002; 0.004; 0.008; 0.015; 0.03; 0.06; 0.12; 0.25; 0.5; 1; 2; 4; 8; 
16; 32; >32; 64; 128; 256; >256 
Penicillin (JMI) 
<=0.06; 0.12; 0.25; 0.5; 1; 2; 4; 8; 16; >16; 32; 64; 128; 256; >256 
Tetracycline (JMI) 
<=0.12; 0.25; 0.5; 1; 2; 4; 8; 16; 32; 64; >64; 128; 256; 512; >512 
Spectinomycin (JMI) 
<=4; 8; 16; 32; 64; 128; 256; >256; 512; >512 
Gentamicin (JMI) 
<=1; 2; 4; 8; 16; 32; >32; 64; 128; 256; >256 
Susceptibility Interpretations 


 
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• 
Susceptibility interpretations will be calculated and reported by the central laboratory and will be 
based on the CLSI M100 and EUCAST guidelines in effect at that time the bacterial isolate is 
tested. 
• 
Since CLSI or EUCAST breakpoints for certain drug/bug combinations can change in new yearly 
editions of the guidelines, as GSK and/or the central laboratory become aware of relevant 
breakpoint changes, the central laboratory will identify any reports which would qualify as 
needing a change in interpretation (e.g., a MIC value that was originally reported as susceptible, 
and would now be considered resistant based on the new breakpoint) and will issue amended 
reports. 
• 
The final clinical database will report interpretations according to the most recent CLSI M100 
and EUCAST interpretations regardless of what the breakpoints were at the time the isolate was 
initially tested. 
• 
A NG isolate will be defined as MDR if it is reported as resistant (or nonsusceptible for drugs 
without a resistant breakpoint) to: 
o At least 1 of the antibiotic classes currently generally recommended for treatment 
(ESCs [oral and injectable ones are considered separately] and spectinomycin) and ≥2 
of the following: penicillin, ciprofloxacin, or azithromycin 
• 
A NG isolate will be defined as extensively-drug resistant (XDR) if it is reported as resistant) (or 
nonsusceptible for drugs without a resistant breakpoint) to: 
o ≥2 of the antibiotic classes currently generally recommended for treatment (ESCs [oral 
and injectable ones are considered separately] and spectinomycin) and 
o All 3 of the following: penicillin, ciprofloxacin, and azithromycin (Note: if isolate meets 
XDR criteria, MDR flag is not added) 
• 
 
Molecular Testing 
CCI


 
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• 
All N. gonorrhoeae isolates will be submitted to a 3rd party laboratory for whole genome 
sequencing and screened for mutations in the quinolone-resistance determinant region (QRDR) 
of gyrA, and gyrB (encodes for DNA gyrase), and parC and parE (encodes for topoisomerase IV) 
genes. 
• 
All isolates will also be subjected to molecular typing by multilocus sequence typing (MLST) and 
N. gonorrhoeae multiantigen sequence typing (NG-MAST) to determine clonality. 
• 
Additional molecular analysis for antibiotic resistance markers will be conducted on a subset of 
NG isolates based on strain specific susceptibility profiles and may include, but is not limited to: 
– Beta-lactams 
• 
Penicillinase genes (TEM-1) 
• 
mtrCDE and mtrR multidrug efflux pumps (Pen/tet/Mac/ceph R isolates) 
• 
penA and ponA (penicillin binding protein mutations) 
• 
penB (porins that effect influx of penicillins, cephalosporins and 
tetracycline) 
– Fluoroquinolone resistance 
• 
Expression of NorM 
– Macrolide resistance 
• 
macAB and repressor gene promoter and/or coding sequences 
• 
23S rRNA (peptidyltransferase loop of domain V) 
• 
MLSb genes (rRNA methylases) 
– Tetracycline resistance 
• 
rpsJ (ribosomal protein S10) 
• 
TetM (ribosomal protection protein) 
– Spectinomycin resistance 
• 
rpsE (30S ribosomal protein S5) 
Extra NAAT Specimens 


 
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Note: Sites are instructed to take one urogenital NAAT specimen for the central laboratory analysis per 
patient at any study visit. There may be instances where sites sampled both a urogenital aliquot (urine) 
and a urogenital swab specimen for the central laboratory urogenital NAAT at the same visit/timepoint. If 
both aliquot and swab records are available but the result for one of them is missing or cannot be 
determined, the record with the available result will be kept in the analysis. 
Data handling in instances where results are available for both specimen types will be as outlined below.  
a. Male patients: 
1. If both the aliquot (preferred specimen for male) and the swab is NG negative, report the 
aliquot negative result and omit the swab negative result. 
2. If both the aliquot and the swab are NG positive, report the aliquot positive result and omit the 
swab positive result. 
3. If one of the specimens is negative and the other positive, report the positive, regardless of 
the specimen type. (This would apply to any visit, for example, if at baseline the aliquot was 
reported as positive but at test of cure the aliquot was negative but the swab was positive, the 
positive swab result would be reported at TOC and the aliquot at baseline.) 
b. Female patients: 
1. If both the aliquot and the swab (preferred specimen for females) is negative, report the swab 
negative result and omit the aliquot negative result. 
2. If both the aliquot and the swab is positive, report the swab positive result and omit the aliquot 
positive result. 
3. If one of the specimens is negative and the other positive, report the positive, regardless of 
the specimen type. (This would apply to any visit, for example, if at baseline the swab was 
reported as positive but at test of cure the swab was negative but the aliquot was positive, the 
positive aliquot result would be reported at TOC and the swab at baseline.) 
Identifying Out-of-Stability samples 
If the culture procedure at the local laboratory date/time is >24 hours after the culture specimen collection 
date/time at the site, then the sample is out-of-stability: 
1. If NG has been isolated in that sample, then the sample can be used as any others to derive 
populations and microbiological responses/outcomes and will be identified as ‘Out of stability – 
NG Pos’. 
2. If NG has not been isolated in that sample, then it is not possible to determine if NG is truly 
absent or if it did not survive. Such results cannot be used to derive populations and 
microbiological responses/outcomes and will be identified as ‘Out of stability – NG Neg’. 
Corresponding TOC outcomes and responses will be unable to determine (failure). 
If missing or partial date/time information prevents determination of whether a sample is out-of-stability or 
not, it will be considered as out-of-stability. 


 
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12.4.3. 
Safety 
Adverse Events 
AEs of Special Interest (AESI) 
• 
Clostridium difficile events 
• 
Cardiovascular events 
• 
Gastrointestinal events 
• 
Acetylcholinesterase inhibition events 
 
 


 
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List of Cardiovascular AESIs Preferred Terms 
Pulmonary oil microembolism 
Atrioventricular node dispersion 
Peripheral revascularization 
Cardiac arrest 
Supraventricular extrasystoles 
Holiday heart syndrome 
Rebound tachycardia 
Anomalous atrioventricular excitation 
Cardio-respiratory arrest neonatal 
Bundle branch block 
Atrial conduction time prolongation 
Adams-Stokes syndrome 
Cardiac death 
Atrioventricular dissociation 
Paroxysmal arrhythmia 
Atrial flutter 
Cardiac flutter 
Prosthetic cardiac valve thrombosis 
Neonatal sinus bradycardia 
Heart valve incompetence 
Neonatal bradyarrhythmia 
Cardiac valve disease 
Sinus bradycardia 
Metastatic pulmonary embolism 
Bradycardia foetal 
Renal revascularisation surgery 
Junctional ectopic tachycardia 
Angina unstable 
Ventricular fibrillation 
Ventricular extrasystoles 
Accessory cardiac pathway 
Lenegre's disease 
Sinoatrial block 
Atrioventricular block 
Pulseless electrical activity 
Nodal arrhythmia 
Ventricular parasystole 
Rhythm idioventricular 
Paroxysmal atrioventricular block 
Nonreassuring foetal heart rate pattern 
Ogden syndrome 
Ventricular asystole 
Nodal rhythm 
Defect conduction intraventricular 
Bundle branch block left 
Atrial fibrillation 
Heart valve stenosis 
Tachycardia foetal 
Acute myocardial infarction 
Atrioventricular block first degree 
ECG signs of myocardial infarction 
Foetal arrhythmia 
Embolism arterial 
Neonatal tachycardia 
Pulmonary embolism 
Carcinoid heart disease 
Central bradycardia 
Cardiac valve replacement complication 
Sinus arrest 
Degenerative multivalvular disease 
Cardiac fibrillation 
Cardiac valve sclerosis 
Trifascicular block 
Cardiac valve abscess 
Ventricular tachycardia 
Newborn persistent pulmonary hypertension 
Accelerated idioventricular rhythm 
Deep vein thrombosis postoperative 
Bundle branch block bilateral 
Carotid revascularization 
Bundle branch block right 
Transmyocardial revascularization 
Bezold-Jarisch reflex 
Ventricular tachyarrhythmia 
Chronotropic incompetence 
Tachycardia 
Arrhythmia neonatal 
Torsade de pointes 
Inherited cardiac conduction disorder 
Lown-Ganong-Levine syndrome 
Baseline foetal heart rate variability disorder 
Conduction disorder 
Ventricular flutter 
Congenital supraventricular tachycardia 
Lambl's excrescences 
Pacemaker generated arrhythmia 
Periprocedural myocardial infarction 
Wolff-Parkinson-White syndrome 
Congenital pulmonary hypertension 
Long QT syndrome 
Portopulmonary hypertension 
Parasystole 
Deep vein thrombosis 
Cardiac arrest neonatal 
Revascularisation procedure 
Neonatal sinus tachycardia 
Cardiac failure congestive 
Foetal tachyarrhythmia 
Atrioventricular node dysfunction 
Cerebrovascular disorder 
Ventricular pre-excitation 
Pulmonary arterial hypertension 
Supraventricular tachyarrhythmia 
Post procedural pulmonary embolism 
Arrhythmia 
Pulmonary microemboli 
 


