A Double-Blind, Double Dummy, Randomized, Phase 1b, Nitrofurantoin Controlled, Repeat Oral Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics and Microbiological Response of GSK3882347 in Female Participants With Acute Uncomplicated Urinary Tract Infection
Phase: PHASE1
Conditions: Uncomplicated Urinary Tract Infections, Urinary Tract Infections
Sponsor: GlaxoSmithKline

TMF-19102920  
CONFIDENTIAL 
The GSK group of companies 
212943 
 
Protocol Amendment 5 Final  
 
1 
Clinical Study Protocol template V16 dated 24-Jun-2021 
TITLE PAGE 
Protocol Title: A Double-Blind, Double Dummy, Randomized, Phase 1b, Nitrofurantoin 
Controlled, Repeat Oral Dose Study to Investigate the Safety, Tolerability, 
Pharmacokinetics and Microbiological Response of GSK3882347 in Female Participants 
with Acute Uncomplicated Urinary Tract Infection. 
Protocol Number: 212943 Amendment 5 
Compound Number:  GSK3882347  
Brief Title: Safety, tolerability, pharmacokinetic and microbiological investigation of 
GSK3882347 in female participants with urinary tract infections. 
Study Phase: Phase 1b 
Sponsor Name and Legal Registered Address:  
GSK Research & Development Limited 
980 Great West Road 
Brentford 
Middlesex, TW8 9GS 
UK 
Regulatory Agency Identifying Number(s): [Regulatory Agency identifying 
number(s) as appropriate] 
IND 
156644 
Approval Date: 10 Jun 2024 
Medical Monitor Name and Contact Information can be found in the Study 
Reference Manual. 
Sponsor Signatory: 
Jennifer Han, MD, MSCE Senior Clinical Development Director, Clinical Lead Clinical 
Research and Early Programs, Infectious Diseases 
Copyright 2024 the GSK group of companies. All rights reserved. Unauthorized copying 
or use of this information is prohibited. 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
Protocol Amendment 5 Investigator Agreement 
• 
To assume responsibility for the proper conduct of the study at this site. 
• 
That I am aware of and will comply with GCP and all applicable regulatory 
requirements. 
• 
That I will comply with the terms of the clinical study site agreement. 
• 
To ensure that all persons assisting me with the study are adequately informed 
about the GSK study intervention and other study-related duties and functions 
as described in the protocol. 
• 
To cooperate with representative(s) of GSK in the monitoring and data 
management processes of the study with respect to data entry and resolution of 
queries about the data. 

TMF-19102920 
CONFIDENTIAL 
 
212943 
 
 
Protocol Amendment 5 Final 
 
3 
Clinical Study Protocol template V16 dated 24-Jun-2021 
Study identifier 
212943 
Approval date 
10 Jun 2024 
Title 
A Double-Blind, Double Dummy, Randomized, 
Phase 1b, Nitrofurantoin Controlled, Repeat Oral 
Dose Study to Investigate the Safety, Tolerability, 
Pharmacokinetics and Microbiological Response of 
GSK3882347 in Female Participants with Acute 
Uncomplicated Urinary Tract Infection 
Investigator name  
 
 
 
Signature 
 
 
 
Date of signature 
(DD Month YYYY) 
 

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212943 
 
 
Protocol Amendment 5 Final 
 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Document Identifier 
Amendment 5 
10 Jun 2024 
TMF-19102920 
Amendment 4 
05 May 2023 
TMF-14918563 
Amendment 3 
07 October 2022 
TMF-14918563 
Amendment 2 
24 February 2022 
TMF-14449233 
Amendment 1 
17 December 2021 
TMF-14335823 
Original Protocol (00) 
20 August 2021 
TMF-13952282 
Amendment 5 (10 Jun 2024) 
Overall Rationale for the Amendment: Changes to overall number of participants 
randomized, as well as change of one in-person visit to a phone visit to ease 
site/participant burden. 
Section # and 
Name 
Description of 
Change 
Brief Rationale 
1.1 Synopsis 
5 days of dosing 
intervention has been 
added. 
For clarifying the intervention duration. 
1.2 Schema 
Pyuria and nitrite 
have been rewording 
as pyuria or nitrite 
Clarifying urinalysis requirements for 
inclusion 
1.3.2 Schedule 
of activities: 
Cohort 2 & 4.1 
Overall Design  
Removal of Day 4 
outpatient clinical 
visit. 
To reduce participant and site burden and 
improve recruitment, the Day 4 outpatient 
clinic visit has been removed. All relevant 
information as specified in the SoA will be 
collected via a phone call (in the same 
manner as the phone calls already 
conducted on Day 3 and Day 5). Specific 
questions will be asked around any potential 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
Section # and 
Name 
Description of 
Change 
Brief Rationale 
signs or symptoms of worsening UTI (via 
the clinical score) or risks for worsening 
renal function as the in-person blood draw 
has been removed. Option for conducting 
urine pregnancy testing on Day 4 will be 
removed, this should now be conducted on 
Day 2. 
1.3.2. Schedule 
of activities: 
Cohort 2 
Inclusion of 12-lead 
ECG on Day 6. 
As the Day 4 visit has been changed to a 
phone call, the ECG that was to be 
performed on this day will be moved to the 
next in-person study visit, Day 6. 
1.3.2 Schedule 
of activities: 
Cohort 2 
UTI Clinical Signs 
and Symptom Score 
Assessment. 
Day 4 visit is being changed from in-person 
visit to phone call. 
1.3.2 Schedule 
of activities: 
Cohort 2 
Investigators 
Assessment of 
Clinical Resolution 
Response  
Day 4 visit is being changed from in-person 
visit to phone call. 
1.3.2 Schedule 
of activities: 
Cohort 2 
Telephone Call to 
review clinical 
symptoms and AEs. 
Day 4 visit is being changed from in-person 
visit to phone call. 
1.3.2 Schedule 
of activities: 
Cohort 2 
In the header, 
sampling and 
telephone calls 
wording has been 
added and no clinic 
day has been replaced 
with Telephone call 
day.  
Clarification that the rows underneath the 
header include telephone calls on some 
visits. 
 
1.3.2 Schedule 
of activities: 
Cohort 2 
In the header, 
“optional overnight 
admission permitted” 
wording has been 
deleted under 
"Screening". 
The table header text had a typographical 
error - Cohort 2 remains an outpatient only 
option for all study participants. Therefore, 
this text has been removed. 
2.3.1 Risk 
Assessment 
Updated wording 
including additional 
data generated from 
nonclinical studies.  
Removal of 
“Reproductive 
toxicity” as a potential 
risk. 
Risk assessment now captures additional 
data generated from nonclinical studies.  
“Reproductive toxicity” has been removed 
as a potential risk. Definitive animal 
reproductive studies with GSK3882347 
have been conducted in rats and rabbits with 
no hazards identified to date. “Reproductive 
toxicity” is considered as missing 
information at this time.  

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Clinical Study Protocol template V16 dated 24-Jun-2021 
Section # and 
Name 
Description of 
Change 
Brief Rationale 
2.3.1 Risk 
Assessment of 
COVID-19 
Risk of COVID-19. 
This section has been modified to reflect 
that there is no longer a COVID-19 
pandemic, and assessments should be based 
on community incidence. 
4.3 Justification 
for Dose 
Arithmetic mean 
replaced with 
geometric means 
(%CV) from data read 
out of the Study 
212148. 
Text states %CV which is now included, 
and arithmetic mean values updated with 
geometric mean values which are 
statistically appropriate for urine 
concentration and %CV. 
5.1 Inclusion 
criteria 
The participant has 
nitrite OR pyuria (≥10 
WBC/mm3 OR >5 
WBC/HPF OR the 
presence of at least 2+ 
leukocyte esterase) 
from a pre-treatment 
clean-catch midstream 
urine sample based on 
local laboratory 
procedures. 
Clarified that the leukocyte esterase criteria 
should be AT LEAST 2+, as 3+ would also 
qualify. 
5.2 Exclusion 
criteria 
Exclusion criteria 11: 
Updated eGFR range 
from <90 
mL/min/1.73m2 to 
<60 mL/min/1.73m2. 
In consultation with the GSK Nephrology 
Safety Panel and based on the review of 
non-clinical animal data and blinded data 
from the ongoing 212943 study (46 
participants) and available human PK 
information obtained from the completed 
healthy volunteer study (212148), there is 
sufficient evidence to support widening the 
eGFR exclusion criteria from the current 
exclusion of those with eGFR 
<90ml/min/1.73m2 to those with eGFR 
<60ml/min/1.73m2. 
5.2 Exclusion 
criteria 
Exclusion criteria 19 
and 20; removed the 
word “known”. 
For clarification. 
6.1 Study 
Intervention 
Administered 
Replaced AM and PM 
with Dose A and 
Dose B 
While it is ideal for a study participant to 
start the on-therapy visit in the morning, 
switching to Dose A and Dose B allows 
flexibility for study participants that can 
only start the on-therapy portion of the 
study in the evening. 
6.4 Study 
Intervention 
compliance 
Removal of bulk 
supply option 
Bulk supply is no longer applicable as the 
IP is in ready to dispense packaging  

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Clinical Study Protocol template V16 dated 24-Jun-2021 
Section # and 
Name 
Description of 
Change 
Brief Rationale 
8.3.7 Disease 
Related Events 
and/or Disease 
Related 
Outcomes Not 
Qualifying as 
SAEs 
Section deleted. 
Section removed as not applicable to study. 
There are no DREs defined for this study 
nor Disease Related Outcomes that would 
not qualify as SAEs.  
8.3.7 Contact 
information for 
reporting 
SAEs, 
pregnancies 
and study 
holding rules. 
Addition of Table 3 
summarizing contact 
information for 
reporting SAEs, 
pregnancies and study 
holding rules. 
To reinforce contact information already 
provided to the study sites and align with 
protocol template. 
8.3.9 
Participant 
Card 
New section added  
Section added in line with new protocol 
template as it is applicable to this study. 
Section reinforces the requirement for study 
participants to be provided with a 
"participant card", which is already 
described in the SRM. 
8.9.3 Third 
Party Vendors 
This section has been 
deleted. 
“The List of Clinical Laboratories and 
List of key vendors” is merged into a 
single separate document outside of the 
protocol. This provides flexibility to teams 
to update the list without amending the 
protocol. 
9.2 Analysis 
Sets 
Exposed Population is 
replaced by 
Randomized 
Population and in 
description ‘eligible’ 
word has been 
removed. 
The Exposed Population was renamed to 
more accurately reflect its definition and to 
align with new GSK protocol template. 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
Section # and 
Name 
Description of 
Change 
Brief Rationale 
10.1.3 
Informed 
consent process  
Updates to the master 
ICF around use of 
samples for research 
related and unrelated 
to this study. 
Aligned with the updates to the master ICF 
template  
10.7 Appendix 
7: COVID 
Pandemic 
Considerations 
This section has been 
deleted. 
This Appendix has been deleted as we are 
no longer in a pandemic so this is not 
relevant. 
11 References 
Reference for IB 
updated.  
Reference for 
Prescribing 
Information for the 
comparator has been 
added. 
Reference for EAU 
guidelines updated. 
An interim update to the investigator 
brochure was generated.  
This reference has been added as per new 
template instructions to avoid copyright 
infringements. 
EAU guidelines has been updated and is 
now dated 2024.  
Investigator 
Agreement 
Investigator 
Agreement page has 
been added. 
To align with new GSK protocol template. 
2.2 Background 
7.1.1 Liver 
Chemistry 
Stopping 
Criteria 
7.2 Participant 
Discontinuation 
/ Withdrawal 
from the 
Clinical Study 
8 Study 
Assessments 
and Procedures 
8,2,4 Clinical 
Safety 
Laboratory 
Tests 
8.3.4 
Additional changes 
were made where 
applicable to align 
with latest protocol 
template. 
To align with new GSK protocol template 
(v3.0, 10 January 2024). 
 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
Section # and 
Name 
Description of 
Change 
Brief Rationale 
Regulatory 
Reporting 
Requirements 
for SAEs 
8.3.7 Contact 
information for 
reporting 
SAEs, 
pregnancies 
and study 
holding rules 
10.1.3 
Informed 
Consent 
Process 
10.1.4 Data 
Protection 
10.1.5 
Committees 
Structure 
10.1.6 
Dissemination 
of Clinical 
Study Data 
10.1.7 Data 
Quality 
Assurance 
10.2 Clinical 
Laboratory 
tests 
10.3.1 
Definition of 
AE 
10.3.4 
Recording, 
assessment, and 
follow-up of 
AE, SAE and 
pregnancies 
10.3.5 
Reporting of 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
Section # and 
Name 
Description of 
Change 
Brief Rationale 
SAE and 
pregnancies to 
GSK 
10.10 
Abbreviations, 
Definition of 
Terms and 
Trademarks  
Throughout 
Document 
Administrative and 
editorial changes were 
made where 
applicable to align 
table numbers, 
formatting, and cross 
references. 
To maintain consistency with template 
guidance. 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
TABLE OF CONTENTS 
PAGE 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ..................................... 4 
1. 
PROTOCOL SUMMARY ........................................................................................ 16 
1.1. 
Synopsis ..................................................................................................... 16 
1.2. 
Schema ...................................................................................................... 19 
1.3. 
Schedule of Activities (SoA) ........................................................................ 20 
1.3.1. 
Cohort 1: Intensive PK Profiling During an Inpatient 
Intervention Period ....................................................................... 20 
1.3.1.1. 
Cohort 1 Detailed Urine PK Sampling ......................... 29 
1.3.1.2. 
Cohort 1 Detailed Plasma PK Sampling ..................... 30 
1.3.2. 
Cohort 2 Reduced PK Sampling During an Outpatient 
Intervention Period ....................................................................... 30 
2. 
INTRODUCTION .................................................................................................... 40 
2.1. 
Study Rationale .......................................................................................... 40 
2.2. 
Background ................................................................................................ 40 
2.3. 
Benefit/Risk Assessment ............................................................................ 40 
2.3.1. 
Risk Assessment ......................................................................... 41 
2.3.2. 
Benefit Assessment ..................................................................... 49 
2.3.3. 
Overall Benefit: Risk Conclusion .................................................. 49 
3. 
OBJECTIVES AND ENDPOINTS AND/OR ESTIMANDS ....................................... 49 
4. 
STUDY DESIGN .................................................................................................... 53 
4.1. 
Overall Design ............................................................................................ 53 
4.2. 
Scientific Rationale for Study Design .......................................................... 54 
4.3. 
Justification for Dose .................................................................................. 55 
4.4. 
End of Study Definition ............................................................................... 56 
5. 
STUDY POPULATION ........................................................................................... 57 
5.1. 
Inclusion Criteria ......................................................................................... 57 
5.2. 
Exclusion Criteria ........................................................................................ 58 
5.3. 
Lifestyle Considerations .............................................................................. 61 
5.3.1. 
Meals and Dietary Restrictions .................................................... 61 
5.3.2. 
Other Lifestyle Restrictions and Recommendations ..................... 62 
5.4. 
Screen Failures........................................................................................... 62 
5.5. 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study Intervention ................. 63 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT THERAPY .............................. 63 
6.1. 
Study Intervention(s) Administered ............................................................. 63 
6.2. 
Preparation, Handling, Storage and Accountability ..................................... 64 
6.3. 
Measures to Minimize Bias: Randomization and Blinding ........................... 64 
6.4. 
Study Intervention Compliance ................................................................... 65 
6.5. 
Dose Modification ....................................................................................... 65 
6.6. 
Continued Access to Study Intervention after the End of the Study ............ 66 
6.7. 
Treatment of Overdose ............................................................................... 66 
6.8. 
Concomitant Therapy.................................................................................. 67 
6.8.1. 
Permitted Medication and Non-Drug Therapies ........................... 67 

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6.8.2. 
Prohibited Medication and Non-Drug Therapies........................... 67 
6.8.3. 
Rescue Medicine ......................................................................... 68 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ..................................................................... 69 
7.1. 
Discontinuation of Study Intervention .......................................................... 69 
7.1.1. 
Liver Chemistry Stopping Criteria ................................................ 70 
7.1.2. 
QTc Stopping Criteria .................................................................. 70 
7.1.3. 
Study Specific Stopping Criteria ................................................... 71 
7.2. 
Participant Discontinuation/Withdrawal from the Clinical Study ................... 71 
7.3. 
Lost to Follow Up ........................................................................................ 72 
8. 
STUDY ASSESSMENTS AND PROCEDURES ..................................................... 73 
8.1. 
Efficacy Assessments ................................................................................. 74 
8.1.1. 
Clinical Evaluation: Symptom of uUTI and Clinical 
Resolution Response ................................................................... 74 
8.1.2. 
Microbiology Outcome and Response ......................................... 75 
8.2. 
Safety Assessments ................................................................................... 77 
8.2.1. 
Physical Examinations ................................................................. 77 
8.2.2. 
Vital Signs .................................................................................... 77 
8.2.3. 
Electrocardiograms ...................................................................... 78 
8.2.4. 
Clinical Safety Laboratory Tests .................................................. 78 
8.2.4.1. 
Suspected Clostridioides difficile infection .................. 79 
8.2.4.2. 
Management of participants with changes in 
serum creatinine ......................................................... 79 
8.2.5. 
Pregnancy Testing ....................................................................... 79 
8.2.6. 
Diary Card ................................................................................... 80 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and Other 
Safety Reporting ......................................................................................... 80 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information ................................................................................... 80 
8.3.2. 
Method of Detecting AEs and SAEs ............................................. 81 
8.3.3. 
Follow-up of AEs and SAEs ......................................................... 81 
8.3.4. 
Regulatory Reporting Requirements for SAEs ............................. 81 
8.3.5. 
Pregnancy ................................................................................... 82 
8.3.6. 
Cardiovascular and Death Events ................................................ 82 
8.3.7. 
Contact information for reporting SAEs, pregnancies and 
study holding rules ....................................................................... 83 
8.3.8. 
Adverse Events of Special Interest .............................................. 83 
8.3.9. 
Participant card ............................................................................ 83 
8.4. 
Pharmacokinetics ....................................................................................... 83 
8.4.1. 
Pharmacodynamics ..................................................................... 84 
..................................... 84 
8.5. 
Genetics ..................................................................................................... 84 
8.6. 
Biomarkers ................................................................................................. 84 
8.7. 
Immunogenicity Assessments ..................................................................... 84 
8.8. 
Health Economics ....................................................................................... 84 
8.9. 
Administrative and general/baseline procedures ......................................... 85 
8.9.1. 
Collection of demographic data .................................................... 85 
8.9.2. 
Medical history ............................................................................. 85 
9. 
STATISTICAL CONSIDERATIONS ........................................................................ 85 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
9.1. 
Statistical Hypotheses................................................................................. 85 
9.2. 
Analysis Sets .............................................................................................. 85 
9.3. 
Statistical Analyses ..................................................................................... 86 
9.3.1. 
General Considerations ............................................................... 86 
9.3.2. 
Primary Endpoint(s)/Estimands(s) Analysis ................................. 86 
9.3.3. 
Secondary Endpoint(s)/Estimand(s) Analysis .............................. 87 
9.3.4. 
Exploratory Endpoint(s) Analysis ................................................. 88 
.................................................. 88 
.................................................. 89 
10. SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS ............................................................................................... 91 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations ............................................................................................ 91 
10.1.1. 
Regulatory and Ethical Considerations ........................................ 91 
10.1.2. 
Financial Disclosure ..................................................................... 91 
10.1.3. 
Informed Consent Process .......................................................... 92 
10.1.4. 
Data Protection ............................................................................ 93 
10.1.5. 
Committees Structure .................................................................. 93 
10.1.5.1. Safety Review Team .................................................. 93 
10.1.6. 
Dissemination of Clinical Study Data ........................................... 94 
10.1.7. 
Data Quality Assurance ............................................................... 95 
10.1.8. 
Source Documents ...................................................................... 96 
10.1.9. 
Study and Site Start and Closure ................................................. 96 
10.1.10. Publication Policy ......................................................................... 97 
10.2. 
Appendix 2: Clinical Laboratory Tests ......................................................... 97 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting ....................................... 99 
10.3.1. 
Definition of AE ............................................................................ 99 
10.3.2. 
Definition of SAE ........................................................................ 101 
10.3.3. 
Definition of Cardiovascular Events ........................................... 102 
10.3.4. 
Recording, assessment, and Follow-Up of AE, SAE and 
pregnancies ............................................................................... 102 
10.3.5. 
Reporting of SAE and pregnancies to GSK ................................ 105 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance ..................................... 106 
10.4.1. 
Definitions: ................................................................................. 106 
10.4.2. 
Contraception Guidance: ........................................................... 108 
10.5. 
Appendix 5: Genetics ................................................................................ 109 
10.6. 
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments ............................................................................................ 110 
10.7. 
Appendix 7: Division of Microbiology and Infectious Diseases Adult 
Toxicity Tables for Adverse Event Assessment......................................... 112 
10.8. 
Appendix 8: Algorithm for Determining Qualifying E. coli Pathogen .......... 116 
10.9. 
Appendix 9: Algorithm for Detecting Suspected C. difficile infection .......... 117 
10.10. Appendix 10: Abbreviations, Definition of Terms and Trademarks ............ 118 
10.11. Appendix 11: Protocol Amendment History ............................................... 126 
11. REFERENCES ..................................................................................................... 137 
 
 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
LIST OF TABLES 
PAGE 
Table 1 
Study Intervention(s) Administered......................................................... 63 
Table 2 
Timeframes for submitting SAE and pregnancy reports to GSK ............. 81 
Table 3 
Contact information for reporting SAEs, pregnancies and study 
holding rules ........................................................................................... 83 
Table 4 
Operating characteristics of selected criteria of interest.......................... 90 
Table 5 
Protocol-required Safety Laboratory Tests ............................................. 98 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
LIST OF FIGURES 
PAGE 
Figure 1 
Study Schematic for Cohort 1: Full Intensive PK Sampling as 
Inpatient ................................................................................................. 19 
Figure 2 
Study Schematic for Cohort 2: Reduced PK Sampling as 
Outpatient .............................................................................................. 19 
Figure 3 
Algorithm for qualifying E. coli Pathogen .............................................. 116 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
1. 
PROTOCOL SUMMARY 
1.1. 
Synopsis 
Protocol Title: A Double-Blind, Double-Dummy, Randomized, Phase 1b, Nitrofurantoin 
Controlled, Repeat Oral Dose Study to Investigate the Safety, Tolerability, 
Pharmacokinetics and Microbiological Response of GSK3882347 in Female Participants 
with Acute Uncomplicated Urinary Tract Infection. 
Brief Title: Safety, tolerability, pharmacokinetic and microbiological investigation of 
GSK3882347 in female participants with urinary tract infections. 
Rationale: GSK3882347 is a novel, bacterial attachment inhibitor, designed to treat or 
prevent uncomplicated urinary tract infections (uUTI) caused by Escherichia coli (E. 
coli). GSK3882347 prevents attachment and invasion of the bladder mucosa via 
inhibition of type 1 fimbrial adhesion, (FimH) protein function on E. coli, which cause 
approximately 70% to75% of all urinary tract infections (UTIs) [Dielubanza, 2011; 
Barber, 2013, Overcash, 2020, Wagenlehner, 2020]. GSK3882347 binds to the FimH 
adhesin on type 1 pili of E. coli, preventing bacterial adhesion to the bladder mucosal 
surface by disrupting the interaction between FimH and the mammalian mannose-rich 
glycoproteins, such as uroplakin Ia and integrins in the bladder. 
 
 
 
  
The purpose of this Phase 1b Proof-of-Mechanism (PoM) study is primarily to evaluate 
the microbiological efficacy of GSK3882347 in females with acute uUTI. 
Objectives and Endpoints and Estimands: 
Objectives 
Endpoints 
Primary 
• 
To assess the microbiological efficacy of 
GSK3882347 at the Test of Cure (ToC) visit in 
participants with uUTI who have qualifying E. coli at 
baseline 
• 
Microbiological response at the ToC Visit 
Secondary 
• 
To evaluate the safety and tolerability following 
oral dosing for 5 days of GSK3882347 in 
participants with uUTI 
• 
Occurrence of adverse events (AEs) and serious 
adverse events (SAEs)  
• 
Clinically significant changes from baseline in 
laboratory values (hematology, chemistry and 
urinalysis), vital signs and 12 lead 
electrocardiogram (ECG) readings 
• 
To evaluate the plasma and urine pharmacokinetic 
(PK) concentrations following
oral 
dosing for 5 days of GSK3882347 in participants 
with uUTI 
Plasma: 
• 
GSK3882347 concentration 
Urine 
• 
Urine concentration at 22-24h interval collection 
post-dose 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
Objectives 
Endpoints 
Exploratory* 
• 
To evaluate the resolution of clinical symptoms 
over time of GSK3882347 in participants with uUTI 
caused by E. coli 
• 
Clinical resolution response on Day 2 through to 
Day 6 (when collected and as data permit), ToC 
and Follow-up Visit 
• 
To evaluate the resolution of clinical symptoms 
over time of GSK3882347 in participants with uUTI 
caused by E. coli using an exploratory scoring 
system 
• 
Clinical symptom score outcome and response 
on Days 1 through to Day 6 (when collected and 
as data permit), ToC and Follow-up Visit 
* Details regarding the exploratory analyses will be described in the statistical analysis 
plan (SAP). Some exploratory data may not be available until after the main database 
lock and may be analysed/reported separately. 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
Overall Design: 
This Phase 1b study is a double-blind, double-dummy, nitrofurantoin controlled study 
designed primarily to evaluate microbiological response. Nitrofurantoin will be included 
in the study to ensure unbiased reporting of safety events. The clinical response 
 
 with GSK3882347 will be evaluated as exploratory 
endpoints in this study. 
 
