Conditions: Gastrointestinal Diseases
Allocation: RANDOMIZED | Intervention model: CROSSOVER
Enrollment: 61
Healthy volunteers: yes

Brief summary:
The purpose of this study is to evaluate bioequivalence parameters of esomeprazole capsules 20 mg (test product) vs. esomeprazole capsules 20 mg (reference product) under fasted conditions.

Detailed description:
This will be a single center, single dose, single-blind, randomized, two-sequence, two-period crossover, bioequivalence study in healthy adult participants with at least a 7-day washout period. The study will consist of an ambulant screening day within 28 days prior to first product administration and two study periods.

Arms:
arm 1: Participants will be randomly assigned to receive Esomeprazole 20 mg delayed-release one capsule once daily as oral administration on day 1 of period 1 and will receive Esomeprazole 20 mg delayed-release one capsule (Nexium 24HR) once daily as oral administration on day 1 of period 2. Participants are instructed to consume the entire amount of ambient temperature water (240 milliliter \[mL\]) along their investigational product. There will be washout period of 7 days between two treatment periods. arm 2: Participants will be randomly assigned to receive Esomeprazole 20 mg delayed-release one capsule (Nexium 24HR) once daily as oral administration on day 1 of period 1 and will receive Esomeprazole 20 mg delayed-release one capsule once daily as oral administration on day 1 of period 2. Participants are instructed to consume the entire amount of ambient temperature water (240 milliliter \[mL\]) along their investigational product. There will be washout period of 7 days between two treatment periods.

Interventions: intervention 1: Esomeprazole 20 mg Delayed-Release Capsules intervention 2: Esomeprazole 20 mg Delayed-Release Capsules (Nexium 24HR)
Intervention descriptions: intervention 1: Esomeprazole 20 mg delayed-release capsules will be given as one capsule once daily as oral administration. intervention 2: Esomeprazole 20 mg delayed-release capsules (Nexium 24HR) will be given as one capsule once daily as oral administration.

Protocol document:
Prot_000.pdf: 
GSK Consumer Healthcare 
Clinical Protocol 
Protocol Number: 218246 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 1 of 72 
CLINICAL PROTOCOL 
A randomized, single blind, single center, single dose, two period, 
two sequence crossover bioequivalence study of esomeprazole 
20 mg delayed-release capsules (Catalent, Guayama) compared to 
the esomeprazole 20 mg delayed-release capsules (Nexium 24HR] 
AstraZeneca Södertälje) in healthy adult subjects under fasted 
conditions 
Protocol Number: 
218246 
Compound/Product Name: 
Nexium 24HR 
United States (US) Investigational 
New Drug (IND) Number: 
Not applicable 
European Clinical Trials Database 
(EudraCT) Number: 
Not applicable 
Other Regulatory Agency Identified 
Number: 
Health Canada CTA number HC6-024-
c259857 
Phase: 
I 
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This document contains confidentiality statements that are not relevant for this 
publicly available version


GSK Consumer Healthcare 
Clinical Protocol 
Protocol Number: 218246 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
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Sponsor Information 
Sponsor Name & Legal 
Registered Address 
GlaxoSmithKline Consumer Healthcare 
(UK) Trading Limited 
980 Great West Road, 
Brentford, 
Middlesex, 
TW8 9GS, 
United Kingdom (UK) 
Sponsor Contact Details 
GlaxoSmithKline Consumer Healthcare 
(GSK CH) 
184 Liberty Corner Rd., Warren, NJ 07059 
United State 
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GSK Consumer Healthcare 
Clinical Protocol 
Protocol Number: 218246 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 3 of 72 
Document History 
Document 
Version Summary of Changes 
Original protocol 
1.0 
Not applicable (N/A) 
Amendment 1 
2.0 
•
Page 1: included Health Canada CTA number
•
Table 1-1 Schedule of Activities:  Inclusion exclusion
criteria check is performed on Day 1 instead of Day -1
•
Exclusion criteria # 22 change for clarification
•
Section 5.5.1 change for clarification
•
Section 5.5.4 change for clarification
•
Table 6.1 Investigational/Study product Supplies Product
Master Formulation Code (MFC) corrected
•
Section 6.1 change for clarification
•
Section 7.1 change of text on withdrawal criteria
•
Section 8.2.1: Inclusion exclusion criteria check is
performed on Day 1 instead of Day -1
•
Section 8.2.2: Inclusion exclusion criteria check is
performed on Day 1 instead of Day -1
•
Section 8.2.5: Inclusion exclusion criteria check is
performed on Day 1 instead of Day -1
•
Section 8.2.6: Inclusion exclusion criteria check is
performed on Day 1 instead of Day -1
•
Section 9.3.1: text deleted for consistency with the
process
•
Section 12.3.8 corrected text
Amendments incorporate all revisions to date, including amendments made at the request of 
country health authorities, institutional review boards/ethics committees (IRBs/ECs), etc.   
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


G S K C o ns u m er Healt hcare 
Cli nical Pr ot oc ol 
Pr ot oc ol N u m ber: 2 1 8 2 4 6  
Pr o pert y of G S K C o ns u mer Healt hcare - C o nfi d e ntial  
M a y n ot b e us e d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o ns e nt of G S K C H 
S O P- 2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 7. 0 
Pa ge 4  of 7 2  
Pri n ci p al I n v e sti g at or Pr ot o c ol A gr e e m e nt P a g e 
I c o nfir m a gree m e nt t o c o n d uct t h e st u d y i n c o m plia nce wit h t h e pr ot oc ol a n d a n y 
a me n d me nts acc or di n g t o t he c urre nt I nter n ati o nal C o nfere nce o n Har m o nisati o n G o o d 
Cli nical Practi ce (I C H G C P) g ui deli nes. 
I ac k n o wle d ge t hat I a m res p o nsi ble f or o v erall st u d y c o n d u ct. I a gree t o p ers o nall y 
c o n d u ct or s u per vise t h e descri be d st u d y. 
I a gree t o e ns ure t hat all ass ociates, c ollea g u es a n d e m pl o yees assisti n g i n t he c o n d uct of 
t he st u d y are i nf or m e d a b o ut t heir o bli gati o ns. Mec ha nis ms are i n pla ce t o e ns ure sit e staff 
recei v es all a p pr o priate i nf or m ati o n t hr o u g h o ut t h e st u d y. 
I a gree t o c o n d uct t his st u d y i n f ull c o nf or ma nc e wit h t he la ws a n d re g ulati o ns of t h e 
c o u ntr y i n w hic h t he rese arc h is c o n d u cte d a n d t he Declarati o n of Helsi n ki. 
I n v esti g at or Na me: 
 
I n v esti g at or Q ualificati o ns: 
B. Sc., M D
I n v esti g at or Si g nat ure: 
Date of Si g n at ure/ A gree me nt: 
D D -M m m -Y Y Y Y
y
t
m
P P D
P P D
P P D
P P D


GSK Consumer Healthcare 
Clinical Protocol 
Protocol Number: 218246 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 5 of 72 
Table of Contents 
Sponsor Information ............................................................................................................ 2 
Document History ............................................................................................................... 3 
Principal Investigator Protocol Agreement Page ................................................................ 4 
Table of Contents ................................................................................................................ 5 
1 
PROTOCOL SUMMARY ................................................................................................ 11 
1.1 
Synopsis ................................................................................................................. 11 
1.2 
Schedule of Activities ............................................................................................ 14 
2 
INTRODUCTION ............................................................................................................. 16 
2.1 
Study Background and Rationale .......................................................................... 16 
2.2 
Benefit/Risk Assessment ....................................................................................... 16 
2.3 
Mechanism of Action/Indication ........................................................................... 16 
3 
STUDY OBJECTIVES AND ENDPOINTS .................................................................... 16 
4 
STUDY DESIGN .............................................................................................................. 18 
4.1 
Overall Design ....................................................................................................... 18 
4.2 
Scientific Rationale for Study Design ................................................................... 19 
4.3 
Justification for Dose ............................................................................................. 19 
4.4 
End of Study Definition ......................................................................................... 19 
5 
STUDY POPULATION .................................................................................................... 20 
5.1 
Type and Planned Number of Subjects ................................................................. 20 
5.2 
Inclusion Criteria ................................................................................................... 20 
5.3 
Exclusion Criteria .................................................................................................. 21 
5.4 
Randomization Criteria .......................................................................................... 23 
5.5 
Lifestyle Considerations ........................................................................................ 23 
5.5.1 
Meals and Dietary Restrictions ............................................................. 23 
5.5.2 
Alcohol, Caffeine and Tobacco ............................................................. 24 
5.5.3 
Activity .................................................................................................. 24 
5.5.4 
Contraception ........................................................................................ 24 
5.6 
Screen Failures ....................................................................................................... 25 
5.7 
Sponsor’s Qualified Medical Personnel ................................................................ 26 
5.8 
Rater/Clinical Assessor Qualifications .................................................................. 26 
6 
INVESTIGATIONAL/STUDY PRODUCTS ................................................................... 26 
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GSK Consumer Healthcare 
Clinical Protocol 
Protocol Number: 218246 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Page 6 of 72 
6.1 
Investigational/Study Product Supplies ................................................................. 26 
6.1.1 
Dosage Form and Packaging ................................................................. 29 
6.1.2 
Preparation and Dispensing ................................................................... 29 
6.2 
Administration ....................................................................................................... 29 
6.2.1 
Medication/Dosing Errors ..................................................................... 30 
6.2.2 
Overdose ............................................................................................... 30 
6.3 
Investigational/Study Product Storage .................................................................. 31 
6.4 
Investigational/Study Product Accountability ....................................................... 31 
6.4.1 
Destruction of Investigational/Study Product Supplies ........................ 32 
6.5 
Blinding and Allocation/Randomization ............................................................... 32 
6.6 
Breaking the Blind ................................................................................................. 32 
6.7 
Compliance ............................................................................................................ 33 
6.8 
Concomitant Medication/Treatment(s) .................................................................. 33 
7 
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ......................................................................... 33 
7.1 
Subject Discontinuation/Withdrawal ..................................................................... 33 
7.2 
Lost to Follow up ................................................................................................... 34 
8 
STUDY PROCEDURES ................................................................................................... 35 
8.1 
Visit 1/Screening ................................................................................................... 35 
8.1.1 
Informed Consent .................................................................................. 35 
8.1.2 
Demographics ....................................................................................... 36 
8.1.3 
Inclusion/Exclusion Criteria.................................................................. 36 
8.1.4 
Medical History and Prior Medication/Treatment ................................ 36 
8.1.5 
Subject Eligibility.................................................................................. 36 
8.1.6 
Screening Procedures ............................................................................ 36 
8.2 
Study Period........................................................................................................... 37 
8.2.1 
Period 1/Day -1 ..................................................................................... 38 
8.2.2 
Period 1/Day 1....................................................................................... 39 
8.2.3 
Period 1/Day 2....................................................................................... 39 
8.2.4 
Washout Period ..................................................................................... 40 
8.2.5 
Period 2/Day -1 ..................................................................................... 40 
8.2.6 
Period 2/Day 1....................................................................................... 41 
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Clinical Protocol 
Protocol Number: 218246 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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8.2.7 
Period 2/Day 2....................................................................................... 42 
8.2.8 
End of Study .......................................................................................... 42 
8.3 
Study Conclusion ................................................................................................... 42 
8.4 
Follow-up Visit ...................................................................................................... 43 
9 
STUDY ASSESSMENTS ................................................................................................. 43 
9.1 
Screening Assessments .......................................................................................... 43 
9.2 
Safety and Other Assessments ............................................................................... 43 
9.2.1 
Laboratory Tests .................................................................................... 43 
9.2.2 
Serology ................................................................................................ 45 
9.2.3 
Urine drug screen .................................................................................. 45 
9.2.4 
Alcohol test ........................................................................................... 45 
9.2.5 
Pregnancy Testing ................................................................................. 45 
9.2.6 
Physical Examinations .......................................................................... 46 
9.2.7 
Height and Weight ................................................................................ 46 
9.2.8 
Blood Pressure and Pulse Rate .............................................................. 46 
9.2.9 
Respiratory Rate .................................................................................... 47 
9.2.10 
Temperature .......................................................................................... 47 
9.2.11 
COVID-19 Test ..................................................................................... 47 
9.2.12 
Electrocardiogram ................................................................................. 47 
9.3 
Pharmacokinetics (PK) .......................................................................................... 48 
9.3.1 
Plasma for analysis of esomeprazole .................................................... 48 
9.3.2 
Shipment of Pharmacokinetic Samples ................................................. 48 
9.4 
Blood Volume ........................................................................................................ 49 
10 ADVERSE EVENT AND SERIOUS ADVERSE EVENTS ........................................... 49 
10.1 
Definition of an Adverse Event (AE) .................................................................... 49 
10.2 
Definition of a Serious Adverse Event (SAE) ....................................................... 50 
10.3 
Time Period and Frequency for Collecting AE and SAE Information .................. 52 
10.4 
Reporting Procedures ............................................................................................. 52 
10.4.1 
Reporting of an Adverse Event ............................................................. 53 
10.4.2 
Reporting of a Serious Adverse Event .................................................. 53 
10.5 
Evaluating Adverse Events .................................................................................... 54 
10.5.1 
Assessment of Intensity......................................................................... 54 
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Clinical Protocol 
Protocol Number: 218246 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 8 of 72 
10.5.2 
Assessment of Causality ....................................................................... 54 
10.6 
Follow-up of AEs and SAEs .................................................................................. 55 
10.7 
Withdrawal Due to an Adverse Event ................................................................... 56 
10.8 
Regulatory Reporting Requirements for SAEs ...................................................... 56 
10.9 
Pregnancy .............................................................................................................. 57 
10.9.1 
Time Period for Collecting Pregnancy Information .............................. 57 
10.9.2 
Action to be Taken if Pregnancy Occurs .............................................. 57 
10.10 Regulatory Reporting Requirements for Medical Device Incidents ...................... 57 
11 DATA MANAGEMENT .................................................................................................. 58 
11.1 
Case Report Form .................................................................................................. 58 
11.2 
Data Handling ........................................................................................................ 59 
11.2.1 
Data Queries .......................................................................................... 59 
11.3 
External Data ......................................................................................................... 59 
12 STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................. 60 
12.1 
Sample Size Determination ................................................................................... 60 
12.2 
Populations for Analysis ........................................................................................ 60 
12.3 
Statistical Analyses ................................................................................................ 60 
12.3.1 
Primary Analysis(es) ............................................................................. 61 
12.3.2 
Secondary Analysis(es) ......................................................................... 62 
12.3.3 
Safety Analysis(es) ................................................................................ 62 
12.3.4 
Other Analysis(es) ................................................................................. 63 
12.3.5 
Exclusion of Data from Analysis .......................................................... 63 
12.3.6 
Demographic and Baseline Characteristics ........................................... 63 
12.3.7 
Study Drug/Product Compliance and Use of Other Therapies ............. 63 
12.3.8 
Handling of Dropouts and Missing Data .............................................. 63 
12.3.9 
Interim Analysis .................................................................................... 64 
13 STUDY GOVERNANCE CONSIDERATIONS .............................................................. 64 
13.1 
Quality Control ...................................................................................................... 64 
13.2 
Quality Assurance .................................................................................................. 64 
13.3 
Regulatory and Ethical Considerations ................................................................. 65 
13.3.1 
Institutional Review Board/ Ethics Committee ..................................... 65 
13.3.2 
Ethical Conduct of the Study ................................................................ 65 
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Clinical Protocol 
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Page 9 of 72 
13.3.3 
Subject Information and Consent .......................................................... 66 
13.3.4 
Subject Recruitment .............................................................................. 66 
13.3.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP ............................................................................................... 66 
13.4 
Posting of Information on Publicly Available Clinical Trial Registers ................. 67 
13.5 
Provision of Study Results to Investigators ........................................................... 67 
13.6 
Records Retention .................................................................................................. 67 
13.7 
Conditions for Terminating the Study ................................................................... 68 
14 REFERENCES .................................................................................................................. 69 
15 APPENDICIES .................................................................................................................. 70 
15.1 
ABBREVIATIONS ............................................................................................... 70 
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Clinical Protocol 
Protocol Number: 218246 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 10 of 72 
List of in text tables 
Table 1-1 
Schedule of Activities ........................................................................... 14 
Table 3-1 
Study Objectives and Endpoints ........................................................... 16 
Table 6-1 
Investigational/Study Product Supplies ................................................ 27 
Table 6-2 
Sundry Items ......................................................................................... 28 
Table 9-1 
Laboratory Tests .................................................................................... 44 
Table 9-2 
Blood Volume ....................................................................................... 49 
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Clinical Protocol 
Protocol Number: 218246 
Property of GSK Consumer Healthcare - Confidential  
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Page 11 of 72 
1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Short Title: 
A bioequivalence study of 20 mg esomeprazole delayed-release capsule (Catalent, Guayama) 
compared to the current marketed 20 mg esomeprazole delayed-release capsule (Nexium 24HR, 
AstraZeneca [AZ] Södertälje) in healthy adult subjects under fasting conditions. 
Background and Rationale: 
This study will be conducted to support the registration of Catalent (Winchester, KY) and 
Guayama (Puerto Rico) (Encapsulation Only) as alternate sites by determining whether the 
esomeprazole capsules 20 mg pellets manufactured at Catalent and encapsulated at Guayama 
(CG) (test product) are bioequivalent to esomeprazole capsules 20 mg from AZ (reference 
product) under fasted conditions. The data collected will be used for registration and approval 
for the esomeprazole capsules 20 mg from Catalent and Guayama (Encapsulation Only). 
Objectives and Endpoints: 
Objective(s) 
Endpoint(s) 
Primary 
Demonstrate the bioequivalence of 
esomeprazole 20 mg delayed-release capsules 
from Catalent Guayama (CG) compared to 
esomeprazole 20 mg delayed-release capsules 
from AstraZeneca Södertälje (AZ) under fasted 
conditions 
•
Cmax  (The maximum observed post-
dose concentration; obtained without
interpolation)
•
AUC0-t (The area under the plasma
concentration versus time curve
calculated from time 0 to the last
measurable sampling time point, t,
computed using the linear trapezoidal
rule)
Secondary 
Pharmacokinetics 
Assess the pharmacokinetic profile 
•
AUC0-inf (The area under the plasma
concentration versus time curve
calculated from time 0 to infinity AUC0-inf
= AUC0-t + C(t)/λz where C(t) is the
concentration at the last measurable
sampling time point and λz is the
terminal elimination rate constant)
•
%AUCex (Percentage of AUC0-inf
obtained by extrapolation, calculated as
(1－[AUC0-t /AUC0-inf] )×100)
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Clinical Protocol 
Protocol Number: 218246 
Property of GSK Consumer Healthcare - Confidential  
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Page 12 of 72 
•
λz (The terminal elimination rate
constant computed as the slope of the
regression line of ln (C(t)) on time. The
regression should generally involve at
least 3 consecutive measurable
concentrations that decrease over time)
•
tmax (The time of the maximum
observed post-dose concentration)
•
t1/2 (The elimination half-life computed
as t1/2 = ln(2)/ λz)
Safety 
Assess the safety profile (local and systemic) of 
both products 
•
Monitoring and recording of adverse
events
•
Physical examination
•
Vital signs
•
Laboratory tests
Study Design: 
This is a single center, single dose, single-blind, randomized, two-sequence, two-period 
crossover, bioequivalence study in healthy adult subjects with at least a 7-day washout period.  
The study is intended to dose in more than one group; all groups will be dosed at the same 
clinical site and the same protocol requirements and procedures will be followed within each 
group. 
Blood will be sampled regularly at scheduled times for 24 hours following treatment.   
Subjects will be randomly assigned to one of 2 treatment sequences and receive a single dose 
of one of the following treatments in each period following a crossover design:  
Treatment A: esomeprazole 20 mg capsules from CG in the fasted state (Test) 
Treatment B: esomeprazole 20 mg capsules from AZ in the fasted state (Reference) 
The study will consist of an ambulant screening day within 28 days prior to first product 
administration and two study periods. In each period, subjects will be confined from the day 
before dosing (Day -1) until 24 hours post-dosing (Day 2), during which pharmacokinetic (PK) 
blood samples will be obtained within 1 hour prior to dosing (pre-dose) and 0.5, 0.75, 1, 1.25, 
1.5, 1.75, 2, 2.25, 2.5, 2.75 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 16, and 24 hours after drug 
administration. Carry-over effects will be avoided by a wash-out interval of at least 7 days 
between investigational product administrations. 
Following an overnight fast of at least 10 hours, subjects will receive the investigational product 
in the fasted state with approximately 240 mL of ambient temperature water. Subjects will be 
instructed to consume the entire amount of water along with their investigational product. 
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