 
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Cerebral revascularization 
Supraventricular tachycardia 
Timothy syndrome 
Sinusoidal foetal heart rate pattern 
Heart alternation 
Bradyarrhythmia 
Reperfusion arrhythmia 
Tachycardia paroxysmal 
Foetal heart rate disorder 
Sinus tachycardia 
Atrial parasystole 
Wandering pacemaker 
Atrial tachycardia 
Withdrawal arrhythmia 
Bifascicular block 
Foetal heart rate acceleration abnormality 
Atrioventricular block complete 
Pacemaker syndrome 
Sudden cardiac death 
Structural valve deterioration 
Sinus node dysfunction 
Cardiac valve thickening 
Sudden death 
Post procedural myocardial infarction 
Cardio-respiratory arrest 
Pulmonary hypertension 
Arrhythmia supraventricular 
Obstetrical pulmonary embolism 
Neonatal tachyarrhythmia 
Heart block congenital 
Bradycardia 
Atrioventricular block second degree 
Congenital heart valve incompetence 
Extrasystoles 
Cardiac valve rupture 
Brugada syndrome 
Heart valve calcification 
Wolff-Parkinson-White syndrome congenital 
Cardiac valve discolouration 
BRASH syndrome 
Cardiac valve vegetation 
Ventricular arrhythmia 
Congenital heart valve disorder 
Foetal heart rate deceleration abnormality 
Myocardial infarction 
Long QT syndrome congenital 
Silent myocardial infarction 
Agonal rhythm 
Septic pulmonary embolism 
Frederick's syndrome 
Coronary revascularization 
Bradycardia neonatal 
Atrioventricular conduction time shortened 
Shone complex 
Sinus arrhythmia 
Transient ischaemic attack 
Tachyarrhythmia 
Cerebrovascular accident 
Postural orthostatic tachycardia syndrome 
 
 
 


 
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 List of Acetylcholinesterase Inhibition AESIs Preferred Terms 
Abdominal discomfort 
Generalised non-convulsive epilepsy 
Abdominal pain 
Generalised tonic-clonic seizure 
Abdominal pain lower 
Heart rate decreased 
Abdominal pain upper 
Hyperhidrosis 
Abdominal symptom 
Hyperkinesia 
Abdominal tenderness 
Hypocalcaemic seizure 
Asthma 
Hypoglycaemic seizure 
Atonic seizures 
Hyponatraemic seizure 
Atypical benign partial epilepsy 
Idiopathic generalised epilepsy 
Autonomic seizure 
Idiopathic partial epilepsy 
Bradyarrhythmia 
Irregular breathing 
Bradycardia 
Lacrimation increased 
Bronchial hyperreactivity 
Lafora's myoclonic epilepsy 
Bronchospasm 
Lennox-Gastaut syndrome 
Clonic convulsion 
Myoclonic epilepsy 
Cold sweat 
Nausea 
Convulsions local 
Night sweats 
Convulsive threshold lowered 
Partial seizures 
Defaecation urgency 
Partial seizures with secondary generalisation 
Diarrhoea 
Petit mal epilepsy 
Drooling 
Psychomotor hyperactivity 
Dyspnoea 
Retching 
Dyspnoea at rest 
Salivary hypersecretion 
Dyspnoea exertional 
Seizure 
Epigastric discomfort 
Seizure cluster 
Epilepsy 
Simple partial seizures 
Epilepsy with myoclonic-atonic seizures 
Status asthmaticus 
Faeces soft 
Status epilepticus 
Febrile convulsion 
Sweat gland disorder 
Febrile infection-related epilepsy syndrome 
Syncope 
Flatulence 
 
Focal dyscognitive seizures 
Tonic clonic movements 
Frequent bowel movements 
Tonic convulsion 
Frontal lobe epilepsy 
Unilateral bronchospasm 
Gastrointestinal disorder 
Vomiting 
Gastrointestinal pain 
Vomiting projectile 
Gastrointestinal tract irritation 
Wheezing 
Adverse Events with Missing Relationship or Missing Serious Indicator 
• If the relationship to study treatment is missing for a treatment-emergent AE (TEAE), then the TEAE 
will be considered related to the study treatment. 
• If the serious indicator “Was event serious?” is missing, the AE will be considered as SAE. 
• Adverse events with missing relationship or missing serious indicator will be presented as it is in 
listings but will be treated as related AEs or SAEs in summary tables. 
 
Laboratory Parameters 
If a laboratory value which is expected to have a numeric value for summary purposes, has a non-detectable 
level reported in the data base, where the numeric value is missing, but typically a character value starting 
with ‘<=’, ‘>=’, ‘>’, ‘<’ (or indicated as less than x or greater than x in the comment field) or is present, the 
number of significant digits (i.e. decimal places) in the observed values will be used to determine how much 
to add or subtract in order to impute the corresponding numeric value. 


 
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Laboratory Parameters 
1. Example 1: 2 significant digits = ‘<= x’ becomes x – 0.01 (Note: also applies to ‘<x’) 
2. Example 2: 1 significant digit = ‘>= x’ becomes x + 0.1 (Note: also applies to ‘>x’) 
3. Example 3: 0 significant digits = ‘<=x’ becomes x – 1 (Note: also applies to ‘>x’) 
 


 
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12.5. 
Appendix 5: Reporting Standards for Missing Data 
12.5.1. 
Premature Withdrawals 
Element 
Reporting Detail 
General 
• 
Participant study treatment completion is defined as if the participant has taken all 
doses of the study treatment and completed the TOC Visit. Participants who 
discontinue study treatment will not be considered withdrawn from the study and should 
attend the TOC and Follow-up Visits as applicable. 
• 
Participant study completion (i.e., as specified in the protocol) is defined as if the 
participant has completed all study visits including the Follow-up Visit. 
• 
Withdrawn participants will not be replaced in the study. 
• 
All available data from participants who were withdrawn from the study will be listed 
and data will be included in summary tables and figures as described in Section 5.6 on 
Analysis Visits. 
12.5.2. 
Handling of Missing Data 
Element 
Reporting Detail 
General 
• 
Missing data occurs when any requested data is not provided, leading to blank fields 
on the collection instrument: 
o These data will be indicated by the use of a “blank” in participant listing displays. 
Unless all data for a specific visit are missing in which case the data is excluded 
from the table. 
o Answers such as “Not applicable” and “Not evaluable” are not considered to be 
missing data and should be displayed as such. 
Primary and 
Secondary 
Efficacy 
• 
Participants who do not return for the TOC visit will be treated as failures. 
• 
Participants who withdraw from the study prior to TOC will be considered not 
achieving success for the microbiological response. Microbiological outcome for 
these participants will be imputed as failures. 
• 
Any participant in whom a determination of the baseline pathogen microbiological 
outcome cannot be made at TOC (e.g., no bacteriological sample taken for culture, 
sample lost, sample plated out of stability, etc.) will be considered as failures. 
Outliers 
• 
Any participants excluded from the summaries and/or statistical analyses will be 
documented along with the reason for exclusion in the clinical study report. 
12.5.2.1. 
Handling of Missing and Partial Dates 
Element 
Reporting Detail 
General 
• 
Partial dates will be displayed as captured in participant listing displays. 
Adverse 
Events 
• 
The eCRF allows for the possibility of partial dates (i.e., only month and year) to be 
recorded for AE start and end dates; that is, the day of the month may be missing. In 
such a case, the following conventions will be applied for calculating the time to onset 
and the duration of the event: 
o Missing Start Day: First of the month will be used unless this is before the start 
date of study treatment; in this case the study treatment start date will be used and 
hence the event is considered On-treatment as per Appendix 2 
o Missing Start Time: Midnight 0:00:00 will be used for AEs with missing start time to 
determine if it’s AChE-I. 


 
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Element 
Reporting Detail 
o Missing Stop Day: Last day of the month will be used, unless this is after the stop 
date of study treatment; in this case date the study treatment stop date will be 
used. 
• 
Completely missing start or end dates will remain missing, with no imputation applied. 
Consequently, time to onset and duration of such events will be missing. 
• 
Adverse events with entirely missing or unknown start dates will be assumed to be 
on-treatment and also treatment emergent for reporting purposes. 
Concomitant 
Medications/
Medical 
History 
• 
Partial dates for any concomitant medications recorded in the CRF will be imputed 
using the following convention: 
o If the partial date is a start date, a '01' will be used for the day and 'Jan' will be 
used for the month 
o If the partial date is a stop date, a '28/29/30/31' will be used for the day (dependent 
on the month and year) and 'Dec' will be used for the month 
• 
The recorded partial date will be displayed in listings. 


 
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12.6. 
Appendix 6: Values of Potential Clinical Importance 
12.6.1. 
ECG 
ECG Parameter 
Units 
Potential Clinically Important Range 
Lower 
Upper 
Absolute 
Absolute QTc Interval 
msec 
 
>450 
Absolute PR Interval 
msec 
< 110 
> 220 
Absolute QRS Interval 
msec 
< 75 
> 110 
NOTES: 
1. Represent further subdivisions of ECG values for analysis. 
12.6.2. 
Vital Signs 
Vital Sign Parameter 
(Absolute) 
Units 
Potentially Clinically Important Range 
Lower 
Upper 
Systolic Blood Pressure 
mmHg 
< 85 
> 160 
Diastolic Blood Pressure 
mmHg 
< 45 
> 100 
Heart Rate 
bpm 
< 40 
> 110 


 
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12.7. 
Appendix 7: Division of Microbiology and Infectious 
Diseases Toxicity Tables for Adverse Event Assessment 
12.7.1. 
Laboratory Values 
12.7.1.1. 
Adults 
For adults, laboratory abnormalities will be graded according to the modified US National institute 
of Allergy and Infectious Diseases Division of Microbiology and Infectious Diseases (DMID) criteria 
[DMID, 2007a]. Laboratory results are converted to SI units. 
HEMATOLOGY 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hemoglobin 
9.5 to 
10.5 gm/dL 
8.0 to 
9.4 gm/dL 
6.5 to 7.9 gm/dL 
<6.5 gm/dL 
Absolute Neutrophil 
Count 
1000 to 
1500 /mm3 
750 to 
999 /mm3` 
500 to 749 /mm3 
<500 /mm3 
Platelets 
75,000 to 
99,999 /mm3 
50,000 to 
74,999 /mm3 
20,000 to 
49,999 /mm3 
<20,000 /mm3 
White Blood Cells 
11,000 to 
13,000 /mm3 
13,001 to 
15,000 /mm3 
15,001 to 
30,000 /mm3 
>30,000 or <1000 /mm3 
% Polymorphonuclear 
Leukocytes + Band 
Cells 
>80% 
90 to 95% 
>95% 
N/A 
N/A=not applicable; ULN=upper limit of normal. 
 