. The study will be separated into 2 
cohorts. Cohort 1 will have an inpatient Treatment period and PK analysis will be 
conducted at frequent timepoints. Cohort 2 will have an outpatient Treatment period and 
PK analysis will be conducted less frequently, at key trough timepoints. 
Brief Summary: 
The purpose of this study is to evaluate the safety, tolerability, PK and microbiological 
response of GSK3882347 capsules in adult female participants with uUTI. 
Study details include: 
• 
The study duration will be up to 31 days 
• 
The treatment duration will be up to 5 continuous days 
• 
The visit frequency will be a total of 9 visits in Cohort 1 and 6 visits in Cohort 2. 
Number of Participants: 
A maximum of 122 participants assuming the evaluability rate observed to date, will be 
randomly assigned to GSK3882347 or nitrofurantoin in a 3:1 ratio. However, 
randomization into the study will be stopped when approximately 21 evaluable 
participants (an evaluable participant is defined as a participant with E. coli (≥104 Colony 
Forming Units [CFU]/mL) confirmed as the causative pathogen for their infection at their 
baseline assessment are enrolled on to the GSK3882347 
 arm and complete a ToC 
visit. In the event that the evaluability rate is lower than anticipated 
 
 
the maximum number of randomized participants could increase up to 141. 
Intervention Groups and Duration: As stated within Number of Participants above 
with 5 days of dosing intervention. 
Data Monitoring/ Other Committee: A GSK Safety Review Team will monitor blinded 
safety data. 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
1.2. 
Schema 
Figure 1 
Study Schematic for Cohort 1: Full Intensive PK Sampling as 
Inpatient 
 
Figure 2 
Study Schematic for Cohort 2: Reduced PK Sampling as Outpatient 
 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
1.3. 
Schedule of Activities (SoA) 
1.3.1. 
Cohort 1: Intensive PK Profiling During an Inpatient Intervention Period 
Cohort 1: Intensive PK 
Procedure 
Screening #  
(Day -1, can 
be on Day 1) 
Cohort 1: Intensive PK & Clinic Visits [Days] 
Notes: 
# E-consent may be used.  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Clinic Constrained Intervention 
Period [Days] 
6 
 
ToC 
(D10 to 
D13)      
5 to 8 
days 
post 
treatmen
t 
E.D.^ 
Follow-
Up     
(28±3 
days 
followin
g first  
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3 
4 
5 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
Pre-screen ICF available for 
local dipstick urinalysis 
(nitrite and leukocyte 
esterase) and pregnancy test 
Inclusion and exclusion 
criteria 
X 
X* 
 
 
 
 
 
 
 
 
 
 
*If required and remaining 
criteria to confirm. 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Full physical examination  
X* 
 
 
 
 
 
 
 
 
X 
X 
X 
* Height and weight 
measured only at screening 
Medical history (includes 
substance usage and Family 
history of premature CV 
disease) 
X 
 
 
 
 
 
 
 
 
 
 
 
Substances: Drugs, Alcohol 
Including the number of 
UTIs participant has had in 
the last 12 months and 
within the last 2 years 
Urine Drug and Alcohol 
Observational Assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 1: Intensive PK 
Procedure 
Screening #  
(Day -1, can 
be on Day 1) 
Cohort 1: Intensive PK & Clinic Visits [Days] 
Notes: 
# E-consent may be used.  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Clinic Constrained Intervention 
Period [Days] 
6 
 
ToC 
(D10 to 
D13)      
5 to 8 
days 
post 
treatmen
t 
E.D.^ 
Follow-
Up     
(28±3 
days 
followin
g first  
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3 
4 
5 
COVID test 
X* 
 
 
 
 
 
 
X 
 
X 
X 
X 
Rapid turnaround tests 
*Additional parallel 
polymerase chain reaction 
(PCR) sample  
Urine pregnancy test  
(for women of child bearing 
potential) 
X^ 
 
 
X* 
X* 
X* 
X* 
 
 
X 
X@ 
 
^ Can be completed as a 
prescreen if Prescreen ICF 
signed.  
* One on-therapy test should 
be conducted either on D2, 
D3, D4 or D5. 
@ = If E.D is post Day 6 
onward. 
Follicle-stimulating hormone 
and estradiol (as needed for 
women of non-childbearing 
potential only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 1: Intensive PK 
Procedure 
Screening #  
(Day -1, can 
be on Day 1) 
Cohort 1: Intensive PK & Clinic Visits [Days] 
Notes: 
# E-consent may be used.  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Clinic Constrained Intervention 
Period [Days] 
6 
 
ToC 
(D10 to 
D13)      
5 to 8 
days 
post 
treatmen
t 
E.D.^ 
Follow-
Up     
(28±3 
days 
followin
g first  
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3 
4 
5 
HIV, Hepatitis B and C 
monitoring sample collection 
and assessment of history at 
screening  
X 
 
 
 
 
 
 
 
 
 
 
 
If test otherwise performed 
within 3 months prior to 
first dose of study 
intervention, testing at 
screening is not required. 
Laboratory assessments 
(haematology, chemistry 
include liver chemistries and 
urinalysis)  
X* 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
*Sample at screening 
processed by local labs 
(Point of Care tests may be 
utilised when appropriate 
and are described in Section 
10.2): urine dipsticks (nitrite 
and leukocyte esterase) can 
be completed as a pre-screen  
On therapy samples will be 
obtained pre-dose. 
12-lead ECG 
X 
 
X 
 
 
X* 
 
 
 
X 
X 
X 
Triplicate ECG for 
screening, single ECG for 
all subsequent visits. 
*Obtained pre-dose 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 1: Intensive PK 
Procedure 
Screening #  
(Day -1, can 
be on Day 1) 
Cohort 1: Intensive PK & Clinic Visits [Days] 
Notes: 
# E-consent may be used.  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Clinic Constrained Intervention 
Period [Days] 
6 
 
ToC 
(D10 to 
D13)      
5 to 8 
days 
post 
treatmen
t 
E.D.^ 
Follow-
Up     
(28±3 
days 
followin
g first  
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3 
4 
5 
Vital signs 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
Triplicate measurements of 
blood pressure and pulse 
rate will be obtained at 
screening and baseline and 
averaged. Single 
measurements will be 
obtained pre-dose at all 
other timepoints. 
Admission to clinical unit 
X* 
X 
 
 
 
 
 
 
 
 
 
 
* Can be admitted on the 
day of screening;  
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 1: Intensive PK 
Procedure 
Screening #  
(Day -1, can 
be on Day 1) 
Cohort 1: Intensive PK & Clinic Visits [Days] 
Notes: 
# E-consent may be used.  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Clinic Constrained Intervention 
Period [Days] 
6 
 
ToC 
(D10 to 
D13)      
5 to 8 
days 
post 
treatmen
t 
E.D.^ 
Follow-
Up     
(28±3 
days 
followin
g first  
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3 
4 
5 
Genetic blood sample 
(optional) 
 
X 
 
 
 
 
 
 
 
 
 
 
Pre-dose (baseline), 
Germline genetic research 
may be described in a 
separate ICF or as part of a 
combined informed consent 
form (ICF). A separate 
signature is required where 
participantparticipation is 
optional.  
This sample differs from 
urine bacterial samples that 
will be collected for 
potential genetic analysis. 
Study intervention 
administration 
 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 1: Intensive PK 
Procedure 
Screening #  
(Day -1, can 
be on Day 1) 
Cohort 1: Intensive PK & Clinic Visits [Days] 
Notes: 
# E-consent may be used.  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Clinic Constrained Intervention 
Period [Days] 
6 
 
ToC 
(D10 to 
D13)      
5 to 8 
days 
post 
treatmen
t 
E.D.^ 
Follow-
Up     
(28±3 
days 
followin
g first  
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3 
4 
5 
AE review 
 
 
=========================→ 
X 
X 
Record AE from time of 
first dose of study 
Treatment. 
Stool sample collected and 
tested if the Investigator 
suspects Clostridioides 
difficile (C. difficile) 
infection during the study. 
For CV related events see 
Section 8.3.6 
SAE review 
X 
X 
==========================→ 
X 
X 
Record SAE from time 
informed consent signed. 
Concomitant medication 
review 
 
X 
=========================→* 
X 
X 
*Including any rescue 
medication (Section 6.8.3) 
UTI Clinical Symptom Score 
Assessment  
X 
X* 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
*Considered screening and 
Pre-dose baseline 
assessment if screening visit 
is on Day 1. 
The same personnel should 
make the assessment for the 
participant throughout the 
study, where possible.  

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 1: Intensive PK 
Procedure 
Screening #  
(Day -1, can 
be on Day 1) 
Cohort 1: Intensive PK & Clinic Visits [Days] 
Notes: 
# E-consent may be used.  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Clinic Constrained Intervention 
Period [Days] 
6 
 
ToC 
(D10 to 
D13)      
5 to 8 
days 
post 
treatmen
t 
E.D.^ 
Follow-
Up     
(28±3 
days 
followin
g first  
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3 
4 
5 
Investigators Assessment of 
Clinical Resolution Response 
 
 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
The same Investigator 
should make the assessment 
for the participant 
throughout the study, where 
possible. 
PK Urine samples 
 
X 
X* 
X 
X 
X 
X* 
 
 
 
X+ 
 
*Serial PK; see detailed PK 
Table Section 1.3.1.1 
+ If Study Intervention is 
discontinued on Day 1 to 
Day 5, collect samples per 
protocol for corresponding 
day on Table Section 1.3.1.1 
for the last PK collection(s).   

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 1: Intensive PK 
Procedure 
Screening #  
(Day -1, can 
be on Day 1) 
Cohort 1: Intensive PK & Clinic Visits [Days] 
Notes: 
# E-consent may be used.  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Clinic Constrained Intervention 
Period [Days] 
6 
 
ToC 
(D10 to 
D13)      
5 to 8 
days 
post 
treatmen
t 
E.D.^ 
Follow-
Up     
(28±3 
days 
followin
g first  
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3 
4 
5 
Urine Microbiology Bacterial 
sample 
 
X@ 
 
X* 
X* 
X* 
X* 
X@ 
 
X@ 
X 
X 
Clean-catch midstream urine 
sample sent to central labs 
 
 
 
 
 
 
  
 
  
*Pre-dose 
 
 
PK Plasma samples 
 
X 
X* 
X 
X 
X 
X* 
X 
 
 
X+ 
 
*Serial PK; see detailed PK 
Table Section 1.3.1.2 
+ If Study Intervention is 
discontinued on Day 1 to 
Day 5, collect samples per 
protocol corresponding day 
on Table Section 1.3.1.2 as 
the last PK collection(s). 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 1: Intensive PK 
Procedure 
Screening #  
(Day -1, can 
be on Day 1) 
Cohort 1: Intensive PK & Clinic Visits [Days] 
Notes: 
# E-consent may be used.  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Clinic Constrained Intervention 
Period [Days] 
6 
 
ToC 
(D10 to 
D13)      
5 to 8 
days 
post 
treatmen
t 
E.D.^ 
Follow-
Up     
(28±3 
days 
followin
g first  
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3 
4 
5 
Meals 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Daily fluids 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Discharged from clinical unit 
 
 
 
 
 
 
 
X 
 
 
 
 
 
# A site may use an electronic method to obtain participant signature as long as it conforms to 21CFR part 11 and is approved by IRB 
1. Baseline data will be collected at pre-dose on Day 1 (except for triplicate ECG which uses Day -1 screening) 
2. All screening activities to occur within 24 hrs of dosing. Local Lab results may be extended 24+6hrs as long as report assessed prior to 
dosing. 
3. The 24 hour screening period starts from the signing of the main ICF. 
4. Point of Care tests may be utilized when appropriate and describe in Section 10.2 for day -1 screening visit and only on prior 
agreement with GSK 
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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
1.3.1.1. 
Cohort 1 Detailed Urine PK Sampling 
VISIT DAY 
 Cohort 1: Intensive PK: Urine 
 
Intervals: Hours (h)1 
 
Pre-dose 
0-2h 
2-4h 
4-6h 
6-8h 
8-10h 
10-12h 
12-22h 
22-24h 
Notes 
Day 1  
X 
X 
X 
X 
X 
X 
X 
X 
X 
Participants will void bladder prior to dosing 
and this predose urine sample will be 
retained as a control (not combined with 0-
2hr urine collection). 
Day 2  
 
 
 
 
 
 
 
 
X 
22-24 hours post – Day 2 dose 
Day 3 
 
 
 
 
 
 
 
 
X 
22-24 hours post – Day 3 dose 
Day 4 
 
 
 
 
 
 
 
 
X 
22-24 hours post – Day 4 dose 
Day 5 
 
X 
X 
X 
X 
X 
X 
X 
X 
22- 24 hours post – Day 5 dose 
1. The weight of each urine collection will be accurately measured and recorded at the end of each interval prior to aliquoting.  
2. Baseline data will be collected at pre dose on Day 1 (except for triplicate ECG which uses Day -1 screening) 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
1.3.1.2. 
Cohort 1 Detailed Plasma PK Sampling 
VISIT DAY 
 Cohort 1: Intensive PK: Plasma 
 
Hours (h) 
 
Pre-
dose 
0.25h 
0.5h 
1h 
1.5h 
2h 
4h 
6h 
8h 
12h 
16h 
Notes 
Day 1  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Day 2  
X 
 
 
 
 
 
 
 
 
 
 
24 hours post – Day 1 dose 
Day 3 
X 
 
 
 
 
 
 
 
 
 
 
24 hours post – Day 2 dose 
Day 4 
X 
 
 
 
 
 
 
 
 
 
 
24 hours post – Day 3 dose 
Day 5 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Day 6 
X 
 
 
 
 
 
 
 
 
 
 
24 hours post – Day 5 dose 
1.3.2. 
Cohort 2 Reduced PK Sampling During an Outpatient Intervention Period 
Cohort 2: Reduced PK 
Procedure 
Screening 
# 
(Day -1 
or can be 
on Day 1)  
Cohort 2: Reduced PK Sampling & Clinic Visits and Telephone calls [Days] 
Notes: 
# E-consent may be used  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Outpatient Clinic intervention Period 
[Days] *= Telephone call day 
6 
 
ToC (D10 to 
D13)       5 
to 8 days 
post 
treatment 
E.D.^ 
Follow-
Up       
(28 ±3 
days 
following 
first 
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3* 
4* 
5* 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Prescreen ICF available for 
local urinalysis dipstick 
(nitrite and leukocyte 
esterase) and pregnancy test 
Inclusion and exclusion 
criteria 
X 
X* 
 
 
 
 
 
 
 
 
 
 
*If required and remaining 
criteria to confirm. 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 2: Reduced PK 
Procedure 
Screening 
# 
(Day -1 
or can be 
on Day 1)  
Cohort 2: Reduced PK Sampling & Clinic Visits and Telephone calls [Days] 
Notes: 
# E-consent may be used  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Outpatient Clinic intervention Period 
[Days] *= Telephone call day 
6 
 
ToC (D10 to 
D13)       5 
to 8 days 
post 
treatment 
E.D.^ 
Follow-
Up       
(28 ±3 
days 
following 
first 
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3* 
4* 
5* 
 
Full physical examination  
X* 
 
 
 
 
 
 
 
 
X 
X 
X 
* Height and weight 
measured only at screening  
Medical history (includes 
substance usage and 
Family history of 
premature CV disease) 
X 
 
 
 
 
 
 
 
 
 
 
 
Substances: Drugs, Alcohol 
Including the number of UTIs 
participant has had in the last 
12 months and within the last 
2 years 
Urine Drug, Alcohol 
Observational Assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Past and current medical 
conditions   
X 
 
 
 
 
 
 
 
 
 
 
 
Including the number of UTIs 
participant has had in the last 
12 months and within the last 
2 years 
COVID-19 test 
X 
 
X# 
X# 
 
 
 
X# 
 
X 
X 
X 
Rapid turnaround tests 
# Additional rapid turnaround 
test if required by local sites. 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 2: Reduced PK 
Procedure 
Screening 
# 
(Day -1 
or can be 
on Day 1)  
Cohort 2: Reduced PK Sampling & Clinic Visits and Telephone calls [Days] 
Notes: 
# E-consent may be used  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Outpatient Clinic intervention Period 
[Days] *= Telephone call day 
6 
 
ToC (D10 to 
D13)       5 
to 8 days 
post 
treatment 
E.D.^ 
Follow-
Up       
(28 ±3 
days 
following 
first 
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3* 
4* 
5* 
 
Urine pregnancy test  
(for women of child 
bearing potential) 
X^ 
 
 
X* 
 
 
 
 
 
X 
X@ 
 
^ Can be completed as a 
prescreen if Prescreen ICF 
signed. 
* One on-therapy test should 
be conducted on D2  
@ = If E.D is post Day 6 
onward. 
Follicle-stimulating 
hormone and estradiol (as 
needed in women of non-
childbearing potential 
only) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
HIV, Hepatitis B and C 
monitoring sample 
collection and assessment 
of history at screening 
X 
 
 
 
 
 
 
 
 
 
 
 
If test otherwise performed 
within 3 months prior to first 
dose of study intervention, 
monitoring sample at 
screening is not required. 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 2: Reduced PK 
Procedure 
Screening 
# 
(Day -1 
or can be 
on Day 1)  
Cohort 2: Reduced PK Sampling & Clinic Visits and Telephone calls [Days] 
Notes: 
# E-consent may be used  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Outpatient Clinic intervention Period 
[Days] *= Telephone call day 
6 
 
ToC (D10 to 
D13)       5 
to 8 days 
post 
treatment 
E.D.^ 
Follow-
Up       
(28 ±3 
days 
following 
first 
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3* 
4* 
5* 
 
Laboratory assessments 
(haematology, chemistry 
include liver chemistries 
and urinalysis) 
X* 
X 
 
X 
 
 
 
X 
 
X 
X 
X 
*Sample at screening 
processed by local labs: urine 
dipsticks (nitrite and 
leukocyte esterase) can be 
completed as a prescreen  
On therapy samples will be 
obtained pre-dose. 
See footnote 
12-lead ECG 
X 
 
X 
 
 
 
 
X 
 
X 
X 
X 
Triplicate ECG at screening 
and single ECG at all 
subsequent visits. 
 
Vital signs 
X 
X 
X 
X 
 
 
 
X 
 
X 
X 
X 
Triplicate measurements of 
blood pressure and pulse rate 
will be obtained at screening 
and baseline and averaged. 
Single measurements will be 
obtained pre-dose at all other 
timepoints. 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 2: Reduced PK 
Procedure 
Screening 
# 
(Day -1 
or can be 
on Day 1)  
Cohort 2: Reduced PK Sampling & Clinic Visits and Telephone calls [Days] 
Notes: 
# E-consent may be used  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Outpatient Clinic intervention Period 
[Days] *= Telephone call day 
6 
 
ToC (D10 to 
D13)       5 
to 8 days 
post 
treatment 
E.D.^ 
Follow-
Up       
(28 ±3 
days 
following 
first 
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3* 
4* 
5* 
 
Genetic sample (optional) 
 
X 
 
 
 
 
 
 
 
 
 
 
Pre-dose (baseline), Germline 
genetic research may be 
described in a separate ICF or 
as part of a combined ICF. A 
separate signature is required 
where participant 
participation is optional.  
This sample differs from 
urine bacterial samples that 
will be collected for potential 
genetic analysis.  
Study intervention 
administration 
 
 
X 
X 
X* 
X* 
X* 
 
 
 
 
 
* Supplies for home 
administration, supplied at 
previous site visit; patients 
may also be sent home with 
PM dose on clinic days  
Patient Diary Distribution 
and Review 
 
 
X 
X* 
 
X* 
 
X* 
 
 
 
 
Paper diaries to record date 
and time medication taken 
and conmeds  
*Review and record diary 
entries in in electronic case 
report form (eCRF) (Day 6 is 
review only) 

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Clinical Study Protocol template V16 dated 24-Jun-2021 
 
Cohort 2: Reduced PK 
Procedure 
Screening 
# 
(Day -1 
or can be 
on Day 1)  
Cohort 2: Reduced PK Sampling & Clinic Visits and Telephone calls [Days] 
Notes: 
# E-consent may be used  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Outpatient Clinic intervention Period 
[Days] *= Telephone call day 
6 
 
ToC (D10 to 
D13)       5 
to 8 days 
post 
treatment 
E.D.^ 
Follow-
Up       
(28 ±3 
days 
following 
first 
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3* 
4* 
5* 
 
AE review 
 
 
====================================→ 
X 
X 
Record AE from time of first 
dose of study Treatment.  
Stool sample collected and 
tested if the Investigator 
suspects Clostridioides 
difficile (C. difficile) infection 
during the study. 
For CV related events see 
Section 8.3.6  
SAE review 
X 
X 
====================================→ 
X 
X 
Record SAE from time 
informed consent signed. 
Concomitant medication 
review 
 
X 
 ==================================→ * 
X 
X 
*Including any rescue 
medication (Section 6.8.3.) 

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Cohort 2: Reduced PK 
Procedure 
Screening 
# 
(Day -1 
or can be 
on Day 1)  
Cohort 2: Reduced PK Sampling & Clinic Visits and Telephone calls [Days] 
Notes: 
# E-consent may be used  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Outpatient Clinic intervention Period 
[Days] *= Telephone call day 
6 
 
ToC (D10 to 
D13)       5 
to 8 days 
post 
treatment 
E.D.^ 
Follow-
Up       
(28 ±3 
days 
following 
first 
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3* 
4* 
5* 
 
UTI Clinical Signs and 
Symptom Score 
Assessment 
X 
X# 
 
X 
 
X* 
 
X 
 
X 
X 
X 
#Considered screening and 
Pre-dose baseline assessment 
if screening visit is on Day 1. 
The same personnel should 
make the assessment for the 
participant throughout the 
study, where possible. 
*Assessment of the UTI 
clinical signs and symptoms 
score must be conducted via 
telephone. The investigator 
should also assess for any 
nausea, vomiting, diarrhea or 
poor fluid intake that may 
pose a potential risk to renal 
function.  
Investigators Assessment 
of Clinical Resolution 
Response 
 
 
 
X 
 
X* 
 
X 
 
X 
X 
X 
The same Investigator(s) 
should make the assessment 
for the participant throughout 
the study, where possible. 
 
*The Investigators 
Assessment of Clinical 
Resolution Response must be 
conducted via telephone. 

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Cohort 2: Reduced PK 
Procedure 
Screening 
# 
(Day -1 
or can be 
on Day 1)  
Cohort 2: Reduced PK Sampling & Clinic Visits and Telephone calls [Days] 
Notes: 
# E-consent may be used  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Outpatient Clinic intervention Period 
[Days] *= Telephone call day 
6 
 
ToC (D10 to 
D13)       5 
to 8 days 
post 
treatment 
E.D.^ 
Follow-
Up       
(28 ±3 
days 
following 
first 
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3* 
4* 
5* 
 
Telephone Call to review 
clinical symptoms and 
AEs 
 
 
 
 
X 
X 
X 
 
 
 
 
 
If contact cannot be made, 3 
separate attempts should be 
made to speak with the 
participant. 
. 
PK Urine sample 
 
 
 
X* 
 
 
 
X* 
 
 
X+ 
 
*= Pre dose, 24h after 
previous dose 
Participants will void bladder 
prior to dosing. Sample will 
be accurately weighed and 
recorded prior to aliquoting. 
+ If Study Intervention is 
discontinued no samples will 
be collected at subsequent 
visits. 