G S K C o ns u mer Healt hcare  
Cli nical Pr ot oc ol  
Pr ot oc ol N u m ber: 2 1 8 2 4 6  
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 7. 0  
Pa ge 1 3  of 7 2  
S u bjects s h o ul d s wall o w t he i n vesti gati o nal pr o d uct w h ole a n d s h o ul d n ot c he w or ma ni p ulate 
t he me dicati o n pri or t o s wall o wi n g. 
I n or der t o sta n dar dize t he c o n diti o ns o n P K sa m pli n g da ys, all s u bjects s h o ul d refrai n fr o m 
l yi n g do w n, eati n g, a n d dri n ki n g be vera ges ot her t ha n water d uri n g t he first 4  h o urs after d osi n g. 
Asi de fr o m ti me of pr o d uct a d mi nistrati o n, wat er will be all o we d a d li bit u m  e x ce pt wit hi n 
1  h o ur bef ore a n d 1  h o ur after i n vesti gati o nal pr o d uct a d mi nistrati o n.  
F or  eac h s u bject t he d urati o n of st u d y p artici pati o n is 3 7  da ys of w hic h u p t o 2 da ys c o nfi ne d 
i n eac h peri o d (t otal of u p t o 4 da ys c o nfi ne d).  
St u d y Pr o d u ct s : 
T e st Pr o d u ct  
R ef er e n c e Pr o d u ct  
Pr o d u ct N a m e  
e s o m e pr a z ol e 2 0 m g 
d el a y e d -r el e a s e c a p s ul e s 
e s o m e pr a z ol e 2 0 m g 
d el a y e d -r el e a s e c a p s ul e s 
( N e xi u m 2 4 H R) ( C a n a di a n 
a v ail a bl e pr o d u ct)  
 
D o s e/ A p pli c ati o n  
O n e c a p s ul e a d mi ni str ati o n  
O n e c a p s ul e a d mi ni str ati o n  
R o ut e of A d mi ni str ati o n  
Or al  
Or al  
T y p e a n d Pl a n n e d N u m b er of S u bj e ct s : 
A s ufficie nt n u m ber of m ale a n d fe m ale s u bjects will be scree ne d t o ra n d o mize a p pr o xi matel y 
4 9 t o e ns ure at least 4 1 e val ua ble s u bjects ( refer t o secti o n 1 2. 1) c o m plete t he st u d y.  
St atistic al Met h o ds:  
T he P K a nal ysis set will be use d f or t he P K e val uati o ns. It i ncl u des all s u bjects of t he P K 
p o p ulati o n  w h o c o m plete b ot h treat me nt peri o ds, a n d f or w hic h t he rele va nt P K para meters (at 
least A U C0 -t or C ma x ) ca n be deri v e d. S u bjects wit h baseli ne c o n ce ntr at i o n > 5 % of t he i n di vi d ual 
C ma x  f or eit her p eri o d will be e x cl u de d fr o m t h e P K a nal ysis set. T his a nal ysis set will be use d 
i n s u m maries, t he pri mar y P K a n al ysis, a n d t h e sec o n dar y P K a n al ysis. 
T he P K para m eters t hat will be use d i n t he pri mar y a nal yses are  A U C 0 -t a n d C ma x . 
A li near mi x e d effects m o del will be fit t o t he l o g -tr a nsf or me d P K p ara meters ( A U C0 -t a n d 
C ma x ), as t he de pe n de nt v aria ble, a n d tr eat me nt, se q ue nce, a n d p eri o d as fi x e d effects. S u bject 
neste d wit hi n se q u e nce will be a ra n d o m effect. T he treat me nt least-s q u ares m ea ns ( L S Ms), 
differe n ce b et wee n treat me nt L S Ms, a n d 9 0 % c o nfi de nce i nter val ( CI) f or t he differe nce will 
2 1 8 2 4 6 | Pr ot oc ol A me n d me nt  1 4 Mar 2 0 2 2 | T M F- 2 1 8 1 0 6 | 1. 0
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be computed. The adjusted mean difference and the 90% CIs for the differences will be 
exponentiated to provide estimates of the ratio of adjusted geometric means (test/reference) and 
90% CIs for the ratio. If all study subjects are not recruited from the same enrollment pool and 
the study doses in more than one group, the statistical model may be modified to reflect the 
multigroup nature of the study. Bioequivalence will be declared for AUC0-t if the 90% 2-sided 
CI for the ratio lies completely within the range of 0.8-1.25 and for Cmax if the point estimate 
for the ratio lies completely within the range of 0.8-1.25. No further adjustments for multiplicity 
of the co-primary endpoints are necessary as both endpoints must be met in order to achieve 
study success. 
1.2 
Schedule of Activities 
The schedule of activities table provides an overview of the subject visits and study procedures.   
The investigator may schedule visits (unplanned visits) in addition to those listed on the 
schedule of activities, to conduct evaluations or assessments required to protect the well-being 
of the subject. 
Table 1-1 
Schedule of Activities 
Procedure/Assessment 
Screening 
Treatment Periods 1 and 2a 
End of study 
visit* 
Study day 
-28 to -2 
-1 
1 
2 
2 
Confinement 
 
x 
x 
 
 
Discharge 
 
 
 
x 
 
Informed consent 
x 
 
 
 
 
Demography 
x 
 
 
 
 
Medical history 
x 
 
 
 
 
Physical examinationb 
x 
x 
 
 
x 
Height, weight, BMI 
x 
 
 
 
 
Vital signs (BP, PR, RR, 
BT) 
x 
xc 
xc 
xc 
x 
12-lead ECG 
x 
 
 
 
 
Laboratory tests 
x 
 
 
 
x 
COVID-19 testd 
x 
x 
 
x 
x 
Virology 
x 
 
 
 
 
Urine pregnancy teste 
x 
 
 
 
x 
Serum pregnancy teste 
 
x 
 
 
 
FSHf 
x 
 
 
 
 
Urine drug screen 
x 
x 
 
 
 
Urine cotinine test 
x 
x 
 
 
 
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Procedure/Assessment 
Screening 
Treatment Periods 1 and 2a 
End of study 
visit* 
Study day 
-28 to -2 
-1 
1 
2 
2 
Alcohol breath test 
x 
x 
 
 
 