 
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CHEMISTRIES 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Hyponatremia 
130 to 
135 mEq/L 
123 to 
129 mEq/L 
116 to 
122 mEq/L 
<116 mEq/L or abnormal 
sodium with mental 
status changes or 
seizures 
Hypernatremia 
146 to 
150 mEq/L 
151 to 
157 mEq/L 
158 to 
165 mEq/L 
>165 mEq/L or abnormal 
sodium with mental 
status changes or 
seizures 
Hypokalemia 
3.0 to 
3.4 mEq/L 
2.5 to 
2.9 mEq/L 
2.0 to 2.4 mEq/L 
or intensive 
replacement 
therapy of 
hospitalization 
required 
<2.0 mEq/L or abnormal 
potassium with paresis, 
ileus, or life-threatening 
arrhythmia 
Hyperkalemia 
5.6 to 
6.0 mEq/L 
6.1 to 
6.5 mEq/L 
6.6 to 7.0 mEq/L 
>7.0 mEq/L or abnormal 
potassium with 
life-threatening 
arrhythmia 
Hypoglycemia 
55 to 
64 mg/dL 
40 to 
54 mg/dL 
30 to 39 mg/dL 
<30 mg/dL or abnormal 
glucose with mental 
status changes or coma 
Hyperglycemia 
(nonfasting and no 
prior diabetes) 
116 to 
160 mg/dL 
161 to 
250 mg/dL 
251 to 
500 mg/dL 
>500 mg/dL or abnormal 
glucose with 
ketoacidosis or seizures 
Hypocalcemia 
(corrected for 
albumin) 
8.4 to 
7.8 mg/dL 
7.7 to 
7.0 mg/dL 
6.9 to 6.1 mg/dL 
<6.1 mg/dL or abnormal 
calcium with 
life-threatening 
arrhythmia or tetany 
Hypercalcemia 
(corrected for 
albumin) 
10.6 to 
11.5 mg/dL 
11.6 to 
12.5 mg/dL 
12.6 to 
13.5 mg/dL 
>13.5 mg/dL or 
abnormal calcium with 
life-threatening 
arrhythmia 
Hypomagnesemia 
1.4 to 
1.2 mEq/L 
1.1 to 
0.9 mEq/L 
0.8 to 0.6 mEq/L 
<0.6 mEq/L or abnormal 
magnesium with 
life-threatening 
arrhythmia 
Hyperbilirubinemia 
(when 
accompanied by 
any increase in 
other liver function 
test) 
1.1 to 
<1.25 × ULN 
1.25 to 
<1.5 × ULN 
1.5 to 
1.75 × ULN 
>1.75 × ULN 
Hyperbilirubinemia 
(when other liver 
function tests are 
1.1 to 
<1.5 × ULN 
1.5 to 
<2.0 × ULN 
2.0 to 
3.0 × ULN 
>3.0 × ULN 


 
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CHEMISTRIES 
in the normal 
range) 
Blood urea 
nitrogen  
1.25 to 
2.5 × ULN 
2.6 to 
5 × ULN 
5.1 to 10 × ULN 
>10 × ULN 
Creatinine 
1.1 to 
1.5 × ULN 
1.6 to 
3.0 × ULN 
3.1 to 
6.0 × ULN 
>6 × ULN or dialysis 
required 
Rx=therapy; ULN=upper limit of normal. 


 
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CHEMISTRIES 
ENZYMES 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Aspartate aminotransferase (AST) 1.1 to 
<2.0 × ULN 
2.0 to 
<3.0 × ULN 
3.0 to 
8.0 × ULN 
>8.0 × ULN 
Alanine aminotransferase (ALT) 
1.1 to 
<2.0 × ULN 
2.0 to 
<3.0 × ULN 
3.0 to 
8.0 × ULN 
>8.0 × ULN 
Alkaline Phosphatase 
1.1 to 
<2.0 × ULN 
2.0 to 
<3.0 × ULN 
3.0 to 
8.0 × ULN 
>8.0 × ULN 
ULN=upper limit of normal. 
URINALYSIS 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Proteinuria 
1+ or 
200 mg to 1 gm 
loss/day 
2 to 3+ or 
1 to 2 gm 
loss/day 
4+ or 
2 to 3.5 gm loss/day 
Nephrotic syndrome 
or 
>3.5 gm loss/day 
Hematuria 
Microscopic only 
<10 RBC/hpf 
Gross, no 
clots 
>10 RBC/hpf 
Gross, with or 
without clots, 
or red blood cells 
casts 
Obstructive or  
required transfusion 
HPF=high powered field; RBC=red blood cells. 
 
12.7.1.2. 
Adolescent Participants 
For adolescent participants over 12 years of age and less than 18 years of age, the adult 
DMID will be applied for all parameters with the exception of serum creatinine which 
will be graded programmatically according to the modified DMID pediatric toxicity 
criteria [DMID, 2007b]. Laboratory results are converted to SI units. 
CHEMISTRIES 
 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Creatinine 
1.0 to 1.7 x ULN  
1.8 to 2.4 x ULN  
2.5 to 3.5 x ULN  
>3.5 x ULN 
ULN=upper limit of normal. 


 
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12.8. 
Appendix 8: Abbreviations & Trademarks 
12.8.1. 
Abbreviations 
Abbreviation 
Description 
ADaM 
Analysis Data Model 
AE 
Adverse Event 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
AR 
Adverse Reaction 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical 
BMI 
Body Mass Index 
CDISC 
Clinical Data Interchange Standards Consortium 
CFU 
Colony-Forming Units 
CI 
Confidence Interval 
CLSI 
Clinical and Laboratory Standards Institute 
CT 
Chlamydia trachomatis 
DBF 
Database Freeze 
DBR 
Database Release 
DMID 
Division of Microbiology and Infectious Diseases 
DP 
Decimal Places 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EUCAST 
European Committee on Antimicrobial Susceptibility Testing 
FDA 
Food and Drug Administration 
GSK 
GlaxoSmithKline 
HDL 
Headline TFL 
ICE 
Intercurrent Event 
ICH 
International Conference on Harmonization 
IDSL 
Integrated Data Standards Library 
ITT 
Intent-To-Treat 
LLN 
Lower Limit of Normal 
MALDI-TOF MS 
Matrix assisted laser desorption ionization-time of flight mass spectrometry 
Mgen 
Mycoplasma genitalium 
MIC 
Minimum Inhibitory Concentration 
MN 
Miettinen and Nurminen 
NAAT 
Nucleic Acid Amplification Test 
NG 
Neisseria gonorrhoeae 
RAP 
Reporting and Analysis Plan 
SAC 
Statistical Analysis Complete 
SAE 
Serious AE 
SD 
Standard Deviation 
SDTM 
Study Data Tabulation Model 
SOC 
System Organ Class 
SRM 
Study Reference Manual 


 
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Abbreviation 
Description 
TEAE 
Treatment-emergent AE 
TFL 
Table/Figure/Listing 
TOC 
Test-of-Cure 
ULN 
Upper Limit of Normal 
WBC 
White Blood Cell 
12.8.2. 
Trademarks 
Trademarks of the GlaxoSmithKline 
Group of Companies 
 
Trademarks not owned by the 
GlaxoSmithKline Group of Companies 
GSKDrug 
 
MedDRA 
 
 
SAS 
 
 
WHODrug 


 
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12.9. 
Appendix 9: List of Data Displays 
12.9.1. 
Data Display Numbering 
The following numbering will be applied for RAP generated displays: 
Section 
Tables 
Figures 
Study Population 
1.101 to 1.502 
1.101 to 1.102 
Efficacy 
2.101 to 2.340 
2.101 to 2.202 
Safety 
3.101 to 3.506 
3.101 to 3.403 
Section 
Listings 
ICH Listings 
101 to 1303 
12.9.2. 
Mock Example Shell Referencing 
Non IDSL specifications will be referenced as indicated and if required example mock-up 
displays provided in each tables, listings, and figures shells. 
Section 
Figure 
Table 
Listing 
Study Population 
POP_Fn 
POP_Tn 
POP_Ln 
Efficacy 
EFF_Fn 
EFF_Tn 
EFF_Ln 
Safety 
SAFE_Fn 
SAFE_Tn 
SAFE_Ln 
NOTES:  
• 
Non-Standard displays are indicated in the ‘IDSL / Example Shell’ or ‘Programming Notes’ column as ‘[Non-
Standard] + Reference.’ 
12.9.3. 
Deliverables 
Delivery  
Description 
DS 
During Study 
SAC 
Final Statistical Analysis Complete 
NOTE: 
• 
A blinded dry run will be performed during the study (DS). 
• 
For outputs presented by phenotypic/genotypic subcategories or MIC susceptibility by drugs sort according to 
the alphabetic order of the categories/drugs. 
• 
Some TFLs designated as being for SAC deliverable may be provided at All Analyses Complete (i.e. all output to 
support the writing of the CSR and disclosures). The final list of TFLs to be provided at SAC and AAC will be 
documented outside of the RAP. 