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Cohort 2: Reduced PK 
Procedure 
Screening 
# 
(Day -1 
or can be 
on Day 1)  
Cohort 2: Reduced PK Sampling & Clinic Visits and Telephone calls [Days] 
Notes: 
# E-consent may be used  
^E.D = early 
discontinuation/withdrawal; 
see early discontinuation 
section 
Outpatient Clinic intervention Period 
[Days] *= Telephone call day 
6 
 
ToC (D10 to 
D13)       5 
to 8 days 
post 
treatment 
E.D.^ 
Follow-
Up       
(28 ±3 
days 
following 
first 
dose) 
1 
(Pre-
Dose) 
1 
(Post- 
Dose) 
2 
3* 
4* 
5* 
 
Urine Microbiology 
Bacterial sample 
 
X@ 
 
X* 
 
 
 
X@ 
 
X@ 
X 
X 
Clean-catch midstream urine 
sample sent to central labs 
 
 
 
 
 
 
 
 
 
  
*Pre-dose 
 
 
PK Plasma sample 
 
 
 
X* 
 
 
 
X* 
 
 
X+ 
 
*= Pre dose, 24h after 
previous dose 
+ If Study Intervention is 
discontinued no samples will 
be collected at subsequent 
visits. 
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• 
The Competent Authority (CA) and independent ethics committee (IEC) will be informed of any safety issues that constitute a 
substantial amendment and require alteration of the safety monitoring scheme or amendment of the informed consent form (ICF). The 
changes will be approved by the CA and the IEC before implementation. 
• 
# A site may use an electronic method to obtain participant signature as long as it conforms to 21CFR part 11 and is approved by 
IRB: Baseline data will be collected at pre dose on Day 1 (except for triplicate ECG which uses Day -1 screening) 
• 
All screening activities to occur with 24 hrs of dosing. Lab results may be extended 24 +6 hrs as long as report assessed prior to 
dosing. 
• 
The 24 hour screening period starts from the signing of the main ICF. 
• 
Point of Care tests may be utilized when appropriate and describe in Section 10.2 for day -1 screening visit and only on prior 
agreement with GSK 
 

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2. 
INTRODUCTION 
2.1. 
Study Rationale  
GSK3882347 is a novel, bacterial attachment inhibitor, designed to treat or prevent 
uncomplicated urinary tract infections (uUTI) caused by Escherichia coli (E. coli). 
During an acute uUTI, E. coli binds and enters bladder mucosa cells via the bacterial 
FimH-containing pili. Within the uroepithelial cells the bacteria rapidly divide and are 
subsequently released from the mucosal cells into the bladder prompting further cycles of 
attachment, invasion and replication. When used for the treatment of acute bacterial 
infection, as is proposed in this Phase 1b study, it is anticipated that GSK3882347 will be 
present in the urine of study participants at sufficiently high concentrations to prevent 
binding of the E. coli which are released into the bladder during these replicative bursts, 
thus halting further infection cycles and leading to microbiological and clinical resolution 
of disease. [Flores-Mireles, 2015]. 
2.2. 
Background 
GSK3882347 binds to the FimH adhesin on type 1 pili of E. coli, preventing bacterial 
adhesion to the bladder mucosal surface by disrupting the interaction between FimH and 
the mammalian mannose-rich glycoproteins, such as uroplakin Ia and integrins in the 
bladder. 
 
 
  
For Macrobid (Control Active comparator), detailed description of pharmacology, 
efficacy and safety are provided in the current [Macrobid Prescribing Information, 2024]. 
2.3. 
Benefit/Risk Assessment 
More detailed information about the known and expected benefits and risks and 
reasonably expected adverse events (AEs) of GSK3882347 and Nitrofurantoin may be 
found in the Investigator’s Brochure 
] and the 
locally approved prescribing information (Summary Product Characteristics), 
respectively. 
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2.3.1. 
Risk Assessment 
Potential Risk 
of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Study Intervention: GSK3882347 
Key potential risk: 
Gastrointestinal 
toxicity 
(including body 
weight loss, 
decreased food 
consumption 
and 
dehydration), 
for awareness. 
Nonclinical 
In a 14-day definitive toxicity study, dogs 
given ≥
 mg/kg/day had severe body weight 
loss, decreased food consumption, 
dehydration, emesis and abnormal feces. Dogs 
given 
 mg/kg/day were euthanized early 
due to severity of body weight loss. 
Pregnant rabbits given ≥
 mg/kg/day had 
severe body weight loss and decreased food 
consumption after 1 to 2 weeks of daily 
dosing, which resulted in early euthanasia and 
1 early death at 
 mg/kg/day. 
These changes in dogs and rabbits resulted in 
early euthanasia or death at the doses stated.  
In a 13 week toxicity study in dogs, doses up 
to 
 mg/kg/day were tolerated with non-
adverse signs of salivation and emesis 
throughout the dosing period. 
Dosing for a maximum of 5 days. 
Standard clinical monitoring with elicitation of clinical symptoms; 
physical examinations and routine safety blood haematology and 
chemistry tests (Section 1.3). 
Monitoring for AEs. Any GI event will be monitored and recorded 
for severity according to DMID (division of microbiology and 
infectious diseases) adult toxicity guidance (Section 10.7). 
 
 
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Potential Risk 
of Clinical 
Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
Clinical 
During the first time in human (FTIH) 
(212148) study in healthy participants, there 
were no reports of any gastrointestinal serious 
adverse events. 
There were two non-serious gastrointestinal 
AEs reported that were considered related to 
study treatment (mild intermittent diarrhoea in 
2 participants). One participant received 
placebo and one received GSK3882347 
 mg 
 for 7 days. In both cases the diarrhea was 
mild in severity and recovered within 48 
hours. 
Renal Changes 
Nonclinical 
Dogs given ≥
 mg/kg/day for 14 days had 
minimal to slight degeneration/ regeneration 
with changes in clinical pathology parameters 
(increased serum urea nitrogen and creatinine) 
which also correlated with clinical signs of 
dehydration as these dose levels were not 
considered tolerated. 
In a 14-day 
 toxicity study in rats, 
minimal to moderate tubule cell hypertrophy 
was noted in the kidney of animals given ≥
 
mg /kg /day, slight tubule cell degeneration 
/necrosis of tubule cells was also noted in one 
Dosing at a lower dose and for shorter duration than the regimen 
used in the FTIH study 
 mg 
 for a maximum of 5 days). 
Standard clinical monitoring with elicitation of clinical symptoms; 
physical examinations and routine safety blood haematology, 
chemistry tests and urinalysis (Section 1.3). 
Monitoring for AEs. Any renal event will be monitored and 
recorded for severity according to DMID (division of microbiology 
and infectious diseases) adult toxicity guidance (Section 10.7). 
Monitoring of serum creatinine levels with follow up assessments 
obtained for any change from baseline >1.5X (Section 8.2.4.2) 
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Potential Risk 
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Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
male given 
 mg /kg /day. In the urinary 
bladder epithelial cell hypertrophy was noted 
in animals given ≥
 mg/kg/day. These renal 
and bladder findings were not accompanied by 
changes in clinical pathology or alterations of 
urinalysis endpoints. 
In a 14-day BID 
 investigative 
study in rats, minimal to moderate tubular 
degeneration/regeneration was seen in rats 
given ≥
 mg/kg/day twice daily (total daily 
dose ≥
 mg/kg/day) which survived for the 
duration of the study, along with multifocal 
proximal tubule and/or collecting duct hyaline 
droplets, minimal to mild/slight multifocal 
medullary collecting duct hypertrophy and 
minimal to slight hypertrophy in the bladder. 
There were also decreases in serum chloride 
and potassium but no changes in urea or 
creatinine. 
In a 13-week toxicity study, 5 rats given 
 
mg/kg/day were euthanized in moribund 
condition between Days 26 and 88 (with body 
weight loss and clinical signs of non-
tolerability including dehydration) following 
 administration of GSK3882347. 
The clinical condition was attributed to tubular 
 
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Significance 
Summary of Data/Rationale for Risk 
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degeneration/ regeneration in the kidney. 
Other urinary tract findings included tubular 
dilatation, interstitial mononuclear cell 
infiltration, neutrophilic inflammation in the 
papilla and epithelial and urothelial 
hypertrophy/ hyperplasia of the papilla lining, 
pelvis and/or urinary bladder, respectively. In 
addition, there were increases in serum urea, 
creatinine, phosphorus and potassium and 
increased urinary protein and glucose 
excretion in rats given 
 mg/kg/day.  
In a 26-week rat toxicity study, there was a 
slight increased incidence of tubule basophilia 
(graded as minimal) in the kidney of males at 
 mg/kg/day and increased incidence of 
hyaline droplet accumulation (graded as 
minimal) in the kidney tubular epithelium of 
males at ≥
 mg/kg/day, both which may be 
an exacerbation of spontaneous changes. In 
the urinary bladder epithelium 
hypertrophy/hyperplasia was noted in of males 
at ≥
 mg/kg/ day and females at ≥
 
mg/kg/day. At 
 mg/kg/day there was an 
increase in mean urine microalbumin and 
urine clusterin concentration (females only). 
Changes in urinary biomarkers and 
microscopic renal findings were considered 
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Significance 
Summary of Data/Rationale for Risk 
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fully recovered after 8 weeks off-dose, the 
urinary bladder changes at 
 mg/kg/day 
were still present after 8 weeks off-dose but 
occurred with decreased incidence suggesting 
partial reversal. 
In a 14 day 
 toxicity study in dogs, 
minimal to slight degeneration/ regeneration 
was observed in the kidney with changes in 
clinical pathology parameters (increased 
serum urea nitrogen and creatinine) at doses 
≥
 mg/kg/day, these changes also correlated 
with clinical signs of dehydration as these 
dose levels were not considered tolerated. 
In a 39-week toxicity study in dogs there was 
an increased incidence of non-adverse tubular 
degeneration/regeneration in males at ≥
mg/kg/day and in females at 
 mg/kg/day. 
These changes were not seen after the 8-week 
recovery period. Additionally, unclassified 
urinary crystals were noted in the urine 
microscopic evaluation of a few animals at 
 mg/kg/day, during the dosing period. 
Clinical 
During the FTIH (212148) study 
in healthy participants, there were no reports 
of any renal associated adverse events. In this 
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Significance 
Summary of Data/Rationale for Risk 
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study participants received up to 
 mg 
 
dose for 7 days. 
Other 
Nitrofurantoin 
(Macrobid) 
The most frequent AEs possibly or probably 
related to oral nitrofurantoin treatment are 
nausea (8%), headache (6%), and flatulence 
(1.5%). There is also a need to monitor for C. 
difficile-associated diarrhea during 
nitrofurantoin treatment. 
Refer to locally approved nitrofurantoin 
prescribing information for specific details 
relating to nitrofurantoin. 
Nitrofurantoin is contraindicated for patients 
with anuria, oliguria, or significant 
impairment of renal function; pregnant 
patients at term (38 to 42 weeks’ gestation), 
during labour and delivery, or when the onset 
of labour is imminent; neonates under 1 month 
of age; and patients with a previous history of 
cholestatic jaundice/hepatic dysfunction 
associated with nitrofurantoin. 
Rare adverse reactions that generally occur in 
patients receiving treatment for 6 months or 
longer are acute, subacute, or chronic 
pulmonary reactions, with potential insidious 
Monitoring of clinical parameters and AEs (SoA Section 1.3) will 
be conducted, and treatment monitoring and evaluation criteria 
(Section 7.1.1) will be utilized to mitigate hepatic effects. 
The exclusion criteria for this study include contraindications to 
nitrofurantoin use, exclude participants at risk for nitrofurantoin 
adverse reactions, and Section 5.2 participants with a history of 
sensitivity to nitrofurantoin, or components thereof (Section 5.2). 
Participants must agree not to use antacid preparations containing 
magnesium trisilicate or uricosuric drugs during study intervention 
(Section 5.2). 
Suspected C. difficile infection will be managed according to a 
prespecified algorithm provided in Section 10.9. 
Information on the prevalence and duration of effect and onset of 
actions associated with discolouration is limited. To further 
minimize the risk of unblinding due to urine discolouration sites will 
be asked to ensure personnel that are collecting urine samples are 
separate from personnel conducting the assessment of clinical 
resolution of symptoms and the personnel conducting the clinical 
symptom scoring assessments. 
Precautions related to nitrofurantoin are summarized in detail in the 
Study Reference Manual. 
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Significance 
Summary of Data/Rationale for Risk 
Mitigation Strategy 
development of chronic pulmonary reactions 
(diffuse interstitial pneumonitis or pulmonary 
fibrosis, or both). 
Peripheral neuropathy has occurred, which 
may be enhanced for patients with anemia, 
diabetes mellitus, electrolyte imbalance, 
vitamin B deficiency, and debilitating disease. 
Nitrofurantoin has induced the occurrence of 
hemolytic anemia of the primaquine-
sensitivity type, which appear to be linked to a 
glucose-6-phosphate dehydrogenase 
deficiency in the red blood cells of the 
affected patients. 
Hepatic reactions, including hepatitis, 
cholestatic jaundice, chronic active hepatitis, 
and hepatic necrosis, occur rarely. 
Concomitant administration of nitrofurantoin 
with antacids containing magnesium trisilicate 
reduces both the rate and extent of absorption, 
and uricosuric drugs, such as probenecid and 
sulfinpyrazone, can inhibit renal tubular 
secretion of nitrofurantoin. 
Uncommon, side effects include dark coloured 
urine, changes in facial skin colour. There is 
little information on the details (e.g. 

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prevalence and onset and duration) however, 
there may be a risk for unblinding within the 
study. 
Potential 
increased risk 
of participants 
and site staff 
contracting 
coronavirus 
disease 2019 
(COVID-19). 
 
Participation within a healthcare environment 
may increase risk of contracting COVID-19. 
Exposure to other participants and staff may 
increase risk of exposure. 
While no longer in a pandemic state, depending on incidence rates 
in the community, COVID-19 (severe acute respiratory syndrome 
coronavirus-2 [SARS-CoV-2]) may pose a challenge to integrity of 
the trial, protection of participants’ rights, safety and wellbeing and 
the safety of clinical trial staff. Therefore, risk mitigation strategies 
have been introduced and will be evaluated on an ongoing basis per 
each country. 
• Monitoring for the clinical presentation of COVID-19 
signs/symptoms. 
• Conduct study at sites which have appropriate mitigation 
strategies in place. 
• Rapid turnaround COVID testing at screening. Parallel PCR 
testing for 5-day inpatient period in Cohort 1. Rapid Turnaround 
testing at all other visits requiring COVID testing. See SoA 
Section 1.3. 
 

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2.3.2. 
Benefit Assessment 
2.3.3. 
Overall Benefit: Risk Conclusion 
Potential medical benefit may be derived for participants randomised to the nitrofurantoin 
arm as this is a recommended treatment for uUTI. Participants randomised to the 
GSK3882347 arm in this study may not receive any therapeutic benefit as the efficacy 
profile is unknown. This is a blinded study and Investigator and Participant will not know 
the randomised treatment assignment. All the participants will be contributing to the 
development of a potential novel therapy in an area of unmet need. 
The anticipated benefits of GSK3882347 are its use will not contribute to the rising 
resistance rates observed with conventional antibiotic therapies, and, due to its narrow 
spectrum of activity and mode-of-action, minimal dysbiosis is anticipated. 
3. 
OBJECTIVES AND ENDPOINTS AND/OR ESTIMANDS 
Objectives 
Endpoints 
Primary 
• 
To assess the microbiological efficacy 
of GSK3882347 at the Test of Cure 
(ToC) visit in participants with uUTI 
who have qualifying E. coli at baseline 
• 
Microbiological response at the ToC 
Visit 
Secondary 
• 
To evaluate the safety and tolerability 
following 
 oral dosing for 5 
days of GSK3882347 in participants 
with uUTI 
• 
Occurrence of adverse events (AEs) 
and serious adverse events (SAEs)  
• 
Clinically significant changes from 
baseline in laboratory values 
(hematology, chemistry and 
urinalysis), vital signs and 12lead 
electrocardiogram (ECG) readings at 
each visit 
• 
To evaluate the plasma and urine 
pharmacokinetic (PK) concentrations 
following 
 oral dosing for 5 
days of GSK3882347 in participants 
with uUTI 
Plasma: 
• 
GSK3882347 concentration 
Urine 
• 
Urine concentration at 22-24h 
interval collection post-dose 
Exploratory* 
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Objectives 
Endpoints 
• 
To evaluate the resolution of clinical 
symptoms over time of GSK3882347 
in participants with uUTI caused by E. 
coli 
• 
Clinical resolution response on Day 
2 through to Day 6 (when collected 
and as data permit), ToC and 
Follow-up Visit 
• 
To evaluate the resolution of clinical 
symptoms over time of GSK3882347 
in participants with uUTI caused by E. 
coli using an exploratory scoring 
system 
• Clinical symptom score outcome and 
response on Days 1 through to Day 6 
(when collected and as data permit), 
ToC and Follow-up Visit 
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Objectives 
Endpoints 
* Details regarding the exploratory analyses will be described in the statistical analysis 
plan (SAP). Some exploratory data may not be available until after the main database 
lock and may be analysed/reported separately. 
Estimands for Primary Endpoint  
The primary clinical question of interest is: What is the microbiological response for 
GSK3882347 assessed at ToC in participants with acute uUTI caused by E. coli 
uropathogens at Baseline who completed the planned course of treatment (5 days) and 
had no major deviations from protocol that would prevent evaluation of efficacy (as 
defined in the Study Deviation Rules Document). Use of rescue medication will be set to 
non-responder in the endpoint definition 
The Primary estimand is described by the following attributes: 
• 
Population: Female participants with acute uUTI with a qualifying baseline E. coli 
uropathogen (Section 10.8) at baseline who completed the planned course of 
treatment (5 days) and had no major deviations from protocol that would prevent 
evaluation of efficacy 
• 
Treatment condition: GSK3882347 
 given orally
 for 5 days 
• 
Variable: Microbiological response at ToC visit 
• 
Summary measure: Frequency and percentage of participants with microbiological 
response (responder/non-responder) in GSK3882347 treatment group  
• 
Main intercurrent events anticipated: 
o Use of rescue medication prior to ToC visit- Composite strategy 
o This intercurrent event is captured through the definitions of microbiological 
response (see Section 9.3.2) and will be considered as non-responders. 
o Participants who are lost to follow-up prior to ToC, have a missing/unevaluable 
sample at ToC, discontinue study treatment due to any reason (withdrawal of 
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consent/AEs/missed doses) will not be included in the analysis and may be 
replaced at the discretion of the Sponsor. 
• 
Rationale for estimand: 
Use of rescue medication may impact microbiological outcomes, therefore, the definition 
of a successful microbiological response precludes the use of rescue medications. In this 
small, early phase, proof of mechanism study, interest lies in the treatment effect of 
participants who completed the planned course of treatment and follow important 
components of the study protocol. 
Details of supportive estimands may be provided in the SAP.  
Estimand for Secondary Endpoints 
The secondary clinical questions of interests are, 
1. To evaluate the safety and tolerability following 
 oral dosing for 5 days of 
GSK3882347 in adult female participants with uUTI 
The estimand is described by the following attributes: 
• 
Population: Female participants with acute uUTI. 
• 
Treatment condition: GSK3882347
 given orally
 for 5 days. 
• 
Variables:  
o Occurrence of adverse events (AEs) and serious adverse events (SAEs) 
o Clinically significant changes from baseline in laboratory values (haematology, 
chemistry and urinalysis), vital signs and 12 lead electrocardiogram (ECG) 
readings at each visit. 
• 
Summary measure: Frequency and percentages for AEs, SAEs, laboratory values, 
vital signs and ECG values.  
• 
Main intercurrent events anticipated: 
o Use of rescue medication -While on treatment strategy 
▪ Rescue medication could influence safety reporting and therefore, only 
safety data while participants are taking the study intervention will be 
considered for the analysis.  
o Discontinuation from the treatment due to any reasons (withdrawal of consent 
/AEs (if not part of the endpoint definition, for e.g., in AE and SAE)/missed 
doses)-Treatment policy strategy 
▪ The occurrence of this intercurrent event is considered irrelevant in 
evaluating safety, as interest lies in the full safety profile. 
2. To evaluate the plasma and urine PK parameters following 
 oral dosing for 
5 days of GSK3882347 
The estimand is described by the following attributes: 
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• 
Population: Female participants with acute uUTI 
• 
Treatment condition: GSK3882347 given orally 
 for 5 days 
• 
Variables:  
o Plasma: 
▪ 
: AUC(0-inf), Cmax, and tmax collected on Day 1 
▪ 
 Day 5 AUC (0-24), Cmax, and tmax collected following 5th 
dose, pre-dose Ctau and AUC(0-tau) 
▪ Urine: 
▪ Urine concentration at 22-24h collection following dose on Day 1 and Day 
5, as data permit 
▪ Amount excreted in urine (Ae) of unchanged GSK3882347, fraction of the 
dose excreted in urine (fe), and renal clearance (CLr), as data permit. 
• 
Summary measure: Mean, 95% confidence interval (CI), standard deviation (SD), 
median, minimum and maximum for non-transformed data of all PK parameters. 
Geometric mean, 95% CI of geometric mean, SD and coefficient of variation (CV) 
of geometric mean, for log transformed data for all PK parameters except for Tmax. 
• 
Main intercurrent events anticipated: 
o Use of rescue medication  
o Discontinuation from the treatment due to any reasons (AEs/withdrawal of 
consent/missed doses) 
All these intercurrent events will be handled using while on treatment strategy as PK data 
will be collected only when participants are on treatment. 
4. 
STUDY DESIGN 
4.1. 
Overall Design 
• 
This Phase 1b study is a double-blind, double-dummy, nitrofurantoin-controlled 
study, designed primarily to evaluate microbiological response at the ToC visit and 
safety, tolerability and PK response following 
 oral dosing for 5 days of 
GSK3882347 in adult female participants with uUTI. Nitrofurantoin will be included 
in the study to ensure unbiased reporting of safety events. Clinical resolution and 
clinical symptom score will be part of the exploratory objectives of this proof of 
mechanism study. A detailed review of the microbiological characterization and time 
to response will also be explored. Aside from microbiological characterization no 
formal statistical comparisons of GSK3882347 and nitrofurantoin are planned. 
 
 All participants who provide informed consent and 
meet the study entry criteria will be randomized to receive either 
 
GSK3882347 or 100 mg BID nitrofurantoin in a 3:1 ratio. Safety assessments will be 
conducted throughout the study duration; pre-treatment and post-treatment urine and 
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plasma PK collections will be performed and appropriate microbiological, clinical 
 assessments will also be conducted. 
• 
As this is a first in patient study in women with uUTI, who are essentially otherwise 
healthy, it was considered a high patient burden to ask all participants to remain in-
house for the duration of dosing. Further considerations in the study design included 
a lack of sites where the study could be run plus the recruitment challenges that 
mandating an in-house stay would bring. As it is not considered necessary to obtain 
full PK profiles from every study participant, and to ease participant burden, there 
will be 2 participant cohorts in the study: 
• 
Cohort 1 is an inpatient cohort: For this cohort, intensive PK sampling will be 
conducted during the intervention period and more frequent analyses of 
microbiological and clinical response to therapy will be assessed. 
• 
Cohort 2 is an outpatient cohort: The PK, microbiological, and clinical 
responses to therapy will be assessed less frequently in this cohort. 
• 
It is anticipated that there will be a limited number of Study Sites permitted to recruit 
Cohort 1, these Sites may also be allowed to enroll Cohort 2 at the same time, as 
agreed by GSK. 
• 
Participants will consent using the materials corresponding to the cohort they are 
joining, either Cohort 1 or Cohort 2.  
• 
If at any time during the study, participants experience new or worsening signs and 
symptoms of UTI, they will be assessed (at site visits or in discussion over 
telephone, see SoA) and treated per the investigator’s judgment. 
• 
The screening period can be up to 24 hours prior to the first day of dosing. The 
Treatment period will consist of 5 days. 
• 
Cohort 1 participants will be discharged from the clinic on Day 6 and asked to 
return for the ToC visit 5-8 days following the last day of dosing. Participants 
will be asked to attend a Follow-up Visit ~28 days after the start of Treatment. 
The duration of the study will be approximately 28 days. 
• 
Cohort 2 participants will attend outpatient visits on Days 1, 2, and 6 and asked 
to return for the ToC visit 5-8 days following the last day of dosing. Participants 
will be asked to attend a Follow-up Visit ~28 days after the start of Treatment. 
For treatment discontinuation and participant withdrawal, see discontinuation criteria 
section. 
 
4.2. 
Scientific Rationale for Study Design 
This Phase 1b study is designed primarily to evaluate microbiological response of 
GSK3882347 in female participants with uUTI. The sample size is not sufficiently large 
to enable firm conclusions to be made around therapeutic efficacy (clinical and 
microbiological outcomes and response) in relation to Standard of Care (SoC). However, 
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it will provide a preliminary assessment of the microbiologic efficacy of GSK3882347 in 
this patient population. This is important to establish prior to initiating larger Phase 2/3 
studies.  
As this will be the first study to evaluate GSK3882347 in females with UTI, safety is a 
key secondary endpoint for the study. The safety of GSK3882347 has previously been 
evaluated in one FTIH study (212148) and no safety issues were observed; there are no 
additional safety concerns with this proposed study in participants with ongoing uUTI 
infection. 
 
 (see Section 
4.3), 
 
  
Due to the specificity of GSK3882347 for E. coli, it is anticipated that its use will not 
lead to the dysbiosis caused by other treatments which also eradicate other genera such as 
Lactobacillus, which are important in maintaining gut homeostasis and are protective 
against UTI. This in turn should lead to reductions in the overgrowth of bacteria and 
yeast in the vagina, e.g. Candida albicans which is a common consequence of antibiotic 
therapy and can itself lead to long term issues with recurrence. 
 