Inclusion/exclusion 
assessment 
x 
 
Xg 
 
 
Randomizationh 
 
 
x 
 
 
Drug administration 
 
 
x 
 
 
PK blood samplingi 
 
 
x 
x 
 
Concomitant treatments 
x 
x 
x 
x 
x 
Adverse eventsj 
x 
x 
x 
x 
x 
Abbreviations: BMI, BP, PR, RR, BT, ECG, FSH, PK 
Footnotes: 
*These assessments are also to be conducted for subjects who discontinue study drug. End of Study 
visit will occur before discharge, on study Day 2 of Period 2.  
aThe washout period between each drug administration will be at least 7 days.  
bA full physical examination will be performed at screening and a brief physical examination will be 
performed on Day -1 in each treatment period and end of study. 
cBlood pressure (BP), pulse rate (PR), respiratory rate (RR), oral body temperature (BT): pre-treatment 
on Day 1 (within 1 hour before drug administration) of each treatment period. Oral body temperature 
(BT) on Day -1 and Day 2 of each treatment period (Note: oral body temperature performed on Day 2 
of Period 2 can be used as the oral body temperature required at End of Study). 
dBefore the first dosing two consecutive tests (locally approved tests [PCR or Antigen]) separated > 24 
hours will be performed: one test at screening within 72 hours of admission and one test at check-in 
(Day-1). Before the second dosing two consecutive tests (locally approved tests [PCR or Antigen]) 
separated > 24 hours will be performed: one test during the washout period within 72 hours of 
admission and one test at check-in (Day-1). If the first test is > 72 hours prior to unit admission, 
subjects should be advised to self -quarantine until entrance to the unit while awaiting final testing 
clearance. Subjects who report symptoms suggestive of COVID-19 while in the research unit should 
be isolated in the unit or at home and tested for COVID-19 infection using an approved molecular test. 
One test (locally approved tests [PCR or Antigen]) should be performed before releasing the subject 
from the unit in each period or at early discontinuation. 
e for all females of childbearing potential. 
fFSH done only in females who have been amenorrhoeic for 12 months 
gAt the discretion of the Investigator, subjects could continue the study if any deviation to the 
inclusion/exclusion criteria does not anticipate to alter study integrity. 
hRandomization conducted prior to the first dosing (Period 1). 
iPK blood samples will be collected within 1 hour prior to dosing (pre-dose), and at 0.5, 0.75, 1, 1.25, 
1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 16, and 24 hours following dosing in 
each treatment period. 
jAEs will be collected from time of informed consent. 
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2 
INTRODUCTION 
Nexium 24HR, an esomeprazole 20 mg unbanded delayed-release capsule, is approved for 
non-prescription use in Canada. Esomeprazole 20 mg delayed-release capsules are currently 
manufactured at AstraZeneca (AZ) in Södertälje, Sweden. GSK CH plans to manufacture 
esomeprazole 20 mg pellets at Catalent (Winchester, KY). Encapsulation and finished product 
release will occur at both Catalent (Winchester, KY) and Guayama (Puerto Rico). The sites 
(Catalent and Guayama) will be registered as alternate to AZ. 
2.1 
Study Background and Rationale 
This study will be conducted to support the registration of Catalent and Guayama 
(Encapsulation Only) as alternate sites by determining whether the esomeprazole capsules 
20 mg pellets manufactured at Catalent and capsulated at Guayama (CG) (test product) are 
bioequivalent to esomeprazole capsules 20 mg from AZ (reference product) under fasted 
conditions. The data collected will be used for registration and approval for the esomeprazole 
capsules 20 mg from Catalent and Guayama (Encapsulation Only). 
2.2 
Benefit/Risk Assessment  
Complete information for this product may be found in the single reference safety document 
(SRSD), which for this study is the Nexium 24HR Health Canada Product Monograph (Date of 
Revision: April 3, 2020). 
2.3 
Mechanism of Action/Indication 
Esomeprazole is the pure S-enantiomer of racemic omeprazole and suppresses gastric acid 
secretion by specific inhibition of the H+/K+-adenosine triphosphatase enzyme system at the 
secretory surface of the gastric parietal cell. Because esomeprazole blocks the final step of acid 
production, this activity leads to inhibition of both basal and stimulated acid secretion. Oral 
esomeprazole has demonstrated impressive efficacy and safety profiles in the prescription 
treatment of the following disease states: symptomatic GERD, erosive esophagitis, duodenal 
ulcers, Helicobacter pylori-associated gastric ulcers, risk reduction of non-steroidal anti-
inflammatory drug associated peptic ulcers, and hypersecretory conditions, such as Zollinger-
Ellison Syndrome. Nexium 24HR is available for self selection over the counter and is indicated 
for treatment of frequent heartburn for 14 days. 
3 
STUDY OBJECTIVES AND ENDPOINTS 
Table 3-1 
Study Objectives and Endpoints 
Objective(s) 
Endpoint(s) 
Primary 
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Demonstrate the bioequivalence of 
esomeprazole 20 mg delayed-release capsules 
from Catalent Guayama (CG) compared to 
esomeprazole 20 mg delayed-release capsules 
from AstraZeneca Södertälje (AZ) under fasted 
conditions 
• 
Cmax  (The maximum observed post-
dose concentration; obtained without 
interpolation) 
• 
AUC0-t (The area under the plasma 
concentration versus time curve 
calculated from time 0 to the last 
measurable sampling time point, t, 
computed using the linear trapezoidal 
rule) 
Secondary 
Pharmacokinetics 
Assess the pharmacokinetic profile 
• 
AUC0-inf (The area under the plasma 
concentration versus time curve 
calculated from time 0 to infinity AUC0-inf 
= AUC0-t + C(t)/λz where C(t) is the 
concentration at the last measurable 
sampling time point and λz is the 
terminal elimination rate constant) 
• 
%AUCex (Percentage of AUC0-inf 
obtained by extrapolation, calculated as 
(1－[AUC0-t /AUC0-inf] )×100) 
• 
λz (The terminal elimination rate 
constant computed as the slope of the 
regression line of ln (C(t)) on time. The 
regression should generally involve at 
least 3 consecutive measurable 
concentrations that decrease over time) 
• 
tmax (The time of the maximum 
observed post-dose concentration) 
• 
t1/2 (The elimination half-life computed 
as t1/2 = ln(2)/ λz) 
Safety 
Assess the safety profile (local and systemic) of 
both products 
• 
Monitoring and recording of adverse 
events  
• 
Physical examination 
• 
Vital signs 
• 
Laboratory tests 
This study will be considered successful if bioequivalence is demonstrated between 
esomeprazole 20 mg delayed-release capsules from CG and the esomeprazole 20 mg 
delayed-release capsules from AZ.  
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4 
STUDY DESIGN  
4.1 
Overall Design 
This is a single center, single dose, single-blind, randomized, two-sequence, two-period 
crossover, bioequivalence study in healthy adult subjects with at least a 7-day washout period.  
The study is intended to dose in more than one group; all groups will be dosed at the same 
clinical site and the same protocol requirements and procedures will be followed within each 
group. 
Blood will be sampled regularly at scheduled times for 24 hours following treatment.    
Subjects will be randomly assigned to one of 2 treatment sequences and receive a single dose 
of one of the following treatments in each period following a crossover design:  
Treatment A: esomeprazole 20 mg capsules from CG in the fasted state (Test) 
Treatment B: esomeprazole 20 mg capsules from AZ in the fasted state (Reference) 
The study will consist of an ambulant screening day within 28 days prior to first product 
administration and two study periods. In each period, subjects will be confined from the day 
before dosing (Day -1) until 24 hours post-dosing (Day 2), during which time pharmacokinetic 
(PK) blood samples will be obtained within 1 hour prior to dosing (pre-dose) and 0.5, 0.75, 1, 
1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 10, 12, 16, and 24 hours after drug 
administration. Carry-over effects will be avoided by a wash-out interval of at least 7 days 
between investigational product administrations. 
Following an overnight fast of at least 10 hours, subjects will receive the investigational product 
in the fasted state with approximately 240 mL of ambient temperature water. Subjects will be 
instructed to consume the entire amount of water along with their investigational product. 
Subjects should swallow the investigational product whole and should not chew or manipulate 
the medication prior to swallowing. 
In order to standardize the conditions on PK sampling days, all subjects should refrain from 
lying down, eating, and drinking beverages other than water during the first 4 hours after dosing. 
Aside from time of product administration, water will be allowed ad libitum except within 
1 hour before and 1 hour after investigational product administration. 
For each subject the duration of study participation is 37 days of which up to 2 days confined 
in each period (total of up to 4 days confined). 
Figure 4-1 
Study design 
Screening 
Period 1 and 2a 
End of study 
Day -28 to -2 
Day -1 to 2 
Day 2 of Period 2 
a Washout period of at least 7 days between each dosing 
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A sufficient number of male and female subjects will be screened to randomize approximately 
49 to ensure at least 41 evaluable subjects (refer to section 12.1) complete the entire study.  
4.2 
Scientific Rationale for Study Design 
Blinding is required as per Canadian regulation. This will be a single-blind study. 
Subject will be blinded to treatment; test and reference product are identical.  
The degree of blinding will depend on the assessment as follows: 
• Personnel performing the bioanalytical analysis will be blinded to the randomized 
treatment.  
• Personnel involved in the collection, monitoring, revision, or evaluation of AEs will 
be blinded to the randomization. 
• Personnel who could have an impact on the outcome of the study will be blinded to the 
randomization. 
• Designated pharmacy personnel at the clinical site not directly involved with the 
clinical aspects of the trial will prepare and dispense the study medication and will be 
aware of the randomization code. 
A crossover design, using the same subjects to test each product, will be used to reduce 
variability. 
The blood sampling times have been chosen based on the information available particularly on 
esomeprazole absorption, as well as its elimination. 
Non smokers have been chosen as the population for this study to reduce variability. 
The following guidance have been followed for designing the study: 
• Guidance document, Comparative Bioavailability Standards: Formulations Used for 
System Effects (Health Canada 2018) 
• Guidance document, Conduct and Analysis of Comparative Bioavailability Studies 
(Health Canada 2018) 
4.3 
Justification for Dose 
This is a study to assess the bioequivalence of the test product to a commercial reference 
product. 
4.4 
End of Study Definition 
A subject is considered to have completed the study if he or she has completed all phases of the 
study including the last visit or the last scheduled procedure shown in the Schedule of Activities. 
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The end of this study is defined as the date of the last visit of the last subject to complete the 
study. 
5 
STUDY POPULATION 
5.1 
Type and Planned Number of Subjects 
A sufficient number of male and female subjects will be screened to randomize approximately 
49 to ensure at least 41 evaluable subjects (refer to section 12.1) complete the entire study.  
An enrolled subject is one who has agreed to participate in the clinical study following 
completion of the informed consent process directly and successfully met eligibility criteria to 
proceed beyond the screening visit as applicable for the protocol design.  
This study can fulfill its objectives only if appropriate subjects are enrolled. The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate. All relevant medical and non-medical conditions should be taken into 
consideration when deciding whether a subject is suitable for this protocol.   
Subject eligibility to participate in the clinical study should be reviewed and documented by an 
appropriate member of the investigator’s study team before subjects are included in the study. 
5.2 
Inclusion Criteria 
An individual must meet all the following inclusion criteria to be eligible to be included into 
the study: 
1. Evidence of a personally signed and dated informed consent document indicating that the 
subject has been informed of all pertinent aspects of the study before any assessment is 
performed. 
2. Male or female subject who, at the time of screening, is between the ages of 18 and 
55 years, inclusive. 
3. Subject who is willing and able to comply with scheduled visits, treatment plan, laboratory 
tests, and other study procedures. 
4. Healthy subject, which is defined as in general good physical health, as judged by the 
investigator and no clinically relevant abnormalities identified by a detailed medical 
history, full physical examination, including blood pressure and pulse rate measurement, 
12-lead ECG or clinical laboratory tests. 
5. Body Mass Index (BMI) of 18.5 to 30.0 kg/m2; and a total body weight ≥50.0 kg for males 
and ≥45.0 kg for females. 
6. Subject with two negative tests (one at screening within 72 hours of admission and one at 
check on Day-1) for active COVID-19, separated by > 24 hours. 
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7. Female subject of childbearing potential and at risk for pregnancy must agree to use a highly 
effective method of contraception throughout the study and for at least 30 days after the last 
dose of assigned treatment. Female subjects who are not of childbearing potential must meet 
requirements in the Contraception section of protocol. 
5.3 
Exclusion Criteria 
A subject with any of the following characteristics/conditions will not be included in the study: 
1. Subject who is an investigational site staff member directly involved in the conduct of the 
study and his/her family members, site staff member otherwise supervised by the 
investigator, or subject who is a GSK employee directly involved in the conduct of the 
study. 
2. Participation in other studies involving investigational drug(s) within 30 days prior to 
study entry and/or during study participation. 
3. Acute or chronic medical or psychiatric condition or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study. 
4. Pregnant female subject. 
5. Breastfeeding female subject. 
6. Known or suspected intolerance or hypersensitivity or photosensitivity to the study 
materials (or closely related compounds) or any of their stated ingredients. 
7. Diagnosis of long QT syndrome or QTc > 450 msec for males and > 470 msec for females 
at screening. 
8. Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or 
over 140 mmHg, diastolic blood pressure lower than 50 or over 90 mmHg, or pulse rate 
less than 50 or over 100 bpm). 
9. A subject unwilling or unable to comply with Lifestyle Considerations described in this 
protocol.  
10. Use of any medication (including over-the-counter medications and herbal remedies) 
within 2 weeks before first scheduled study drug administration or within less than 
10 times the elimination half-life of the respective drug (whichever is longer), or is 
anticipated to require any concomitant medication during that period or at any time 
throughout the study. Allowed treatments are: 
• systemic contraceptives and hormone replacement therapy, as long as female subject 
is on stable treatment for at least 3 months before first scheduled study drug 
administration and continues treatment throughout the study;  
• occasional use of acetaminophen (up to 2 g daily). 
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11. Evidence or history of clinically significant laboratory abnormality, hematological, renal, 
endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease 
within the last 5 years that may increase the risk associated with study participation. 
12. Clinically relevant chronic or acute infectious illnesses or febrile infections within two 
weeks prior to start of the study. 
13. Subject with signs and symptoms suggestive of COVID-19 (i.e. fever, cough, etc)* within 
14 days of inpatient admission. *as defined by WHO or local guidance) 
14. Subject with known COVID-19 positive contacts in the past 14 days. 
15. Any vaccination, including COVID-19 vaccine, within 14 days prior to the first dose. 
16. Any surgical or medical condition which may significantly alter the absorption, 
distribution, metabolism or excretion of any drug substance but not limited to any of the 
following: 
• History of major gastrointestinal tract surgery such as gastrectomy, 
gastroenterostomy, bowel resection, gastric bypass, gastric stapling or gastric banding 
(note: this is not applicable for minor abdominal surgery without significant tissue 
resection, e.g., appendectomy and herniorrhaphy); 
• History of inflammatory bowel disease; 
• History or current evidence of renal disease or impaired renal function at screening as 
indicated by abnormal levels of serum creatinine (> 123 µmol/L for males 
and > 95 µmol/L for females) or BUN (≥ 12.0 mmol/L) or the presence of clinically 
significant abnormal urinary constituents (e.g. albuminuria);  
• History or current evidence of ongoing hepatic disease or impaired hepatic function at 
screening. A candidate will be excluded if more than one of the following lab value 
deviations are found: 1) AST (≥ 1.2 ULN), ALT (≥ 1.2 ULN), 2) GGT (≥ 1.2 ULN), 
ALP (≥ 1.2 ULN), 3) bilirubin (≥ 48 µmol/L for males and ≥ 30 µmol/L for females) 
or CK (≥ 3 ULN). A single deviation from the above values is acceptable and will not 
exclude the candidate, unless specifically advised by the investigator; 
• Evidence of urinary obstruction or difficulty in voiding at screening; 
• History or clinical evidence at screening of pancreatic injury or pancreatitis. 
17. Subject has a history of drug abuse or investigator has evidence of current drug abuse with 
drug classes that include but are not limited to barbiturates, tricyclic antidepressants, 
amphetamines, benzodiazepines, cocaine, opiates, cannabis or any other drugs (verified by 
urine drug screen or other reliable evidence). 
18. Evidence, as reported by an alcohol breath testing, for current alcohol abuse or reports a 
regular average alcohol consumption exceeding 18 g (women) or 35 g (men) of pure 
alcohol per day, i.e. 1 drink/day for women or 2 drinks/day for men (1 drink = 150 mL of 
wine or 360 mL of beer or 45 mL of hard liquor) within 6 months of screening. 
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19. Subject reported regular consumption of > 5 cups of coffee or tea per day (or equivalent 
consumption of ≥ 500 mg xanthine per day using other products) 
20. Smoker, defined as the use of tobacco or nicotine products during the 3 months prior to 
screening until admission to the unit or a positive urine cotinine test at screening. 
21. A subject who is unwilling to abstain from tobacco or nicotine-containing product use 
during the study.  
22. Subject reports consumption of any drug metabolizing enzyme (e.g. CYP3A4 or other 
cytochrome P450 enzymes) inducing or inhibiting aliments, beverages or food 
supplements (e.g. broccoli, Brussels sprouts, grapefruit, grapefruit juice, star fruit, St. 
John’s Wort etc.) within 2 weeks prior to admission to the unit. 
23. Positive results in any of the virology tests for HIV antigen and antibody,  HCV Ab, 
HbsAg, and HBcAb (IgG + IgM). 
24. Performance of unaccustomed strenuous physical exercise (body building, high 
performance sports) from 2 weeks prior to admission and throughout the entire study. 
25. Allergy to skin disinfecting agents, tape, or latex rubber, whenever appropriate 
substitutions cannot be applied or in the investigator’s opinion may pose a risk to the 
candidate. 
26. Any condition not identified in the protocol that in the opinion of the investigator would 
confound the evaluation and interpretation of the study data or may put the subject at risk 
27. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding 
volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 
499 mL within 56 days prior to the first dose. 
28. Subject who has previously been enrolled in this study. 
5.4 
Randomization Criteria 
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria.  
5.5 
Lifestyle Considerations 
5.5.1 
Meals and Dietary Restrictions 
• Subjects must abstain from all food and drink (except water) at least 4 hours prior to 
any safety laboratory evaluations and 10 hours prior to investigational product 
administration. Water is permitted until 1 hour prior to investigational product 
administration.  
• Water may be consumed without restriction beginning 1 hour after dosing. 
• Non-caffeinated drinks (except grapefruit or grapefruit-related citrus fruit juices – see 
below) may be consumed with meals and the evening snack. 
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• Lunch will be provided approximately 4 hours after dosing. 
• Dinner will be provided approximately 12 hours after dosing. 
• An evening snack may be permitted approximately 2 hours after evening meal. 
• Subjects will not be allowed to eat or drink grapefruit or grapefruit-related citrus fruits 
(e.g. Seville oranges, pomelos, papaw, dragon fruit, kiwi fruit, mango, passion fruit, 
pomegranate, rambutan, star fruit or products that contain these fruits) from 2 weeks 
prior to admission to the unit until collection of the final pharmacokinetic blood 
sample.  
• Meals intake during the study will also be standardized.  
5.5.2 
Alcohol, Caffeine and Tobacco 
• Subjects will abstain from alcohol for 48 hours prior to admission to the clinical site 
in each period and continue abstaining from alcohol until collection of the final 
pharmacokinetic sample of each study period. Subjects will undergo an alcohol breath 
test at screening, at admission to each treatment period and at the discretion of the 
investigator. 
• Subjects will abstain from caffeine-containing products for 48 hours prior to the start 
of dosing until collection of the final pharmacokinetic sample of each study period.  
• Subjects will abstain from the use of tobacco- or nicotine-containing products 
including nicotine patches and other delivery devices such as electronic cigarettes or 
vaporizers) from screening and throughout the study.  
5.5.3 
Activity 
• Subjects will not be permitted to assume a fully recumbent position for 4 hours 
following dosing. 
• Subjects will abstain from strenuous exercise (e.g. heavy lifting, weight training, 
calisthenics, aerobics) for the duration of the study. Walking at a normal pace will be 
permitted. 
• Subjects will abstain from strenuous exercise (e.g., heavy lifting, weight training, 
calisthenics, aerobics) for at least 48 hours prior to each blood collection for clinical 
laboratory tests and throughout the entire study. Walking at a normal pace will be 
permitted. 
5.5.4 
Contraception 
All female subjects who are of childbearing potential and are sexually active and at risk for 
pregnancy must agree to use a highly effective method of contraception consistently and 
correctly for the duration of the active study period and for 30 days after the last dose of 
investigational product. The investigator or his or her designee, in consultation with the subject, 
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will confirm that the subject has selected an appropriate method of contraception for the 
individual subject from the permitted list of contraception methods (see below) and instruct the 
subject in its consistent and correct use. Subjects need to affirm that they meet the criteria for 
the correct use of at least 1 of the selected methods of contraception. The investigator or his or 
her designee will discuss with the subject the need to use highly effective contraception 
consistently and correctly according to the schedule of activities and document such 
conversation in the subject’s chart. In addition, the investigator or his or her designee will 
instruct the subject to call immediately if the selected contraception method is discontinued. 
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (i.e., perfect use) and 
include the following: 
1. Established use of oral, inserted, injected, transdermal, or implanted hormonal 
methods of contraception is allowed provided the subject plans to remain on the same 
treatment throughout the entire study and has been using that hormonal contraceptive 
for an adequate period of time to ensure effectiveness as deemed appropriate by the 
investigator; 
2. Intrauterine contraceptive device (IUD); 
3. Male condom or female condom used WITH a spermicide (i.e., foam, gel, film, 
cream, or suppository); 
4. Male sterilization with absence of sperm in the post-vasectomy ejaculate; 
5. Bilateral tubal ligation / bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label); 
6. Female who meets the criteria for non-childbearing potential as described below: 
Female subjects of non-childbearing potential must meet at least one of the following criteria: 
• Achieved postmenopausal status, defined as follows: cessation of regular menses 
for at least 12 consecutive months with no alternative pathological or physiological 
cause; and have a serum follicle-stimulating hormone (FSH) level 40 mIU/mL; 
• Have undergone a documented (included self-reported) hysterectomy and/or 
bilateral oophorectomy. 
All other female subjects (including females with tubal ligations) will be considered to be of 
childbearing potential. 
5.6 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not subsequently randomized. To ensure transparent reporting of screen failure subjects, a 
minimal set of screen failure information will include demography, screen failure details (e.g. 
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 218246 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 26 of 72 
withdrawal of consent), eligibility criteria, any protocol deviations and any adverse events or 
incidents as applicable.  
Individuals who do not meet the criteria for participation in this study (screen failure) may not 
be re-screened. 
5.7 
Sponsor’s Qualified Medical Personnel 
Contact information for the sponsor's appropriately qualified medical personnel for the study is 
documented in the Study Contact List located in the investigator study master file held at the 
study site. 
The contact number is only to be used by investigational staff seeking advice on medical 
questions or problems in the event that the established communication pathways between the 
investigational site and the study team are not available.   
The contact number is not intended for direct use by study subjects. To facilitate access to 
appropriately qualified medical personnel on study-related medical questions or problems, 
subjects will be provided with a contact card. The contact card will provide, as a minimum, 
protocol identifiers, the subject’s study identification number, contact information for the 
investigational site, and contact details in the event that the investigational site cannot be 
reached to provide advice on a medical question or problem identified by a healthcare 
professional other than the investigator.   
5.8 
Rater/Clinical Assessor Qualifications  
No rater/clinical assessor qualifications are required for this study. 
6 
INVESTIGATIONAL/STUDY PRODUCTS 
For the purposes of this study, per International Conference on Harmonization (ICH) 
guidelines, and GSK policy, 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. 
This includes a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use.  
6.1 
Investigational/Study Product Supplies 
The selection of the Reference product (the currently marketed and commercially available 
esomeprazole 20 mg capsules from AZ), will be based on assay content to ensure that this 
product does not differ by more than 5% from that of the batch used as Test product 
(esomeprazole 20 mg capsules from CG). 
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 8 2 4 6  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 7. 0  
Pa ge 2 7  of 7 2  
T he f oll o wi n g st u d y pr o d ucts will be s u p plie d b y t he Cli nical S u p plies De part me nt, G S K C H:  
T a bl e 6 -1  
I n v e sti g ati o n al/ St u d y Pr o d u ct S u p pli e s 
 