 
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12.9.4. 
Study Population Tables 
Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
Participant Disposition 
1.101.  
Intent-to-
Treat 
ES1 
Summary of Participant Disposition 
  
DS, SAC 
1.102.  
Micro-ITT 
ES1 
Summary of Participant Disposition 
  
DS, SAC 
1.103.  
Intent-to-
Treat 
SD1 
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment 
 
DS, SAC 
1.104.  
Micro-ITT 
SD1 
Summary of Treatment Status and Reasons for Discontinuation 
of Study Treatment 
 
DS, HDL, SAC 
1.105.  
Intent-to-
Treat 
NS1 
Summary of Number of Participants Enrolled by Region, 
Country, and Site ID  
  
DS, SAC 
1.106.  
Screened 
ES6 
Summary of Screen Status and Reasons for Screening Failures 
 
DS, SAC 
1.107.  
Screened 
SP1 
Summary of Study Populations 
  
DS, HDL, SAC 
1.108.  
Intent-to-
Treat 
SP2 
Summary of Exclusions from Study Population 
 
DS, SAC 
Protocol Deviation 
1.201.  
Intent-to-
Treat 
DV1 
Summary of Important Protocol Deviations 
 
DS, SAC 
Demographic and Baseline Characteristics 
1.301.  
Intent-to-
Treat 
DM1 
Summary of Demographic Characteristics 
 
DS, SAC 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
1.302.  
Micro-ITT 
DM1 
Summary of Demographic Characteristics 
 
DS, HDL, SAC 
1.303.  
Intent-to-
Treat 
DM6 
Summary of Race and Racial Combinations 
 
DS, SAC 
1.304.  
Intent-to-
Treat 
DM11 
Summary of Age Ranges 
 
DS, SAC 
1.305.  
Intent-to-
Treat 
POP_T1 
Summary of Disease Characteristics and Renal Impairment at 
Baseline 
Summarized by body site. 
DS, SAC 
1.306.  
Intent-to-
Treat 
MH4 
Concordance of Local and Central Laboratory Culture 
Identification of NG at Baseline Visit 
Numbers are determined using the 
local and central laboratory 
identification results from NG 
culture. By body site 
DS, SAC 
1.307.  
Intent-to-
Treat 
MH4 
Concordance of Central Laboratory Culture Identification and 
Central Laboratory NAAT NG Test Result at Baseline Visit 
Numbers are determined using the 
central lab NAAT and central lab 
culture results for NG only. By body 
site. 
DS, SAC 
1.308.  
Intent-to-
Treat 
POP_T2 
Summary of Recovery Rate for NG at Baseline Visit by Culture 
(CLSI) 
Number/Rates are determined 
using the central laboratory 
identification for NG; summarized 
by sex and sexual orientation, body 
site and age 
Overall and by 
phenotypic/genotypic subcategory 
DS, SAC 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
1.309.  
Intent-to-
Treat 
POP_T2 
Summary of Recovery Rate for NG at Baseline Visit by Culture 
(EUCAST) 
Number/Rates are determined 
using the central laboratory 
identification for NG; summarized 
by sex and sexual orientation, body 
site and age 
Overall and by 
phenotypic/genotypic subcategory 
DS, SAC 
1.310.  
Intent-to-
Treat 
MH1 
Summary of Past and Current Medical Conditions 
 
DS, SAC 
1.311.  
Micro-ITT 
MH1 
Summary of Past and Current Medical Conditions 
 
DS, SAC 
1.312.  
Intent-to-
Treat 
LB1 
Summary of Serology Results  
  
DS, SAC 
1.313.  
Micro-ITT 
LB1 
Summary of Serology Results  
  
DS, SAC 
1.314.  
Intent-to-
Treat 
SU1 
Summary of Substance Use 
  
DS, SAC 
1.315.  
Micro ITT 
SU1 
Summary of Substance Use 
  
DS, SAC 
1.316.  
Intent-to-
Treat 
POP_T3 
Summary of Social Sexual History at Baseline 
Includes recreational drug use, 
number of sexual partners 
DS, SAC 
1.317.  
Micro ITT 
POP_T3 
Summary of Social Sexual History at Baseline 
Includes recreational drug use, 
number of sexual partners 
DS, HDL, SAC 
Prior and Concomitant Medications 
1.401 
Intent-to-
Treat 
CM1 
Summary of Prior Medications 
Subset this table by prior antibiotics 
and prior medications  
DS, SAC 
1.402 
Micro-ITT 
CM1 
Summary of Prior Medications 
Subset this table by prior antibiotics 
and prior medications  
 


 
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Study Population Tables 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
1.403 
Intent-to-
Treat 
CM1 
Summary of Concomitant Medications 
Subset this table: display separate 
summaries for systemic 
concomitant medications, non-
systemic concomitant medications, 
systemic antibiotics taken for the 
disease under study, systemic 
antibiotics taken for another 
disease/condition and prohibited 
(non-antibiotic) medications 
DS, SAC 
1.404 
Micro-ITT 
CM1 
Summary of Concomitant Medications 
Subset this table: display separate 
summaries for systemic 
concomitant medications, non-
systemic concomitant medications, 
systemic antibiotics taken for the 
disease under study, systemic 
antibiotics taken for another 
disease/condition and prohibited 
(non-antibiotic) medications 
DS, SAC 
1.405 
Micro-ITT 
- 
Summary of Participants Mis-stratified or Randomized Pooled 
Strata is Not Equal to Actual Pooled Strata 
 
DS, SAC 
Others 
1.501 
Intent-to-
Treat 
NS1 
Summary of Number of Participants Enrolled by Country and 
Site ID Relative to COVID-19 Pandemic Measure 
 
DS, SAC 
1.502 
Intent-to-
Treat 
PAN4 
Summary of COVID-19 Pandemic Visit Impacts 
 
DS, SAC 
 


 
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12.9.5. 
Study Population Figures 
Study Population: Figures 
No. 
Population 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
1.101 
Intent-to-Treat 
PKPL1P 
Bar Plot of NG Isolates Recovered at Baseline 
Categorized by body site 
DS, SAC 
1.102 
Intent-to-Treat 
PKPL1P 
Bar Plot of Social Sexual History at Baseline 
Categorized sexual orientation, 
recreational drug use, and # of 
sexual partners 
DS, SAC 
 
12.9.6. 
Efficacy Tables 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Microbiological Response 
2.101. 
Micro-ITT 
EFF_T1 
Analysis of Microbiological Outcome and Response Rate of 
Urogenital Gonorrhea at the TOC Visit 
Only for urogenital site and NG 
DS, HDL, SAC 
2.102. 
Micro-ITT 
EFF_T1 
Treatment by Strata Tests of Homogeneity for Percent of 
Participants with Microbiological Success of Urogenital Gonorrhea 
at the TOC Visit 
 
DS, SAC 
2.103. 
 ME 
EFF_T1 
Summary of Microbiological Outcome and Response of Urogenital 
Gonorrhea at the TOC Visit 
Only for urogenital site and NG 
DS, HDL, SAC 
2.104. 
Micro-ITT 
EFF_T1 
Sensitivity Analysis of Microbiological Outcome and Response of 
Urogenital Gonorrhea at the TOC Visit with Multiple Imputation 
 
DS, SAC 
2.105. 
Micro-ITT 
EFF_T2 
Sensitivity Analysis of Microbiological Outcome and Response of 
Urogenital Gonorrhea at the TOC Visit with Tipping Point Analysis 
 
DS, SAC 


 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.106. 
Micro-ITT  
(CAPA) 
EFF_T1 
Supplementary Analysis of Microbiological Outcome and Response 
at the TOC Visit (Excluding Sites with CAPA Exclusion 
Requirements) 
This will be produced for the 
primary analysis population 
subset to exclude Sites with 
CAPA Exclusion Requirements 
DS, SAC 
2.107. 
Micro-ITT 
EFF_T1 
Summary of Microbiological Outcome and Response of Urogenital 
Gonorrhea at the TOC Visit by Actual Strata 
For urogenital site and NG in the 
Actual strata (age/sex and 
sexual orientation/age*sex and 
sexual orientation) 
DS, SAC 
2.108. 
 ME 
EFF_T1 
Summary of Microbiological Outcome and Response of Urogenital 
Gonorrhea at the TOC Visit by Actual Strata 
For urogenital site and NG in the 
Actual strata (age/sex and 
sexual orientation/age*sex and 
sexual orientation) 
DS, SAC 
2.109. 
Micro-ITT 
EFF_T1 
Summary of Microbiological Outcome and Response of Urogenital 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups -CLSI) 
For urogenital site and NG in the 
other strata specified in RAP, 
including Sex and Sexual 
Orientation. Include phenotypic 
and genotypic subcategory 
analysis for subgroups including 
age, sex and sexual orientation, 
region, country and FDA region 
DS, SAC 
2.110. 
 ME 
EFF_T1 
Summary of Microbiological Outcome and Response of Urogenital 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups -CLSI) 
For urogenital site and NG in the 
other strata specified in RAP, 
including Sex and Sexual 
Orientation. Include phenotypic 
and genotypic subcategory 
analysis for subgroups including 
age, sex and sexual orientation, 
region, country and FDA region 
DS, SAC 


 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.111 
Micro-ITT 
EFF_T1 
Summary of Microbiological Outcome and Response of Urogenital 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups – EUCAST) 
For urogenital site and NG in the 
other strata specified in RAP, 
including Sex and Sexual 
Orientation. Include phenotypic 
and genotypic subcategory 
analysis for subgroups including 
age, sex and sexual orientation, 
region, country 
DS, SAC 
2.112 
 ME 
EFF_T1 
Summary of Microbiological Outcome and Response of Urogenital 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups - EUCAST) 
For urogenital site and NG in the 
other strata specified in RAP, 
including Sex and Sexual 
Orientation. Include phenotypic 
and genotypic subcategory 
analysis for subgroups including 
age, sex and sexual orientation, 
region, country and FDA region 
DS, SAC 
2.113 
Micro-ITT  
EU 
EFF_T1 
Sensitivity Analysis of Microbiological Outcome and Response Rate 
of Urogenital Gonorrhea at the TOC Visit Using EUCAST 
Breakpoints 
Only for urogenital site and NG. 
Conditional output: if the Micro-
ITT EUCAST population is the 
same as the Micro-ITT 
population then this output does 
not need to be produced. 
DS, SAC 
2.201. 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T1 
Summary of Microbiological Outcome and Response of Pharyngeal 
and Rectal Gonorrhea at the TOC Visit 
Only for pharyngeal and rectal 
body site and NG 
DS, SAC 