 
 
 
 
 
  
4.3. 
Justification for Dose 
GSK3882347 
The oral GSK3882347 dose in this study is 
 for 5 days. A 5-day dosing 
duration is in alignment with current treatment guidelines for efficacious antibacterial 
treatment of uUTI in women, which typically ranges from 3 to 7 days [Gupta, 2011, 
NICE, 2018, EAU, 2024]. The safety and tolerability of oral doses up to 
 
 
 has been evaluated in Phase 1 Study 212148 and there were neither SAE reports nor 
clinically significant changes in the laboratory data, vital signs, or electrocardiogram. All 
reported AEs were mild/moderate in intensity and had fully resolved by the time of 
participant discharge from the study. 
 
 
 
 
. 
 
 
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 However, unlike 
traditional antibiotics, GSK3882347 is a novel, bacterial attachment inhibitor for which 
translation from the murine acute cystitis model has not been validated in patients with 
acute uUTI. 
 
 
 Given that the bladder is the site of action of 
GSK3882347, the use of GSK3882347 urine PK data is appropriate for selecting the 
GSK3882347 
 
 oral dose for 5 days for study in the treatment of participants 
with uUTI. 
 
 
 
 
 
Mean plasma exposure following a dose of
 × 
 was below the safety 
margin established in the rat 14-day GLP toxicity study, No-observed-adverse-effect 
Level (NOAEL) of 
/kg/day. There was 4-fold and 3-fold coverage for Day 1 and 
Day 7 AUC(0-24), respectively; there was 3.4-fold and 3.1-fold coverage to the Day 1 
and Day 7 Cmax, respectively. 
 
 
 
Nitrofurantoin (Macrobid) 
The oral nitrofurantoin dose in this study is 100 mg BID, a total daily dose of 200 mg, for 
5 days. The label indicates, for treatment of uUTI caused by susceptible strains of E. coli 
or S. saprophyticus, in adults and paediatric patients over 12 years of age, a 100 mg BID 
dose for up to 7 days (refer to locally approved prescribing information). The labelled 7-
day dosing duration of nitrofurantoin was based on clinical registration studies from 
several decades ago. More recently, a 5-day dosing duration of nitrofurantoin was shown 
to be efficacious for the treatment of uUTI in women [Gupta, 2007] and a treatment 
duration of 3-5 days for nitrofurantoin is in alignment with current treatment guidelines 
[Gupta, 2011, NICE, 2018, EAU, 2024]. 
4.4. 
End of Study Definition 
The end of the study is defined as the date of the last visit of the last participant in the 
study it is expected to be the last scheduled procedure shown in the Schedule of 
Activities for the last participant in the study at the Follow-up Visit. 
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A participant is considered to have completed the study if all periods of the study up to 
and including the Follow-up Visit have been completed. 
5. 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
Note: Enrolled means a participant's, or their legally acceptable representative’s, 
agreement to participate in a clinical study following completion of the informed consent 
process and screening. Potential participants who are screened for the purpose of 
determining eligibility for the study, but do not participate in the study, are not 
considered enrolled, unless otherwise specified by the protocol. A participant will be 
considered enrolled if the informed consent is not withdrawn prior to participating in any 
study activity after screening. 
5.1. 
Inclusion Criteria 
Participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age 
a. 
Participant must be ≥18 years of age and ≤70 years of age at the time of signing the 
informed consent. 
Type of Participant and Disease Characteristics 
b. The participant has 2 or more of the following clinical signs and symptoms of uUTI 
with onset <96 hours of the screening assessment: dysuria, frequency, urgency, or 
lower abdominal pain. 
c. 
The participant has nitrite OR pyuria (≥10 WBC/mm3 OR >5 WBC/HPF OR the 
presence of at least 2+ leukocyte esterase) from a pre-treatment clean-catch 
midstream urine sample based on local laboratory procedures. 
Weight 
d. Body mass index (BMI) ≥19.0 kg/m2). 
Sex and Contraceptive/Barrier Requirements 
e. 
A female participant is eligible to participate if she is not pregnant or breastfeeding, 
and one of the following conditions applies: 
o Is a woman of non-childbearing potential (WONCBP) as defined in Section 10.4: 
Contraceptive and Barrier Guidance. 
OR 
o Is a woman of childbearing potential (WOCBP) and using a contraceptive 
method that is highly effective, with a failure rate of <1%, as described in 
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last dose of study intervention or 5 days after the last dose of study intervention 
for WOCBP choosing hormonal contraceptives (including double barrier 
contraception as stated in Section 10.4). The investigator should evaluate 
potential for contraceptive method failure (e.g., noncompliance, recently 
initiated) in relationship to the first dose of study intervention. 
• A WOCBP must have a negative highly sensitive pregnancy test (urine as required by 
local regulations) before the first dose of study intervention. See Section 8.2.5 
Pregnancy Testing 
• Additional requirements for pregnancy testing during and after study intervention are 
located in Section 8.2.5. 
• The investigator is responsible for review of medical history, menstrual history, and 
recent sexual activity to decrease the risk for inclusion of a woman with an early 
undetected pregnancy. 
Informed Consent 
f. 
Capable of giving signed informed consent as described in Section 10.1.3 which 
includes compliance with the requirements and restrictions listed in the ICF and in 
this protocol. 
5.2. 
Exclusion Criteria 
Participants are excluded from the study if any of the following criteria apply: 
Medical Conditions 
1. Positive highly sensitive urine pregnancy test at screening. 
2. Women that are currently lactating and or breast feeding. 
3. The participant has a BMI ≥40.0 kg/m2 or a BMI ≥35.0 kg/m2 with obesity-related 
health conditions such as high blood pressure or uncontrolled diabetes (defined as a 
non-fasting glucose value >300 mg/dL or based on investigator judgment). 
4. 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., renal transplant recipients, participants with clinically significant persistent 
granulocytopenia [absolute neutrophil count <1000/µL], and participants receiving 
immunosuppressive therapy, including corticosteroid therapy [e.g. ≥40 mg/day 
prednisolone or equivalent for >1 week or; prednisolone or equivalent ≥20 mg/day 
for >2 weeks or; prednisolone or equivalent ≥10 mg/day for >6 weeks]). 
5. The participant has any surgical or medical condition (active or chronic) that may 
interfere with drug absorption, distribution, metabolism, or excretion of the study 
intervention (e.g., ileostomy or malabsorption syndrome). Participants who have had 
a gastric bypass or a cholecystectomy are excluded from the study. 
6. The participant has uUTI that is known or suspected to be due to fungal, parasitic, or 
viral pathogens; or known or suspected to be due to Pseudomonas aeruginosa or any 

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Enterobacterales other than E. coli 
 as the contributing 
pathogen. 
7. The participant has symptoms known or suspected to be caused by another disease 
process, such as asymptomatic bacteriuria, overactive bladder, chronic incontinence, 
or chronic interstitial cystitis, that may interfere with the clinical efficacy 
assessments. 
8. The participant has an anatomical or physiological anomaly that predisposes the 
participant to UTIs or may be a source of persistent bacterial colonization, including 
calculi, obstruction or stricture of the urinary tract, primary renal disease (e.g., 
polycystic renal disease), or neurogenic bladder, or the participant has a history of 
anatomical or functional abnormalities of the urinary tract (e.g., chronic 
vesicoureteral reflux, detrusor insufficiency). 
9. The participant has an indwelling catheter, nephrostomy, ureteral stent, or other 
foreign material in the urinary tract. 
10. The participant who, in the opinion of the investigator, has an otherwise complicated 
UTI, an active upper UTI (e.g., pyelonephritis, urosepsis), signs and symptoms onset 
≥96 hours before the screening assessment, or a temperature ≥101°F/38°C, flank 
pain, chills, or any other manifestations suggestive of upper UTI. 
11. The participant has anuria, oliguria, or significant impairment of renal function 
(eGFR <60 mL/min/1.73m2 [calculated using CKD-EPI 2021; Inker, 2021] or serum 
creatinine >1.5 x upper limit of normal [ULN] at screening). Note: Please reference 
the Study Reference Manual for guidance on calculating the eGFR during screening. 
12. The participant presents at enrollment with a suspected sexually transmitted 
infection. 
13. The participant has congenital long QT syndrome or known prolongation of the 
corrected QT (QTc) interval. 
14. The participant has uncompensated heart failure, defined as New York Heart 
Association Class ≥III. 
15. The participant has severe left ventricular hypertrophy. 
16. The participant has a family history of QT prolongation or sudden death. 
17. The participant has a recent history of vasovagal syncope or episodes of 
symptomatic bradycardia or bradyarrhythmia within the last 12 months. 
18. 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 Fridericia formula, machine, or manual overread.  
19. The participant has an alanine transferase (ALT) value >2 × ULN. 
20. The participant has a bilirubin value >1.5 × ULN (isolated bilirubin >1.5 × ULN is 
acceptable if bilirubin is fractionated and direct bilirubin <35%). 
21. 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 
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gallstones), including viral hepatitis or moderate-to-severe liver insufficiency (Child 
Pugh class B or C). 
22. History of positive human immunodeficiency virus (HIV) antibody or 
antibody/antigen test. 
23. History of presence of Hepatitis B surface antigen (HBsAg) within 3 months prior to 
first dose of study intervention. 
24. History of Hepatitis C antibody test result within 3 months prior to first dose of study 
intervention. 
• 
NOTE: Participants with a history of a positive Hepatitis C antibody due to prior 
resolved disease can be enrolled, only if there is a history of a confirmatory negative 
Hepatitis C ribonucleic acid (RNA). 
25. History of a Positive Hepatitis C RNA test result within 3 months prior to first dose 
of study intervention. 
26. Substance abuse: Active substance abuse or a history of substance abuse (in the 
opinion of the Principal Investigator) within 6 months prior to the initial Screening 
visit. Note that documented medical use of marijuana or occasional recreational use 
of marijuana is permitted. 
27. A positive confirmation of COVID-19 infection, or high clinical index of suspicion 
for COVID-19. 
28. The participant has a history of significant cardiac, endocrinologic, haematologic, 
pulmonary, metabolic, renal (including significant or chronic proteinuria, but 
excluding transient proteinuria in the setting of infection), hepatic, immunologic, 
urologic, neurologic, dermatologic, psychiatric or gastrointestinal conditions that, in 
the opinion of the investigator places the participant at unacceptable risk or would 
make adhering to study procedures for the duration of the study difficult. 
Prior/Concomitant Therapy 
29. The participant has received treatment with other systemic antimicrobials or 
systemic antifungals within 1 week (or 10 weeks for dalbavancin or oritavancin 
before study entry). 
30. The participant does not agree to adhere to the concomitant therapy restrictions as 
described in Section 6.8.2 from the Screening Visit through to the Follow-Up Visit. 
Prior/Concurrent Clinical Study Experience 
31. Participation in the study would result in loss of blood or blood products in excess of 
500 mL within 56 days. 
32. Exposure to more than 4 new chemical entities within 12 months prior to the first 
dosing day. 
33. Current enrollment or past participation within the last 30 days or 5 half-lives, 
whichever is longer, before signing of consent in any other clinical study involving 
an investigational study intervention or any other type of medical research.  

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Other Exclusions 
34. The participant resides in a nursing home or dependent care-type facility. 
35. The participant, in the judgment of the investigator, would not be able or willing to 
comply with the protocol or complete study follow-up. 
36. Regular alcohol consumption within 6 months prior to the study defined as: 
o An average weekly intake of >14 units for females.  
o One unit is equivalent to approximately to 8 g of alcohol: a half-pint (250 ml) of 
beer, one glass (125 mL) of wine or one (35 mL) measure of spirits. 
38. Known hypersensitivity to any of the study interventions, or components thereof, or 
drug or other allergy that, in the opinion of the investigator or medical monitor, 
contraindicates participation in the study. 
39. Contraindication for nitrofurantoin. E.g., hypersensitivity to the active substance, 
other nitrofurans or to any of the excipients, renal dysfunction, known Glucose-6-
phosphate Dehydrogenase (G6PD) deficiency, acute porphyria.  
5.3. 
Lifestyle Considerations 
5.3.1. 
Meals and Dietary Restrictions 
Dietary restrictions: 
• 
There are no known or predicted dietary restrictions for GSK3882347 however, 
because nitrofurantoin will be a blinded comparator in the study and it is 
recommended to take with food (e.g. at mealtimes), the same advice will be given to 
all study participants. 
• 
Water is allowed as desired except one hour before and two hours after dosing, 
except for the glass of water needed to administer the study intervention (e.g. 
maximum 240 mL). 
• Participants should not alter their usual dietary habits (including alcohol consumption 
and tobacco use) from their considered normal whilst participating in the study 
including during the on-treatment phase (from start of screening until the Day 5 22-24 
h PK samples have been taken on Day 6). 
• Participants should not take dietary or herbal supplements, probiotics (drinks/tablets), 
antacid preparations containing magnesium trisilicate, uricosuric drugs or alternative 
medications for the treatment of uUTI (including cranberry juice or tablets/capsules, 
methenamine hippurate, D-mannose) until completion of the Follow-up Visit, unless, 
in the opinion of the investigator and Medical Monitor, the medication will not 
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5.3.2. 
Other Lifestyle Restrictions and Recommendations 
• Participants will be requested to abstain from sexual activity from the Screening Visit 
through the ToC Visit to prevent possible re-infection. 
• Participants should not alter their usual hygiene habits from their considered normal 
(e.g. new washing routine or sanitary products) from the Screening Visit through the 
ToC Visit. 
• Participants will be requested to adhere to local COVID-19 prevention advice for the 
purpose of minimizing any potential risk of infection and potential outbreak at study 
sites and exposure to other participants and staff. Participants will be monitored for 
clinical presentation of COVID-19 signs and symptoms and will be asked to 
communicate any signs or symptoms to the site prior to site visits. 
5.4. 
Screen Failures 
A screen failure occurs when a participant who consents to participate in the clinical 
study is not subsequently randomized. 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, any protocol deviations and any 
serious adverse events (SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may be rescreened if the reason for screen failure is: 
• An ECG or lab value that, in the opinion of the investigator and/or Medical Monitor, 
is spurious or needs to be reconfirmed. 
• Scheduling of Day 1 visit falls outside of 24 hrs; however participant will remain 
within 96 hours of symptom onset. 
This reconfirmation should only be conducted once and if the participant does not meet 
the inclusion criteria following this second analysis, they will be deemed a screen failure. 
If the participant meets the study inclusion criteria following this repeat analysis they will 
retain the original participant number. 
Individuals with an acute UTI who do not meet all of the criteria for participation in this 
study (screen failure), who are not randomised and do not receive GSK3882347, may be 
considered for future study enrollment if they have a subsequent UTI infection provided 
the original UTI infection had been appropriately treated with SoC and the subsequent 
infection was at least 4 weeks after the resolution of the original UTI infection. If such a 
situation arises, inclusion of the participant in the study should be discussed on a case-by-
case basis with the medical monitor. In this situation, a participant should only be 
rescreened once. 
Rescreened participants should be assigned a new participant number. 

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5.5. 
Criteria for Temporarily Delaying 
Enrollment/Randomization/Administration of Study 
Intervention 
There are no planned criteria for temporarily delaying the study. Section 6.5. Dose 
Modification contains instructions for unplanned events. 
6. 
STUDY INTERVENTION(S) AND CONCOMITANT 
THERAPY 
Study intervention is defined as any investigational intervention(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a study participant according 
to the study protocol. 
6.1. 
Study Intervention(s) Administered 
Table 1 
Study Intervention(s) Administered 
Intervention Label 
 
 
Intervention on Label 
GSK3882347+ Placebo 
Nitrofurantoin + Placebo 
Intervention 
Description 
Active Pharmaceutical Ingredient (API) 
alone and with placebo to match 
Nitrofurantoin dosing schedule (100 mg 
BID). 
Nitrofurantoin alone and with placebo to 
match GSK3882347 dosing schedule. 
Type  
Drug 
Drug 
Dose Formulation  
Capsule 
Capsule 
Unit Dose Strength(s)  
 
100 mg/capsule 
Dosage Level(s) 
100 mg BID 
Total Duration  
Participants will receive 
 
for 
5 days 
Participants will receive 100 mg BID for 
5 days 
Route of 
Administration 
Oral 
Study medication will be administered by 
the study personnel (or self-
administered in Cohort 2) during each 
dosing day with approximately 240 mL 
of water and with food. 
Oral 
Study medication will be administered by the 
study personnel (or self-administered in 
Cohort 2) during each dosing day with 
approximately 240 mL of water and with food. 
Use 
Experimental, Placebo 
Safety-comparator, Placebo 
IMP and NIMP 
IMP 
IMP 
Sourcing 
Provided centrally by the GSK 
Provided centrally by the GSK 
Packaging and 
Labeling 
Study intervention will be provided in 
High Density Polyethylene (HDPE) 
bottles. Each bottle will be labeled as 
required per country requirement. 
Study intervention will be provided in HDPE 
bottles. Each bottle will be labeled as 
required per country requirement. 
*Please refer to the SRM for further guidance on the Dose A and Dose B drug 
administration interval.  
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6.2. 
Preparation, Handling, Storage and Accountability 
Details on storage, handling, and allowable excursions for GSK3882347 investigational 
product (IP), nitrofurantoin and Placebo will be provided in the Technical Terms of 
Supply (TTS). Storage for IP and nitrofurantoin is room temperature (not to exceed 
30oC). 
1. A description of the detailed methods and materials required for preparation of 
GSK3882347, nitrofurantoin and Placebo are provided in the TTS. 
2. The capsules will be provided by GSK as per instructions in the TTS that will be 
reviewed and approved by GSK prior to use. 
3. The investigator or designee must confirm appropriate temperature conditions have 
been maintained during transit for all study intervention received and any 
discrepancies are reported and resolved before use of the study intervention. 
4. Only participants enrolled in the study may receive study intervention and only 
authorized site staff may supply or administer study intervention. All study 
interventions 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 site staff. 
5. The investigator, institution, or the head of the medical institution (where applicable) 
is responsible for study intervention accountability, reconciliation, and record 
maintenance (i.e., receipt, reconciliation, and final disposition records). 
6. Further guidance and information for the final disposition of unused study 
intervention are provided in the Technical Agreement. 
7. Under normal conditions of handling and administration, study intervention is not 
expected to pose significant safety risks to site staff. 
8. A Safety Data Sheet /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. 
6.3. 
Measures to Minimize Bias: Randomization and Blinding 
This is a randomized double-blind study and participants will be randomized to receive 
either GSK3882347 
 for 5 days or nitrofurantoin in a 3:1 allocation 
ratio using an interactive response technology (IRT). All participants will be randomized 
before the study is initiated, information and directions for the IRT will be provided to 
each study site. As the study treatment taken during the study will be double-blinded, 
neither the participant nor immediate study personnel (i.e., investigators,) will know 
which study treatment the participant is receiving. 
 
 
 
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On the day the patient is to receive the first dose of study intervention, a designated 
member of the site staff will contact the IRT to obtain the study treatment assignment and 
dispense therapy accordingly. A patient is considered randomized when the site personnel 
receive the treatment assignment associated with the patient entered into the IRT. 
A participant may continue in the study if that participant’s intervention assignment is 
unblinded. The event or condition which led to the unblinding will be recorded in the 
case report form (CRF). 
GSK’s Global Clinical Safety and Pharmacovigilance (GCSP) staff may unblind the 
intervention assignment for any participant with an SAE. If the SAE requires that an 
expedited regulatory report be sent to one or more regulatory agencies, a copy of the 
report, identifying the participant’s intervention assignment, may be sent to investigators 
in accordance with local regulations and/or GSK policy. 
6.4. 
Study Intervention Compliance 
COHORT 1 
• When participants are dosed at the site, they will receive study intervention directly 
from the investigator or designee, under medical supervision. The date and time of 
each dose administered in the clinic will be recorded in the source documents. The 
dose of study intervention 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 intervention. Study site staff will examine each participant’s mouth to 
ensure that the study intervention was ingested. 
COHORT 2 
• When participants self-administer study intervention(s) at home, compliance with 
randomized study intervention will be assessed by direct questioning and collection 
of diary cards (Section 8.2.6) during the site visits and documented in the source 
documents and relevant form. Deviation(s) from the prescribed dosage regimen 
should be recorded. 
• A record of the quantity of randomised study intervention dispensed to and 
administered by each participant must be maintained and reconciled with study 
intervention and compliance records. Intervention start and stop dates, including dates 
for intervention delays will also be recorded. 
6.5. 
Dose Modification 
No dose modifications will be permitted. 
The Principal Investigator and the GSK Medical Monitor will review the following and 
dosing will be temporarily halted, and no further participants will be dosed until a full 
safety review of the data has taken place if: 

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• 
One (1) or more participants experience a SAE which has a reasonable possibility of 
being causally related to study intervention. 
• 
Two (2) or more participants experience a severe or clinically significant non-serious 
adverse event (based upon investigator judgment) which has a reasonable possibility 
of relation to study intervention. 
• 
Three (3) or more participants experience the same adverse event of moderate 
severity which has a reasonable possibility of relation to study intervention. 
Relevant reporting and discussion with the medical monitor, relevant personnel, and if it 
is considered necessary an independent safety review committee comprising GSK senior 
physicians not directly involved in the study, will take place before resumption of dosing. 
The above criteria will apply even if measured PK parameters are below the pre-specified 
PK stopping criteria, and every effort will be made to take a blood sample at the time of 
the AE for PK analysis. 
6.6. 
Continued Access to Study Intervention after the End of the 
Study 
Following the study there will be no further intervention. 
6.7. 
Treatment of Overdose 
GSK does not recommend specific treatment for an overdose with GSK3882347. There is 
no specific antidote for overdose with a FimH 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. 
Occasional incidents of acute overdosage of nitrofurantoin have not resulted in any 
specific symptoms other than vomiting (refer to locally approved prescribing 
information). Induction of emesis is recommended. There is no specific antidote, but a 
high fluid intake should be maintained to promote urinary excretion of the drug. Refer to 
the drug label for overdose information regarding nitrofurantoin. 
In the event of an overdose, the investigator/treating physician should withhold from 
further dosing and: 
1. Contact the GSK medical monitor immediately. 
2 Closely monitor the participant for AE/SAE and laboratory abnormalities until 
GSK3882347 can no longer be detected systemically (at least 3 days). 
3 Obtain a plasma sample for PK analysis within 3 days from the date of the last dose 
of study intervention if requested by the medical monitor (determined on a case-by-
case basis). 
4 Document the quantity of the excess dose as well as the duration of the overdosing in 
the CRF. 

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Decisions regarding dose interruptions or modifications will be made by the investigator 
in consultation with the Medical Monitor based on the clinical evaluation of the 
participant. 
6.8. 
Concomitant Therapy 
6.8.1. 
Permitted Medication and Non-Drug Therapies 
Permissible medicines are Paracetamol or Acetaminophen, at doses of 2 grams/day, 
which may be used at any time during the study and topical (including suppository) anti-
fungal creams (e.g. miconazole, nystatin) may be used to treat symptoms in those 
participants who develop vulvovaginal candidiasis.  
Female contraception is permitted in accordance with the guidance provided in Section 
10.4.  
Concomitant medications not specifically prohibited in the study (See Section 6.8.2 
below) are permitted in line with the exclusion criteria. The medical monitor should be 
contacted if there are any questions about the permitted and prohibited medications.  
6.8.2. 
Prohibited Medication and Non-Drug Therapies 
Treatment with systemic antimicrobials or systemic antifungals within 1 week (or 10 
weeks if dalbavancin or oritavancin) prior to study entry is prohibited and participants 
should not start any new probiotic capsules/tablets during the study to prevent any 
potential alterations in the gastrointestinal or vaginal microbiome. 
Participants may not receive the following treatments within 7 days (or 14 days if the 
drug is a potential enzyme inducer) or 5 half-lives (whichever is longer) before the first 
dose of the study until completion of the follow-up visit: 
• 
Antacid preparations containing magnesium trisilicate, uricosuric drugs, vitamins 
and dietary or herbal supplements 
• 
Alternative medications for the treatment of uUTI (including cranberry juice or 
tablets/capsules, methenamine hippurate, D-mannose) 
• 
Any medications which are strong inhibitors of cytochrome P450 enzymes 
(including oral treatments for vulvovaginal candidiasis, e.g. fluconazole) 
• 
Any medications which inhibit OAT3 (e.g. diflunisal, probenecid) 
• 
Potassium containing compounds for the treatment of bladder symptoms. 
• 
Immunosuppressants (as described in the exclusion criteria #4, Section 5.2) 
• 
Drugs which have the potential for DDIs with nitrofurantoin, e.g. quinolone 
antibiotics.  
• 
Known nephrotoxic medications are prohibited (e.g. ACE inhibitors, Angiotensin 
receptor blockers) and regular NSAID use should be avoided. 