T e st Pr o d u ct  
R ef er e n c e Pr o d u ct  
Pr o d u ct N a m e  
e s o m e pr a z ol e 2 0 m g 
d el a y e d -r el e a s e c a p s ul e s 
e s o m e pr a z ol e 2 0 m g 
d el a y e d -r el e a s e c a p s ul e s 
( N e xi u m 2 4 H R) ( C a n a di a n 
a v ail a bl e pr o d u ct)   
 
P a c k D e si g n  
b ottl e s  
b ottl e s  
Di s p e n si n g D et ail s  
o n e c a p s ul e o n c e d ail y  
o n e c a p s ul e o n c e d ail y  
Pr o d u ct M a st er F or m ul ati o n 
C o d e ( M F C)  
 
 
D o s e/ A p pli c ati o n  
O n e c a p s ul e a d mi ni str ati o n  
O n e c a p s ul e a d mi ni str ati o n  
R o ut e of A d mi ni str ati o n  
Or al  
Or al  
U s a g e I n str u cti o n s  
•  
A d mi ni st er st u d y 
m e di c ati o n wit h 2 4 0 m L 
of a m bi e nt t e m p er at ur e 
w at er  
•  
I n str u ct s u bj e ct s t o 
c o n s u m e t h e e ntir e 
a m o u nt of w at er al o n g 
wit h t h eir i n v e sti g ati o n al 
pr o d u ct  
•  
A d mi ni st er st u d y 
m e di c ati o n wit h 2 4 0 m L 
of a m bi e nt t e m p er at ur e 
w at er  
•  
I n str u ct s u bj e ct s t o 
c o n s u m e t h e e ntir e 
a m o u nt of w at er al o n g 
wit h t h eir i n v e sti g ati o n al 
pr o d u ct  
R et ur n R e q uir e m e nt s  
All  u n u s e d s a m pl e s t o b e 
r et ur n e d 
All u n u s e d s a m pl e s t o b e 
r et ur n e d 
2 1 8 2 4 6 | Pr ot oc ol A me n d me nt  1 4 Mar 2 0 2 2 | T M F- 2 1 8 1 0 6 | 1. 0
C CI
C CI
C CI


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 218246 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 28 of 72 
Table 6-2 
Sundry Items 
Sundry items to be supplied: 
Item 
Supplied 
By 
Pack 
Design 
Dispensing 
Details 
Return/Disposal Details 
Used Samples 
Unused 
Samples 
Acon 10 Drugs Split 
Cup 
Site/CRO 
Commercial 
pack 
Use as per 
study schedule 
Discard/destroy at 
site using site 
disposal procedures 
To keep 
at site 
BD Vacutainer®, 
Urine Collection 
Tubes and Kits, BD 
Medical 
Site/CRO 
Commercial 
pack 
Use as per 
study schedule 
Discard/destroy at 
site using site 
disposal procedures 
To keep 
at site 
Clearview hCG 
Combo -Pregnancy 
Tests 
Site/CRO 
Commercial 
pack 
Use as per 
study schedule 
Discard/destroy at 
site using site 
disposal procedures 
To keep 
at site 
COT One Step 
Cotinine Test Device Site/CRO 
Commercial 
pack 
Use as per 
study schedule 
Discard/destroy at 
site using site 
disposal procedures 
To keep 
at site 
Microtube 2mL PP 
Jupé, Sans 
Bouchons 
Site/CRO 
Commercial 
pack 
Use as per 
study schedule 
Discard/destroy at 
site using site 
disposal procedures 
To keep 
at site 
Tube BD Plastique 
EDTA K2 3mL 
Lavande 
Site/CRO 
Commercial 
pack 
Use as per 
study schedule 
Discard/destroy at 
site using site 
disposal procedures 
To keep 
at site 
Tube BD Plastique 
SST 3.5mL 
Site/CRO 
Commercial 
pack 
Use as per 
study schedule 
Discard/destroy at 
site using site 
disposal procedures 
To keep 
at site 
Tube BD plastique 
5mL SST 
Site/CRO 
Commercial 
pack 
Use as per 
study schedule 
Discard/destroy at 
site using site 
disposal procedures 
To keep 
at site 
Urine Collection Cup 
with Integrated 
Transfer Device 
Site/CRO 
Commercial 
pack 
Use as per 
study schedule 
Discard/destroy at 
site using site 
disposal procedures 
To keep 
at site 
Urine Collection 
Tube Plastic 8mL 
Site/CRO 
Commercial 
pack 
Use as per 
study schedule 
Discard/destroy at 
site using site 
disposal procedures 
To keep 
at site 
Regular Polyester 
Swab with Plastic 
Applicator 
Biomedical 
Laboratory  
Commercial 
pack 
Use as per 
study schedule 
Discard/destroy at 
biomedical 
laboratory facility 
using biomedical 
laboratory disposal 
procedures 
To keep 
at site 
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 8 2 4 6  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 7. 0  
Pa ge 2 9  of 7 2  
E q ui vale nt ite ms ca n als o be use d base d o n s u p plier a vaila bilit y . Detaile d i nstr ucti o ns f or t he 
ret ur n of st u d y pr o d uct/st u d y s u p plies f or t he acc o u nta bilit y c h ec ks a n d s u bse q ue nt destr u cti o n 
w hic h will be pr o vi de d b y G S K C H d uri n g t he st u d y i n ti me f or st u d y cl ose o ut visit.  S u n dr y 
ite ms will be s u p plie d b y t he site/ ve n d or a n d will be discar de d or destr o ye d at t he cli nical site. 
6. 1. 1  
D o s a g e F or m a n d P a c k a gi n g  
Ca ps ules  will be s u p plie d t o t he cli nical site as pac k a ge d b ottle s f or dis pe nsi n g b y t h e p har mac y.  
T he c o nte nt of t he pr o d uct la bels will be i n acc or da nce wit h all a p plica ble re g ulat or y 
re q uire me nts a n d will b e t he res p o nsi bilit y of t he G S K C H Gl o bal Cli nical S u p plies gr o u p. 
Eac h st u d y la bel will c o ntai n, b ut n ot be li mite d t o, pr ot oc ol n u m ber, dir ecti o ns f or use a n d 
st ora ge re q uire me nts.  
Care s h o ul d be t a ke n wit h t he s u p plie d pr o d ucts a n d t heir la bels s o t hat t h e y are m ai ntai ne d i n 
g o o d c o n diti o n. It is i m p orta nt t hat all la bels re mai n i ntact a n d le gi ble f or t he d urat i o n of t he 
st u d y. S u bjects s h o ul d be i nstr ucte d t o n ot re m o ve or deface a n y part of t h e st u d y la bel.  
All pr o d ucts s u p plie d are f or use o nl y i n t his cli nical st u d y a n d s h o ul d n ot be use d f or a n y ot her 
p ur p ose.  
6. 1. 2  
Pr e p ar ati o n a n d Di s p e n si n g  
S u bjects will be as si g ne d t o pr o d ucts i n acc or da n ce wit h t he ra n d o mizati o n sc he d ule ge nerate d 
b y 
, pri or t o t he start of t he st u d y, usi n g vali date d s oft w are. 
Es o meraz ole ca ps ul es  will be dis pe nse d b y q ualifie d site pers o n nel  ( u n bli n de d) per t he 
d osa ge/a d mi nistra ti o n i nstr ucti o ns. T hese staff me m bers will n ot be i n v ol ve d i n a n y s afet y, 
effic ac y ass ess me nts or ot her as pects of t he st u d y t hat c o ul d be i nfl ue n ce d b y t he k n o wle d ge of 
w hic h pr o d uct a s u bject has bee n assi g n e d t o us e. A n a d diti o nal me m ber of site staff s h o ul d 
e ns ure t he dis pe nsi n g pr oce d ures are c o m plete d acc uratel y.  
6. 2  
A d mi ni str ati o n  
O nl y s u bjects e nr olle d i n t he st u d y ma y recei ve st u d y pr o d ucts a n d o nl y a ut h orize d site staff 
ma y s u p pl y or a d mi nister st u d y pr o d ucts. All st u d y i nter ve nti o ns m ust be st ore d i n a sec ure, 
e n vir o n me ntall y c o ntr oll e d, a n d m o nit ore d ( ma n u al or a ut o mat e d) area i n acc or da nce wit h t he 
la bele d st ora ge c o n diti o ns wit h access li mite d t o t he a ut h orize d site staff o nl y. 
F oll o wi n g a n o v er ni g ht fast of least 1 0  h o urs, s u bjects will recei ve i n vesti gati o nal pr o d uct. 
I n v esti gat or site pers o n n el will a d mi nister i n vesti gati o nal pr o d uct d uri n g eac h p eri o d wit h 
a m bie nt te m perat ure wat er t o a t otal v ol u me of 2 4 0  m L a n d will i nstr uct s u bjects t o c o ns u me 
t he e ntire a m o u nt of water al o n g wit h t heir i n vesti gati o nal pr o d uct. A ha n d a n d m o ut h c hec k 
will be perf or me d t o e ns ure c o ns u m pti o n of t he me dicati o n.  
2 1 8 2 4 6 | Pr ot oc ol A me n d me nt  1 4 Mar 2 0 2 2 | T M F- 2 1 8 1 0 6 | 1. 0
P P D


GSK Consumer Healthcare 
Clinical Protocol 
Protocol Number: 218246 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 30 of 72 
Subjects will swallow the investigational product whole and will not manipulate or chew the 
medication prior to swallowing. To standardize the conditions on pharmacokinetic sampling 
days, all subjects will be required to refrain from lying down (except when required by 
procedures), eating, and drinking beverages for the first 4 hours after dosing. Water may be 
given after 1 hour post-dosing.  
6.2.1 
Medication/Dosing Errors 
Medication/dosing errors may result, in this study, from the administration or consumption of: 
•
the wrong product,
•
by the wrong subject,
•
at the wrong time,
•
or at the wrong dosage.
Such medication/dosing errors occurring to a study subject are to be captured in the CRF. In the 
event of medication dosing error, the sponsor should be notified immediately and under no 
circumstance should this exceed 24 hours. 
Medication/dosing errors are reportable irrespective of the presence of an associated AE, 
including: 
•
Medication/dosing errors involving subject exposure to any of the study products;
•
Potential medication/dosing errors or uses outside of what is foreseen in the protocol
that do or do not involve the participating subject.
If a medication/dosing error is accompanied by an AE, as determined by the investigator, the 
medication/dosing error and, any associated adverse event(s) are to be captured in the CRF AE 
form.  
6.2.2 
Overdose 
An overdose is a deliberate or inadvertent administration of a product at an amount higher than 
specified in the protocol. 
Overdose is not likely to occur in this study. 
Overdose per se is not an AE. However, any clinical sequelae of an overdose should be reported 
as an AE (and serious adverse event (SAE), if appropriate). For reporting, follow the AE and 
SAE reporting instructions. 
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 218246 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 31 of 72 
6.3 
Investigational/Study Product Storage  
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study products received and any discrepancies are reported and 
resolved before use according to the supplied shipping documentation. 
The investigator, or designee, will ensure that all study products are stored in a secured area 
with controlled access under required storage conditions and in accordance with applicable 
regulatory requirements and the product label.   
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products). This should be 
captured from the time of first product receipt throughout the study. Even for continuous 
monitoring systems, a log or site procedure that ensures active daily evaluation for excursions 
should be available. The operation of the temperature-monitoring device and storage unit (for 
example, refrigerator), as applicable, should be regularly inspected to ensure it is maintained in 
working order.  
Any excursions from the product-label storage conditions should be reported to appropriate site 
staff upon discovery and communicated to sponsor as soon as possible. The site should actively 
pursue options for returning the product to the storage conditions as described in the labeling, 
as soon as possible. Excursions from the storage requirements, including any actions taken, 
must be documented as a protocol deviation and reported to the Sponsor.   
Once an excursion is identified, the affected product (or products) must be quarantined and not 
used until the sponsor provides documentation of permission to use. Use of any of the affected 
product(s) prior to sponsor approval will be considered a protocol deviation.   
6.4 
Investigational/Study Product Accountability 
All products supplied are for use only in this clinical study and should not be used for any other 
purpose. 
All study products must be received by a designated person at the study sites, handled and stored 
safely and properly, and kept in a secured location to which only the staff have access. Upon 
receipt, all study products should be stored according to the instructions specified on the product 
labels. Study products are to be dispensed only to subjects enrolled in the study in accordance 
with the protocol, by authorized site staff. 
The investigative site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of all the product supplies. All study products will be accounted for using the 
investigational/study product accountability form/record. The investigator is responsible for 
study product accountability, reconciliation, and record maintenance.  
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 8 2 4 6  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 7. 0  
Pa ge 3 2  of 7 2  
T he acc o u nt a bilit y rec or ds m ust be a vail a ble f or i ns pecti o n b y t h e st u d y m o nit or d uri n g t he 
st u d y. M o nit ori n g of pr o d uct acc o u nta bilit y will b e perf or me d b y t he m o nit or d uri n g site visits 
a n d at t he c o m pleti o n of t he st u d y.  
6. 4. 1  
D e str u cti o n of I n v e sti g ati o n al/ St u d y Pr o d u ct S u p pli e s  
At t he e n d of  t he st u d y, t h e in vesti gat or or a n a p pr o priate desi g nee, a n d a re prese ntati ve of G S K 
C H (st u d y m o nit or) will i n ve nt or y all use d a n d u n use d st u d y pr o d ucts a n d s u n dr y ite ms. T h e 
i n vesti gati o nal/st u d y pr o d uct acc o u nt a bilit y rec or d f or ret ur ne d st u d y pr o d ucts will t he n be 
c o m plete d. All st u d y pr o d uct ( use d a n d u n use d) f or t his cli nical st u d y (i ncl u di n g e m pt y 
pac ka gi n g b ottles ), will be ret ur ne d f or destr u cti o n t o t he G S K C H Cli nical S u p plies 
De part me nt or d esi g n ate d ve n d or usi n g t he ret ur n i nstr ucti o ns pr o vi de d. D etaile d i nstr ucti o ns 
f or t he ret ur n of st u d y pr o d uct/st u d y s u p plies f or t he acc o u nta bilit y c hec ks a n d s u bse q ue nt 
destr ucti o n will be pr o vi de d b y G S K C H d uri n g t he st u d y i n ti me f or st u d y cl ose o ut visit.  
6. 5  
Bli n di n g a n d All o c ati o n/ R a n d o mi z ati o n  
T he i n vesti gat or’s k n o wle d ge of t he tr eat me nt s h o ul d n ot i nfl ue nce t he decisi o n t o  e nr oll a 
partic ular s u bject or affect t he or der i n w hi c h s u bjects are e nr olle d.  
 will pr o vi de a ra n d o mizati o n sc he d ule t o t he i n vesti gat or a n d, i n acc or da nce 
wit h t he ra n d o mizati o n n u m bers, t he s u bject will r ecei ve t he st u d y tr eat me nt re gi me n assi g n e d 
t o t he c orres p o n di n g ra n d o mizati o n n u m ber. 
Treat me nts will be pr o vi de d i n a bli n d ma n ner.  Pers o n nel i n v ol ve d i n t he c ollecti o n, m o nit ori n g, 
re visi o n, or e val uati o n of a d vers e e ve nts, pers o n nel of t he bi oa nal ytical de part me nt, a n d 
pers o n nel w h o c o ul d h a v e a n i m pact o n t h e o utc o me of t he st u d y , i ncl u di n g G S K/
 
statisticia ns, pr ogra m mers, scie ntist s, D M st u d y ma na gers, cli nical st u d y tea m e x ce pt Gl o bal 
s u p pl y, a n d 
 P K a nal yst, will n ot ha ve pri or access t o t he ra n d o mizati o n c o de . 
6. 6  
Br e a ki n g t h e Bli n d  
A pa per c o p y of t he ra n d o mizati o n list will be ke pt b y t he 
 researc h p har mac y 
gr o u p i n a pa per e n v el o pe, w hic h itself will be i nserte d i n a plastic e n vel o pe cl ose d wit h a sec ure 
seal wit h t he me dicati o n d oc u me nts, i n a sec ure place wit h c o ntr olle d access, t hr o u g h o ut t he 
st u d y. T h e plastic e n vel o pe will be i de ntifi e d i n a wi n d o w, wit h at least t he t y pe of c o nte nt a n d 
t he pr oject n u m ber. A f or m will als o be pr o vi de d f or d oc u me nti n g t he o p e ni n g a n d cl osi n g of 
t he plastic e n vel o pe at 
. M ore o ver, t he electr o nic versi o n of t he lists will be ke pt 
at 
 o n a c o ntr olle d access dir ect or y. After t he e n d of st u d y a n d f oll o wi n g  
 