 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.202. 
 ME Rectal, 
ME 
Pharyngeal 
EFF_T1 
Summary of Microbiological Outcome and Response of Pharyngeal 
and Rectal Gonorrhea at the TOC Visit 
Only for pharyngeal and rectal 
body site and NG 
DS, SAC 
2.203. 
Micro-ITT 
Rectal 
EFF_T1 
Summary of Microbiological Outcome and Response of Rectal 
Gonorrhea at the TOC Visit by Actual Strata 
Only for rectal body site and NG 
for Actual strata (sex and sexual 
orientation, age) 
DS, SAC 
2.204. 
 ME Rectal 
EFF_T1 
Summary of Microbiological Outcome and Response of Rectal 
Gonorrhea at the TOC Visit by Actual Strata 
Only for rectal body site and NG 
for Actual strata (sex and sexual 
orientation, age) 
DS, SAC 
2.205. 
Micro-ITT 
Rectal 
EFF_T1 
Summary of Microbiological Outcome and Response of Rectal 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups - CLSI) 
Only for rectal body site and NG 
in the other strata specified in 
RAP 
DS, SAC 
2.206. 
 ME Rectal 
EFF_T1 
Summary of Microbiological Outcome and Response of Rectal 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups - CLSI) 
Only for rectal body site and NG 
in the other strata specified in 
RAP 
DS, SAC 
2.207. 
Micro-ITT 
Rectal 
EFF_T1 
Summary of Microbiological Outcome and Response of Rectal 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups - EUCAST)  
Only for rectal body site and NG 
in the other strata specified in 
RAP 
DS, SAC 
2.208. 
 ME Rectal 
EFF_T1 
Summary of Microbiological Outcome and Response of Rectal 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups - EUCAST) 
Only for rectal body site and NG 
in the other strata specified in 
RAP 
DS, SAC 
2.209. 
Micro-ITT 
Pharyngeal 
EFF_T1 
Summary of Microbiological Outcome and Response of Pharyngeal 
Gonorrhea at the TOC Visit by Actual Strata 
Only for pharyngeal body site 
and NG for Actual Strata (sex 
and sexual orientation, age) 
DS, SAC 


 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.210. 
 ME 
Pharyngeal 
EFF_T1 
Summary of Microbiological Outcome and Response of Pharyngeal 
Gonorrhea at the TOC Visit by Actual Strata 
Only for pharyngeal body site 
and NG for Actual Strata (sex 
and sexual orientation, age) 
DS, SAC 
2.211. 
Micro-ITT 
Pharyngeal 
EFF_T1 
Summary of Microbiological Outcome and Response of Pharyngeal 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups - CLSI) 
Only for pharyngeal body site 
and NG in the other strata 
specified in RAP 
DS, SAC 
2.212. 
 ME 
Pharyngeal 
EFF_T1 
Summary of Microbiological Outcome and Response of Pharyngeal 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups - CLSI) 
Only for pharyngeal body site 
and NG in the other strata 
specified in RAP 
DS, SAC 
2.213. 
Micro-ITT 
Pharyngeal 
EFF_T1 
Summary of Microbiological Outcome and Response of Pharyngeal 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups - EUCAST) 
Only for pharyngeal body site 
and NG in the other strata 
specified in RAP 
DS, SAC 
2.214. 
 ME 
Pharyngeal 
EFF_T1 
Summary of Microbiological Outcome and Response of Pharyngeal 
Gonorrhea at the TOC Visit by Other Subgroups (Phenotypic 
Subgroups - EUCAST) 
Only for pharyngeal body site 
and NG in the other strata 
specified in RAP 
DS, SAC 
2.215. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal  
EFF_T1 
Summary of Microbiological Outcome and Response for NG at TOC 
Visit by Body Site 
Include all body sites urogenital, 
rectal, pharyngeal 
DS, SAC 
2.216. 
ME, 
ME Rectal, 
ME 
Pharyngeal 
EFF_T1 
Summary of Microbiological Outcome and Response for NG at TOC 
Visit by Body Site 
Include all body sites urogenital, 
rectal, pharyngeal 
DS, SAC 


 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
Bacteriology Assessments and Microbiological Outcome and Response 
2.30
101 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
(CLSI) 
By body site. 
DS, SAC 
2.30
102 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Geographic Location (CLSI) 
By body site and region 
By body site and country 
By body site and United States 
region 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
103 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Sex and Sexual Orientation (CLSI) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
104 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Phenotypic/Genotypic Subgroups (CLSI) 
By body site and 
phenotype/genotype 
DS, SAC 


 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.30
201 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
(CLSI) 
By body site. 
DS, SAC 
2.30
202 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Geographic Location (CLSI) 
By body site and region 
By body site and country 
By body site and United States 
region 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
203 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Sex and Sexual Orientation (CLSI) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
204 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Phenotypic/Genotypic Subgroups (CLSI) 
By body site and 
phenotype/genotype 
DS, SAC 
2.30
301 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
(EUCAST) 
By body site. 
DS, SAC 


 
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Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.30
302 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Geographic Location (EUCAST) 
By body site and region 
By body site and country 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
303 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Sex and Sexual Orientation (EUCAST) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
304 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Phenotypic/Genotypic Subgroups (EUCAST) 
By body site and 
phenotype/genotype 
DS, SAC 
2.30
401 
ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
(EUCAST) 
By body site. 
DS, SAC 
2.30
402 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Geographic Location (EUCAST) 
By body site and region 
By body site and country 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 


 
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109 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.30
403 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Sex and Sexual Orientation (EUCAST) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
404 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of MICs and Susceptibility Results against NG by Visit 
and Phenotypic/Genotypic Subgroups (EUCAST) 
By body site and 
phenotype/genotype 
DS, SAC 
2.30
501 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit (CLSI) 
By body site. 
DS, SAC 
2.30
502 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Geographic Location (CLSI) 
By body site and region 
By body site and country 
By body site and United States 
region 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
503 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Sex and Sexual Orientation (CLSI) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
110 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.30
504 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Phenotypic/Genotypic Subgroups (CLSI) 
By body site and 
phenotype/genotype 
DS, SAC 
2.30
601 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit (CLSI) 
By body site. 
DS, SAC 
2.30
602 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Geographic Location (CLSI) 
By body site and region 
By body site and country 
By body site and United States 
region 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
603 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Sex and Sexual Orientation (CLSI) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
604 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Phenotypic/Genotypic Subgroups (CLSI) 
By body site and 
phenotype/genotype 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
111 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.30
701 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit (EUCAST) 
By body site. 
DS, SAC 
2.30
702 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Geographic Location (EUCAST) 
By body site and region 
By body site and country 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
703 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Sex and Sexual Orientation (EUCAST) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
704 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Phenotypic/Genotypic Subgroups (EUCAST) 
By body site and 
phenotype/genotype 
DS, SAC 
2.30
801 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit (EUCAST) 
By body site. 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
112 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.30
802 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Geographic Location (EUCAST) 
By body site and region 
By body site and country 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
803 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Sex and Sexual Orientation (EUCAST) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
804 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T3 
Summary of Disk Diffusion Results and Susceptibility against NG by 
Visit and Phenotypic/Genotypic Subgroups (EUCAST) 
By body site and 
phenotype/genotype 
DS, SAC 
2.30
901 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug (CLSI) 
By body site. 
DS, SAC 
2.30
902 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and Geographic 
Location (CLSI) 
By body site and region 
By body site and country 
By body site and United States 
region 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
113 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.30
903 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and Sex and Sexual 
Orientation (CLSI) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.30
904 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and 
Phenotypic/Genotypic Subgroups (CLSI) 
By body site and 
phenotype/genotype 
DS, SAC 
2.31
001 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug (CLSI) 
By body site. 
DS, SAC 
2.31
002 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and Geographic 
Location (CLSI) 
By body site and region 
By body site and country 
By body site and United States 
region 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.31
003 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and Sex and Sexual 
Orientation (CLSI) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
114 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.31
004 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and 
Phenotypic/Genotypic Subgroups (CLSI) 
By body site and 
phenotype/genotype 
DS, SAC 
2.31
101 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug (EUCAST) 
By body site. 
DS, SAC 
2.31
102 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and Geographic 
Location (EUCAST) 
By body site and region 
By body site and country 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.31
103 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and Sex and Sexual 
Orientation (EUCAST) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.31
104 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and 
Phenotypic/Genotypic Subgroups (EUCAST) 
By body site and 
phenotype/genotype 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
115 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.31
201 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug (EUCAST) 
By body site. 
DS, SAC 
2.31
202 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and Geographic 
Location (EUCAST) 
By body site and region 
By body site and country 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.31
203 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and Sex and Sexual 
Orientation (EUCAST) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.31
204 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T4 
Distribution of MIC Results against NG by Drug and 
Phenotypic/Genotypic Subgroups (EUCAST) 
By body site and 
phenotype/genotype 
DS, SAC 
2.31
301 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug (CLSI) 
By body site. 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
116 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.31
302 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and 
Geographic Location (CLSI) 
By body site and region 
By body site and country 
By body site and United States 
region 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.31
303 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and Sex 
and Sexual Orientation (CLSI) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.31
304 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and 
Phenotypic/Genotypic Subgroups (CLSI) 
By body site and 
phenotype/genotype 
DS, SAC 
2.31
401 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug (CLSI) 
By body site. 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
117 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.31
402 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and 
Geographic Location (CLSI) 
By body site and region 
By body site and country 
By body site and United States 
region 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.31
403 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and Sex 
and Sexual Orientation (CLSI) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.31
404 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and 
Phenotypic/Genotypic Subgroups (CLSI) 
By body site and 
phenotype/genotype 
DS, SAC 
2.31
501 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug (EUCAST) By body site. 
DS, SAC 
2.31
502 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and 
Geographic Location (EUCAST) 
By body site and region 
By body site and country 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
118 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.31
503 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and Sex 
and Sexual Orientation (EUCAST) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.31
504 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and 
Phenotypic/Genotypic Subgroups (EUCAST) 
By body site and 
phenotype/genotype 
DS, SAC 
2.31
601 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug (EUCAST) By body site. 
DS, SAC 
2.31
602 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and 
Geographic Location (EUCAST) 
By body site and region 
By body site and country 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 
2.31
603 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and Sex 
and Sexual Orientation (EUCAST) 
By body site and sex and sexual 
orientation 
By phenotype/genotype within 
each subgroup (for urogenital 
site only) 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
119 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.31
604 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T5 
Distribution of Disk Diffusion Results against NG by Drug and 
Phenotypic/Genotypic Subgroups (EUCAST) 
By body site and 
phenotype/genotype 
DS, SAC 
2.317. 
Intent-to-
Treat 
EFF_T6 
Summary of Reduction in Susceptibility with >= 4-fold Increase in 
MIC by Drug for Neisseria gonorrhoeae 
By body site. 
DS, HDL, SAC 
2.318. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T7 
Summary of Microbiological Success at TOC Visit by MIC Result 
(CLSI) against NG at Baseline 
By MIC result for Gepotidacin, 
Azithromycin, and Ceftriaxone  
By phenotypic/genotypic 
subcategories 
DS, SAC 
2.319. 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T7 
Summary of Microbiological Success at TOC Visit by MIC Result 
(CLSI) against NG at Baseline 
By MIC result for Gepotidacin, 
Azithromycin, and Ceftriaxone  
DS, SAC 
2.320. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T7 
Summary of Microbiological Success at TOC Visit by MIC Result 
(EUCAST) against NG at Baseline 
By MIC result for Gepotidacin, 
Azithromycin, and Ceftriaxone  
By phenotypic/genotypic 
subcategories 
DS, SAC 
2.321. 
ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T7 
Summary of Microbiological Success at TOC Visit by MIC Result 
(EUCAST) against NG at Baseline 
By MIC result for Gepotidacin, 
Azithromycin, and Ceftriaxone  
By phenotypic/genotypic 
subcategories 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
120 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.322. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T8 
Summary of Microbiological Success at TOC Visit by Disk Diffusion 
Result against NG at Baseline 
 