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In vitro, GSK3882347 mediated the induction of CYP3A4, CYP2B6 and 2C9 in human 
hepatocytes. The risk of GSK3882347 perpetrating a clinical drug-drug interaction (DDI) 
when co-dosed with substrates sensitive to induction of CYP3A4, CYP2B6 & CYP2C9 
was evaluated using mechanistic static equations per the regulatory guidance (FDA & 
EMA); the data suggested that GSK3882347 had the potential to be a moderate inducer 
of CYP3A4 in the clinic (% decrease in AUC of sensitive substrate ≥50 - <80) and a 
weak inducer of CYP2B6 and CYP2C9 (% decrease in AUC of sensitive substrates <50).  
Thereafter, although a thoroughly verified and qualified GSK3882347 PBPK model 
predicted that there was no risk of CYP induction-mediated DDIs with sensitive CYP 
substrates, including ethinyl estradiol, it is proposed to mitigate the risk of CYP3A4 
induction with a formal clinical DDI study at a later date. Notwithstanding, sensitive 
substrates (with the exception of oral contraceptives) of CYP3A4, 2B6 and 2C9 should 
be excluded (see FDA table of sensitive substrates (Table 2.1)). 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-and-drug-
interactions-table-substrates-inhibitors-and-inducers#table2-1 
6.8.3. 
Rescue Medicine 
If participants do not respond clinically (participants experience new, worsening or non-
resolving signs and symptoms of uUTI) to randomised medication, they should be given 
rescue medication. They will be considered a treatment failure and will be provided 
rescue medication by site as per SoC [Gupta, 2011]. 
Use of rescue medications is allowable at any time during the study. The requirement for 
the use of rescue medications should be assessed by the Investigator in accordance with 
site procedure and treatment guidelines [Gupta, 2011]. If clinically acceptable (and onset 
of a severe infection is not suspected), rescue medication should be postponed until the 
next clinical symptom resolution assessment during the On-Therapy period. 
Pathogen identification or in vitro resistance of recovered uropathogens alone, is not a 
reason for study treatment discontinuation through the On-Therapy period. Patients can 
resolve their infection spontaneously and in the absence of treatment [Little, 2009]. 
The date and time of rescue medication administration as well as the name and dosage 
regimen of the rescue medication must be recorded. 
Rescue medication to be prescribed by Site Investigator as required and as assessed by 
the Investigator and in consultation with the Medical Monitor if required by the 
Investigator. The decision to prescribe rescue medication resides with the Investigator. A 
combined clinical and laboratory (e.g. serum creatinine and other haematological and 
biochemical parameters) assessment should be used to prior to withdrawal of study 
intervention.  
The Investigator can request the participant’s baseline, enrolling microbiology culture to 
help in the assessment and additional suitable SoC if required [Gupta, 2011]. Note: The 
potential for a drug-drug interaction with next line therapy (e.g., trimethoprim-
sulfamethoxazole) has been reviewed and is permitted in the study. 

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If antibiotic rescue medication is given, the participant will complete an early 
discontinuation visit as per the SoA and will not be required to attend any other 
subsequent visits. 
7. 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
Discontinuation of specific sites or of the study as a whole are detailed in Section 10.1.9. 
7.1. 
Discontinuation of Study Intervention 
In rare instances, it may be necessary for a participant to permanently discontinue study 
intervention. All Participants who discontinue study intervention should have an early 
withdrawal/discontinuation visit. Plasma and urine PK sample(s) should be collected as 
per SoA on the corresponding day as the participants last day of PK sample collection (s). 
Participants may voluntarily discontinue study intervention at any time. The investigator 
may also, at his or her discretion, discontinue the participant from study intervention at 
any time and initiate appropriate alternative therapy (Section 6.8.3. Rescue Medication). 
Reasons for study intervention discontinuation may include the following: 
• 
Adverse event 
• 
Investigator discretion 
• 
Lost to follow-up 
• 
Participant decision 
• 
Participant reached protocol-defined stopping criteria. 
The reason for study intervention discontinuation will be recorded in the eCRF. 
Participants who discontinue study intervention for the reasons above, but not due to the 
requirement of rescue medication, will not be considered withdrawn from the study and 
should attend all subsequent study visits (see Section 1.3). They will remain in the study 
to be evaluated for safety and efficacy, PK samples will not be collected following the 
treatment discontinuation and early withdrawal/discontinuation visit. See the SoA for 
data to be collected at the time of discontinuation of study intervention and follow-up and 
for any further evaluations that need to be completed. 
If study intervention is permanently discontinued due to the requirement of rescue 
medication, the participant will complete an early study discontinuation visit and no other 
visits will be required. 

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7.1.1. 
Liver Chemistry Stopping Criteria 
Liver chemistry stopping criteria with increased monitoring and follow-up 
assessments have been designed to assure participant safety and evaluate liver event 
etiology. 
Discontinuation of study intervention for abnormal liver tests is required when: 
• 
a participant meets one of the conditions outlined in the algorithm or  
• 
in the presence of abnormal liver chemistry not meeting protocol-specified stopping 
rules, if the investigator believes that it is in the best interest of the participant. 
Study intervention will be discontinued for a participant if liver chemistry stopping 
criteria are met 
Phase 1 Liver Chemistry Stopping Criteria – Liver Stopping Event Algorithm 
 
Abbreviations: ALT = alanine transaminase; INR = international normalized ratio; SAE = serious adverse event; ULN = 
upper limit of normal. 
Refer to Section 10.6 for required Liver Safety Actions and Follow up Assessments.  
7.1.2. 
QTc Stopping Criteria 
A participant who meets either bulleted criteria based on the average of triplicate ECG 
readings will be withdrawn from study intervention: 
• 
QTc >500 msec OR Uncorrected QT >600 msec 
• 
Change from baseline of QTc >60 msec 

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For patients with underlying bundle-branch block, follow the discontinuation criteria 
listed below: 
Baseline QTc with Bundle Branch 
Block 
Discontinuation QTc with Bundle 
Branch Block 
<450 msec 
>500 msec 
450 – 480 msec 
≥530 msec 
• 
If a clinically significant finding is identified (including, but not limited to changes 
from baseline in QT interval corrected using Fridericia’s formula [QTcF] after 
enrollment, the investigator or qualified designee will determine if the participant 
can continue in the study and if any change in participant management is needed. 
This review of the ECG printed at the time of collection must be documented. Any 
new clinically relevant finding should be reported as an AE. 
7.1.3. 
Study Specific Stopping Criteria 
Participants who report symptoms suggestive of COVID-19 while in the study and 
research unit should adhere to local COVID-19 isolation and or prevention advice and 
where applicable tested for SARS-CoV-2 infection using an approved test. Sites local 
COVID-19 related procedures should be followed. 
Withdrawal of participants from the study will be at the discretion of the Principal 
Investigator or designee, but should first be discussed and agreed with the GSK Medical 
Monitor. Further study related procedures, except those required for participant safety 
and well-being, should be paused until the discussion is complete. 
Participants who test positive for SARS-CoV-2 infection during the course of the study 
will be withdrawn (after discussion with the GSK Medical Monitor and Principal 
Investigator [PI]) and will be replaced at the discretion of the Sponsor and in consultation 
with the PI. 
7.2. 
Participant Discontinuation/Withdrawal from the Clinical 
Study 
• 
A participant may withdraw from the study at any time at their own request or may 
be withdrawn at any time at the discretion of the investigator for safety, behavioral, 
or compliance reasons. This is expected to be uncommon. 
• 
Investigators will attempt to contact participants who do not return for scheduled 
visits or follow-up. 
• 
At the time of discontinuing from the study, if possible, an early discontinuation/ 
withdrawal visit should be conducted, as shown in the SoA. See SoA for data to be 
collected at the time of study discontinuation and follow-up and for any further 
evaluations that need to be completed. 
• 
The participant will be permanently discontinued from the study intervention and the 
study at that time. 

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• 
All data and samples collected up to and including the date of withdrawal of/last 
contact with the participant will be available for the study analyses. 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 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, they can request destruction of any 
samples taken and not tested, and the investigator must document this in the site 
study records. 
• 
The primary reason for participant discontinuation from the study will be 
documented in the eCRF based on the list below: 
o Adverse event 
o Investigator discretion 
o Lost to follow-up 
o Participant decision 
o Participant reached protocol-defined stopping criteria 
• 
Participants who are discontinued from the study because of AEs/SAEs must be 
clearly distinguished from participants who are discontinued for other reasons. 
Investigator will follow participants who are discontinued from the study due to an 
AE/SAE until the event is resolved. 
7.3. 
Lost to Follow Up 
A participant will be considered lost to follow-up if they repeatedly fail to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The site must attempt to contact the participant and reschedule the missed visit as 
soon as possible, counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain whether the participant wishes to and/or should 
continue in the study. 
• 
Before a participant is deemed lost to follow-up, the investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s registered 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, they will be considered to have 
withdrawn from the study. 

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8. 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the SoA. 
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the sponsor immediately upon 
occurrence or awareness to determine if the participant should continue or discontinue 
study intervention. 
Adherence to the study design requirements, including those specified in the SoA, is 
essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to 
record details of all participants screened and to confirm eligibility or record reasons for 
screening failure, as applicable. 
Participants who have signed informed consent but are not eligible to proceed should be 
recorded in the eCRF with a status of “screen failure. 
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 timeframe defined in the SoA. A pre-screen is available if required for the 
collection of a urine sample to determine eligibility based on a urinalysis dipstick for 
pyuria and nitrite and pregnancy. 
To minimize the amount of time that participants spend at the clinic, e-Consent may be 
utilized. The site may use an electronic method to obtain participant signatures as long as 
it conforms to 21 CFR Part 11 and is approved by IRB. 
Laboratory and analyte results that could unblind the study will not be reported to 
investigative sites or other blinded personnel unless rescue medication is necessary or 
until the study has been unblinded. 
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 500 mL. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues 
with the samples. 
If assessments are scheduled for the same nominal time, then the assessments should 
occur in the following order: 
1. 12-lead ECG 
2. Vital signs & physical exam 
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4. Urine microbiology collections 
5. Pharmacokinetic urine collections 
6. Pharmacokinetic and safety sample and blood draws (haematology, chemistry and 
urinalysis, to be conducted after clinical symptom scores at screening) 
7. 
 
8.1. 
Efficacy Assessments 
Planned timepoints for all efficacy assessments are provided in the SoA. 
8.1.1. 
Clinical Evaluation: Symptom of uUTI and Clinical Resolution 
Response 
Clinical Symptoms 
Clinical symptoms of uUTI will be recorded as follows: 
Clinical 
Symptoms 
None 
Mild 
Symptom is 
easily tolerated, 
causing minimal 
discomfort and 
not interfering 
with everyday 
activities 
Moderate 
Symptom is 
sufficiently 
discomforting to 
interfere with 
normal everyday 
activities 
Severe 
Symptom 
prevents 
normal 
everyday 
activities 
Score 0 
Score 1 
Score 2 
Score 3 
Dysuria 
 
 
 
 
Frequency 
 
 
 
 
Urgency 
 
 
 
 
Lower abdominal 
or suprapubic 
pain 
 
 
 
 
Scores will be recorded by the Investigator or a qualified designee. When possible, the 
same scorer should be used at all assessment time points. 
At screening the participant must present with at least 2 signs and symptoms and have a 
total cumulative symptom score ≥2 for randomisation to the study. There are 4 symptoms 
categories, including: Dysuria, Frequency, Urgency and Lower abdominal or suprapubic 
pain. Each Category is scored from 0 -3. There is a cumulative maximum score of 12. 
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The baseline assessment is collected at the Day 1 pre-dose visit. If the baseline 
assessment is on the same day as the screening assessment, the assessment will be 
considered the screening and baseline score. In this case, the scoring assessment must 
also meet the inclusion criteria. This clinical symptom score will be assessed again at 
each visit post first dose and at the ToC and Follow-up Visit (see SoA). 
The clinical signs and symptom score outcome at each visit will be the cumulative score 
from the clinical symptom table. Clinical symptoms success is defined as normal 
presentation of symptoms with a total cumulative signs and symptom score of zero. The 
time to clinical response will be investigated and key timings for assessment is the ToC 
and Follow-up Visit. 
Clinical Resolution Response 
For the assessment of clinical resolution, the Investigator will be asked to record their 
impression of the clinical status of the participant (resolved/unresolved). The rationale 
being, that resolution using the clinical symptom score may not necessarily result in a 
total score of zero (e.g. if a participant has high frequency at baseline, they would never 
reach a score of 0, yet they may have achieved clinical resolution as assessed by the 
Investigator). The clinical resolution response is the definitive outcome over clinical 
symptom scores. 
When possible, the same Investigator will determine the clinical resolution for each 
participant at each visit post first dose of Treatment. Clinical resolution response 
(resolved/unresolved) will be determined at the ToC and Follow-up Visit. 
Clinical resolution is defined by the following: in the opinion of the Investigator there is 
resolution of signs and symptoms of the uUTI present at Baseline (and no worsening and 
no new signs and symptoms) and no requirement for the use of other antimicrobial 
therapy.  
For participants who are considered unresolved by the Investigator, additional questions 
may be asked regarding their uUTI signs and symptoms. 
8.1.2. 
Microbiology Outcome and Response 
• 
Urine and Microbiology: Bacteriology Samples 
Urine for inclusion criteria, associated with microbiology 
For inclusion into the study, a urine analysis sample is collected during safety 
assessments, which will be used to confirm nitrite or pyuria (≥10 WBC/mm3 or >5 
WBC/HPF or the presence of at least 2+leukocyte esterase) from a screening/ pre-dose 
clean-catch midstream urine sample per local laboratory procedures. Note: Repeat 
baseline urine samples are allowed if contamination, defined as ≥10 squamous epithelial 
cells, is observed under microscopic evaluation. 

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Urine for microbiology bacteriology 
For the microbiology bacteriology samples, a baseline pre-treatment sampling from a 
clean-catch midstream urine sample will be obtained from all randomized participants. 
Samples will be sent to a central laboratory for Gram stain, quantitative bacteriological 
culture, isolate identification, and quantitative PCR (to explore potential FimH-
containing Enterobacterales e.g. E. coli). Baseline qualifying E.coli bacteria (Section 
10.8) and the analysis population is defined in the statistics section and will be assessed 
after randomisation and dosing in the study. 
As per the SoA, at the On-therapy (pre-dose collection), ToC, and Follow-up Visits, a 
clean-catch midstream urine sample will be obtained and sent to a designated central 
laboratory(ies) for Gram stain, quantitative bacteriological culture, and isolate 
identification. 
 
 
 
 
 
. 
• 
Microbiological Outcome and Response 
Only those participants who have a qualifying E. coli identified at Baseline at a level of 
≥104 CFU/mL will be evaluated for microbiological outcome and response 
(Microbiological Modified Per Protocol [Micro-MPP] population). 
Microbiological outcomes capture the highest level of granularity per participant and 
timepoint combination. Each outcome category will be mapped to an associated response 
category for that participant and timepoint combination (multiple outcomes can be 
mapped into the same response category). The statistical analyses use the microbiological 
response variable but the associated microbiological outcome variables are used to 
analyse the data in more detail via descriptive tables/listings and figures. The algorithms 
that list and define each microbiological outcome and associated microbiological 
response may vary by timepoint. 
The microbiological outcome is determined by comparing the Baseline culture results to 
the culture results at each subsequent visit. The absolute CFU counts will be recorded at 
each applicable visit to enable different algorithms to be evaluated via sensitivity 
analyses (e.g. to evaluate the treatment effect when using qualifying criteria of 
≥104 CFU/mL for E.coli ). 
The corresponding microbiological response will also be measured. Microbiological 
success is defined as a reduction in Baseline culture to <103 CFU/mL without the 
participant receiving other systemic antimicrobials. Participant level microbiological 
response will be determined by statistical programming. 
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Note: Additional uropathogen combinations / definitions of qualifying pathogens may be 
explored for microbiological outcome and response (e.g. to evaluate whether 
GSK3882347 has efficacy when there is also a co-infection with a non E. coli 
uropathogen, or if it has efficacy against any FimH expressing uropathogens). 
8.2. 
Safety Assessments 
Planned timepoints for all safety assessments are provided in the SoA. 
8.2.1. 
Physical Examinations 
A complete physical examination will include, at a minimum, assessments of the Skin, 
Cardiovascular, Respiratory, Gastrointestinal and Neurological systems. Height and 
weight will also be measured and recorded (height and weight only at screening exam). 
8.2.2. 
Vital Signs 
• 
Vital signs (to be taken before blood collection for laboratory tests) will include 
tympanic-measured temperature, pulse and respiratory rate, systolic and diastolic 
blood pressure. 
• 
Blood pressure and pulse measurements will be assessed in a semi-supine or seated 
position (dependant on site standard practice) with a completely automated device. 
Manual techniques will be used only if an automated device is not available. 
(consistency of assessment at each site is requested for each participant throughout 
the study) 
• 
Blood pressure and pulse measurements should be assessed after at least 10 minutes 
of rest for the participant in a quiet setting without distractions (e.g., television, cell 
phones). 
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• 
Blood pressure measurements and pulse, when measured in triplicate as in the SoA, 
will consist of 3 consecutive readings recorded at intervals of at least 1 minute and 
the average of the 3 readings will be recorded on the CRF. 
8.2.3. 
Electrocardiograms 
• 
The screening assessment is also considered the baseline assessment. 
• 
Triplicate (screening) and Single (all other study visits unless QTc flag detected) 12-
lead ECG will be obtained as outlined in the SoA (see Section 1.3) using an ECG 
machine that automatically calculates the heart rate and measures PR, QRS, QT, and 
QTc intervals. Refer to Section 7.1.2 for QTc withdrawal criteria and additional QTc 
readings that may be necessary. 
• 
At each timepoint at which triplicate ECGs are required, 3 individual ECG tracings 
should be obtained as closely as possible in succession, but no more than 2 minutes 
apart. 
8.2.4. 
Clinical Safety Laboratory Tests 
• 
See Section 10.2 for the list of clinical laboratory tests to be performed and the SoA 
for the timing and frequency. 
• 
The investigator must review the laboratory report, document this review, and record 
any clinically significant changes occurring during the study as an AE. The 
laboratory reports must be filed with the source documents. 
• 
Abnormal laboratory findings associated with the underlying disease are not 
considered clinically significant, 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 or within 3 days after the last dose of study intervention 
should be repeated until the values return to normal or baseline or are no longer 
considered significantly abnormal by the investigator or medical monitor. 
o If clinically significant values do not return to normal/baseline within a period of 
time judged reasonable by the investigator, the etiology should be identified and 
the sponsor notified. 
• 
In the absence of a diagnosis, abnormal laboratory findings assessments or other 
abnormal results the investigator considers clinically significant will be recorded as 
an AE or SAE, if they meet the definition of an AE or SAE (see Section 10.3.1 and 
Section 10.3.2). 
• 
All protocol-required laboratory tests, as defined in Section 10.2, must be conducted 
in accordance with the laboratory manual and the SoA (Section 1.3). 
• 
If laboratory values from non-protocol specified laboratory tests performed at the 
institution’s local laboratory require a change in participant management or are 
considered clinically significant by the investigator (e.g., SAE or AE or dose 
modification), then the results must be recorded. 

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8.2.4.1. 
Suspected Clostridioides difficile infection 
As per nitrofurantoin prescribing information there have been reports of C.difficile 
infections, through the study routine monitoring of clinical parameters and AEs will be 
conducted to mitigate and assess gastrointestinal effects. If the investigator suspects 
C.difficile infection and or C.difficile-associated diarrhea during 
nitrofurantoin/GSK3883247 treatment, a stool sample will be collected and sent for 
processing at local labs in accordance with local site testing. 
Suspected C. difficile infection will be managed according to a prespecified algorithm 
provided in Section 10.9. 
8.2.4.2. 
Management of participants with changes in serum creatinine 
Automatic lab alerts will be sent by the central lab to the investigator and Medical 
Monitor for increased levels of serum creatinine >1.5× compared to baseline levels.  
Upon receipt of the automatic lab alert, the investigator should perform: 
• 
clinical assessment (e.g. symptoms improvement or deterioration) 
• 
physical examination 
• 
repeat lab tests (urinalysis, hematology and chemistry including any additional 
inflammatory markers) as a split sample (send to local and central lab) 
Such assessments will be performed as soon as possible and may require participants to 
return to clinic as an unscheduled visit, if after clinic constrained intervention period for 
cohort 1 or a non-visit day for cohort 2. 
This will also trigger case discussion between the investigator and Medical Monitor (e.g. 
by phone or email) to ensure assessments are initiated after the flag, to discuss status of 
the participant and additional appropriate management will be initiated by the 
investigator (e.g. no actions required, switch to daily monitoring, discontinue study 
medication, oral rehydration, or others). 
8.2.5. 
Pregnancy Testing 
Refer to Section 5.1 Inclusion Criteria for pregnancy testing entry criteria. 
Pregnancy testing (urine) should be conducted during study intervention period as noted 
in SoA. 
Pregnancy testing (urine) should be conducted at the end of relevant systemic exposure. 
Additional serum or urine pregnancy tests may be performed, as determined necessary by 
the investigator or required by local regulation, to establish the absence of pregnancy at 
any time during the participant’s participation in the study. 

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8.2.6. 
Diary Card 
A paper diary card will be issued to all participants randomised into Cohort 2 on Day 1. 
The diary card will be used to collect medication compliance data and conmeds whilst on 
therapy. The data from the diary card will be used to discuss compliance and conmeds 
information with the participant and will be entered into the eCRF. 
The participant will be asked to bring the diary card with them at each On-Therapy visit. 
If diary card is forgotten at any visit, compliance and conmeds should be discussed at the 
visit and recorded in the participant source documents and entered into the eCRF. The 
participant should be reminded to bring the diary card to the next visit. 
8.3. 
Adverse Events (AEs), Serious Adverse Events (SAEs) and 
Other Safety Reporting 
The definitions of adverse events (AEs) or serious adverse events (SAEs) can be found in 
Section 10.3. 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, 
or the participant's legally authorized representative). 
The investigator and any qualified designees are responsible for detecting, documenting, 
and recording 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 intervention or the 
study, or that caused the participant to discontinue the study intervention or study (see 
Section 7). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 10.3.4 
8.3.1. 
Time Period and Frequency for Collecting AE and SAE 
Information 
• 
All AEs and SAEs will be collected from the start of intervention until the follow-up 
visit at the timepoints specified in the SoA (Section 1.3). However, any SAEs 
assessed as related to study participation (e.g., study intervention, protocol-mandated 
procedures, invasive tests, or change in existing therapy) or related to a GSK product 
will be recorded from the time a participant consents to participate in the study. 
• 
All SAEs will be recorded and reported to the sponsor or designee immediately and 
under no circumstance should this exceed 24 hours, as indicated in Section 10.3. The 
investigator will submit any updated SAE data to the sponsor within 24 hours of it 
being available. 
• 
Investigators are not obligated to actively seek information on AEs or SAEs after 
conclusion of the study participation. However, if the investigator learns of any SAE, 
including a death, at any time after a participant has been discharged from the study, 
and they consider the event to be reasonably related to the study intervention or 
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8.3.2. 
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. 
8.3.3. 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, will be followed until the event is 
resolved, stabilized, otherwise explained, or the participant is lost to follow-up (as 
defined in Section 7.3). Further information on follow-up procedures is given in Section 
10.3. 
8.3.4. 
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 intervention under clinical investigation are met. 
• 
The sponsor has a legal responsibility to notify both the local regulatory authority 
and other regulatory agencies about the safety of a study intervention under clinical 
investigation. The sponsor will comply with country-specific regulatory 
requirements relating to safety reporting to the regulatory authority, Institutional 
Review Boards (IRBs)/Independent Ethics Committees (IECs), and investigators. 
• 
For SAEs, the investigator must always provide an assessment of causality at the 
time of the initial report, as defined in Section 10.3.4 Updating of SAE and 
pregnancy information after removal of write access to the participant’s eCRF. 
• 
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/ package insert and will notify the 
IRB/IEC, if appropriate according to local requirements. 
• 
Investigator safety reports must be prepared for suspected unexpected serious 
adverse reactions (SUSARs) according to local regulatory requirements and sponsor 
policy and forwarded to investigators as necessary. 
Table 2 
Timeframes for submitting SAE and pregnancy reports to GSK 
Type of 
event 
Initial reports 
Follow-up of relevant information on a previous report 
 
Timeframe 
Documents 
Timeframe 
Documents 
SAEs 
24 hours*‡ 
Paper/electronic AEs report 
24 hours* 
Paper/electronic AEs report 
Pregnancies  24 hours* 
Paper pregnancy notification 
report/electronic pregnancy 
report 
24 hours* 
Paper pregnancy follow-up 
report/electronic pregnancy 
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Type of 
event 
Initial reports 
Follow-up of relevant information on a previous report 
 
Timeframe 
Documents 
Timeframe 
Documents 
AE = Adverse event; CRF/eCRF = Case report form/electronic case report form; SAE = Serious adverse event. 
* Timeframe allowed after receipt or awareness of the information by the investigator/site staff. 
‡ Paper AEs Report will be dated and signed by the investigator (or designee). For each SAE, the 
investigator(s) must document in the medical notes that they have reviewed the SAE and have provided an 
assessment of causality. 
8.3.5. 
Pregnancy 
• 
Details of all pregnancies in female participants will be collected after the start of 
study intervention and until at least 3 days after the last dose of study intervention. 
• 
If a pregnancy is reported, the investigator will record pregnancy information on the 
appropriate form and submit it to GSK within 2 weeks of learning of the female 
participant pregnancy. While pregnancy itself is not considered to be an AE or SAE, 
any pregnancy complication or elective termination of a pregnancy for medical 
reasons will be reported as an AE or SAE. 
• 
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported 
as such. 
• 
The participant will be followed to determine the outcome of the pregnancy. The 
investigator will collect follow-up information on the participant and the neonate and 
the information will be forwarded to the sponsor. 
• 
Any post-study pregnancy-related SAE considered reasonably related to the study 
intervention by the investigator will be reported to the sponsor as described in 
Section 8.3.4. 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 in the study will 
discontinue study intervention. 
8.3.6. 
Cardiovascular and Death Events 
For any cardiovascular events detailed in Section 10.3.3. and all deaths, whether or not 
they are considered SAEs, specific Cardiovascular (CV) and Death sections of the CRF 
will be required to be completed. These sections include questions regarding 
cardiovascular (including sudden cardiac death) and non-cardiovascular death. 
The CV CRFs 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 cardiovascular section of the CRF within one week of receipt of a 
CV Event data query prompting its completion. 