 pr oject ma na ger’s a ut h orizati o n, t he ra n d o mizati o n list will be o pe ne d a n d k e pt i n t h e 
me dicati o n bi n der . 
2 1 8 2 4 6 | Pr ot oc ol A me n d me nt  1 4 Mar 2 0 2 2 | T M F- 2 1 8 1 0 6 | 1. 0
P P D
P P D
P P D
P P D
P P D
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 218246 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 33 of 72 
6.7 
Compliance 
Study products will be administered under the supervision of investigator site personnel. A hand 
and mouth check will be performed to ensure consumption of the medication. 
6.8 
Concomitant Medication/Treatment(s) 
Subjects will abstain from all concomitant treatments, except for contraceptives and hormone 
replacement therapy, and those used for the treatment of adverse events unless they jeopardize 
the integrity of the study. The study Sponsor should be immediately informed. Any 
medications, treatments or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) taken during the study, from signing the informed consent, 
must be recorded in the CRF with indication, reason for use, unit dose, daily dose, and start and 
stop dates of administration. All subjects will be questioned about medications/treatments at 
each site visit. 
Medication/treatments taken within 90 days of signing the informed consent form will be 
documented as a prior medication/treatment. Medications/treatments taken after the first dose 
will be documented as concomitant medication/treatments. 
7 
DISCONTINUATION OF STUDY INTERVENTION AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1 
Subject Discontinuation/Withdrawal  
A subject may withdraw from the study at any time at his or her own request or may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral 
reasons, events such as vomiting and diarrhoea which could render the plasma concentration-
time profile unreliable or the inability of the subject to comply with the protocol-required 
schedule of study visits or procedures.   
The following circumstances require discontinuation of study product and/or premature subject 
withdrawal: 
• Protocol violation that may impact the subject’s safety 
• Positive test for COVID-19, conducted during the study, at times deemed necessary by 
investigator 
• Withdrawal of informed consent 
• Subject lost to follow-up  
• Unblinding of the subject  
• Pregnancy 
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 218246 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Page 34 of 72 
If a subject is discontinued or prematurely withdraws from the study, the reason(s) for 
discontinuation or withdrawal and the associated date must be documented in the relevant 
section(s) of the CRF.  
7.2 
Lost to Follow up 
If a subject fails to return to the site for a required study visit the site must attempt to contact 
the subject and reschedule the missed visit as soon as possible and counsel the subject on the 
importance of maintaining the assigned visit schedule and ascertain whether the subject wishes 
to and/or should continue in the study. 
A subject will be considered lost to follow up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. Before a subject is deemed lost to follow 
up, the investigator or designee must make every effort to regain contact with the subject (where 
possible, 3 telephone calls and, if necessary, a certified letter to the subject’s last known mailing 
address or local equivalent methods). These contact attempts should be documented. If contact 
is made with the subject, the investigator should inquire about the reason for withdrawal, request 
that the subject return all products that they had been dispensed and if appropriate request that 
the subject return for a final visit and follow-up with the subject regarding any unresolved 
adverse events (AEs). 
Final safety assessments may be carried out when the subject returns to the study site, at the 
investigator’s discretion, which could include the following: 
• urine pregnancy test, 
• physical examination, 
• safety laboratory tests, 
• seated blood pressure, respiratory rate, oral body temperature and pulse rate measurements. 
Should the subject continue to be unreachable, he/she will be considered to have withdrawn 
from the study and lost to follow up.  
Lack of completion of all or any of the early termination procedures will not be viewed as 
protocol deviations so long as the subject’s safety was preserved. 
If the subject withdraws from the study and withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected. The sponsor may retain and continue to use any data collected before such withdrawal 
of consent. 
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8 
STUDY PROCEDURES 
This section lists the procedures to be completed at each planned study visit. The timing of each 
procedure is listed in the Schedule of Activities section. 
Adherence to the study design requirements, including all procedures are essential and required 
for study conduct. 
8.1 
Visit 1/Screening 
Screening procedures will be conducted by the investigator, or suitably qualified designee. 
Subjects will be screened within 28 days prior to administration of the investigational product 
to confirm that they meet the subject selection criteria for the study.   
The following procedures will be completed: 
8.1.1 
Informed Consent 
The investigator, or designee, must obtain informed consent from each subject participating in 
this study after adequate explanation of the aims, methods, objectives, and potential hazards of 
the study. The informed consent form (ICF) will be signed and dated by the subject. A copy 
will be given to the subject, and the original signed and dated ICF will be maintained in the 
subject’s records. 
The investigator, or designee, must also explain to the subjects that they are completely free to 
refuse to enter the study or to withdraw from it at any time. Appropriate forms for documenting 
a signed and dated consent will be provided by either the investigator or by GSK CH. 
The investigator, or designee, should sign and date the ICF to confirm that the consent process 
was completed correctly after the subject has signed.   
The time the subject signed the informed consent form will be captured as this is the point at 
which all adverse events will be captured from. The date and time of consent will be captured 
in the CRF. 
If, during a subject’s participation in the study, any new information becomes available that 
may affect the subject’s willingness to participate in the study, each ongoing subject should 
receive a copy of this new information and be re-consented into the study. Each subject should 
be provided with a copy of the signed and dated amended consent form. The date of re-consent 
will be recorded on the CRF. 
After signing the ICF, subjects will undergo the screening assessments to confirm that they 
meet all the inclusion criteria and none of the exclusion criteria. If the subject is confirmed 
eligible by the investigator (or designee) to participate in the study the subject is considered 
enrolled in the study. 
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8.1.2 
Demographics 
The following demographic information will be recorded in the CRF: year of birth, gender, 
ethnicity and race.  
Ethnicity and race of subjects will be recorded in accordance with FDA Guidance for Industry: 
Collection of Race and Ethnicity Data in Clinical Trials, 2005. 
8.1.3 
Inclusion/Exclusion Criteria 
Inclusion and exclusion criteria information, as specified in Section 5, will be documented in 
the CRF. 
8.1.4 
Medical History and Prior Medication/Treatment 
Details of relevant medical and surgical history (in the last 5 years), including allergies or drug 
sensitivity, will be documented in the CRF. 
Prior medications/treatments, including prescription and non-prescription drugs, dietary 
supplements and herbal remedies, taken in the last 90 days and prior to signing the informed 
consent form, will be documented in the CRF. 
8.1.5 
Subject Eligibility 
The investigator and/or medically qualified designee will review inclusion/exclusion criteria, 
medical history, prior medications to confirm subject eligibility to participate in the clinical 
trial. This will be documented in the CRF. 
To prepare for study participation, subjects will be instructed on the Lifestyle Considerations 
and any Concomitant Medication/Treatment(s) requirements of the protocol. 
8.1.6 
Screening Procedures 
The following procedures will be completed: 
• Obtain written informed consent and record in the CRF. 
• Review Inclusion and Exclusion criteria and record in the CRF. 
• Collect demography, including year of birth, gender, ethnicity and race and record in 
the CRF. 
• Collect height and weight and calculate BMI. The results for each measurement will be 
recorded in the CRF. 
• Obtain medical history as related to the inclusion/exclusion criteria, including any 
relevant medical or surgical history, allergies or drug sensitivity, history of drug and 
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alcohol use. Significant findings that are present before consent must be included in the 
CRF. 
• Obtain complete medication history of all prescription or nonprescription drugs, and 
dietary and herbal supplements taken within 90 days prior to consent, and record in the 
CRF. 
• Obtain seated blood pressure, pulse rate, respiratory rate and oral body temperature. The 
results for each measurement will be recorded in the CRF. 
• Conduct full physical examination. Any clinically relevant findings will be noted in the 
AE CRF page and enrollment will be based upon investigator judgement. 
• Contraceptive review. 
• Collect single 12 lead ECG. Results (normal or abnormal) and clinical significance will 
be recorded on the CRF. 
• Following at least a 4 hour fast, collect blood and urine specimens for the following, 
and recorded on the CRF: 
• Safety laboratory tests and virology; 
• Urine drug screening; 
• Alcohol screening; 
• Cotinine screening; 
• Serum FSH concentration for any female who has been amenorrheic for at least 
12 consecutive months; 
• Urine pregnancy test for all females of childbearing potential. 
• Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed and any AEs 
recorded in the CRF. 
• Collect nasal/nasopharyngeal swab sample for COVID-19 test within 24 to 72 hours 
prior to check-in (Day -1) in Period 1. Date and time of sample collection and test results 
(positive or negative) will be documented in the CRF. 
8.2 
Study Period 
For the study periods described below, when multiple procedures are scheduled at the same 
time point(s) relative to dosing, the following chronology of events should be adhered to, where 
possible. 
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• Blood pressure/pulse rate: obtain as close as possible to scheduled time, but prior to 
blood specimen collection; 
• Pharmacokinetic blood specimens: obtain at scheduled time. 
Obtain all other procedures as close as possible to the scheduled time but may be obtained 
before or after blood. 
8.2.1 
Period 1/Day -1   
Subjects will be admitted to the clinical site the day prior to Day 1 dosing. 
The following procedures will be completed following admission to the clinical site: 
• Obtain oral body temperature. The results for each measurement will be recorded in the 
CRF. 
• Brief physical examination including evaluation of general appearance, heart, lung. The 
results will be recorded in the CRF. 
• Collect urine for drug screening. The results will be recorded in the CRF. 
• Collect urine for cotinine screening. The results will be recorded in the CRF. 
• Obtain blood for serum β-hCG for all females of childbearing potential. The results 
will be recorded in the CRF (note: blood for serum β-hCG can be obtained at admission 
or in the morning of Day -1). 
• Collect nasal/nasopharyngeal swab sample for COVID-19 test. Date and time of sample 
collection and test results (positive or negative) will be documented in the CRF. 
• Confirm proper contraception is being used and the results will be recorded on the CRF. 
• Collect alcohol breath test. Result will be recorded on the CRF. 
• Meals as required in section 5.5.1. Time and consumption of meals will be recorded on 
CRF. 
• Subjects will begin fasting at least 10 hours prior to dosing on Day 1. 
• Changes in concomitant medication or non-drug treatments/procedures will be 
documented in the CRF. 
• Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed and any AEs 
recorded in the CRF. 
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8.2.2 
Period 1/Day 1  
Prior to dosing, within 1 hour of study drug administration, the following procedures will be 
completed: 
• Obtain seated blood pressure, pulse rate, respiratory rate and oral body temperature. The 
results for each measurement will be recorded in the CRF. 
• Review Inclusion and Exclusion criteria and record in the CRF. 
• Randomization. 
• Collect a blood sample for pharmacokinetic analysis. Time of blood sampling will be 
recorded in the CRF. 
• After all pre-dose procedures have been completed, administer the investigational 
product (see Investigational/Study Products section) and record in the CRF. 
After dosing, the following procedures will be completed: 
• Collect blood samples for pharmacokinetic analysis at the following time points after 
dosing on Day 1: 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 
8, 10, 12, and 16 hours. The time tolerance window for blood samples will be ±1 minute 
for all samples collected before 8 hours post-dose and ±3 minutes for subsequent 
samples. Time of blood sampling will be recorded in the CRF. 
• Meals as required in section 5.5.1. Time and consumption of meals will be recorded on 
CRF. 
• Changes in concomitant medication or non-drug treatments/procedures will be 
documented in the CRF. 
• Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed and any AEs 
recorded in the CRF. 
8.2.3 
Period 1/Day 2  
• Obtain oral body temperature. The results for each measurement will be recorded in the 
CRF. 
• Collect a blood sample for pharmacokinetic analysis at 24 hours post dosing of Day 1 
continuing into Day 2. The time tolerance window for blood sample will be ±3 minutes. 
Time of blood sampling will be recorded in the CRF. 
• Meals as required. Time and consumption of meals will be recorded on CRF. 
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• Changes in concomitant medication or non-drug treatments/procedures will be 
documented in the CRF. 
• Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed and any AEs 
recorded in the CRF. 
• Collect nasal/nasopharyngeal swab sample for COVID-19 test. Date and time of sample 
collection and test results (positive or negative) will be documented in the CRF. 
• After all procedures are completed, subjects are discharged from the clinical site. 
8.2.4 
Washout Period 
• Collect nasal/nasopharyngeal swab sample for COVID-19 test within 24 to 72 hours 
prior to check-in (Day -1) in Period 2. Date and time of sample collection and test 
results (positive or negative) will be documented in the CRF. 
8.2.5 
Period 2/Day -1 
After a washout period of at least 7 days after the first dose (Period 1/Day 1), subjects will be 
admitted to the clinical site the day prior to Day 1 dosing. 
The following procedures will be completed following admission to the clinical site: 
• Collect nasal/nasopharyngeal swab sample for COVID-19 test. Date and time of sample 
collection and test results (positive or negative) will be documented in the CRF. 
• Brief physical examination including evaluation of general appearance, heart, lung. The 
results will be recorded in the CRF. 
• Obtain oral body temperature. The results for each measurement will be recorded in the 
CRF. 
• Collect urine for drug screening. The results will be recorded in the CRF. 
• Collect urine for cotinine screening. The results will be recorded in the CRF. 
• Obtain blood for serum β-hCG for all females of childbearing potential. The results 
will be recorded in the CRF. (note: blood for serum β-hCG can be obtained at 
admission or in the morning of Day -1) 
• Confirm proper contraception is being used and the results will be recorded on the CRF. 
• Collect alcohol breath test. Result will be recorded on the CRF. 
• Meals as required in section 5.5.1. Time and consumption of meals will be recorded on 
CRF. 
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• Subjects will begin fasting at least 10 hours prior to dosing on Day 1. 
• Changes in concomitant medication or non-drug treatments/procedures will be 
documented in the CRF. 
• Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed and any AEs 
recorded in the CRF. 
8.2.6 
Period 2/Day 1  
Prior to dosing, within 1 hour of study drug administration, the following procedures will be 
completed: 
• Obtain seated blood pressure, pulse rate, respiratory rate and oral body temperature. The 
results for each measurement will be recorded in the CRF. 
• Review Inclusion and Exclusion criteria and record in the CRF 
• Collect a blood sample for pharmacokinetic analysis. Time of blood sampling will be 
recorded in the CRF. 
• After all pre-dose procedures have been completed, administer the investigational 
product (see Investigational/Study Products section) and record in the CRF. 
After dosing, the following procedures will be completed: 
• Collect blood samples for pharmacokinetic analysis at the following time points after 
dosing on Day 1: 0.5, 0.75, 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.5, 4, 4.5, 5, 5.5, 6, 
8, 10, 12, and 16 hours. The time tolerance window for blood samples will be ±1 minute 
for all samples collected before 8 hours post-dose and ±3 minutes for subsequent 
samples. Time of blood sampling will be recorded in the CRF. 
• Meals as required in section 5.5.1. Time and consumption of meals will be recorded on 
CRF. 
• Changes in concomitant medication or non-drug treatments/procedures will be 
documented in the CRF. 
• Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed and any AEs 
recorded in the CRF. 
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8.2.7 
Period 2/Day 2  
• Collect a blood sample for pharmacokinetic analysis at 24 hours post dosing of Day 1 
continuing into Day 2. The time tolerance window for blood sample will be ±3 minutes. 
Time of blood sampling will be recorded in the CRF. 
• Meals as required in section 5.5.1. Time and consumption of meals will be recorded on 
CRF. 
• Changes in concomitant medication or non-drug treatments/procedures will be 
documented in the CRF. 
• Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed and any AEs 
recorded in the CRF. 
8.2.8 
End of Study 
The exit examination procedures will be done before check-out from the clinic, on study Day 2 
of Period 2. 
• Obtain seated blood pressure, pulse rate, respiratory rate and oral body temperature. The 
results for each measurement will be recorded in the CRF. 
• Conduct brief physical examination. The results will be recorded in the CRF. 
• Collect nasal/nasopharyngeal swab sample for COVID-19 test. Date and time of sample 
collection and test results (positive or negative) will be documented in the CRF. 
• Obtain blood and urine samples for safety laboratory tests. 
• Collect urine pregnancy test for all females of childbearing potential. The results will 
be recorded in the CRF. 
• Changes in concomitant medication or non-drug treatments/procedures will be 
documented in the CRF. 
• Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed and any AEs 
recorded in the CRF. 
8.3 
Study Conclusion 
The Study Conclusion page of the CRF will be completed for all subjects whether they 
completed all study procedures or if they were discontinued from the study early. If the subject 
discontinued early, at any point during the study, the primary reason for withdrawal should be 
recorded on the Study Conclusion page. 
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If a subject has any clinically significant, study-related abnormalities or AEs at the end of the 
study, the GSK CH medical monitor (or designated representative) should be notified and, the 
subject may be asked to remain at the clinical site or be asked to return for a follow-up visit to 
ensure any issue is resolved or deemed not clinically significant.  
8.4 
Follow-up Visit 
The study site may contact a subject to follow up an AE post-study completion/withdrawal 
and, in some circumstances, request they return to the site for additional follow-up visits (final 
safety assessments). If needed, additional examinations may be carried out at such visits. 
9 
STUDY ASSESSMENTS 
Every effort should be made to ensure that protocol-required tests and procedures are completed 
as described. However, it is anticipated that from time to time there may be circumstances, 
outside the control of the investigator that may make it unfeasible to complete an assessment. 
In these cases, the investigator must take all steps necessary to ensure the safety and well-being 
of the subject. When a protocol-required assessment cannot be performed, the investigator (or 
designee) will document the reason for the missed assessment as a protocol deviation and any 
corrective and preventative actions that he or she has taken to ensure that required processes are 
adhered to as soon as possible. The Sponsor must be informed of any missed assessments in a 
timely manner. 
9.1 
Screening Assessments 
Screening assessments will be performed by appropriately trained staff/clinical examiners at 
the times, and in the order defined in the Study Procedures section of this protocol  
9.2 
Safety and Other Assessments 
The following safety assessments will be performed by appropriately trained staff/clinical 
examiners, at the times and in the order defined in the Study Procedures section of this protocol.   
9.2.1 
Laboratory Tests  
The following laboratory tests/analytical measures will be performed by appropriately trained 
staff/clinical examiners, at the times and in the order defined in in the Study Procedures section 
of this protocol. 
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Table 9-1 
Laboratory Tests 
Hematology 
Chemistry 
Urinalysis 
Drug, cotinine, and 
alcohol screens 
Hematocrit 
Hemoglobin 
Platelet count 
RBC count 
WBC count and 
differential: 
• 
Basophils 
• 
Eosinophils 
• 
Lymphocytes 
• 
Monocytes 
• 
Neutrophils 
Albumin 
ALP 
ALT 
AST 
Calcium 
Chloride 
Creatine kinase 
Creatinine 
GGT 
Glucose 
Phosphorus 
Potassium 
Sodium 
Total bilirubin 
Total protein 
Urea (BUN) 
Bilirubin 
Blood (occult) 
Color and 
appearance 
Glucose 
Ketones 
Leukocyte esterase 
Nitrite 
pH 
Protein 
Specific gravity 
Urobilinogen 
Microscopic 
examinationa  
Amphetamines 
/methamphetamines 
Barbiturates 
Benzodiazepines 
Cocaine 
MDMA 
Methadone 
Opiates 
PCP 
THC 
 