DS, SAC 
2.323. 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T8 
Summary of Microbiological Success at TOC Visit by Disk Diffusion 
Result against NG at Baseline 
 
DS, SAC 
2.324. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T8 
Summary of Microbiological Success at TOC Visit by Susceptibility 
Interpretation (based on CLSI MIC) against NG at Baseline 
 
DS, SAC 
2.325. 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T8 
Summary of Microbiological Success at TOC Visit by Susceptibility 
Interpretation (based on CLSI MIC) against NG at Baseline 
 
DS, SAC 
2.326. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T8 
Summary of Microbiological Success at TOC Visit by Susceptibility 
Interpretation (based on EUCAST MIC) against NG at Baseline 
 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
121 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.327. 
ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T8 
Summary of Microbiological Success at TOC Visit by Susceptibility 
Interpretation (based on EUCAST MIC) against NG at Baseline 
 
DS, SAC 
2.328. 
Intent-to-
Treat 
EFF_T9 
Summary of Gram Stain Results by Visit 
 
DS, SAC 
2.329. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T1 
Summary of NAAT Outcome and Response for NG at TOC Visit  
By body site 
DS, SAC 
2.330. 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T1 
Summary of NAAT Outcome and Response for NG at TOC Visit  
By body site 
DS, SAC 
2.331. 
ME NAAT 
TOC, ME 
NAAT TOC 
Rectal, ME 
NAAT TOC 
Pharyngeal 
EFF_T1 
Summary of NAAT Outcome and Response for NG at TOC Visit  
By body site 
DS, SAC 
2.332. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T1 
Summary of NAAT Outcome and Response for NG at TOC Visit by 
Actual Strata and Other Subgroups (Phenotypic Subgroups - CLSI) 
By body site  Actual strata 
(age/sex and sexual 
orientation/age*sex and sexual 
orientation) and other relevant 
subgroups defined in Section 
5.4.2 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
122 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.333. 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T1 
Summary of NAAT Outcome and Response for NG at TOC Visit by 
Actual Strata and Other Subgroups (Phenotypic Subgroups - CLSI) 
  
By body site   Actual strata 
(age/sex and sexual 
orientation/age*sex and sexual 
orientation) and other relevant 
subgroups defined in Section 
5.4.2 
DS, SAC 
2.334. 
ME NAAT 
TOC, ME 
NAAT TOC 
Rectal, ME 
NAAT TOC 
Pharyngeal 
EFF_T1 
Summary of NAAT Outcome and Response for NG at TOC Visit by 
Actual Strata and Other Subgroups (Phenotypic Subgroups - CLSI) 
  
By body site   Actual strata 
(age/sex and sexual 
orientation/age*sex and sexual 
orientation) and other relevant 
subgroups defined in Section 
5.4.2 
 
DS, SAC 
2.335. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T1 
Summary of NAAT Outcome and Response for NG at TOC Visit by 
Actual Strata and Other Subgroups (Phenotypic Subgroups - 
EUCAST) 
By body site  Actual strata 
(age/sex and sexual 
orientation/age*sex and sexual 
orientation) and other relevant 
subgroups defined in Section 
5.4.2 
DS, SAC 
2.336. 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
EFF_T1 
Summary of NAAT Outcome and Response for NG at TOC Visit by 
Actual Strata and Other Subgroups (Phenotypic Subgroups - 
EUCAST) 
  
By body site   Actual strata 
(age/sex and sexual 
orientation/age*sex and sexual 
orientation) and other relevant 
subgroups defined in Section 
5.4.2 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
123 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.337. 
ME NAAT 
TOC, ME 
NAAT TOC 
Rectal, ME 
NAAT TOC 
Pharyngeal 
EFF_T1 
Summary of NAAT Outcome and Response for NG at TOC Visit by 
Actual Strata and Other Subgroups (Phenotypic Subgroups - 
EUCAST) 
  
By body site   Actual strata 
(age/sex and sexual 
orientation/age*sex and sexual 
orientation) and other relevant 
subgroups defined in Section 
5.4.2 
 
DS, SAC 
2.338. 
Micro-ITT, 
Micro-ITT 
Pharyngeal 
EFF_T1 
Summary of NAAT Outcome and Response for Pharyngeal NG and 
Urogenital Mgen at FU Visit 
 
DS, SAC 
2.339. 
ME NAAT 
FU Mgen, 
ME NAAT 
FU 
Pharyngeal 
EFF_T1 
Summary of NAAT Outcome and Response for Pharyngeal NG and 
Urogenital Mgen at FU Visit 
 
DS, SAC 
2.340. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
EFF_T10 
Summary of NG Beta-Lactamase Production by Visit 
 
DS, SAC 
2.341. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
 
Summary of Missing Data by visit for subjects with Unable to 
Determine Microbiological outcomes at TOC 
 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
124 
Efficacy: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.342. 
Micro-ITT 
 
Summary of Non-Study Systemic Antibiotic Use During Study 
Participation 
 
DS, SAC 
2.343. 
Micro-ITT, 
Micro-ITT 
Rectal, 
Micro-ITT 
Pharyngeal 
 
Summary of Baseline Pathogen Resistance (CLSI) 
 
DS, SAC 
2.344. 
Micro-ITT, 
Micro-ITT 
Rectal, 
Micro-ITT 
Pharyngeal 
 
Summary of Baseline Pathogen Resistance (EUCAST) 
 
DS, SAC 
2.345. 
Intent-to-
Treat 
EFF_T6 
Summary of Reduction in Susceptibility to Study Treatment by 
Phenotypic/Genotypic Subgroups (CLSI) 
By body site and 
phenotypic/genotypic subgroup. 
DS, SAC 
2.346. 
Intent-to-
Treat 
EFF_T6 
Summary of Reduction in Susceptibility to Study Treatment by 
Phenotypic/Genotypic Subgroups (EUCAST) 
By body site and 
phenotypic/genotypic subgroup. 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
125 
12.9.7. 
Efficacy Figures 
Efficacy: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.101. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
PKPL1P 
Percent of Microbiological Success for NG at the TOC Visit by 
Baseline Body Site 
 
DS, SAC 
2.102. 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
PKPL1P 
Percent of Microbiological Success for NG at the TOC Visit by 
Baseline Body Site 
 
DS, SAC 
2.103. 
Micro-ITT 
EFF_F1 
Forest Plot for Microbiological Success Rate Overall and by 
Subgroup 
Categorized sexual orientation, 
recreational drug use and # of 
sexual partners 
DS, SAC 
2.104. 
Micro-ITT 
EFF_F2 
Tipping Point Analysis of Microbiological Response at TOC 
 
DS, SAC 
2.105. 
Micro-ITT 
PKPL1P 
Percent of Microbiological Success for Urogenital NG at the 
TOC Visit by Social Sexual History 
Categorized sexual orientation, 
recreational drug use and # of 
sexual partners 
DS, SAC 
2.201. 
Micro-ITT, 
Micro-ITT 
Rectal,  
Micro-ITT 
Pharyngeal 
PKPL1P 
Percent of NAAT Success for NG at the TOC Visit by Baseline 
Body Site 
 
DS, SAC 


 
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BTZ116577 
 
126 
Efficacy: Figures 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable  
2.202. 
 ME,  
ME Rectal,  
  ME 
Pharyngeal 
PKPL1P 
Percent of NAAT Success for NG at the TOC Visit by Baseline 
Body Site 
 
DS, SAC 
 


 
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BTZ116577 
 
127 
12.9.8. 
Safety Tables 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
Adverse Events (AEs) 
3.101.  
Safety 
SAFE_T1 
Overall Summary of Adverse Events 
 
DS, HDL, SAC 
3.102.  
Safety 
AE5B 
Summary of Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade 
 
DS, HDL, SAC 
3.103.  
Safety 
AE5B 
Summary of Adverse Events by System Organ Class and 
Preferred Term and Maximum Grade and Subgroup Strata 
 
DS, SAC 
3.104.  
Safety 
AE5B 
Summary of Drug-Related Adverse Events by System Organ 
Class and Preferred Term and Maximum Grade 
 
DS, SAC 
3.105.  
Safety 
AE3 
Summary of Common (>= 1%) Adverse Events by Overall 
Frequency 
 
DS, SAC 
3.106.  
Safety 
AE3 
Summary of Common (>=1%) Adverse Events by Overall 
Frequency and Relative Risks 
 