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The Death CRF is provided immediately after the occurrence or outcome of death is 
reported. Initial and follow-up reports regarding death must be completed within one 
week of when the death is reported. 
8.3.7. 
Contact information for reporting SAEs, pregnancies and study 
holding rules 
Table 3 
Contact information for reporting SAEs, pregnancies and study 
holding rules 
Study contact for questions regarding SAEs, 
pregnancies and SAEs linked to device deficiencies. 
 
Study contact for reporting of study holding/stopping 
rules  
Contact GSK’s local and/or medical contacts 
If a holding/stopping rule is met, the investigator must 
immediately inform the GSKs local and/or medical 
contacts. 
Contacts for reporting SAEs, pregnancies and SAEs 
linked to device deficiencies. 
Available 24/24 hours and 7/7 days 
uk.gsk-rd-gcsp-ctsm-admin@gsk.com 
Backup study contact for escalation of holding/stopping 
rules. 
 
Refer to the local study contact information for backup 
contacts.  
GSK = GlaxoSmithKline Biologicals SA; SAE = Serious adverse event. 
8.3.8. 
Adverse Events of Special Interest  
There are no adverse events of special interest in this study. 
8.3.9. 
Participant card 
The investigator (or designee) must provide the participant with a “participant card” 
containing information about the clinical study. The participant must be instructed to 
always keep the participant card in their possession for the duration of the study. In an 
emergency, this card serves to inform the responsible attending 
physician/caregiver/family member that the participant is in a clinical study and that 
relevant information may be obtained by contacting the investigator(s) or their back up 
8.4. 
Pharmacokinetics 
PK Urine Sample Collection 
• 
Urine samples will be collected as specified in the SoA. The time will be recorded 
for each urine sample collected, and the total urine volume for each participant will 
be recorded over the collection time period. 
• 
From each urine PK interval, a 1 mL aliquot of urine will be collected for PK 
analysis and stored at approximately 70ºC or colder. 
PK Plasma Sample Collection 
• 
Whole blood samples of approximately 1 mL will be collected for measurement of 
plasma concentrations as specified in the SoA. 

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• 
Samples will be used to evaluate the PK of GSK3882347. Samples collected for 
analyses of study intervention plasma concentration may also be used to evaluate 
safety or efficacy aspects related to concerns arising during or after the study. 
Residual PK Plasma samples may be analyzed for other compound-related 
metabolites and the results reported under a separate in vivo/in vitro (IV/IVT), GSK 
protocols. 
• 
Drug concentration information that would unblind the study will not be reported to 
investigative sites or blinded personnel until the study has been unblinded. 
8.4.1. 
Pharmacodynamics 
8.5. 
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 germline (host) 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. 
See Section 10.5. Genetics and Pharmacogenomics for information regarding genetic 
research. Details on processes for collection and shipment and destruction of these 
samples can be found in the SRM. 
8.6. 
Biomarkers 
Biomarkers are not evaluated in this study. 
8.7. 
Immunogenicity Assessments 
Immunogenicity assessments are not conducted in this study. 
8.8. 
Health Economics 
Health economic parameters are not evaluated in this study. 
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8.9. 
Administrative and general/baseline procedures 
8.9.1. 
Collection of demographic data 
Record demographic data such as year of birth, sex, race, and ethnicity in the 
participant’s eCRF.  
Collection of sex, 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. 
8.9.2. 
Medical history 
Obtain the participant’s medical history by interviewing the participant/LAR(s) and/or 
review of the participant’s medical records. Record any pre-existing conditions, signs 
and/or symptoms present prior to the first dose of study intervention in the eCRF. 
9. 
STATISTICAL CONSIDERATIONS 
The SAP will include a more technical and detailed description of the statistical analyses 
described in this section. This section is a summary of the planned statistical analyses of 
the most important endpoints including primary and key secondary endpoints. 
9.1. 
Statistical Hypotheses 
No formal statistical hypotheses will be tested in this study. 
9.2. 
Analysis Sets 
For purposes of analysis, the following populations are defined. 
Population 
Description 
Randomized 
Population 
All participants randomly assigned to study intervention.  
Safety Population 
All randomized participants who receive at least 1 dose of study 
intervention. Participants will be analyzed according to their 
actual intervention received. 
PK Population  
(Sub populations 
identified for Cohort 
1 and Cohort 2) 
All randomized participants who have a valid PK sample taken 
and from whom a measurable plasma or urine concentration, 
even if the concentration below assay’s limit of quantification, 
(for the actual study intervention) received. 
Separate Sub populations will be constructed for participants 
Randomised to Cohort 1 and Cohort 2 who were in the PK 
population. [Note: these sub-populations support analyses 

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Population 
Description 
involving PK parameters that can only be derived from a full 
intensive PK time profile]. 
Microbiological 
Modified Per 
Protocol 
(Micro-MPP) 
Population* 
All participants randomly assigned to study intervention who 
receive all planned doses of study intervention and have a 
Qualifying baseline E. coli from a quantitative bacteriological 
culture of a pre-treatment clean-catch midstream urine 
specimen. 
*The algorithm for determining qualifying E. coli based on microbiology laboratory 
quantitative culture results is provided in the Section 10.8. 
Details of additional populations, including targeting non-E. coli will be provided in the 
SAP. 
9.3. 
Statistical Analyses 
9.3.1. 
General Considerations 
The estimands for primary endpoint, Microbiological response rate and secondary 
endpoints safety and PK are included in Section 3. No formal comparisons against 
Nitrofurantoin are planned as Nitrofurantoin is included in the study only to ensure 
unbiased reporting of safety events and analysis was designed to demonstrate that the 
concept behind the novel mechanism of action of GSK3882347 translates into humans. 
Clinical outcomes, response rates, 
form part of the 
exploratory analysis. Additional exploratory analysis may be conducted on the 
microbiology samples according to other uropathogen in combination with the qualifying 
pathogen and 
 to understand the microbiology response 
rate further depending on the main study results. 
In general, data from Cohorts 1 and 2 will be displayed in a single (combined) 
Table/Figure/Listing; except for selected PK analyses which can only be performed with 
the full serial time profile. 
Microbiological response is the key endpoint used for internal decision-making and 
additional supportive analyses for internal decision-making may focus on the clinical 
resolution at the ToC visit, and 
 
 at ToC and Follow Up visit. 
 
 
9.3.2. 
Primary Endpoint(s)/Estimands(s) Analysis 
The analysis of primary endpoint will be done using the Micro-MPP population. The 
primary endpoint to be estimated is microbiological response at ToC visit in female 
participants with a qualifying baseline E.coli. 
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Microbiological response at the ToC visit is defined as; 
• 
Microbiological Success: Reduction in E. coli count to <103 CFU/mL (no growth) 
for any E. coli identified at ToC visit, without receiving other systemic 
antimicrobials (rescue medications) prior to ToC. 
o If the baseline urine microbiology quantitative culture has >1 E.coli strain 
present at ≥104 CFU/mL, both E. coli strains must have a reduction to <103 
CFU/mL (no growth) to achieve microbiological success. 
• 
Microbiological Failure: All other microbiological outcomes (for example but not 
limited to ≥103 CFU/mL for any E. coli identified at ToC visit), use of rescue 
medication prior to ToC, lost to follow-up before ToC, missing/unevaluable samples 
at ToC, etc). 
Use of rescue medications before ToC is captured through the definitions of 
microbiological response and will be counted as a failures (Composite strategy). 
Participants who are lost to follow-up prior to ToC, have a missing/unevaluable sample at 
ToC, discontinue treatment due to any reasons prior to ToC (withdrawal of 
consent/AEs/missed doses) will be excluded from the analysis and the participant may be 
replaced at the discretion of the Sponsor. The number and percentage of participants with 
each category of microbiological response at ToC visit will be summarized, along with 
95% CI. 
9.3.3. 
Secondary Endpoint(s)/Estimand(s) Analysis 
The secondary endpoints to be evaluated are safety and PK. 
Safety Analysis: 
Safety analyses will be performed using the safety population. All reported AEs 
including SAEs, AE related to study intervention, AEs leading to discontinuation of study 
intervention and/or withdrawal from trial, COVID-19 events etc will be coded using 
MedDRA and summarized by system organ class and preferred terms. 
All AEs, laboratory parameters, ECGs and vital signs for different visits will be reported 
using appropriate descriptive statistics. GSK core data standards will be followed for all 
the safety reporting. 
Pharmacokinetic Analysis: 
Analysis of pharmacokinetic endpoints will be conducted using the pharmacokinetic 
population. 
AUC(0-inf), Cmax, and Tmax from full profiles collected for 
 of 
GSK3882347 on Day 1, AUC(0-24), Cmax, and Tmax from full profiles collected for 
 of GSK3882347 on Day 5 & pre-dose Ctau, AUC(0-tau), Observed 
Accumulation Ratio (Ro) will be determined from plasma concentration data. Urine 
concentration at 22-24h collection following dose on Day 1 and Day 5, amount excreted 
in urine (Ae) of unchanged GSK3882347, fraction of the dose excreted in urine (fe), and 
renal clearance (CLr) will be determined from urine data. 
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Descriptive statistics (n, arithmetic mean, standard deviation, 95% CI, minimum, median 
and maximum) will be calculated for all pharmacokinetic parameters. In addition, 
geometric mean, 95% CI, SD on the log scale and % coefficient of variation between 
participants (CVb) will be provided for log transformed data of PK parameters. 
In general, data from Cohorts 1 and 2 will be analysed together; except for selected PK 
endpoints (AUC(0-inf), Cmax, and Tmax from full profiles collected for 
 of 
GSK3882347 on Day 1, AUC(0-24), Cmax, and Tmax from full profiles collected for 
 of GSK3882347 on Day 5) which can only be performed with the full serial 
time profile and hence data will be analysed only for cohort 1 participants. 
9.3.4. 
Exploratory Endpoint(s) Analysis 
, resolution of clinical symptoms by 
visits, 
 
 at ToC and follow-up visits 
 will be analyzed 
by using appropriate descriptive statistics. 
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1. 
Appendix 1: Regulatory, Ethical, and Study Oversight 
Considerations 
10.1.1. 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with: 
▪ Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) international ethical guidelines 
▪ Applicable ICH Good Clinical Practice (GCP) guidelines 
▪ Applicable laws and regulations 
• 
The protocol, protocol amendments, ICF, IB, and other relevant documents (e.g., 
advertisements) must be submitted to an IRB/IEC by the investigator and reviewed 
and approved by the IRB/IEC before the study is initiated.  
• 
Any amendments to the protocol will require IEC/IRB approval before 
implementation of changes made to the study design, except for changes necessary to 
eliminate an immediate hazard to study participants. 
• 
Protocols and any substantial amendments to the protocol will require health 
authority approval prior to initiation 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/EC 
▪ Notifying the IRB/IEC of SAE 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), International Council for 
Harmonization of Technical Requirements for Pharmaceuticals for Human use 
(ICH) guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies 
(if applicable), European Medical Device Regulation 2017/745 for clinical 
device research (if applicable), and all other applicable local regulations 
10.1.2. 
Financial Disclosure 
Investigators and sub-investigators 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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10.1.3. 
Informed Consent Process 
• 
The investigator or his/her representative will explain the nature of the study, 
including the risk and benefits, to the participant and answer all questions regarding 
the study.  
• 
Participants must be informed that their participation is voluntary. Participants will 
be required to sign a statement of informed consent that meets the requirements of 21 
CFR 50, local regulations, ICH guidelines, privacy and data protector requirements, 
where applicable, and the IRB/IEC or study center. 
• 
Sample testing will be done in accordance with the recorded consent of the 
individual participant. 
• 
Collected samples for the study will be stored as documented in the consent form. 
This storage period begins when the last participant completes the last study visit. 
This timeline can be adapted based on local laws, regulations or guidelines requiring 
different timeframes or procedures. These additional requirements must be formally 
communicated to, discussed and agreed with GSK.  
• 
The medical record must include a statement that written informed consent was 
obtained before the participant was enrolled in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study. 
• 
A copy of the ICF(s) must be provided to the participant. 
Participants who are rescreened are required to sign a new ICF. 
GSK (alone or working with others) may use participant’s coded study data and samples 
and other information to carry out this study; understand the results of this study; learn 
more about the study intervention or about the study disease; publish the results of these 
research efforts; work with government agencies or insurers to have the study 
intervention approved for medical use or approved for payment coverage. 
The ICF contains a separate section that addresses the use of participant data and 
remaining samples for optional further research (related and non-related). The 
investigator or authorized designee will inform each participant of the possibility of 
further research related or not related to the study/disease. Participants will be told that 
they are free to refuse to participate and may withdraw their consent at any time and for 
any reason during the storage period. A separate signature will be required to document a 
participant's agreement to allow any participant data and/or remaining leftover samples to 
be used for further research related and not related to the study/disease. Participants who 
decline further research will tick the corresponding “No” box. There will be separate 
boxes for further research related and further research non-related, and the participant 
may choose to provide consent for neither, one, or both of these. 

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10.1.4. 
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. The level of 
disclosure must also be explained to the participant who will be required to give 
consent for their data to be used as described in the informed consent.  
• 
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. 
• 
The contract between sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. 
• 
Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect 
such data against accidental or unlawful loss, alteration, or unauthorized disclosure 
or access. GSK, third parties working on behalf of GSK and/or institutions working 
with GSK for the purposes of this study are contractually bound to protect participant 
coded data. GSK will protect participant coded data and will only share it as 
described in the ICF. 
10.1.5. 
Committees Structure 
A SRT is in place for each GSK product. It comprises a global cross-functional team 
responsible for the ongoing assessment of benefit-risk for a product. The SRT contribute 
to the continual assessment of incoming new efficacy and safety information 
10.1.5.1. 
Safety Review Team 
• 
To protect the safety interests of participants, a GSK Safety Review Team will 
review blinded safety data in stream on a regular basis throughout study conduct. 
Data reviews will include but are not limited to the following participants: 
o medical monitor, safety team lead, statistician and clinical team lead 
• 
In particular, data will be reviewed by the sponsor for identification of the following 
events that would potentially contribute to a requirement to halt the study. 
o One (1) or more participants experience a SAE which has a reasonable 
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o Two (2) or more participants experience a severe or clinically significant non-
serious adverse event (based upon investigator judgment) which has a reasonable 
possibility of relation to study intervention. 
o Three (3) or more participants experience the same adverse event of moderate 
severity which has a reasonable possibility of relation to study intervention. 
• 
Enrollment will be paused during the review. If a pausing rule is met, a decision will 
be made, based on the review, as to whether enrollment in the study will be allowed 
to resume. 
• 
Case unblinding may be performed for above reviews if necessary. 
10.1.6. 
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 Study Register in compliance with applicable 
regulations/GSK policy. GSK will aim to register protocols summaries prior to study 
start and target results summaries submission within 12 months of 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. The investigator will be 
provided reasonable access to statistical tables, figures, and relevant reports and will 
have the opportunity to review the complete study results at a GSK site or other 
mutually agreeable location. 
• 
GSK will also provide all investigators who participated in the study with a summary 
of the study results and will tell the investigators what treatment their patients 
received. The investigator(s) is/are encouraged to share the summary results with the 
study participant, as appropriate. 
• 
Where required by regulation, the names of the sponsor signatory and investigator 
signatory will be made public. 
• 
Under the framework of the Supporting Health for All through Reinvestment 
(SHARE) initiative, 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. Requests for access may be made 
through www.clinicalstudydatarequest.com. 
• 
GSK will provide the investigator with the randomization codes for their site only 
after completion of the full statistical analysis. 
• 
The procedures and timing for public disclosure of the protocol and results summary 
and for development of a manuscript for publication for this study will be in 
accordance with GSK Policy. 

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• 
GSK intends to make anonymized patient-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. 
10.1.7. 
Data Quality Assurance 
• 
Required participant data relating to the study will be recorded on printed or 
electronic CRFs 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 CRF.  
• 
Guidance on completion of CRFs will be provided in corresponding study 
documentation. 
• 
Quality tolerance limits (QTLs) will be pre-defined in the QTL plan to identify 
systematic issues that can impact participant safety and/or reliability of study results. 
These pre-defined parameters will be monitored during and at the end of the study 
and all deviations from the QTLs and remedial actions taken will be summarized in 
the clinical study report. 
• 
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. 
• 
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 including systems used can be found in the study 
Data Management Plan or equivalent contract research organization (CRO) 
document. 
• 
The sponsor assumes accountability for actions delegated to other individuals (e.g., 
contract research organizations). 
• 
Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for a minimum period of 15 years from the issue 
of the final Clinical Study Report (CSR)/ 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. 

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10.1.8. 
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 and its origin can be found in Source Data 
Acknowledgment. 
• 
The investigator must maintain accurate documentation (source data) that supports 
the information entered in the CRF. 
• 
Study monitors will perform ongoing source data verification to confirm that data 
entered into the CRF 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. 
10.1.9. 
Study and Site Start and Closure 
First Act of Recruitment 
The study start date is the date on which the clinical study will be open for recruitment of 
participants. 
The first act of recruitment is the first site open and will be the study start date. 
Study/Site Termination 
GSK or 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: 
For study termination: 
• 
Discontinuation of further study intervention development. 

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For site termination: 
• 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 or no recruitment of participants (evaluated after a reasonable amount of 
time) by the investigator. 
• If the study is prematurely terminated or 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 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. 
10.1.10. 
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 
site data. In this case, a coordinating investigator will be designated by mutual 
agreement. 
• Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements. 
10.2. 
Appendix 2: Clinical Laboratory Tests 
• 
The tests detailed in Table 5 will be performed by the central and the local 
laboratories as identified below.  
• 
Local laboratory/Point of Care results are required for initial participant screening, 
but otherwise are only required in the event that the central laboratory results are not 
available in time for either study intervention administration and/or a more 
immediate safety evaluation. If a local sample is required after the screening visit, it 
is important that the sample for central analysis is obtained at the same time. 
Additionally, if the local laboratory results are used to make either a study 
intervention decision or response evaluation, the results must be recorded. 
• 
Protocol-specific requirements for inclusion or exclusion of participants are detailed 
in Section 5 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. 
• 
The addresses of the clinical laboratories in charge of the testing can be found 
in the “List of Clinical Laboratories and Key Vendors”. 

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Table 5 
Protocol-required Safety Laboratory Tests 
Laboratory 
Assessments 
Parameters 
Hematology# 
Platelet count  
RBC Indices: 
Mean corpuscular volume 
(MCV) 
Mean corpuscular Hemoglobin 
(MCH) 
%Reticulocytes (including 
absolutes) 
White Blood Cell (WBC) 
count with differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Red Blood Cell (RBC) 
count 
Hemoglobin 
 
Hematocrit 
 
 
Clinical 
Chemistry1# 
Blood Urea Nitrogen 
(BUN) 
Potassium 
Aspartate 
aminotransferase 
(AST)/ Serum 
Glutamic-Oxaloacetic 
Transaminase (SGOT) 
Total and direct 
bilirubin 
 
Creatinine (including 
eGFR) 
Sodium 
Alanine 
aminotransferase 
 (ALT)/ Serum 
Glutamic-Pyruvic 
Transaminase (SGPT) 
Total protein 
 
Glucose (non-
fasting) 
Calcium 
Alkaline phosphatase2 
 
Routine Urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, leukocyte esterase by 
dipstick 
• 
Microscopic examination (if blood or protein is abnormal) 
• 
Urine protein/creatinine ratio. Urine creatinine and protein values as well as the ratios 
will be reported in the central lab results.  
Pregnancy testing 
• 
Highly sensitive urine human chorionic gonadotropin (hCG) pregnancy test (as needed 
for women of childbearing potential)3 
Other Screening 
Tests 
• 
Follicle-stimulating hormone and estradiol (as needed in women of nonchildbearing 
potential only) 
• 
Urine drug screen to include at minimum: amphetamines, barbiturates, cocaine, opiates, 
cannabinoids and benzodiazepines  
• 
 Serology (HIV antibody, hepatitis B surface antigen [HBsAg], and hepatitis C virus 
antibody) 
• 
COVID-19 testing (Lateral flow/rapid turnaround test and a parallel Molecular PCR (in 
Cohort 1) for screening as per SoA; lateral flow/rapid turnaround test at all other visits as 
required by local regulation or the Institutional Review Board/Independent Ethics 
Committee) 
All study-required laboratory tests will be performed by a central laboratory, with the 
exception of: 
• 
Urinalysis (including drug screen) at screening (excluding microbiology urine sample 
unless required for non-protocol related SoC) 
• 
Hematology and Chemistry at screening 
• 
Urine pregnancy test 
• 
COVID lateral flow/rapid turnaround test  
• 
Suspected Clostridioides difficile infection 

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Laboratory 
Assessments 
Parameters 
NOTES : 
1. 
Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 7.1 and Section 10.6 All events of ALT 3 × upper limit of normal 
(ULN) and total 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 to 
GSK in an expedited manner (excluding studies of hepatic impairment or cirrhosis). 
2. 
If alkaline phosphatase is elevated, consider fractionating. 
3. 
Local urine testing will be standard for the protocol unless serum testing is required by local regulation or 
IRB/IEC. 
# Point of Care 
 Point of Care assessments may be used for the following Local laboratory tests on Day -
1 (screening visit) only [assessments include Haematology and Clinical Chemistry] 
The point of care devices are described in the SRM and may only be used under prior 
agreement with GSK 
Investigators must document their review of each laboratory safety report. 
10.3. 
Appendix 3: AEs and SAEs: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
10.3.1. 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a clinical study participant, 
temporally associated with the use of a study intervention, whether or not 
considered related to the study intervention. 
• 
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 intervention. 
 
• 
Definition of Unsolicited and Solicited AE 
• 
An unsolicited adverse event is an adverse event that was not solicited using a 
participant diary and that is communicated by a participant who has signed the 
informed consent. Unsolicited AEs include serious and non-serious AEs. 
• 
Potential unsolicited AEs may be medically attended (i.e., symptoms or illnesses 
requiring a hospitalization, emergency room visit, or visit to/by a healthcare 
provider). The participants will be instructed to contact the site as soon as possible 
to report medically attended event(s), as well as any events that, though not 
medically attended, are of participant concern. Detailed information about reported 
unsolicited AEs will be collected by qualified site personnel and documented in 
the participant’s records. 

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• 
Unsolicited AEs that are not medically attended nor perceived as a concern by the 
participant will be collected during an interview with the participants and by 
review of available medical records at the next visit. 
• 
Solicited AEs are predefined local and systemic events for which the participant is 
specifically questioned, and which are noted by the participant in their diary.  
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g., ECG, 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 condition detected or diagnosed after study intervention administration even 
though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected intervention- intervention 
interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
intervention or a concomitant medication. Overdose per se will not be reported as 
an 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. 
 
Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety 
assessments that 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). 

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Events NOT Meeting the AE Definition  
• 
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. Pre-existing 
diseases will be recorded in the medical history section of the eCRF. 
• 
Hospitalization for elective treatment of a pre-existing condition (known or 
diagnosed before signing the informed consent) that did not worsen from baseline. 
10.3.2. 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose, meets 
one or more of the criteria listed: 
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 admitted 
(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. 
d. Results in persistent or significant 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) that 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: 
• 
Possible Hy’s Law case: ALT≥3xULN AND total bilirubin ≥2xULN (>35% 
direct bilirubin) or international normalized ratio (INR) >1.5 must be reported 
as SAE 

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An SAE is defined as any untoward medical occurrence that, at any dose, meets 
one or more of the criteria listed: 
• 
Medical or scientific judgment should be exercised by the investigator in 
deciding whether SAE reporting is appropriate in other situations such as 
significant medical events that may jeopardize the participant or may require 
medical or surgical intervention to prevent one of the other outcomes listed in 
the above definition. These events should usually be considered serious. 
o Examples of such events include invasive or malignant cancers, intensive 
treatment for allergic bronchospasm, blood dyscrasias, convulsions, or 
development of intervention dependency or intervention abuse. 
10.3.3. 
Definition of Cardiovascular Events 
Cardiovascular Events (CV) Definition: 
Investigators will be required to fill out the specific CV event page of the CRF for the 
following AEs and SAEs: 
• 
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 
10.3.4. 
Recording, assessment, and Follow-Up of AE, SAE and 
pregnancies 
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. 
• 
It is not acceptable for the investigator to send photocopies of the participant’s 
medical records to GSK in lieu of completion of the GSK required form. 
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 

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AE and SAE Recording 
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 investigator will make an assessment of intensity for each AE and SAE reported 
during the study and assign it to one of the following categories:  
• 
Mild: Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated. 
• 
Moderate: Minimal, local or non-invasive intervention indicated; limiting age-
appropriate instrumental Activities of Daily Living (ADL). Instrumental ADL 
refers to preparing meals, shopping for groceries or clothes, using the telephone, 
managing money, etc. 
• 
Severe: Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling, limiting 
self-care ADL. Self-care ADL refers to bathing, dressing and undressing, feeding 
self, using the toilet, taking medications, and not bedridden. 
 