Urine cotinine test 
Alcohol breath test  
Serology 
Hormone 
panel - females only 
 
 
HBsAg 
HBcAb (IgG + IgM) 
HCV Ab 
HIV antigen/antibody 
 
Serum FSHb 
Serum pregnancy testc 
Urine pregnancy testd 
 
 
Definitions:  RBC= red blood cell; WBC= white blood cells; AST= aspartate transaminase; ALT= 
alanine transaminase; GGT= gamma-glutamyl transpeptidase; BUN= blood urea nitrogen; MDMA= 
3,4- methylenedioxymethamphetamine; PCP=  phencyclidine; THC= tetrahydrocannabinol; HBsAg= 
hepatitis B surface antigen; HBcAb= Hepatitis B core antibody; HCV Ab= hepatitis C virus antibodies; 
HIV= human immunodeficiency virus; FSH= follicle-stimulating hormone. 
ain the event of abnormal findings 
bFSH done at screening only in females who have been amenorrhoeic for 12 months 
cAll female subjects of childbearing potential will be tested for serum human chorionic gonadotropin 
(hCG) at Day -1 of each period 
eAll female subjects of childbearing potential will undergo a urine pregnancy test at Screening and End 
of Study. 
Additional laboratory results may be reported on these samples because of the method of 
analysis or the type of analyzer used by the clinical laboratory; or as derived from calculated 
values. These additional tests would not require additional collection of blood. Unscheduled 
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clinical labs may be obtained at any time during the study to assess any perceived safety 
concerns. 
Subjects may undergo random urine drug screening at the discretion of the investigator; the 
result would be recorded in the CRF. Drug screening conducted prior to dosing must be negative 
for subjects to receive investigational product.  
Any remaining serum/plasma from samples collected for clinical safety labs will be destroyed 
at the end of the study. 
9.2.2 
Serology 
Virus serology will be performed at times specified in the Study Procedures section of this 
protocol for HIV antigen and antibody, hepatitis B surface antigen (HBsAg), hepatitis B core 
antibody (HBcAb) (IgG + IgM) and hepatitis C virus antibody (HCV Ab). Serology will be 
performed by using the same sample drawn for chemistry; therefore, no additional blood needs 
to be drawn for serology. In case of a positive finding in virus serology screen, the subject must 
be excluded from trial participation. 
9.2.3 
Urine drug screen 
Urine will be collected at times specified in the Study Procedures section of this protocol. In 
case of a positive finding for any substance class, the subject must be discontinued from the 
trial (or excluded from trial participation in case of positive findings at the screening visit). 
9.2.4 
Alcohol test 
An alcohol breath test will be conducted at times specified in the Study Procedures section of 
this protocol. In case of a positive finding in the alcohol test, the subject must be discontinued 
from the trial. 
9.2.5 
Pregnancy Testing 
For all female subjects of childbearing potential, a urine pregnancy test, will be performed at 
screening and end of study and a serum pregnancy test will be performed on Day -1 of each 
period. Results will be obtained prior to dosing during each period.   
The investigator and site personnel will remind subjects at each visit to inform site personnel if 
their menstrual cycle has changed or if they have any other reason to suspect they may be 
pregnant (e.g. had unprotected intercourse since the last visit). 
A negative pregnancy result is required before the subject may receive the investigational 
product. Pregnancy tests will also be done whenever one menstrual cycle is missed during the 
active study period (or when potential pregnancy is otherwise suspected). Pregnancy tests may 
also be repeated as per request of IRBs/ECs or if required by local regulations. 
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In the case of a positive confirmed pregnancy, the subject will be withdrawn from 
administration of investigational product and from the study. 
9.2.6 
Physical Examinations  
Physical examinations may be conducted by a physician, trained physician's assistant, or nurse 
practitioner as acceptable according to local regulation. A full physical examination will include 
head, ears, eyes, nose, mouth, skin, heart and lung examinations, lymph nodes, gastrointestinal, 
musculoskeletal, vascular and neurological systems.   
A brief physical examination will be focused on general appearance, the respiratory and 
cardiovascular systems, as well as towards subject reported symptoms. 
Any untoward findings identified on physical exams conducted after the administration of the 
first dose of investigational product will be captured as an adverse event, if those findings meet 
the definition of an adverse event. 
9.2.7 
Height and Weight  
Height in centimeters (cm) and body weight in kilograms (kg) to the nearest 0.1 kilogram will 
be measured. 
For measuring weight, a scale with appropriate range and resolution is used and must be placed 
on a stable, flat surface. Subjects must remove shoes, bulky layers of clothing, and jackets so 
that only light clothing remains. They must also remove the contents of their pockets and remain 
still until during measurement of weight.  
BMI will be calculated in kg/m2. 
9.2.8 
Blood Pressure and Pulse Rate  
Additional collection times, or changes to collection times of blood pressure and pulse rate will 
be permitted, as necessary at the discretion of the investigator, to ensure appropriate collection 
of safety data. 
Seated blood pressure should be measured with the subject’s arm supported at the level of the 
heart and recorded to the nearest mmHg after a minimum 5 minutes of rest. The same arm 
(preferably the dominant arm) will be used throughout the study.   
A calibrated blood pressure cuff of the same proper size will be used to measure blood pressure 
each time. The use of an automated device for measuring blood pressure and pulse rate is 
acceptable, although, when done manually, pulse rate will be measured in the brachial/radial 
artery for at least 30 seconds. When the timing of these measurements coincides with a blood 
collection, blood pressure and pulse rate should be obtained prior to the nominal time of the 
blood collection. 
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9.2.9 
Respiratory Rate 
Respiratory rate will be measured after approximately 5 minutes rest in seated position by 
observing and counting the respirations of the subject for 30 seconds and multiplied by 2. When 
blood pressure is to be taken at the same time, respiration measurement will be done after the 
5 minutes of rest and before blood pressure measurement. 
9.2.10 
Temperature 
Body temperature will be measured orally. 
9.2.11 
COVID-19 Test 
Nasal/nasopharyngeal swab will be collected to test for COVID-19 using PCR or antigen test, 
at times specified in the Study Procedure section. Two consecutive negative tests for active 
COVID-19 separated by > 24 hours are required for inclusion in the study: one test will be done 
at screening within 72 hours of admission and one test will be done on Day -1 in Period 1. 
For detection of COVID-19, test/s are to be performed as follows: 
• During the screening 
• At check-in (Day -1 of each period)  
• During the washout period 
• At discharge from Period 1 and end of study or early discontinuation 
• At any time during residential period in study, when subjects report symptoms suggestive 
of COVID-19 
If the first test is > 72 hours prior to unit admission, subjects should be advised to self-quarantine 
until entrance to the unit while awaiting final testing clearance. Subjects who report symptoms 
suggestive of COVID-19 while in the research unit should be isolated in the unit or at home and 
tested for COVID-19 infection using an approved molecular test. 
9.2.12 
Electrocardiogram 
A standard 12 lead ECG will be performed at screening. Interpretation of the tracing must be 
made by a qualified physician or designee and documented on the ECG section of the CRF. 
Each ECG tracing should be kept in the source documents at the study site. Results or any 
clinically significant abnormalities should be reported in the CRF. Clinically significant 
abnormalities should also be recorded on the Adverse Event CRF. Clinically significant 
findings must be discussed with the GSK CH Clinical Project Lead (CPL) prior to enrolling the 
subject in the study. Subjects should be in a quiet environment and not speak during the resting 
period or measurement. Generally, ECGs should not be collected within 3 hours after food or 
beverage consumption. 
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 8 2 4 6  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 7. 0  
Pa ge 4 8  of 7 2  
9. 3  
P h ar m a c o ki n eti c s ( P K)  
T we nt y -t hree ( 23 ) bl o o d sa m ples will be c ollecte d f or p har mac o ki n etic a nal ysis: wit hi n 1 h o ur  
pri or t o d osi n g ( pre -d os e), a n d at 0. 5, 0. 7 5, 1, 1. 2 5, 1. 5, 1. 7 5, 2, 2. 2 5, 2. 5, 2. 7 5, 3, 3. 5, 4, 4. 5, 5, 
5. 5, 6, 8, 1 0, 1 2, 1 6, a n d 2 4  h o urs f oll o wi n g d osi n g i n eac h tr eat me nt p eri o d . Ti me zer o (“ 0 ”) 
as refere nce f or p ost -d os e P K sa m pli n gs is defi n e d as t he ti me of dr u g a d mi nistrati o n. Ti me 
zer o will be rec or de d i n t he C R F. A dea d -v ol u me i ntra ve n o us cat heter will be use d f or bl o o d 
c ollecti o n t o a v oi d m ulti ple s ki n p u nct ures, w he n a p pr o priate. Ot her wise, bl o o d sa m ples will 
be c ollecte d b y dir ect ve ni p u nct ure.  
9. 3. 1  
Pl a s m a  f or a n al y si s of e s o m e pr a z ol e  
D uri n g all st u d y p eri o ds, bl o o d sa m ples ( 3  m L) t o pr o vi de a mi ni m u m of 1  m L plas ma f or 
p har mac o ki netic a nal ysis will be c ollect e d i nt o a p pr o priatel y la bele d t u bes c o ntai ni n g K 2E D T A  
at ti mes s pecifie d i n t he pr ot oc ol.  T he ti me t olera nce wi n d o w f or bl o o d sa m ples will be 
± 1  mi n ute f or all sa m ples c ol lecte d bef ore 8 h o urs p ost-d ose a n d ± 3 mi n utes f or s u bse q ue nt 
sa m ples. 
T he act ual ti mes ma y c h a n ge b ut t he n u m ber of sa m ples will re mai n t he sa me. All eff orts will 
be ma de t o o btai n t he p h ar mac o ki netic s a m ples at t he e x act n o mi nal ti me relati ve t o d osi n g.  
Sa m ples will be a nal yze d usi n g a v ali date d a n al ytical met h o d i n c o m plia nce wit h a p plica bl e 
 sta n dar d o perati n g pr oce d ures. 
T he P K s a m ples m ust b e pr ocesse d a n d s hi p pe d as i n dicate d i n t he A nal ytical Met h o d ol o g y 
I nf or mati o n S heet ( A MI S) t o mai ntai n sa m ple i nte grit y. A n y de viati o ns fr o m t he P K pr ocessi n g 
ste ps, i ncl u di n g a n y acti o ns ta ke n, m ust  be d oc u me nte d a n d re p ort e d t o t he s p o ns or.   O n a 
case-b y -cas e basis, t he s p o ns or ma y ma ke a det er mi nati o n as t o w het her sa m ple i nte grit y has 
bee n c o m pr o mi se d. A n y sa m ple dee me d o utsi de of esta blis he d sta bilit y, or of q uesti o na ble 
i nte grit y, will be c o nsi dere d a pr ot o c ol de viati o n. 
9. 3. 2  
S hi p m e nt of P h ar m a c o ki n eti c S a m pl e s  
W he n a p plica ble, sa m ples will be tra ns p orte d t o t he assa y la b i n at least t w o se parat e s hi p m e nts, 
wit h eac h set of ali q u ots i n se parate s hi p me nts. O nce t he assa y la b c o nfir ms recei pt of t he first 
s hi p me nt, t he sec o n d set of ali q u ots ma y b e se nt. T he sa m ples s h o ul d be pac ke d o n s ufficie nt 
dr y ic e t o kee p t h e m fr oze n f or at least 7 2 h o urs.  
All P K sa m ples will be st ore d u ntil t he y are pr o perl y dis p ose d of at t he e n d of its rete nti o n 
peri o d (i.e., u ntil st u d y re p ort is iss ue d), or us ef ul life (i.e., u ntil e x pir y of st a bilit y), u p o n writte n 
re q uest b y S p o ns or, or u p o n recei pt of a re q u est t o destr o y t he P K sa m ples d ue t o wit h dra wal 
of c o nse nt. N o sa m ple will be retai ne d be y o n d 2 years fr o m last partici pa nt last visit.  
2 1 8 2 4 6 | Pr ot oc ol A me n d me nt  1 4 Mar 2 0 2 2 | T M F- 2 1 8 1 0 6 | 1. 0
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9.4 
Blood Volume 
The total blood sampling volume for each subject in this study is approximately 161 mL. The 
table below reflects approximate sample volumes needed for each measured endpoint. The 
actual collection times of blood sampling may change, but the total number of PK blood samples 
will not increase. Additional blood samples may be taken for safety assessments at the 
discretion of the investigator or GSK CH. 
Table 9-2 
Blood Volume 
Sample Type 
Sample 
Volume 
(mL) 
Number of Sampling Times 
Total Volume 
(mL) 
Screening 
Study Period 
End of Study 
Safety Labs  
8 
1 
 
1 
16 
Serum Pregnancy 
Test 
3.5 
 
2 
 
7 
PK 
3 
 
46 
 
138 
TOTAL 
 
 
 
 
161 
This total volume does not include discarded blood from pre-draws used to remove fluid from flushed 
catheters, if applicable.   
10 
ADVERSE EVENT AND SERIOUS ADVERSE EVENTS 
The investigator and any qualified designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study product or the study, or that caused the 
subject to discontinue the study product or study. 
10.1 
Definition of an Adverse Event (AE) 
An AE is any untoward medical occurrence in a clinical study subject, temporally associated 
with the use of a study product including any washout or lead-in product (or medical device), 
whether or not considered related to the study product, including any washout or lead-in product 
(or medical device). 
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 product including any washout or lead-in product (or medical device). 
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 sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
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Protocol Number: 218246 
 
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medical and scientific judgment of the investigator (i.e., not related to progression of 
underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study product administration even though 
it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
product 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. 
Events NOT meeting the AE definition:  
• Any clinically significant abnormal laboratory findings (if applicable) or other abnormal 
safety assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the subject’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 subject’s 
condition.  
• Medical or surgical procedure (e.g. endoscopy, appendectomy) is not the AE. The 
condition that leads to the procedure is an AE (e.g. appendicitis). 
• Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.  
10.2 
Definition of a Serious Adverse Event (SAE) 
A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse 
outcome is serious. If an event is not an AE per definition above, then it cannot be an SAE even 
if serious conditions are met (e.g. hospitalization for signs/symptoms of the disease under study, 
death due to progression of disease). 
A serious adverse event is any untoward medical occurrence at any dose that: 
• Results in death 
• Is life-threatening  
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▪ The term 'life-threatening' in the definition of 'serious' refers to an event in which 
the subject 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. 
• Requires inpatient hospitalization or prolongation of existing hospitalization  
▪ In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. 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. 
• 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) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
• Results in congenital anomaly/birth defect 
• Other situations: 
▪ Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the subject 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. 
▪ Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse. 
Note: Classification of an AE as ‘serious’ is based on the outcome of the event and is a factor 
in determining reporting requirements. 
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Protocol Number: 218246 
 