DS, SAC 
3.107.  
Safety 
AE3 
Summary of Acetylcholinesterase-Inhibition Adverse Events by 
Overall Frequency and Relative Risks 
 
DS, SAC 
3.108.  
Safety 
AE3 
Summary of Common (>= 1%) Adverse Events by Overall 
Frequency and Subgroup Strata 
 
DS, SAC 
3.109.  
Safety 
AE3 
Summary of Common (>= 1%) Non-Serious Adverse Events by 
System Organ Class and Preferred Term (Number of 
Participants and Occurrences) 
 
DS, SAC 
3.110.  
Safety 
AE13 
Summary of Common (>= 1%) Grade 2 to 5 Adverse Events 
Overall Frequency 
 
DS, SAC 
3.111.  
Safety 
AE5B 
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term and Maximum Grade 
 
DS, SAC 


 
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BTZ116577 
 
128 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
3.112.  
Safety 
AE16 
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term (Number of participants and Occurrences) 
 
DS, SAC 
3.113.  
Safety 
AE5B 
Summary of Serious Adverse Events by System Organ Class 
and Preferred Term and Maximum Grade and Subgroup Strata 
 
DS, SAC 
3.114.  
Safety 
AE5B 
Summary of Drug-Related Serious Adverse Events by System 
Organ Class and Preferred Term and Maximum Grade 
 
DS, SAC 
3.115.  
Safety 
AE3 
Summary of Non-Fatal Serious Adverse Events 
 
DS, SAC 
3.116.  
Safety 
AE3 
Summary of Drug-Related Non-Fatal Serious Adverse Events 
 
DS, SAC 
3.117.  
Safety 
AE5B 
Summary of Cardiovascular and Gastrointestinal Adverse 
Events of Special Interest by System Organ Class and Preferred 
Term and Maximum Grade 
 
DS, SAC 
3.118.  
Safety 
AE5B 
Summary of Acetylcholinesterase-Inhibition Adverse Events of 
Special Interest by System Organ Class and Preferred Term and 
Maximum Grade 
 
DS, SAC 
3.119.  
Safety 
AE5B 
Summary of Acetylcholinesterase-Inhibition Adverse Events of 
Special Interest by Number of Events and Unique Preferred 
Terms 
a table to summarize the number 
and % of participants experiencing 
1, 2, 3, 4, 5 or more events and 1, 
2, 3, 4, >=5 distinct PTs 
DS, SAC 
3.120.  
Safety 
AE5B 
Summary of Acetylcholinesterase-Inhibition Adverse Events of 
Special Interest by Number of Events and Unique Preferred 
Terms and Subgroup Strata 
 
DS, SAC 
3.121.  
Safety 
ESI2B 
Summary of Onset, Duration, and Lag Time of 
Acetylcholinesterase-Inhibition Event 
Summary table to present statistics 
(mean, median, max, min) of time to 
first event, duration, and lag time 
since last dose for ACHE-I, non-GI 
AChE-I, and GI AChE-I events 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
129 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
3.122.  
Safety 
ESI2B 
Summary of Onset, Duration and Lag Time of 
Acetylcholinesterase-Inhibition Event by Subgroup Strata 
Subgroup defined in RAP for safety 
analysis 
DS, SAC 
3.123.  
Safety 
AE5B 
Summary of Adverse Events Leading to Discontinuation of 
Study Treatment or Withdrawal from Study by System Organ 
Class and Preferred Term and Maximum Grade 
 
DS, SAC 
3.124.  
Safety 
 
Summary of Non-Serious Drug Related Adverse Events by 
System Organ Class and Preferred Term 
 
DS, SAC 
Laboratory 
3.201.  
Safety 
LB1 
Summary of Clinical Chemistry Values Change from Baseline  
  
DS, SAC 
3.202.  
Safety 
LB16 
Summary of Emergent Chemistry Laboratory Values by 
Maximum Grade Increase from Baseline 
  
DS, SAC 
3.203.  
Safety 
LB1 
Summary of Hematology Laboratory Values Change from 
Baseline 
  
DS, SAC 
3.204.  
Safety 
LB16 
Summary of Emergent Hematology Laboratory Values by 
Maximum Grade Increase from Baseline 
  
DS, SAC 
3.205.  
Safety 
UR3 
Summary of Urinalysis Dipstick Results 
  
DS, SAC 
Vital Signs and Liver Events 
3.301.  
Safety 
VS1 
Summary of Change from Baseline in Vital Signs  
 
DS, SAC 
3.302.  
Safety 
VS7 
Summary of Worst-Case Vital Signs Results Relative to 
Potential Clinical Importance Criteria Post-Baseline Relative to 
Baseline 
 
DS, SAC 
3.303.  
Safety 
LIVER1 
Summary of Liver Monitoring/Stopping Event Reporting 
 
DS, SAC 
3.304.  
Safety 
LIVER10 
Summary of Hepatobiliary Laboratory Abnormalities 
 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
130 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
 Family History 
3.401.  
Safety 
FH1 
Summary of Family History of Cardiovascular Risk Factors 
 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
131 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
Adverse Events (Adverse Reactions) 
3.501  
Safety 
Template Table 
1 Incidence rate 
and group 
difference by 
MedDRA 
classification 
(Pharma 
Layout) 
Summary of Treatment Emergent Adverse Events by System 
Organ Class, High Level Term and Preferred Term - Safety 
 
DS, SAC 
3.502  
Safety 
Template Table 
1 Incidence rate 
and group 
difference by 
MedDRA 
classification 
(Pharma 
Layout) 
Summary of Treatment Emergent Adverse Events by System 
Organ Class, High Level Term and Preferred Term with High 
Level Term Meeting the Quantitative Assessment Criteria - 
Safety 
 
DS, SAC 
3.503  
Safety 
Template Table 
1 Incidence rate 
and group 
difference by 
MedDRA 
classification 
(Pharma 
Layout) 
Summary of Treatment Emergent Adverse Events by System 
Organ Class, High Level Term and Preferred Term by 
Subgroups - Safety 
 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
132 
Safety: Tables 
No. 
Population 
IDSL / 
Example Shell 
Title  
Programming Notes 
Deliverable 
3.504  
Safety 
Template Table 
2 AE13 
Incidence rate 
of AE according 
to different 
attributes 
(by treatment 
group) 
Incidence Rate of Treatment Emergent Adverse Event 
According to Different Attributes by Treatment Group - Safety 
 
DS, SAC 
3.505  
Safety 
Template Table 
3 - AE5A 
Incidence rate 
of AE according 
to severity 
(by treatment 
group) 
Summary of Treatment Emergent Adverse Events by High Level 
Term and Maximum Grade - Safety 
 
DS, SAC 
3.506  
Safety 
Template Table 
4 AE6 - 
Incidence rate 
of AE according 
to time of first 
occurrence 
Summary of Cumulative Incidence of Treatment Emergent 
Adverse Events (High Level Terms) by Time to First Occurrence 
- Safety 
 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
133 
12.9.9. 
Safety Figures 
Safety: Figures 
No. 
Populatio
n 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.101.  
Safety 
AE10 
Plot of Common (>=1%) Adverse Events and Proportion of 
Participants 
 
DS, SAC 
3.102.  
Safety 
AE11 
Cumulative Distribution of Time to First Gastrointestinal Event 
 
DS, SAC 
3.103.  
Safety 
EFF_F3 
Stacked Bar Chart of Acetylcholinesterase Inhibition Cumulative 
Grade 
Programming note: Y axis label is 
“Percentage of Subjects (%)” colors 
should not use red or blue to avoid 
misinterpretation with treatment 
arms. Grade scale is 0 best-case for 
participant to 4 worst case for 
participant. 
Ordering of AChE-I grouping. 
1. 
AChE-I 
2. 
non-GI AChE-I 
DS, SAC 
3.104.  
Safety 
EFF_F3 
Stacked Bar Chart of non- Gastrointestinal Acetylcholinesterase 
Inhibition Cumulative Grade 
 
DS, SAC 
3.105.  
Safety 
EFF_F3 
Bar Chart of Gastrointestinal Events by Grade in Percentage of 
Participants over Time 
 
DS, SAC 
3.106.  
Safety 
AE10 
Plot of Acetylcholinesterase Inhibition Events  Relative Risk 
 
DS, SAC 
3.201.  
Safety 
LIVER14 
Plot of Maximum Post-Baseline vs Baseline Alanine 
Aminotransferase 
 
DS, SAC 
3.202.  
Safety 
LIVER9 
Plot of Maximum Total Bilirubin vs Maximum Post Baseline 
Alanine Aminotransferase 
 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
134 
Safety: Figures 
No. 
Populatio
n 
IDSL / 
Example 
Shell 
Title  
Programming Notes 
Deliverable 
3.203.  
Safety 
LB11 
Liver Function Tests Participant Profiles 
 
DS, SAC 
BENEFIT/RISK  
3.301.  
Micro-ITT, 
Safety 
EFF_T4 
Forest plot for Benefit/Risk 
 
DS, SAC 
Adverse Events (Adverse Reactions) 
3.401  
Safety 
Template 
Visual 1 
double dot 
plot 
Dot Plot for Treatment Emergent Adverse Events by High Level 
Term - Safety 
 
DS, SAC 
3.402.  
Safety 
Template 
Visual 3 
Heatmap 
Heatmap of Risk Ratios for Treatment Emergent Adverse Event 
High Level Terms that Meet the Screening Criteria by System 
Organ Class - Safety 
 
DS, SAC 
3.403.  
Safety 
Template 
Visual 5 
Kaplan 
Meier 
curve 
Kaplan Meier Curve for Treatment Emergent Potential AR Event 
by Treatment - Safety 
 