Assessment of Causality 
• 
The investigator is obligated to assess the relationship between study intervention 
and each occurrence of each AE/SAE. The investigator will use clinical judgment 
to determine the relationship. 
• 
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. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other 
risk factors, as well as the temporal relationship of the event to study intervention 
administration will be considered and investigated. 
• 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information, for marketed products, in his/her assessment. 
• 
For each AE/SAE, the investigator must document in the medical notes that they 
have 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. However, it is very 
important that the investigator always make an assessment of causality for 
every event before the initial transmission of the SAE data to GSK. 

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• 
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. 
 
Assessment of Outcomes 
The investigator will assess the outcome of all serious and nonserious unsolicited AEs 
recorded during the study as: 
• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only). 
 
Follow-up of AE, SAE, pregnancies and any other events of interest 
• 
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 post-
mortem findings including histopathology.  
• 
New or updated information will be recorded in the originally submitted 
documents. 
• 
The investigator will submit any updated SAE data to GSK within 24 hours of 
receipt of the information. 
After the initial AE/SAE/pregnancy, the investigator is required to proactively follow 
each participant at subsequent visits/contacts. All SAEs, will be followed until the 
event is resolved, stabilized, otherwise explained, or the participant is lost to follow-up. 
Other nonserious AEs must be followed until the study follow up visit, as set out in the 
SoA, or until the participant is lost to follow-up. 
Follow-up during the study 
AEs documented at a previous visit/contact and defined as not recovered/not resolved 
or recovering/resolving will be reviewed at subsequent visits/contacts until the study 
follow up visit, as set out in the SoA.  

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Follow-up of AE, SAE, pregnancies and any other events of interest 
If a participant dies during their participation in the study or during a recognized 
follow-up period, GSK will be provided with any available postmortem findings, 
including histopathology. 
Follow-up of pregnancies 
Pregnant participants will be followed to determine the outcome of the pregnancy. At 
the end of the pregnancy, whether full-term or premature, information on the status of 
the mother and child will be forwarded to GSK using the paper pregnancy follow-up 
report/electronic pregnancy report and the AE Report if applicable. Generally, the 
follow-up period does not need to be longer than 6 to 8 weeks after the estimated date 
of delivery. 
Regardless of the reporting period for SAEs in this study, if the pregnancy outcome is 
an SAE, it should always be reported as such 
Furthermore, the investigator must report any SAE occurring as a result of a poststudy 
pregnancy that is considered by the investigator to be reasonably related to the study 
intervention, to GSK.as described in the Section 10.3.5. 
 
Updating of SAE and pregnancy information after removal of write access to the 
participant’s eCRF 
• 
When additional SAE, or pregnancy information is received after write access to 
the participant’s eCRF is removed, new or updated information should be recorded 
on the appropriate paper report, with all changes signed and dated by the 
investigator. The updated report should be sent to the study contact for reporting 
SAEs (see Section 8.3.3). 
 
10.3.5. 
Reporting of SAE and pregnancies to GSK 
SAE Reporting to GSK via Electronic Data Collection Tool 
• 
The primary mechanism for reporting SAE to GSK will be the electronic data 
collection tool. 
• 
If the electronic system is unavailable, then the site will use the paper SAE data 
collection tool (see next section) to report the event within 24 hours. 
• 
The site will enter the SAE data into the electronic system as soon as it becomes 
available. 
• 
After the study is completed at a given 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 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 

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has been taken off-line, then the site can report this information on a paper SAE 
form (see next section) or to the medical monitor/SAE coordinator by telephone. 
• If the site during the course of the study or poststudy becomes aware of any 
serious, nonserious AEs, pregnancy exposure, related to any GSK product that is 
not part of the study design, they will report these events to GSK or to the 
concerned CA via the national spontaneous reporting system. These will be 
classified as spontaneous ICSRs. 
• 
Contacts for SAE reporting can be found in the SRM and Section 8.3.7 
 
SAE Reporting to GSK via Paper Data Collection Tool 
• Facsimile transmission of the SAE paper data collection tool is the preferred 
method to transmit this information to the medical monitor or the SAE coordinator. 
• In rare circumstances and in the absence of facsimile equipment, notification by 
telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
• Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE data collection tool within the designated reporting time 
frames. 
• 
Contacts for SAE reporting can be found in the SRM and Section 8.3.7 
10.4. 
Appendix 4: Contraceptive and Barrier Guidance  
10.4.1. 
Definitions: 
Woman of Childbearing Potential (WOCBP) 
Women in the following categories are considered WOCBP (fertile): 
1. Following menarche 
2. From the time of menarche until becoming post-menopausal unless permanently 
sterile (see below) 
Notes: 
• A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o 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, confirmation with more than one FSH measurement 
is required.  

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o Females on HRT and whose menopausal status is in doubt will be required to use 
one of the non-estrogen hormonal 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. 
• Permanent sterilization methods (for the purpose of this study) include: 
o Documented hysterectomy 
o Documented bilateral salpingectomy 
o Documented bilateral oophorectomy 
• For individuals with permanent infertility due to an alternate medical cause other than 
the above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), 
investigator discretion should be applied to determining study entry. 
• Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
If fertility is unclear (e.g., amenorrhea in adolescents or athletes) and a menstrual cycle 
cannot be confirmed before first dose of study intervention, additional evaluation should 
be considered. 
Woman of Nonchildbearing Potential (WONCBP) 
Women in the following categories are considered WONCBP: 
1. Premenopausal female with permanent infertility due to one of the following (for the 
purpose of this study): 
a) Documented hysterectomy 
b) Documented bilateral salpingectomy 
c) Documented bilateral oophorectomy 
• 
For individuals with permanent infertility due to an alternate medical cause 
other than the above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal 
dysgenesis), investigator discretion should be applied to determining study 
entry. 
Note: Documentation can come from the site personnel’s review of the participant’s 
medical records, medical examination, or medical history interview. 
2. Postmenopausal female 
A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. 
o 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, confirmation with more than one FSH 
measurement is required. 

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o Females on HRT and whose menopausal status is in doubt must discontinue 
HRT to allow confirmation of postmenopausal status before study enrollment. 
10.4.2. 
Contraception Guidance: 
During the study participants are asked to consent and adhere to the study lifestyle 
restrictions by adhering to abstinence of sexual activity through the study to prevent 
exacerbation of clinical and microbiological outcomes associated with their 
infection. 
However, the following guidance on contraception requirements should still be 
discussed with the participant around acceptable contraceptive requirements. 
CONTRACEPTIVESa ALLOWED DURING THE STUDY IF PARTICPANT IS 
NOT ABLE TO ABSTAIN INCLUDE: 
Highly Effective Methodsb That Have Low User Dependency Failure rate of <1% 
per year when used consistently and correctly. 
Implantable progestogen-only hormone contraception associated with inhibition of 
ovulationc 
Intrauterine device (IUD) 
Intrauterine hormone-releasing system (IUS)c 
Bilateral tubal occlusion 
Azoospermic partner (vasectomized or due to a medical cause) 
Azoospermia is a highly effective contraceptive method provided that the partner 
is the sole sexual partner of the woman of childbearing potential and the absence 
of sperm has been confirmed. If not, an additional highly effective method of 
contraception should be used. Spermatogenesis cycle is approximately 90 days. 
Note: documentation of azoospermia for a male participant can come from the site 
personnel’s review of the participant’s medical records, medical examination, or 
medical history interview. 
Highly Effective Methodsb That Are User Dependent Failure rate of <1% per year 
when used consistently and correctly. 
Combined (estrogen- and progestogen-containing) hormonal contraception associated 
with inhibition of ovulationc 
• 
oral 
• 
intravaginal 
• 
transdermal 
• 
injectable 
Progestogen-only hormone contraception associated with inhibition of ovulation 
• 
oral 
• 
injectable 

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• 
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 
intervention. 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. 
a. 
Contraceptive use should be consistent with local regulations regarding the use of 
contraceptive methods for those participating in clinical studies. 
5 Failure rate of <1% per year when used consistently and correctly. Typical use 
failure rates differ from those when used consistently and correctly. 
6 Male condoms must be used in addition to hormonal contraception. If locally 
required, in accordance with Clinical Trial Facilitation Group (CTFG) guidelines, 
acceptable contraceptive methods are limited to those which inhibit ovulation as 
the primary mode of action. 
Note: Periodic abstinence (calendar, sympto-thermal, post-ovulation methods), 
withdrawal (coitus interruptus), spermicides only, and lactational amenorrhea method 
(LAM) are not acceptable methods of contraception. Male condom and female condom 
should not be used together (due to risk of failure from friction). 
10.5. 
Appendix 5: Genetics 
USE/ANALYSIS OF DEOXYRIBONUCLEIC ACID (DNA) 
• Genetic variation may impact a participant’s response to study intervention, 
susceptibility, severity and progression of disease. Variable response to study 
intervention 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 IRB/IEC allow, a blood sample will be collected for germline 
DNA analysis 
• DNA samples will be used for research related to GSK3882347, nitrofurantoin or 
UTI and related diseases. They may also be used to develop tests/assays including 
diagnostic tests) related to GSK3882347 or study interventions of this drug class, and 
UTI. Genetic research may consist of the analysis of one or more candidate genes or 
the analysis of genetic markers throughout the genome or analysis of the entire 
genome (as appropriate) 
• Additional analyses of DNA samples may be conducted 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 GSK3882347 or study interventions 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.  

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• The samples will be retained while research on GSK3882347 (or study interventions 
of this class) or UTI continues but no longer than 15 years after the last subject last 
visit or other period as per local requirements. 
10.6. 
Appendix 6: Liver Safety: Required Actions and Follow-up 
Assessments  
Phase 1 liver chemistry stopping criteria have been designed to assure participant safety 
and to evaluate liver event etiology  
Phase 1 Liver Chemistry Stopping Criteria and Required Follow Up Assessments  
Liver Chemistry Stopping Criteria – Liver Stopping Event 
 
ALT-absolute 
 
ALT≥3xULN 
If ALT≥3xULN AND total bilirubin1,2  2xULN (>35% direct bilirubin) OR international 
normalized ratio (INR)>1.5, Report as an SAE. 
 
Required Actions, Monitoring and Follow up Assessments  
Actions 
Follow Up Assessments 
• 
Immediately discontinue study intervention  
• 
Report the event to GSK within 24 hours 
• 
Complete the liver event form, and complete an 
SAE data collection tool if the event also meets 
the criteria for an SAE2 
• 
Perform liver event follow up assessments as 
described in the Follow Up Assessment column. 
• 
Monitor the participant until liver chemistries 
resolve, stabilise, or return to within baseline 
(see MONITORING) 
 
MONITORING: 
If ALT≥3xULN AND total bilirubin 2xULN or INR 
>1.5:  
• 
Repeat liver chemistries (include ALT, AST, 
alkaline phosphatase, total bilirubin and INR) 
and perform liver event follow up assessments 
within 24 hours 
• 
Monitor participant twice weekly until liver 
chemistries resolve, stabilise or return to within 
baseline 
• 
A specialist or hepatology consultation is 
recommended 
• 
Viral hepatitis serology3 
• 
Obtain INR and recheck with each liver chemistry 
assessment until the aminotransferases values show 
downward trend 
• 
Obtain blood sample for pharmacokinetic (PK) 
analysis within 3 days of last dose4 
• 
Obtain serum creatine phosphokinase (CPK), lactate 
dehydrogenase (LDH), gamma-glutamyl transferase 
(GGT), glutamate dehydrogenase (GLDH) and serum 
albumin. 
• 
Fractionate bilirubin, if total bilirubin2xULN 
• 
Obtain complete blood count with differential to 
assess eosinophilia 
• 
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, on the 
liver event form  
• 
Record use of concomitant medications on the 
concomitant medications CRF page including 
acetaminophen, herbal remedies, recreational drugs 
and other over the counter medications. 
• 
Record alcohol use on the liver event alcohol intake 
form 
If ALT≥3xULN AND total bilirubin  2xULN or INR >1.5 
obtain the following in addition to the assessments listed 
above: 

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Liver Chemistry Stopping Criteria – Liver Stopping Event 
If ALT≥3xULN AND total bilirubin < 2xULN and 
INR ≤1.5:  
• 
Perform liver chemistries (include ALT, AST, 
alkaline phosphatase, total bilirubin and INR) 
and perform liver event follow up assessments 
within 24-72 hours  
• 
Monitor participant weekly until liver chemistries 
resolve, stabilize or return to within baseline 
RESTART/RECHALLENGE 
Do not restart/rechallenge participant with 
study intervention since not allowed per 
protocol; continue participant in the study for 
any protocol specified follow up assessments. 
 
• 
Anti-nuclear antibody, anti-smooth muscle antibody, 
Type 1 anti-liver kidney microsomal antibodies, and 
quantitative total immunoglobulin G (IgG) or gamma 
globulins. 
• 
Serum acetaminophen adduct assay should be 
conducted (where available to assess potential 
acetaminophen contribution to liver injury unless 
acetaminophen use is very unlikely in the preceding 
week (e.g., where the participant has been resident in 
the clinical unit throughout). 
• 
Liver imaging (ultrasound, magnetic resonance, or 
computed tomography) to evaluate liver disease; 
complete liver imaging form. 
• 
Liver biopsy may be considered and discussed with 
local specialists if available for instance: 
o 
In participants when serology raises the 
possibility of autoimmune hepatitis (AIH) 
o 
In participants when suspected DILI progresses 
or fails to resolve on withdrawal of study 
intervention 
o 
In participants with acute or chronic atypical 
presentation. 
• 
 If liver biopsy is conducted, then complete liver 
biopsy form 
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation testing is 
unavailable, record presence of detectable urinary bilirubin on dipstick, indicating direct bilirubin elevations 
and suggesting liver injury.  
2. All events of ALT  3xULN and total bilirubin 2xULN (>35% direct bilirubin) or ALT 3xULN and INR>1.5, which 
may indicate severe liver injury (possible ‘Hy’s Law’), must be reported as an SAE(excluding studies of hepatic 
impairment or cirrhosis); the INR threshold value stated will not apply to participants receiving anticoagulants 
3. Includes: hepatitis A Immunoglobulin M (IgM) antibody; HbsAg and HBcAb; hepatitis CRNA; Cytomegalovirus IgM 
antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, obtain heterophile antibody or 
monospot testing); hepatitis E IgM antibody  
4. Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior to 
pk blood sample draw on the CRF. 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 SRM 

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10.7. 
Appendix 7: Division of Microbiology and Infectious 
Diseases Adult Toxicity Tables for Adverse Event 
Assessment 
 

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10.8. 
Appendix 8: Algorithm for Determining Qualifying E. coli 
Pathogen 
In addition to other criteria defined in the Inclusion Criteria, only participants with a 
qualifying E. coli uropathogen at Baseline from a quantitative bacteriology culture of a 
pre-treatment cleancatch midstream urine specimen will be included in the 
Microbiological (Micro-MPP) Population. Please refer to the analysis plan for additional 
details. The algorithm for determining qualifying E. coli uropathogen based on 
microbiology laboratory quantitative culture results is provided below. 
Figure 3 
Algorithm for qualifying E. coli Pathogen 
 

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10.9. 
Appendix 9: Algorithm for Detecting Suspected C. difficile 
infection 
 

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10.10. 
Appendix 10: Abbreviations, Definition of Terms and 
Trademarks 
ACE 
Angiotensin-converting enzyme 
ADL  
Activities of Daily Living  
ADR 
Adverse Drug Reaction 
AE  
Adverse Event  
Ae  
Amount Excreted in Urine  
AIDS 
Acquired Immuno Deficiency Syndrome 
ALT  
Alanine Aminotransferase   
API  
Active Pharmaceutical Ingredient  
AST  
Aspartate Aminotransferase  
AST 
Antimicrobial Susceptibility Testing 
BCRP 
Breast cancer resistance protein 
BID  
Bis In Die (Twice A Day)  
BMI  
Body Mass Index  
BP 
Blood Pressure 
BUN  
Blood Urea Nitrogen  
C. difficile  
Clostridioides difficile  
CA  
Competent Authority   
CFR  
Code of Federal Regulations  
CFU  
Colony Forming Unit  
CI  
Confidence Interval  
CIOMS  
Council for International Organizations of Medical Sciences  
COVID-19  
Coronavirus Disease 2019  
CRF 
Case Report Form 
CRO  
Contract Research Organization  
CSR  
Clinical Study Report  
CTFG  
Clinical Trial Facilitation Group  
CV  
Cardiovascular  
CV 
Coefficient of Variation 
CVb 
Coefficient of Variation Between Subjects 
CYP  
Cytochrome P450 3A4  
DDI  
Drug-drug Interaction  
DMID  
Division of Microbiology and Infectious Diseases  
DNA  
Deoxyribonucleic Acid  
CCI
CCI
CCI
CCI
CCI

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E. coli  
Escherichia coli  
ECG  
Electrocardiogram  
eCRF  
Electronic Case Report Form  
ED  
Early discontinuation   
eGFR 
Estimated Glomerular Filtration Rate 
EIA 
Enzyme-linked Immunosorbent Assay 
EMA  
European Medicines Agency  
FDA  
Food and Drug Administration  
FeV1 
Forced Expiratory Volume in 1 second 
FimH 
type 1 fimbrial adhesin 
A mannose-specific adhesin located on the tip of type 1 fimbriae of E. 
coli 
FSH  
Follicle-stimulating Hormone  
FTIH  
First Time in Human  
G6PD  
Glucose-6-phosphate Dehydrogenase  
GCP  
Good Clinical Practice  
GCSP  
Global Clinical Safety and Pharmacovigilance  
GDH  
Glutamate Dehydrogenase  
GI  
Gastrointestinal   
GLP  
Good Laboratory Practice  
GSK  
GlaxoSmithKline  
HAI  
Hemagglutinin Inhibition  
HBsAg  
Hepatitis B Surface Antigen  
hCG  
Human Chorionic Gonadotropin  
HDPE  
High Density Polyethylene  
HIV  
Human Immunodeficiency Virus  
HPF 
High Power Field 
HRT  
Hormone Replacement Therapy  
IB  
Investigator’s Brochure  
ICF  
Informed Consent Form  
ICH  
International Council for Harmonization of Technical Requirements 
for Pharmaceuticals for Human Use  
IEC  
Independent Ethics Committee  
IgM 
Immunoglobulin M 
IMP 
Investigational Medicinal Product 
INR  
International Normalized Ratio  
IP  
Investigational Product  
IRT  
Interactive Response Technology   
ITT  
Intent to Treat  
IUD  
Intrauterine Device  
IUS  
Intrauterine Hormone-releasing System  
IV 
Intravenous 
IV/IVT 
In Vivo/In Vitro 
Kg  
Kilogram  
CCI

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L  
Liter  
LAM  
Lactational Amenorrhea Method  
MedDRA  
Medical Dictionary for Regulatory Activities  
Mg  
Milligram  
MI response  
Microbiological Response  
Micro-MPP 
Microbiological Modified Per Protocol 
mL  
Millilitre  
Msec  
Millisecond  
NAAT  
Nucleic Acid Amplification Test  
NOAEL  
No-observed-adverse-effect Level  
NSAID 
Non-steroidal anti-inflammatory drugs 
OAT 
Organic anion transporter 
PBPK  
Physiologically Based Pharmacokinetic  
PCR  
Polymerase Chain Reaction  
PD  
Pharmacodynamic  
PI 
Principal Investigator 
PK  
Pharmacokinetic  
POC 
Point of Care 
PoM 
Proof-of-Mechanism  
  
  
QRS  
ECG waveform 
QT  
ECG waveform 
QTc  
Corrected QT; The measure of time between the start of the Q Wave 
and the end of the T Wave  
QTcF  
Corrected QT Interval Using Fridericia’s Formula  
QTL  
Quality Tolerance Limits  
RBC  
Red Blood Cell  
RNA 
Ribonucleic Acid  
Ro  
Observed Accumulation Ratio  
Rx 
Therapy 
SAE 
Serious Adverse Event  
SAP 
Statistical Analysis Plan  
SARS-CoV-2 
Severe acute respiratory syndrome coronavirus-2 
SD  
Standard Deviation  
SHARE Initiative Supporting Health for All through Reinvestment Initiative 
SoA 
Schedule of Activities  
SoC  
Standard of Care  
SRM 
Study Reference Manual  
SUSARs  
Suspected Unexpected Serious Adverse Reactions  
ToC  
Test of Cure  
TTS  
Technical Terms of Supply  
ULN  
Upper Limit of Normal   
UTI  
Urinary Tract Infection  
WBC 
White Blood Cell 
 
CCI
CCI
CCI

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Term 
Definition 
ADR 
An AE where a causal relationship between a medicinal 
product and the AE is at least a reasonable possibility, i.e., the 
relationship cannot be ruled out. 
In the context of a clinical trial, an ADR can be serious or 
nonserious. Serious ADRs may be subject to expedited 
reporting if they are considered unexpected (see SUSAR 
definition). 
For marketed products, ADRs are subject to expedited 
reporting within the country where they are authorized. 
Background treatment 
Type of medicinal product administered to each of the clinical 
trial participant, regardless of randomization group, to treat 
the indication that is the object of the study. Background 
treatment is generally considered to be the current standard of 
care for the particular indication. In these trials, the IMP is 
given in addition to the background treatment and 
safety/efficacy are assessed. The protocol may require that the 
IMP plus the background treatment is compared with an 
active comparator or with placebo plus background treatment. 
Blinding 
A procedure in which 1 or more parties to the study are kept 
unaware of the intervention assignment in order to reduce the 
risk of biased study outcomes. The level of blinding is 
maintained throughout the conduct of the study, and only 
when the data are cleaned to an acceptable level of quality 
will appropriate personnel be unblinded or when required in 
case of a SAE. 
In a double-blind study, the participant, the investigator, and 
sponsor staff who are involved in the treatment or clinical 
evaluation of the participants and the review or analysis of 
data are all unaware of the intervention assignment. 
Partially-blind is to be used for study designs with different 
blinding levels between different groups, e.g., double-blinded 
consistency lots which are open with respect to the control 
group. 
Caregiver 
A “caregiver” is someone who: 
• 
lives in the close surroundings of a participant and has a 
continuous caring role or 
• 
has substantial periods of contact with a participant and is 
engaged in their daily health care (e.g., a relative of the 
participant, a nurse who helps with daily activities in case 
of residence in a nursing home). 
In the context of a clinical study, a caregiver could include an 
individual appointed to oversee and support the participant’s 
compliance with protocol-specified procedures. 
Certified copy 
A copy (irrespective of the type of media used) of the original 
record that has been verified (e.g., by a dated signature or by 

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Term 
Definition 
generation through a validated process) to have the same 
information, including data that describe the context, content, 
and structure, as the original. 
Challenge agent 
A product given to trial participants to produce a 
physiological response that is necessary before the 
pharmacological action of the IMP can be assessed. 
Child in care 
A child who has been placed under the control or protection 
of an agency, organization, institution or entity by the courts, 
the government, or a government body, acting in accordance 
with powers conferred on them by law or regulation. The 
definition of a child in care can include a child cared for by 
foster parents or living in a care home or institution, provided 
that the arrangement falls within the definition above. The 
definition of a child in care does not include a child who is 
adopted or has an appointed legal guardian. 
Co-administered 
product 
A product given to clinical trial participants as required in the 
protocol as part of their standard care for a condition that is 
not the indication for which the IMP is being tested and is 
therefore not part of the objective of the study. 
Comparator 
Any product used as a reference (including placebo, marketed 
product, GSK, or non-GSK) for an investigational product 
being tested in a clinical trial. This is any product that is being 
used to assess the safety, efficacy, or other measurable value 
against the test product (IMP). 
Decentralized trial 
platform 
A digital engagement technology allowing for the remote 
delivery and access to trials for participants, sites, and 
sponsors. 
DFP shipments 
Home pickup of collected biological specimens, or pickup and 
return of unused/partially used/expired trial materials for 
return to investigator site. 
DTP shipments 
Shipping of IMP, laboratory kits, devices, etc., to the 
participant’s residence under secure and controlled conditions. 
Eligible 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Essential documents 
Documents that individually and collectively permit 
evaluation of the conduct of a study and the quality of the data 
produced. 
Intercurrent event 
Event occurring after study intervention initiation that affects 
either the interpretation or the existence of the measurements 
associated with the clinical question of interest. 
Intervention number 
A number identifying the intervention assigned to a 
participant, according to intervention allocation. 
Investigational 
Product or 
Investigational 
Medicinal Product  
A pharmaceutical form of an active substance or placebo 
being tested or used as a reference in a clinical trial, including 
products already with a marketing authorization but used or 
assembled (formulated or packaged) in a way different from 