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10.3 
Time Period and Frequency for Collecting AE and SAE 
Information 
All AEs, and therefore all SAEs will be collected immediately after a subject provides consent 
to participate in the study by the completion (signature) of the ICF and until 5 days following 
last administration of the study product.  
Medical occurrences that began before obtaining informed consent will be recorded in the 
Medical History/Current Medical Conditions section of the CRF not the AE section. 
All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours. 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 AEs or SAEs after the conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time 
after a subject has been discharged from the study, and he/she considers the event to be 
reasonably related to the study product or study participation, the investigator must promptly 
notify the sponsor. 
10.4 
Reporting Procedures 
The investigator and any designees are responsible for detecting, documenting and reporting 
events that meet the definition of an AE and remain responsible for following up on AEs that 
are serious, considered related to the study product(s), participation in the study, or a study 
procedure, or that caused the subject to discontinue the study product or study.  
Spontaneous reporting of adverse events and those elicited by asking subjects to respond to 
non-leading such as “How do you feel” will be assessed and any AE’s recorded in the CRF and 
reported appropriately. 
The investigator (or medically qualified designee) is to report all directly observed AEs and all 
AEs spontaneously reported by the study subject. In addition, each study subject will be 
questioned about AEs.  
Each AE is to be assessed to determine if it meets the criteria for a SAE. If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate. 
When an AE occurs, it is the responsibility of the investigator (or medically qualified designee) 
to review all documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
The investigator or site staff will then record all relevant information regarding an AE in the 
CRF and all details relating to an SAE in the paper SAE Form provided. 
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Protocol Number: 218246 
 
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It is not acceptable for the investigator (or medically qualified designee) to send photocopies 
of the subject’s medical records to GSK CH in lieu of completion of the AE CRF page/SAE 
form. 
There may be instances when copies of medical records for certain cases are requested by GSK 
CH. In this instance, all subject identifiers, except for the subject number, will be redacted on 
the copies of the medical records prior to submission to GSK CH. 
The investigator (or medically qualified designee) will attempt to establish a diagnosis of the 
event based on signs, symptoms, and/or other clinical information. The diagnosis will then be 
documented as the AE/SAE where known and not the individual signs/symptoms. (e.g. upper 
respiratory tract infection, seasonal allergy, etc. instead of runny nose). 
AEs elicited by the investigator (or medically qualified designee) in a standard manner at the 
study visits should also be recorded in the AE section of the CRF and/or using the SAE form 
(subject to the classification of the AE). Care will be taken not to introduce bias when 
questioning a subject about any changes in their health. Open-ended and non-leading verbal 
questioning should be used. 
10.4.1 
Reporting of an Adverse Event 
All AEs will be reported on the AE page of the CRF by the investigator or site staff. It should 
be noted that the form for collection of SAE information is not the same as the AE CRF. Where 
the same data are collected, the AE CRF page and the SAE form must be completed in a 
consistent manner. For example, the same AE term should be used on both. AEs should be 
reported using concise medical terminology on the CRF as well as on the form for collection of 
SAE information. 
10.4.2 
Reporting of a Serious Adverse Event 
In addition to recording the details of each AE on the AE CRF page, an SAE form should be 
completed, as fully as possible. Hard copies of the ‘paper’ SAE form will be provided in the 
investigator study master file. Original SAE forms will be retained in the investigator study 
master file. 
It is essential to enter the following information:  
• Protocol and subject identifiers 
• Subject demography 
• Description of events, with diagnosis if available 
• Investigator opinion of relationship to study product (or study procedure, if appropriate) 
• Criterion for seriousness. 
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 8 2 4 6  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 7. 0  
Pa ge 5 4  of 7 2  
T he f oll o wi n g are desir a ble a n d are of partic ul ar rele va nce f or i n vesti gat or a n d G S K C H 
assess me nt of t he S A E re p ort:  
•  Date of o nset of A E  
•  Date A E st o p pe d, if rele v a nt  
•  St u d y pr o d uct start dat e  
•  St u d y pr o d uct e n d d ate if rele va nt  
•  Acti o n ta ke n i n relati o n t o t he st u d y pr o d u ct  
•  O utc o me if k n o w n  
T he S A E f or m, c o m plete d as f ull y as p ossi ble, m ust be se nt t o t he Case Ma na ge me nt Gr o u p, 
Gl o bal 
Cli nical 
Safet y a n d 
P har mac o vi gila n ce at 
G S K 
C H (
), wit h c o p y t o t he a p pr o priate G S K C H St u d y Ma n a ger as s o o n as p ossi ble, 
b ut n ot l ater t h a n 2 4 h o urs after st u d y site pers o n nel lear n of t he e v e nt. T he G S K C H St u d y 
Ma na ger will be res p o nsi ble f or f or war d i n g t h e S A E f or m t o ot her G S K C H pers o n nel as 
a p pr o priate.  
1 0. 5  
E v al u ati n g A d v er s e E v e nt s  
1 0. 5. 1  
A s s e s s m e nt of I nt e n sit y  
T he i n vesti gat or or me dicall y q u alifie d desi g nee will ma ke a n assess me nt of i nte nsit y f or eac h 
A E re p orte d d uri n g t he st u d y a n d will assi g n it t o o ne of t he f oll o wi n g cate g ories:  
•  Mil d: A n e ve nt t hat is easil y t olerate d b y t h e s u bject, ca usi n g mi ni mal disc o mf ort a n d 
n ot i nterferi n g wit h e ver y d a y acti vities.  
•  M o derate: A n e v e nt t hat is s ufficie ntl y disc o mf orti n g t o i nterfere wit h n or m al e ver y da y 
acti vities 
•  Se vere: A n e v e nt t hat pre ve nts n or mal e ver y d a y acti vities.  
N O T E: A n A E t hat is assesse d as se vere s h o ul d n ot be c o nf use d wit h a n S A E. Se vere is a 
cate g or y utilize d f or rati n g t he i nte nsit y of a n e v e nt; a n d b ot h n o n -seri o us A Es a n d S A Es ca n 
be assesse d as se vere. F or e x a m ple, a hea d ac he m a y b e se v ere (i nterferes si g nifica ntl y wit h t he 
s u bject's us u al f u ncti o n) b ut w o ul d n ot be classifi e d as seri o us u nless it met o ne of t he criteria 
f or S A Es, liste d a b o ve. A n e ve nt is defi ne d as ‘seri o us’ w he n it meets at least 1 of t he pre defi ne d 
o utc o mes as descri be d i n t he defi niti o n of a n S A E, N O T w he n it is rate d as se vere.  
1 0. 5. 2  
A s s e s s m e nt of C a u s alit y  
T he ca us alit y ass ess me nt is o ne of t he criteria use d w he n d eter mi ni n g re g ul at or y re p orti n g 
re q uire me nts.  
2 1 8 2 4 6 | Pr ot oc ol A me n d me nt  1 4 Mar 2 0 2 2 | T M F- 2 1 8 1 0 6 | 1. 0
P P D


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Protocol Number: 218246 
 
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May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Page 55 of 72 
For each AE (serious and non-serious), the investigator (or medically qualified designee) must 
provide an assessment of causality on the AE CRF page and the SAE form (subject to the 
classification of the AE). The investigator will also document in the medical notes that he/she 
has reviewed the AE and assessed causality, where applicable.  
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. 
Generally, the facts (evidence) or arguments to suggest a causal relationship should be provided. 
The investigator will use clinical judgment to determine the relationship in the determination 
of his/her assessment. Alternative causes, such as underlying disease(s), concomitant therapy, 
other risk factors, and the temporal relationship of the event to the study product will be 
considered and investigated. 
For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
The investigator’s assessment of causality must be provided for all AEs (serious and 
non-serious); the investigator must record the causal relationship in the CRF, as appropriate, 
and report such an assessment in accordance with the SAE reporting requirements if applicable. 
There may be situations when 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 prior to the initial 
transmission of the SAE data to GSK CH. 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.  
10.6 
Follow-up of AEs and SAEs  
After the initial AE/SAE report, the investigator is required to proactively follow up with each 
subject and provide further information on the subject’s condition. 
All AEs (serious and non-serious) will be followed until resolution, until the condition 
stabilizes, until the event is otherwise explained, or until the subject is lost to follow-up.   
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as may be indicated or as requested by GSK CH to elucidate 
as fully as possible the nature and/or causality of the AE. This may include additional laboratory 
tests or investigations, histopathological examinations, or consultation with other health care 
professionals. 
New or updated information will be recorded on the AE CRF page and on the SAE form (subject 
to the classification of the AE). 
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 8 2 4 6  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 7. 0  
Pa ge 5 6  of 7 2  
T he i n vesti gat or will s u b mit a n y u p date d S A E d ata t o G S K C H wit hi n 2 4 h o urs of recei pt of 
t he i nf or mati o n. 
I n v esti gat ors are n ot o bli ge d t o acti vel y s ee k A Es i n f or mer s u bjects. H o we ver, if t he 
i n vesti gat or le ar ns of a S A E, i ncl u di n g d eat h, at a n y ti me after a s u bject h as bee n dis c har ge d 
fr o m t he st u d y, a n d c o nsi ders t he e ve nt reas o n a bl y rel ate d t o t he st u d y pr o d uct or st u d y 
partici pati o n, t he i n vesti gat or will pr o m ptl y n otif y G S K C H b y e maili n g t he i nf or mati o n t o t he 
Case Ma na ge m e nt Gr o u p, Gl o bal Cli nical Safet y a n d P har mac o vi gila nce gr o u p mail b o x at 
G S K (
) wit h a c o p y t o t he a p pr o pri ate G S K C H St u d y 
Ma na ger. T h e G S K C H St u d y Ma n a ger will be res p o nsi ble f or f or war di n g t he S A E f or m t o 
ot her G S K C H pers o n nel as a p pr o priat e . 
T he i n vesti gat or will s u b mit a n y u p dat e d S A E dat a t o G S K C H wit hi n t he desi g nat e d re p orti n g 
ti me fra mes. 
1 0. 7  
Wit h dr a w al D u e t o a n A d v er s e E v e nt  
Wit h dra wal d ue t o A Es s h o ul d be disti n g uis he d fr o m wit h dra wal d ue t o ot her ca us es, acc or di n g 
t o t he defi niti o n of a n A E n ote d earlier, a n d rec or de d o n t he a p pr o priate A E C R F pa ge.  
W he n a s u bject wit h dra ws beca use of a n S A E, t he S A E m ust be re p orte d i n acc or da n ce wit h 
t he re p orti n g re q uire me nts defi ne d. 
1 0. 8  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s 
G S K C H has a le gal res p o nsi bilit y t o n otif y, as a p pr o priate, t he l ocal re g ul at or y a ut h orit y a n d 
ot her re g ulat or y a ut h orities a b o ut t he safet y of a pr o d uct u n der cli nical i n vesti gati o n. Pr o m pt 
n otificati o n of S A Es b y t he i n vesti gat or t o G S K C H is esse ntial s o t hat le gal o bli gati o ns a n d 
et hical res p o nsi bilities t o war ds t he safet y of s u bjects are met.  
G S K C H will c o m pl y wit h c o u ntr y s p ecific re g ulat or y re q uire m e nts relati n g t o safet y re p orti n g 
t o t he re g ulat or y a ut h orit y, I R B/ E C a n d i n vesti gat ors. 
B ot h t he i n vesti gat or a n d t he s p o ns or will c o m pl y wit h all l ocal me dical de vice re p orti n g 
re q uire me nts  
I n v esti gat or safet y re p orts m ust be pre pare d f or s us pecte d u ne x pecte d seri o us a d verse reacti o ns 
( S U S A R) acc or di n g t o l ocal re g ulat or y re q uire m e nts a n d s p o ns or p olic y a n d f or war de d t o 
i n vesti gat ors as n ecessar y. 
A n i n vesti gat or w h o recei ves a n i n vesti gat or safe t y re p ort descri bi n g a S A E or ot her s pecific 
safet y i nf or mati o n e. g. s u m mar y or listi n g of S A E fr o m t he s p o ns or will re vie w a n d t he n file it 
al o n g wit h t he s u p p orti n g d oc u me nt ati o n i n t he i n vesti gat or st u d y master file, a n d will n otif y 
t he I R B/I E C, if a p pro priate acc or di n g t o l ocal re q uire me nts.  
2 1 8 2 4 6 | Pr ot oc ol A me n d me nt  1 4 Mar 2 0 2 2 | T M F- 2 1 8 1 0 6 | 1. 0
P P D


G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 8 2 4 6  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 7. 0  
Pa ge 5 7  of 7 2  
1 0. 9  
Pr e g n a n c y  
1 0. 9. 1  
Ti m e P eri o d f or C oll e cti n g Pr e g n a n c y I nf or m ati o n  
Pre g n a nc y i nf or mati o n will be c ollecte d o n all pre g na nci es re p orte d w hile a fe male s u bject is 
partici pati n g i n t he st u d y fr o m t he si g ni n g of i nf or me d c o ns e nt u ntil 5 da ys aft er last 
a d mi nistrati o n of st u d y pr o d uct.  
1 0. 9. 2  
A cti o n t o b e T a k e n if Pr e g n a n c y O c c ur s  
T h e i n vesti gat or will r ec or d pre g n a nc y i nf or mati o n o n t he a p pr o priate f or m , sca n a n d e-m ail it 
t o t he Case 
Ma na ge me nt Gr o u p, Gl o bal Cli nical Safet y a n d P har mac o vi gila nce mail b o x 
(
) wit h  a c o p y t o t he a p pr o priate G S K C H St u d y 
Ma na ger. T h e G S K C H St u d y Ma n a ger will be res p o nsi ble f or f or war di n g t he pre g na nc y f or m 
t o ot her G S K C H pers o n nel as a p pr o priate. Ori gi nal pre g na n c y i nf or mati o n f or ms will be 
retai ne d i n t he i n vesti gat or st u d y master file.  
T he s u bject will be f oll o we d t o deter mi ne t he o ut c o me of t he pre g n a nc y. I nf or mati o n o n t he 
stat us of t he m ot her a n d i nfa nt / ne o n ate (i ncl u di n g c o nc o mita nt me dicati o ns ta ke n b y t h e 
m ot her d uri n g t he pre g n a nc y) will be f or war de d b y t he i n vesti gat or t he Case Ma na ge me nt 
Gr o u p, Gl o bal Cli nical Safet y a n d P har mac o vi gila nce gr o u p mail b o x at G S K (
) wit h a c o p y t o t he a p pr o priate G S K C H St u d y Ma na ger. T he G S K C H 
St u d y Ma na ger will be r es p o nsi ble f or f or war di n g t he pre g n a nc y f or m t o ot her G S K C H 
pers o n nel as a p pr o priate . Ge nerall y, f oll o w-u p will be n o l o n ger t ha n 6 t o 8 wee ks f oll o wi n g 
t he esti mate d deli ver y date. A n y t er mi nati o n of t h e pre g na n c y will be re p orte d. 
W hile pre g na n c y itself  is n ot c o nsi dere d t o be a n A E, a b n or mal pre g na nc y o utc o mes (e. g. 
s p o nta ne o us a b orti o n, fet al deat h, still birt h, c o n ge nital a n o malies, ect o pic pre g na nc y) are, a n d 
s h o ul d be rec or de d as a n S A E. 
A n y fe male s u bject w h o bec o mes pre g na nt w hile partici pati n g wil l be wit h dra w n fr o m t he 
st u d y. 
1 0. 1 0  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or M e di c al D e vi c e I n ci d e nt s 
T o f ulfill re g ulat or y re p orti n g o bli gati o ns w orl d wi de, t he i n vesti gat or is res p o nsi ble f or t he 
detecti o n a n d d oc u me ntati o n of e ve nts meeti n g t h e defi niti o ns of i n ci de nt or malf u ncti o n t hat 
occ ur d uri n g all peri o ds of t he st u d y i n w hic h t h e me dical de vice is us e d.  
T he i n vesti gat or will pr o m ptl y re p ort all i nci de nts occ urri n g wit h a n y me di cal de vice pr o vi de d 
f or use i n t he st u d y i n or der f or t h e s p o ns or t o f ulfill the le gal res p o nsi bilit y t o n otif y a p pr o priate 
re g ulat or y a ut h orities a n d ot her e ntities a b o ut certai n safet y i nf or mati o n relati n g t o me dical 
de vices bei n g use d i n cli nical st u dies.  
2 1 8 2 4 6 | Pr ot oc ol A me n d me nt  1 4 Mar 2 0 2 2 | T M F- 2 1 8 1 0 6 | 1. 0
P P D
P P D
P P D