DS, SAC 
 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
135 
12.9.10. 
ICH and Non-ICH Listings 
ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
ICH/Non-ICH & Programming 
Notes 
Deliverable  
Participant Disposition 
101 
Intent-to-
Treat 
ES2 
Listing of Reasons for Study Withdrawal 
ICH Listing 
Flag participants who also 
discontinue treatment 
DS, SAC 
102 
Intent-to-
Treat 
SD2 
Listing of Reasons for Study Treatment Discontinuation 
ICH Listing 
DS, SAC 
103 
Intent-to-
Treat 
SP3 
Listing of Participants Excluded from Any Population 
ICH Listing 
DS, SAC 
104 
Screened 
ES7 
Listing of Reasons for Screen Failure 
Non-ICH Listing 
DS, SAC 
Protocol Deviations 
201 
Intent-to-
Treat 
DV2 
Listing of Important Protocol Deviations 
ICH Listing 
Any important deviations related to 
COVID-19 will be captured here 
DS, SAC 
202 
Intent-to-
Treat 
IE3 
Listing of Participants with Inclusion/Exclusion Criteria 
Deviations 
ICH Listing 
 
DS, SAC 
Demographic and Baseline Characteristics 
301 
Intent-to-
Treat 
DM2 
Listing of Demographic and Baseline Characteristics 
ICH Listing 
DS, SAC 
302 
Intent-to-
Treat 
DM9 
Listing of Race 
ICH Listing 
DS, SAC 
303 
Intent-to-
Treat 
MH2 
Listing of Medical Conditions 
ICH Listing 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
136 
ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
ICH/Non-ICH & Programming 
Notes 
Deliverable  
304 
Intent-to-
Treat 
TA1 
Listing of Randomized and Actual Treatments 
Non-ICH Listing 
pre-HDL (post 
unblinding), 
SAC 
305 
Intent-to-
Treat 
SU2 
Listing of Substance Use 
Non-ICH Listing 
DS, SAC 
306 
Intent-to-
Treat 
POP_L1 
Listing of Social Sexual History at Baseline 
Non-ICH Listing 
DS, SAC 
307 
Intent-to-
Treat 
POP_L1 
Listing of Social Sexual History at the TOC Visit, Since Last 
Visit 
Non-ICH Listing 
 
DS, SAC 
Prior and Concomitant Medications 
401 
Intent-to-
Treat 
CM3 
Listing of Prior and Concomitant Medications 
Non-ICH Listing 
Flag systemic antibiotics with 
activity against NG, and if before 
or after TOC or before FU 
DS, SAC 
402 
Intent-to-
Treat 
CM3 
Listing of Concomitant Antibiotic Therapies for Gonorrhea  
Non-ICH Listing 
DS, SAC 
403 
Intent-to-
Treat 
CM3 
Listing of Concomitant Antibiotic Therapies for Chlamydia 
trachomatis or Mycoplasma genitalium after TOC Visit 
Non-ICH Listing 
 
DS, SAC 
Exposure and Treatment Compliance 
501 
Intent-to-
Treat 
EX3 
Listing of Exposure Data 
ICH Listing 
SAC 
502 
Intent-to-
Treat 
EX3 
Listing of Gepotidacin Treatment Compliance 
ICH Listing 
SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
137 
ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
ICH/Non-ICH & Programming 
Notes 
Deliverable  
Efficacy 
601 
Micro-ITT 
EFF_L1 
Listing of Microbiological Outcome and Response for 
Neisseria gonorrhoeae 
Non-ICH Listing 
Include body site 
DS, SAC 
602 
Micro-ITT 
EFF_L1 
Listing of NAAT Outcomes and Responses 
Non-ICH Listing 
Include body site 
DS, SAC 
603 
Intent-to-
treat 
EFF_L2 
Listing of Central Laboratory NAAT Results 
Non-ICH Listing 
Include body site 
DS, SAC 
604 
Intent-to-
treat 
EFF_L3 
Listing of Gram Stain Results from Urogenital Specimens 
Non-ICH Listing 
Only for urogenital site and NG 
DS, SAC 
605 
Intent-to-
treat 
EFF_L4 
Listing of Neisseria gonorrhoeae Culture and Identification 
Non-ICH Listing 
By body site 
DS, SAC 
606 
Intent-to-
treat 
EFF_L4 
Listing of Neisseria gonorrhoeae Urogenital Culture and 
Identification (Additional FDA isolates for Micro ITT FDA 
population) 
Non-ICH Listing 
 
DS, SAC 
607 
Intent-to-
treat 
EFF_L5 
Listing of Susceptibility Results, Microbiological Outcome, and 
Response for Neisseria gonorrhoeae (CLSI) 
Non-ICH Listing 
Include Body Site and by Drug 
DS, SAC 
608 
Intent-to-
treat 
EFF_L5 
Listing of Susceptibility Results, Microbiological Outcome, and 
Response for Neisseria gonorrhoeae (EUCAST) 
Non-ICH Listing 
Include Body Site and by Drug 
DS, SAC 
609 
Intent-to-
treat 
EFF_L6 
Listing of Reduction in Susceptibility (Neisseria gonorrhoeae) 
(CLSI) 
Non-ICH Listing 
Include Body Site and by Drug 
DS, SAC 
610 
Intent-to-
treat 
EFF_L6 
Listing of Reduction in Susceptibility (Neisseria gonorrhoeae)- 
(EUCAST) 
Non-ICH Listing 
Include Body Site and by Drug 
DS, SAC 
611 
Intent-to-
treat 
EFF_L7 
Listing of Genetic Characterization Results (CLSI) 
Non-ICH Listing  
By Body Site 
DS, DAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
138 
ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
ICH/Non-ICH & Programming 
Notes 
Deliverable  
612 
Intent-to-
treat 
EFF_L7 
Listing of Genetic Characterization Results (EUCAST) 
Non-ICH Listing 
By Body Site 
DS, SAC 
613 
Micro-ITT 
EFF_L8 
Listing of Baseline and Post-therapy Results for 
Microbiological Failures (CLSI) 
Non-ICH Listing 
By body site and organism 
DS, DAC 
614 
Micro-ITT 
EFF_L8 
Listing of Baseline and Post-therapy Results for 
Microbiological Failures (EUCAST) 
Non-ICH Listing 
By body site and organism 
DS, SAC 
Adverse Events 
701 
Safety 
AE7 
Listing of Participant Numbers for Individual Adverse Events 
ICH Listing 
 
DS, SAC 
702 
Safety 
AE8CP 
Listing of All Adverse Events 
ICH Listing 
 
DS, SAC 
703 
Safety 
AE2 
Listing of Relationship Between System Organ Class, 
Preferred Term, and Verbatim Text 
Non-ICH Listing 
 
DS, SAC 
Serious and Other Significant Adverse Events 
801 
Safety 
AE14 
Listing of Serious Adverse Events (Fatal and Non-Fatal) 
ICH Listing 
DS, SAC 
802 
Safety 
AE8CP 
Listing of Adverse Events of Special Interest 
ICH Listing 
DS, SAC 
803 
Safety 
SAFE_L1 
Listing of Deaths 
ICH Listing 
DS, SAC 
All Laboratory 
901 
Safety 
LB5A 
Listing of Clinical Chemistry Toxicities of Grade 3 or Higher 
ICH Listing 
DS, SAC 
902 
Safety 
LB5A 
Listing of All Clinical Chemistry Data for Participants with 
Toxicities of Grade 3 or Higher 
ICH Listing 
 
DS, SAC 
903 
Safety 
LB5A 
Listing of Hematology Toxicities of Grade 3 or Higher 
ICH Listing 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
139 
ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
ICH/Non-ICH & Programming 
Notes 
Deliverable  
904 
Safety 
LB5A 
Listing of Hematology Data for Participants with Toxicities of 
Grade 3 or Higher 
ICH Listing 
 
DS, SAC 
905 
Safety 
LB5A 
Listing of Serology Results 
ICH Listing 
 
906 
Safety 
UR2A 
Listing of Urinalysis Data 
ICH Listing 
DS, SAC 
ECG 
1001 
Safety 
EG5 
Listing of All ECG Findings for Participants with an Abnormal 
Finding 
Non-ICH Listing 
 
DS, SAC 
1002 
Safety 
EG3 
Listing of All ECG Values for Participants with Any Value of 
Potential Clinical Importance 
Non-ICH Listing 
 
DS, SAC 
Vital Signs 
1101 
Safety 
VS4 
Listing of All Vital Signs for Participants with Potential Clinical 
Importance Values 
Non-ICH Listing 
 
DS, SAC 
Liver Events and Other Safety Endpoints 
1201 
Safety 
SAFE_L2 
Listing of Clostridium difficile Colitis Results 
Non-ICH Listing 
DS, SAC 
1202 
Safety 
SU2 
Listing of Alcohol Intake at Onset of Liver Event 
Non-ICH Listing 
Conditional Display 
DS, SAC 
1203 
Safety 
LIVER5 
Listing of Liver Monitoring/Stopping Event Reporting 
Non-ICH Listing 
Conditional Display 
DS, SAC 
1204 
Safety 
LIVER7 
Listing of Liver Biopsy Details 
Non-ICH Listing 
Conditional Display 
DS, SAC 
1205 
Safety 
LIVER8 
Listing of Liver Imaging Details 
Non-ICH Listing 
Conditional Display 
DS, SAC 
1206 
Safety 
LIVER15 
Liver Stopping Event Profile 
Non-ICH Listing 
Conditional Display 
DS, SAC 


 
CONFIDENTIAL 
 
 
BTZ116577 
 
140 
ICH: Listings 
No. 
Population 
IDSL / Example 
Shell 
Title  
ICH/Non-ICH & Programming 
Notes 
Deliverable  
1207 
Safety 
PREG1 
Listing of Participants Who Became Pregnant During the 
Study 
Non-ICH Listing 
Conditional Display 
DS, SAC 
COVID-19 
1301 
Intent-to-
Treat 
PAN5A 
Country Level Listing of Start Dates of Waves of COVID-19 
Pandemic Measures 
Non-ICH Listing 
 
DS, SAC 
1302 
Intent-to-
Treat 
PAN7 
Listing of All Participants with Visits and Assessments 
Impacted by COVID-19 Pandemic 
Non-ICH Listing 
 
DS, SAC 
1303 
Safety 
PAN12 
Listing of COVID-19 Assessments and Symptom 
Assessments for Participants with COVID-19 Adverse Events 
Non-ICH Listing 
 
DS, SAC