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Term 
Definition 
the authorized form, or when used for an unauthorized 
indication, or when used to gain further information about the 
authorized form. 
Investigator 
A person responsible for the conduct of the clinical study at a 
study site. If a study is conducted by a team of individuals at a 
study site, the investigator is the responsible leader of the 
team and may be called the principal investigator. 
The investigator can delegate study-related duties and 
functions conducted at the study site to qualified individual or 
party to perform those study-related duties and functions. 
LAR 
An individual, judicial or other body authorized under 
applicable law to consent on behalf of a prospective 
participant to the participant’s participation in the clinical 
study. 
The terms legal representative or legally authorized 
representative are used in some settings. 
LSLV 
The date on which the last participant in a clinical study was 
examined or received an intervention/treatment to collect final 
data for the primary outcome measures, secondary outcome 
measures, and AEs (that is, the last participant’s last visit or 
LSLV). 
Medicinal products 
used to assess 
endpoints 
A product given to the participant in a clinical trial as a tool to 
assess a relevant clinical trial endpoint; it is not being tested 
or used as a reference in the clinical trial. 
Participant 
Term used throughout the protocol to denote an individual 
who has been contacted to participate or who participates in 
the clinical study as a recipient of the study intervention 
(vaccine(s)/product(s)/control). 
Synonym: subject. 
Participant identifier 
A unique identification number assigned to each participant 
who consents to participate in the study. 
Placebo 
An inactive substance or treatment that looks the same as, and 
is given in the same way as, an active drug or 
intervention/treatment being studied. 
PGx 
The ICH E15 Guidance for Industry defines PGx as “the 
study of variation of DNA and RNA characteristics as related 
to drug or treatment response.” 
Pharmacogenetics, a subset of PGx, is “the study of variations 
in DNA sequence as related to drug response.” 
Pharmacogenomic biomarkers include germline (host) DNA 
and RNA as well as somatic changes (e.g., mutations) that 
occur in cells or tissues. 
Pharmacogenomic biomarkers are not limited to human 
samples but include samples from viruses and infectious 
agents as well as animal samples. The term pharmacogenomic 
experiment includes both the generation of new genetic or 

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Term 
Definition 
genomic (DNA and/or RNA) data with subsequent analysis as 
well as the analysis of existing genetic or genomic data to 
understand drug or treatment response (PK, safety, efficacy, 
or effectiveness, mode of action). 
Proteomic and metabolomic biomarker research is not PGx. 
Primary completion 
date 
This is the date that the final participant in the study was 
examined or received an intervention for the purposes of final 
collection of data for the primary outcome, whether the 
clinical study concluded according to the pre-specified 
protocol or was terminated. In other words, Primary 
Completion Achieved is the date of the last contact with the 
participant when data has been collected/intervention done for 
the purpose of data collection for analysis of all primary 
endpoints. 
In the case of clinical studies with more than 1 primary 
outcome measure with different completion dates, this term 
refers to the date on which data collection is completed for all 
of the primary outcomes. This date may occur prior to the 
study end or be the same date as the study end milestone. 
Randomization 
Process of random attribution of intervention to participants to 
reduce selection bias. 
Remote visit 
A visit conducted in the place other than the study site. 
Rescue medication 
Medicine(s) identified in the protocol as those that may be 
administered to the participants when the efficacy of the IMP 
is not satisfactory, or the effect of the IMP is too great and is 
likely to cause a hazard to the participant, or to manage an 
emergency situation. 
Self-contained study 
Study with objectives not linked to the data of another study. 
Source data 
All information in original records and certified copies of 
original records of clinical findings, observations, or other 
activities in a clinical study necessary for the reconstruction 
and evaluation of the study. Source data are contained in 
source documents (original records or certified copies). 
Standard of care 
Medicine(s) for a specific indication, or a component of the 
standard care for a particular medical indication, based on 
national and/or international consensus; there is no regulatory 
significance to this term. 
Products/regimens considered standard of care may differ 
country to country, depending on consensus in individual 
countries. 
Study intervention 
Term used throughout the clinical study to cover all types of 
investigational and non-investigational products including 
medical devices and vaccines intended to be administered to 
the study participants during the study conduct. Procedures 
conducted to manage participants or to collect data are 
excluded from the usage of this term. 

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Term 
Definition 
Study monitor 
An individual assigned by the sponsor and responsible for 
assuring proper conduct of clinical studies at 1 or more 
investigational sites. 
Subcohort 
A group of participants for whom specific study procedures 
are planned as compared with other participants or a group of 
participants who share a common characteristic (e.g., ages, 
vaccination schedule) at the time of enrollment. 
SUSAR 
In a clinical trial, a serious adverse reaction that is considered 
unexpected, i.e., the nature or severity of which is not 
consistent with the reference safety information (e.g., IB for 
an unapproved IMP). All ADRs that are both serious and 
unexpected are subject to expedited reporting. 
Virtual visit 
This term refers to study visits conducted using multimedia or 
technological platforms. 
TRADEMARK INFORMATION 
Trademarks of the GSK group of 
companies 
 
Trademarks not owned by the GSK 
group of companies 
None 
 
Macrobid 
 

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10.11. 
Appendix 11: Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Amendment 4 05 May 2023 
Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of 
Activities: Cohort 2 
Footnote added to 
describe home visits 
for outpatient visits 
Allowance of home visits (with 
prior agreement from GSK) to 
ease scheduling restrictions at 
sites 
1.3 Schedule of 
Activities Cohort 1 and 
Cohort 2 
Footnote added stating 
baseline data will be 
collected at pre dose 
on Day 1 (except for 
triplicate ECG which 
uses Day -1 screening) 
Extension of screening 
lab results to up to 
24hr (plus 6 hrs) 
Footnote added to 
reference Point of Care 
(POC) devices at 
screening 
Clarification of baseline 
timepoint, extension of lab result 
turnaround time and allowance of 
POC devices at screening 
following prior agreement with 
GSK to ease site and patient 
burden at the screening visit  
1.3 Schedule of 
Activities 
Urine and Plasma PK 
predose Cohort 1 
added to main SOA 
To align Main SOA with detailed 
PK sampling SOA 
 
1.3.1. 
Cohort 1: 
Intensive PK Profiling 
During an Inpatient 
Intervention Period 
 
Under Urine 
pregnancy test  
Added: (for women of 
childbearing potential) 
Added text is to clarify that the 
use of pregnancy testing is for 
women of childbearing potential.  
Pregnancy testing is not required 
in women that are confirmed to 
be of nonchildbearing potential. 
1.3.2. 
Cohort 2 
Reduced PK Sampling 
During an Outpatient 
Intervention Period 
Under Urine 
pregnancy test  
Added: (for women of 
childbearing potential) 
Added text is to clarify that the 
use of pregnancy testing is for 
women of childbearing potential.  
Pregnancy testing is not required 
in women that are confirmed to 

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Section # and Name 
Description of Change 
Brief Rationale 
be of nonchildbearing potential. 
2.3.1 Risk Assessment 
Reproductive toxicity 
Update of wording 
regards animal 
reproductive studies  
Animal reproductive studies now 
complete. 
3.Objectives and 
Endpoints and/or 
Estimands 
Primary estimand on 
subjects who 
completed the planned 
course of treatment 
Interest lies in the treatment 
effect of participants who 
completed treatment to establish 
proof of mechanism 
3.Objectives and 
Endpoints  
Secondary and 
exploratory objectives 
for PK updated 
Due to recruitment challenges in 
Cohort 1, there is a risk that the 
following PK parameter analysis 
will not be able to be conducted. 
The following PK parameters, 
which can only be measured 
calculated from data generated in 
Cohort 1, have therefore been 
moved to exploratory. 
Urine 
• Amount excreted in urine 
(Ae) of unchanged 
GSK3882347, fraction of the 
dose excreted in urine (fe), 
and renal clearance (CLr) 
5.1 Inclusion criteria 
Inclusion criteria 3 
updated to increase 
Leukocyte esterase 
threshold to 2+ 
Wording now ‘The 
To help increase the potential for 
participants to have an infection 
that meets the current defined 
evaluability criteria. 
 
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Section # and Name 
Description of Change 
Brief Rationale 
participant has nitrite 
OR pyuria (≥10 
WBC/mm3, OR >5 
WBC/HPF OR the 
presence of 2+ 
leukocyte esterase) 
from a pre-treatment 
clean-catch midstream 
urine sample based on 
local laboratory 
procedures.’ 
5.2 Exclusion criteria 
Exclusion criteria 11 
updated to reference 
eGFR 
Exclusion criteria 11 has 
referenced the units associated 
with estimated Glomerular 
Filtration Rate (eGFR= ml/min/ 
1.73m2) but has incorrectly 
associated these units with 
creatinine clearance (which has a 
standard value in ml/min). 
Therefore, the term creatinine 
clearance has been updated to 
eGFR. For consistency between 
sites, the equation for the 
calculation of the eGFR.  
5.2 Exclusion criteria 
Exclusion criteria 11 
updated to remove 
requirement for 
assessment of urine 
albumin:creatinine 
ratio at screening. 
Assessment of urine 
albumin:creatinine ratio has been 
removed as a requirement at 
screening. Participants with a 
history of proteinuria are 
excluded, as per exclusion criteria 
28. 
Assessment of urine 
protein:creatinine ratio will 
continue to be performed by the 
central labs at Day 1 predose and 
all further laboratory assessment 
timepoints specified in the SoA 
table.  
5.2 Exclusion criteria 
Exclusion criteria 26 
updated to allow 
medical use of 
marijuana  
Marijuana use is legal in some 
US states and therefore is not 
classed as a substance of abuse. 

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Section # and Name 
Description of Change 
Brief Rationale 
‘Substance abuse: 
Active substance abuse 
or a history of 
substance abuse (in the 
opinion of the 
Principal Investigator) 
within 6 months prior 
to the initial Screening 
visit. Note that 
documented medical 
use of marijuana or 
occasional recreational 
use of marijuana is 
permitted  
5.2 Exclusion criteria 
Exclusion criteria 28 
updated to reference 
proteinuria 
Exclusion criteria 28 has been 
updated to clarify that a history of 
significant renal conditions 
includes a history of significant 
or chronic proteinuria.  
5.2 Exclusion criteria 
Exclusion criteria 30  
Correction of criteria 
from ‘must’, to ‘does 
not’ 
The participant does 
not agree to adhere to 
the concomitant 
therapy restrictions as 
described in Section 
6.8.2 from the 
Screening Visit 
through to the Follow 
Up Visit. 
Word change of criteria to correct 
direction of exclusion  
5.4 Screen Failures 
Addition of following 
wording 
Scheduling of Day 1 
visit falls outside of 
24hrs however 
participant will remain 
within 96 hours of 
symptom onset. 
To aid scheduling of day 1 visits 
at site for patients as long as they 
remain to meet all entry criteria 
6.8.2 Prohibited Meds 
Text updated to the 
Correction of grammar 

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Section # and Name 
Description of Change 
Brief Rationale 
following  
Known nephrotoxic 
medications (e.g. ACE 
inhibitors, Angiotensin 
receptor blockers) and 
regular NSAID use 
should be avoided 
8.2.2 Vital Signs 
Flexibility to allow 
semi- supine or seated 
positions for vital sign 
assessment 
To allow sites to adhere to their 
local standard procedures 
8.9 Administrative and 
general baseline 
procedures 
New section added 
outlining justification 
of collection of 
demographic 
information and use of 
third parties 
Mandated text included due to 
new GSK process to justify 
demographic collection and 
transparency of third-party use. 
9.2 Analysis Sets 
Rename ITT 
population to Exposed 
and group by actual 
treatment rather than 
randomised 
Interest lies in treatment effect of 
actual treatment received. This 
population is used for listings 
9.2 Analysis Sets 
Update definition of 
micro-ITT to require 
“all planned doses” 
rather than “at least 1 
dose” and rename as 
Micro-MPP. 
Interest lies in treatment effect 
following 5 days dosing 
Appendix 2 
Clinical Chemistry 
updated to reference 
Exclusion criteria 11 has the 
values of estimated Glomerular 
Filtration Rate (eGFR= ml/min/ 
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Section # and Name 
Description of Change 
Brief Rationale 
eGFR 
1.73m2) but has incorrectly stated 
creatinine clearance (which has a 
standard value in ml/min). 
Therefore, the term creatinine 
clearance has been adjusted to 
eGFR, and the clinical chemistry 
list updated to reflect this 
adjustment. 
Appendix 10.2. Clinical 
Local Laboratory Tests 
Guidance on POC 
assessment at 
screening 
Allowance of POC devices at 
screening following prior 
agreement with GSK to ease site 
and patient burden at the 
screening visit 
Appendix 11 Acronym 
table 
eGFR and POC added 
New acronyms 
Appendix 12: Protocol 
Amendment History- 
PA3 Summary Table  
 
Updated the word 
“and” to “or” in the 
text  
Updated definition of 
pyuria from 
>15WBC/HPF and 
presence of 3+ /large 
leukocyte esterase to 
≥10WBC/mm3 or 
>5WBC/ HPF or  
presence of leukocyte 
esterase. 
For Clarification 
11 References 
Reference for CKD-
EPI added 
Reference for equations to 
calculate eGFR 
Amendment 3 07 Oct 2022 
Overall Rationale for the Amendment: The following updates were made to reduce 
patient burden within this study, expand enrollment criteria and administrative changes. 

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Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of 
Activities (SoA) Cohort 
1 and Cohort 2 
8. Study Assessments 
and Procedures 
Pre-screen ICF 
available for local 
urinalysis (dipstick) 
and pregnancy test. 
Added pre-screening 
language for 
clarification in the SoA 
tables and Section 8 
A pre-screen ICF was added to 
obtain consent for the collection 
of a urine sample to support study 
enrollment (specifically inclusion 
#3) 
2.3.1 Risk Assessment 
Reproductive toxicity 
added as a potential 
risk and CYP3A4 
induction risk. 
This addition is not based on any 
new emerging safety information. 
Instead, it is to clearly state the 
unknown risk of drug exposure in 
pregnant women in this section 
and align risk language with 
wording already entered in the 
protocol (Section 10.4) and study 
documents. 
Pre-existing protocol inclusion 
criteria for WOCBP including 
contraceptive guidance and 
pregnancy testing remain in 
place. Changes added to expand 
the required duration of 
contraception use for WOCBP 
using hormonal contraceptives 
(due to potential CYP3A4 
induction risk) and to clearly state 
in this section that double barrier 
contraception required as already 
stated in Section 10.4). 
5.1 Inclusion Criteria #2 
Updated the onset of 
clinical signs and 
symptoms from ≤72 
hours to <96 hours 
To allow participants further 
flexibility to enroll within the 
study. 
5.1 Inclusion Criteria #3 
8.1.2 Microbiology 
Outcome and Response 
Updated definition of 
pyuria from 
>15WBC/HPF or 
presence of 3+ /large 
leukocyte esterase to 
≥10WBC/mm3 or 
>5WBC/ HPF or 
To expand definition of pyuria 
and therefore further participant 
inclusion into the study. 

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Section # and Name 
Description of Change 
Brief Rationale 
presence of leukocyte 
esterase. 
5.1 Inclusion Criteria #5 
Expanded and added 
clarification to 
contraceptive 
requirements for 
WOCBP using 
hormonal 
contraceptives 
This amendment is not based on 
any new emerging safety 
information. Instead, it is to align 
with the updated risk benefit 
section and align with wording 
already entered in the protocol 
(Section 10.4) and study 
documents. 
Pre-existing protocol inclusion 
criteria for WOCBP including 
contraceptive guidance and 
pregnancy testing remain in 
place. Changes added to expand 
the required duration of 
contraception use for WOCBP 
using hormonal contraceptives 
(due to potential CYP3A4 
induction risk) and to clearly state 
in this section that double barrier 
contraception required as already 
stated in Section 10.4). 
5.2. Exclusion Criteria 
#29 
Prior/Concomitant 
Therapy: updated 
antimicrobials or 
systemic antifungals 
used within 4 weeks to 
within 1 week of study 
entry. 
Changes needed to align with the 
Concomitant Therapy Section 
(6.8.2) of the protocol.  
Dalbavancin or oritavancin 
exclusion changed to ten weeks 
before study start due to the long 
half-life compared to other 
antimicrobials. 
6.8.2 Prohibited 
Medication and Non-
Drug Therapies 
 Updated 
antimicrobials or 
systemic antifungals 
used within 4 weeks to 
within 1 week of study 
entry with the 
exception of 
dalbavancin and 
oritavancin. 
It was determined that a one 
week period prior to study entry 
is sufficient. 
Dalbavancin or oritavancin 
exclusion changed to ten weeks 
before entry due to longer half-
life values compared to other 
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Section # and Name 
Description of Change 
Brief Rationale 
Removed restrictions 
on substrates of BCRP 
and OATP1B1 (e.g. 
statins) 
 
PBPK modelling has superseded 
static equations which initially 
flagged a potential for 
GSK3882347 to perpetrate DDIs 
with substrates of BCRP and 
OATP1B1. The PBPK model has 
since confirmed there is a low 
risk of clinically meaningful 
DDIs with substrates of these 
transporters. 
8 Study Assessments and 
Procedures 
1.3 Schedule of 
Activities (SoA) Cohort 
1 and Cohort 2 
Addition of potential e-
consent 
To allow participants further 
flexibility to enroll within the 
study. 
Various Sections 
Minor editorial updates For clarification 
Amendment 2 24Feb2022 
Section # and Name 
Description of Change 
Brief Rationale 
2.3.1. 
Risk 
Assessment 
Summary of 
nonclinical findings 
and mitigation strategy 
added to the Risk 
Assessment table. 
Pre-clinical risk associated with 
renal changes in rats identified as 
a potential risk of clinical 
significance. 
5.2. Exclusion Criteria 
#11 
 Creatinine clearance 
value changed from 
<60 mL/min/1.73m2 to 
<90 mL/min/1.73m2.  
Pre-clinical risk associated with 
renal changes in rats identified. 
5.2. Exclusion Criteria 
#28 
Criteria updated to 
include a specific list 
of conditions that 
could be exclusionary. 
List added to emphasize the 
desire for relatively healthy study 
population. 
5.2. Exclusion Criteria 
#30 
Reference to the 
relevant protocol 
section added, 
Baseline Visit updated 
to Screening Visit and 
ToC changes to 
Follow up visit. 
Changes needed for clarity and to 
align with the Concomitant 
Therapy Section (6.8.2) of the 
protocol. 

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Section # and Name 
Description of Change 
Brief Rationale 
5.2. Exclusion Criteria 
#37 
Deleted. 
Changes to Exclusion #30 made 
#37 redundant. 
6.3. Measures to 
Minimize Bias: 
Randomization and 
Blinding 
Sentence added 
regarding the use of an 
unblinded team for the 
purpose of the Interim 
Analysis. 
Addition to emphasize the use of 
an internal unblinded team to 
review and conduct interim 
analysis. 
6.8 Concomitant 
Therapy 
Section restructured 
and potential drug-
drug interactions 
added. 
Restructured for clarity, 
additional potential drug-drug 
interaction to reflect FDA 
feedback and specific details 
around nephrotoxic drugs added. 
New Section: 8.2.4.2 
Management of 
participants with changes 
in serum creatinine 
Section 8.2.4.2 added. 
Section added to ensure 
appropriate monitoring of serum 
creatinine changes.  
10.2. Appendix 2: 
Clinical Laboratory Tests 
Table 3 Protocol-
required Safety 
Laboratory Tests 
Additional expected 
results added to table 
and text for the 
collection of a SoC 
microbiology urine 
sample at screening 
added. 
Lab appendix updated to better 
reflect laboratory testing 
originally included during set-up 
of assessments (e.g., addition of 
absolute value included and 
reported in central lab standard 
panels and calculations for serum 
and urine creatinine) and to 
clarify a microbiology urine 
sample at screening can be 
obtained as part of SoC. 
10.7.2. Procedures 
During COVID-19 
Pandemic 
Language added to 
describe circumstances 
and procedures for 
alternate COVID-19 
testing. 
Due to potential inconsistencies 
in availability of rapid antigen 
tests kits (e.g., rise in variants 
creating high demand/low supply 
of kits) alternate testing measures 
were added for these types of 
circumstances. 
Various locations 
Clerical updates. 
Minor corrections to clean 
document. 
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Amendment 1 17-Dec-2021 
Overall Rationale for the Amendment: An inclusion and exclusion criterion were 
modified to enhance study recruitment and the microbiological response definitions were 
clarified based on FDA advice.  
Section # and Name 
Description of Change 
Brief Rationale 
1.3.2. Cohort Reduced 
PK Sampling During an 
Outpatient Intervention 
Period SoA Table 
UTI Clinical Signs and 
Symptom Score 
Assessment at Post 
Dose on Day 1 was 
removed. 
The assessment at this timepoint 
was added in error. 
5.1. Inclusion Criteria 
 Inclusion 3 edited to 
permit participant 
inclusion with nitrite 
or pyuria positive 
urinalysis. 
Edit to inclusion criteria to 
expand the potential participant 
involvement and number of 
evaluable participants in the study 
considering the sensitivities of the 
assays. Wording ‘Nitrite AND 
Pyuria’ replaced with Nitrite OR 
Pyuria’.  
9.3.2. 
Primary 
Endpoint(s)/Estimands(s) 
Analysis 
Definition of 
microbiological 
response clarified.  
Based on FDA advice, the 
definitions for microbiological 
response were revised to clarify 
that a reduction in any/all E. coli 
counts at the ToC visit determine 
the microbiological response.  
Various locations 
Typo and formatting 
issues corrected. 
Minor corrections to clean 
document. 
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11. 
REFERENCES 
Barber AE, Norton JP, Spivak AM, et al. Urinary Tract Infections: Current and Emerging 
Management Strategies. Clinical Infectious Diseases, Volume 57, Issue 5, 1 September 
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Dielubanza EJ, Schaeffer AJ. Urinary tract infections in women. Med Clin North Am. 
2011 Jan;95(1):27-41. 
European Association of Urology (EAU). EAU guidelines. Edn. presented at the EAU 
Annual Congress Paris 2024. ISBN 978-94-92671-23-3. EAU-Guidelines-on-Urological-
Infections-2024.pdf. Accessed May 2024. 
Flores-Mireles A, Walker J, Caparon M, et al, Urinary tract infections: epidemiology, 
mechanisms of infection and treatment options, Nat Rev Microbiol.2015 May; 13(5): 
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Gupta K, Hooton TM, Roberts PL, et al. Short-Course Nitrofurantoin for the Treatment 
of Acute Uncomplicated Cystitis in Women. Arch Intern Med. 2007;167(20):2207–2212.  
Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the 
treatment of acute uncomplicated cystitis and pyelonephritis in women: a 2010 update by 
the Infectious Diseases Society of America and the European Society for Microbiology 
and Infectious Diseases. Clin Infect Dis. 2011;52(5):e103-20. 
Inker LA et al. New Creatinine- and Cystatin C–Based Equations to Estimate GFR 
without Race. NEJM.org. N Engl J Med 2021;385:1737-49 
Little P, Turner S, Rumsby K, et al, Dipsticks and diagnostic algorithms in urinary tract 
infection: development and validation, randomised trial, economic analysis, observational 
cohort and qualitative study, Health Technol Assess. 2009 Mar;13(19):iii-iv, ix-xi, 1-73. 
Macrobid Prescribing Information. Macrobid (Nitrofurantoin Capsules, USP). Accessed 
in May 2024 at 020064Orig1s029lbl.pdf (fda.gov) 
National Institute for Health Care Excellence (NICE). Public Health England. Urinary 
tract infection (lower): antimicrobial prescribing (ng 109). Oct 2018. Urinary tract 
infection (lower): antimicrobial prescribing (nice.org.uk) 
Overcash JS, Tiffany CA, Scangarella-Oman NE, et al, Phase 2a Pharmacokinetic, 
Safety, and Exploratory Efficacy Evaluation of Oral Gepotidacin (GSK2140944) in 
Female Participants with Uncomplicated Urinary Tract Infection (Acute Uncomplicated 
Cystitis), Antimicrob Agents Chemother, 2020 Jun 23;64(7) 
Spaulding, C.N., Klein, Roger D, Ruer, Ségolène, et. al. Selective Depletion of 
uropathigenic E. coli from the gut by a FimH antagonist. Nature, 2017; 546:528-532. 
Wagenlehner, F.M.E., Bjerklund Johansen, T.E., Cai, T. et al. Epidemiology, definition 
and treatment of complicated urinary tract infections. Nat Rev Urol, 2020, 17, 586–600  
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