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 218246 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 58 of 72 
The investigator, or responsible person according to local requirements (e.g. the head of the 
medical institution), will comply with the applicable local regulatory requirements relating to 
the reporting of incidents to the IRB/IEC. 
11 
DATA MANAGEMENT 
As used in this protocol, the term CRF is understood to refer to either a paper form or an 
electronic data record or both, depending on the data collection method.  
For this study, subject data will be entered into an electronic CRF (eCRF), using a validated 
system. Data relating to SAEs, pregnancy and incidents will also be collected on paper forms. 
The investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF. 
The source documents (e.g. hospital records, clinical and office charts, laboratory notes, 
memoranda, subject diaries, questionnaires, evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, microfiches, photographic negatives, 
microfilm or magnetic media, x-rays, subject files and records kept at the pharmacy, at the 
laboratory and at the medico-technical departments involved in the clinical study) which 
contain the source of data recorded in the CRF should be specified. The CRF can be used as a 
source document at the discretion of data management. 
Each subject will be assigned and identified by a unique Screening Subject Number. Any 
reference made to an individual subject within the study must be done using their unique 
Screening Subject Number. 
11.1 
Case Report Form 
A CRF is a printed, optical, or electronic document designed to record the protocol required 
information to be reported to the sponsor on each trial subject. 
For each subject who has given informed consent/assent the CRF must be completed and signed 
by the Principal Investigator (or authorized designee) to certify that the data are complete and 
correct. The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Management of clinical data will be performed in accordance with Third Party BDM Vendor 
applicable standards and data cleaning procedures with oversight by GSK CH to ensure 
integrity of the data, for example, to remove errors and inconsistencies in the data.  
To protect the privacy of subjects, no Personal Information (PI) (including the subject's name 
or initials or full birth date) is to be recorded in the CRF or as part of the query text. 
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 218246 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 59 of 72 
All CRF pages should be completed during a subject assessment when the CRF has been 
designated as the source. Data that is sourced elsewhere should be entered into the CRF in an 
agreed upon timeframe between the Investigator and Sponsor.   
GSK CH will obtain and retain all CRFs and associated study data as applicable at the 
completion of the study.  
11.2 
Data Handling 
Documentation of all data management activities should allow step-by-step retrospective 
assessment of data quality and study performance.  
Any changes or corrections to data will be performed in the Electronic Data Capture (EDC) 
System, and it will include rationale for changes. The EDC system has an audit trail, which will 
provide a complete record of the changes and corrections endorsed by the Investigator. 
Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA) 
and any concomitant medications terms (if applicable) using WHO Drug Dictionary (WHO 
DD). 
11.2.1 
Data Queries 
Programmed edit checks will be generated automatically, as the data are being entered into the 
system. Reports and listings on the CRF data will also be run, in addition to the queries already 
programmed and generated by the system, to raise manual queries as needed for site 
clarification or correction. A query should be issued to update the verbatim towards a codable 
description.  
The study monitor will perform ongoing review of the CRFs in accordance with the monitoring 
plan, 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. 
Any queries will be generated in the EDC System to the Investigator or designee, enabling the 
errors to be addressed in parallel with Data Management review. The study monitor can also 
run reports and listings on the CRFs, to raise manual queries as needed for site clarification or 
correction. 
11.3 
External Data  
External Data are subject data obtained externally to the CRF. These data are generated from 
laboratory instruments, computers or other sources and then transcribed into a file and format 
agreed upon by GSK CH to identify the subject and time point referenced in the CRF and/or 
protocol.  
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 8 2 4 6  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 7. 0  
Pa ge 6 0  of 7 2  
A n a gree d q ualit y c o ntr ol pr ocess w ill be perf or m e d a gai nst t he tra ns cri be d data t o t he s o urce 
t o e ns ure t he acc urac y of t he tra nscri pti o n. T he tra nscri be d data is tra ns mitte d i n a n a gree d u p o n 
f or mat t o G S K C H.  
Rec o nciliati o n will be perf or me d bet w ee n t he tra nscri be d data a n d t he cli nical  data base t o 
e ns ure s u bject a n d ti me p oi nt refere n ce d i n t h e Cli nical Data base m atc h bef ore Cli nical 
Data base Freeze (l oc ki n g of t he data bas e) ca n occ ur.  
1 2  
S T A TI S TI C A L C O N SI D E R A TI O N S A N D D A T A A N A L Y S E S  
1 2. 1  
S a m pl e Si z e D et er mi n ati o n  
A s ufficie nt n u m ber of s u bjects  will be scree ne d t o ra n d o mize a p pr o xi matel y 4 9  t o e ns ure at 
least 4 1 e val ua ble s u bj ects c o m plete t he e ntire st u d y.  
Acc or di n g t o pre vi o us G S K C H st u d y 
 
 
, it is esti mate d a sa m ple of 4 1 s u bjects will pr o vi de at least 
9 0 % p o wer t o esta blis h bi oe q ui vale nce . C o nsi deri n g a dr o p o ut disc o nti n uati o n rate of 1 5 %, 
a p pr o xi matel y 4 9 s u bjects will nee d t o be e nr olle d.  
1 2. 2  
P o p ul ati o n s  for A n al y si s  
T he safet y p o p ulati o n is defi ne d as all ra n d o mize d s u bjects w h o recei ve at least o ne d ose of 
st u d y me dicati o n. 
T he P K p o p ulati o n is defi ne d as all ra n d o mize d s u bjects w h o ha ve at least o ne p ost -d ose P K 
val ue, a n d w h o h a ve  n o maj or pr ot oc ol de viati o ns c o ncer ni n g p h ar mac o ki netics.  
T he f oll o wi n g P K a nal ysis set is defi ne d t o a d dress t he P K o bjecti ves a n d f urt her P K 
c o nsi derati o ns wit hi n t his st u d y:  
P K a nal ysis set i ncl u des all s u bjects of t he P K p o p ulati o n  w h o c o m plete b ot h treat me nt peri o ds , 
a n d f or w hic h t h e rele va nt P K para m eters (at least A U C0 -t or C ma x ) ca n b e deri v e d. S u bjects 
wit h baseli ne c o nce ntr ati o n > 5 % of t he i n di vi d ual C ma x  f or eit her peri o d will be e x cl u de d fr o m 
t he P K a n al ysis s et. T hi s a nal ysis set will be use d i n s u m maries, t he pri mar y P K a nal ysis, a n d 
t he sec o n dar y P K a nal ysis.  
1 2. 3  
St ati sti c al  A n al y s e s  
A d diti o nal details of t he pr o p ose d statistical a nal ysis will be d o c u me nte d i n t he statistical 
re p orti n g a n d a n al ysis pl a n (S A P), w hic h will b e writte n f oll o wi n g fi n alizati o n of t he pr ot oc ol 
a n d pri or t o st u d y u n bli n di n g/a nal ysis (as a p pr o priate).  T his secti o n is a s u m mar y of t he pla n ne d 
statistical a nal yses of t h e m ost i m p orta nt e n d p oi nts i ncl u di n g pri mar y a n d ke y sec o n d ar y 
e n d p oi nts.  
2 1 8 2 4 6 | Pr ot oc ol A me n d me nt  1 4 Mar 2 0 2 2 | T M F- 2 1 8 1 0 6 | 1. 0
C CI


G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 8 2 4 6  
 
Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
Ma y n ot b e use d, di v ul ge d, p u blis he d or ot her wise discl ose d wit h o ut t he c o nse nt of G S K C H  
S O P -2 0 8 6 6 1 Cli nical Pr ot oc ol Te m plate v 7. 0  
Pa ge 6 1  of 7 2  
S A P  creati o n a n d statistical a nal ysis will be perf or me d b y 
.  
P har mac o ki netic varia bles will be calc ulate d b y 
. 
All c o nce ntr ati o n a n d P K data will be liste d. T his i ncl u des a n y dat a f or s u bjects w h o are n ot 
i ncl u de d i n t he a nal ysis (e. g. s u bjects wit h dra w n fr o m t he st u d y d ue t o a d v erse e v e nts).  
1 2. 3. 1  
Pri m ar y A n al y si s( e s)  
Pri m ar y P h ar m a c o ki n eti c s A n al y si s V ari a bl e s  
P K para meters will be deri ve d usi n g t he act ual sa m pli n g ti mes after data base l oc k a n d 
u n bli n di n g a n d are defi ne d as f oll o ws:  
•  C m a x: ma xi m u m o bser ve d p ost -d ose c o nce ntrati o n; o btai ne d wit h o ut i nter p olati o n.  
•  A U C 0 -t: area u n der t he pl as ma c o nce ntrati o n vers us ti me c ur ve calc ulate d fr o m ti me 0 t o 
t he last meas ura ble s a m pli n g ti me p oi nt, t, c o m p ute d usi n g t he li near tra p ez oi dal r ule. 
St ati sti c al M et h o d s:  
T he bi oe q ui val e nce bet w ee n es o me praz ole 2 0 m g dela ye d -release ca ps ules fr o m C G (test) a n d 
es o me praz ole 2 0 m g del a ye d -releas e ca ps ules fr o m A Z ( Refere nce) u n d er faste d c o n diti o ns 
will be assesse d:  
•  T he 9 0 % c o nfi d e nce i nter val f or t he rati o  of ge o m etric mea ns (t est/refere n ce) base d o n 
least-s q uares mea ns fr o m t he A N O V A of t he l n-tr a nsf or me d A U C0 -t m ust be wit hi n 0. 8 t o 
1 .2 5; a n d,  
•  T he rati o of ge o m etric m ea ns (test/refere nce) bas e d o n least -s q uares mea ns fr o m t he 
A N O V A of t h e l n -tra nsf or me d Cma x  m ust be wit hi n 0. 8 t o 1 .2 5.  
A li near mi x e d effects m o del will be fit t o t he l o g -tr a nsf or me d P K p ara meters ( A U C0 -t a n d 
C ma x ), as t he de pe n de nt v aria ble, a n d tr eat me nt, se q ue nce, a n d p eri o d as fi x e d effects. S u bject 
neste d wit hi n se q u e nce will be a ra n d o m effect. T he treat me nt least -s q u ares m ea ns ( L S Ms), 
differe n ce b et wee n treat me nt L S Ms, a n d 9 0 % c o nfi de nce i nter val ( CI) f or t he differe nce will 
be c o m p ute d. T he a dj uste d mea n differe n ce a n d t he 9 0 % CIs f or t he differe n ces will be 
e x p o ne ntiate d t o pr o vi de e sti mates of t he rati o of a dj uste d ge o metric mea ns (test/refere nce) a n d 
9 0 % CIs f or t he rati o. If all st u d y s u bjects are n ot recr uite d fr o m t he s a me e nr oll me nt p o ol a n d 
t he st u d y d os es i n m or e t ha n o ne gr o u p, t he statistical m o del ma y be m o difie d t o reflect t he 
m ulti gr o u p nat ure of t he st u d y. Bi o e q ui vale nce will be declare d f or A U C 0 -t if t he 9 0 % 2-si de d 
CI f or t he rati o lies c o m pletel y wit hi n t he ra n ge of 0. 8 -1. 2 5 a n d f or C ma x  if t he p oi nt esti mate 
f or t he rati o lies c o m pletel y wit hi n t he ra n ge of 0. 8-1. 2 5 . N o f urt her a dj ust me nts f or m ulti plicit y 
of t he c o -pri mar y e n d p oi nts are necessar y as b ot h e n d p oi nts m ust be met i n or der t o ac hie ve 
st u d y s uccess. 
2 1 8 2 4 6 | Pr ot oc ol A me n d me nt  1 4 Mar 2 0 2 2 | T M F- 2 1 8 1 0 6 | 1. 0
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 218246 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 62 of 72 
12.3.2 
Secondary Analysis(es) 
To further assess the PK profile of esomeprazole the following PK parameters will be derived 
using actual sampling times:  
• AUC0-inf: area under the plasma concentration versus time curve calculated from time 0 
to infinity AUC0-inf = AUC0-t + C(t)/λz where C(t) is the concentration at the last 
measurable sampling time point and λz is the terminal elimination rate constant. 
• %AUCex - Percentage of AUC0-inf obtained by extrapolation, calculated as (1－[AUC0-t 
/AUC0-inf] )×100.  
• λz - terminal elimination rate constant computed as the slope of the regression line of ln 
(C(t)) on time. The regression should generally involve at least 3 consecutive 
measurable concentrations that decrease over time.  
• tmax- time of the maximum observed post-dose concentration. 
• t1/2 - elimination half-life computed as t1/2 = ln(2)/ λz. 
The PK parameters (AUC0-inf, %AUCex, λz, tmax, and t1/2) will be summarized for each treatment 
using descriptive statistics same as for the primary PK parameters. 
12.3.3 
Safety Analysis(es) 
The assessment of safety will be based on the frequency and severity of treatment emergent 
AEs (TEAEs) i.e., AEs that are emergent or that worsen after the first study product (test or 
reference) administration. 
The incidence of TEAEs will be summarized by presenting, for each treatment, the number and 
percentage of subjects having any AE, any AE in each MedDRA System Organ Class (SOC) 
and having each individual AE. The subset of AEs suspected of a relationship to study drug will 
be presented in a similar manner. All TEAEs will be also tabulated by severity. Any other 
information collected (e.g., action taken, duration, outcome) will be listed. AEs will be assigned 
to the treatment administered immediately prior to the onset. Adverse events due to COVID-19, 
if any, will be listed and tabulated separately. 
Vital signs including temperature will be summarized by time-point and treatment. Summary 
statistics will include mean, standard deviation, minimum, median, and maximum. No 
inferential statistics will be presented. Data will be listed with abnormal values flagged.  
Medical history and physical examination, as applicable, will be listed with abnormal values 
flagged.  
Laboratory data and ECGs collected at screening and used for inclusion/exclusion criteria will 
be considered source data, and will not be required to be reported, unless otherwise noted.  
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 218246 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 63 of 72 
12.3.4 
Other Analysis(es) 
Not applicable. 
12.3.5 
Exclusion of Data from Analysis  
Subjects who deviate from the protocol will be identified and excluded from the 
pharmacokinetic analyses as agreed by the biostatistician and medical director or designee. 
Exclusion of subjects with baseline > 5% of the Cmax will be determined before database lock 
and unblinding. Exclusion of any data from the analyses will be determined during a Blind Data 
Review (BDR) Meeting prior to database lock. Any reasons for exclusion from an analysis 
population will be listed, if applicable.  
12.3.6 
Demographic and Baseline Characteristics 
Baseline data, relevant screening data, and demographic characteristics will be summarized for 
all randomized subjects. 
12.3.7 
Study Drug/Product Compliance and Use of Other Therapies 
12.3.7.1 Study Drug/Product Compliance 
The number of subjects exposed to each treatment will be tabulated for the safety population. 
Treatment deviations for individual subjects will be listed and summarized.  
12.3.7.2 Prior and Concomitant Medications 
Prior and concomitant medications will be listed for the safety population. 
12.3.8 
Handling of Dropouts and Missing Data  
All existing data for subjects who are dropouts from the study will be included in the 
pharmacokinetic statistical analysis. 
If any concentration data is missing or deviates from the planned time of collection, then the 
pharmacokineticist may calculate the PK parameters using the available data.  
Missing values of λz can be estimated from the subject’s mean λz value from the other 
treatments. If a λz value cannot be calculated from the other treatments, then the λz will be 
obtained from the treatment mean value for subjects with non-missing values of λz in the period 
in which it is not available. This estimated λz can be used to calculate other λz dependent 
variables. This λz value derivation is only applied for pre-dose concentration adjustments. 
For esomeprazole concentration: 
• BLOQ values obtained before the first measurable concentration will be imputed as 
zero. 
218246 | Protocol Amendment  14 Mar 2022 | TMF-218106 | 1.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 218246 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
SOP-208661 Clinical Protocol Template v7.0 
Page 64 of 72 
• BLOQ values obtained after the first measurable concentration will be “Not detectable” 
(ND), which will be shown as missing (explanations will be specified in the footnote of 
TFLs). 
12.3.9 
Interim Analysis  
No interim analysis is planned for this study 
13 
STUDY GOVERNANCE CONSIDERATIONS 
13.1 
Quality Control  
In accordance with applicable regulations including GCP, and GSK CH procedures, GSK CH 
or designee (i.e. third-party vendor) monitors will contact the site prior to the start of the study 
to review with the site staff the protocol, study requirements, and their responsibilities to satisfy 
regulatory, ethical, and GSK CH requirements. 
When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the CRF will serve as the source 
document. 
GSK CH or designee will monitor the study and site activity to verify that the: 
• Data are authentic, accurate, and complete. 
• Safety and rights of subjects are being protected. 
• Study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements. 
The extent and nature of monitoring will be described in a written monitoring plan on file at 
GSK CH. The investigator (or designee) agrees to allow the monitor direct access to all relevant 
documents and agrees to co-operate with the monitor to ensure that any problems detected in 
the course of these monitoring visits are resolved. 
13.2 
Quality Assurance 
To ensure compliance with GCP and all applicable regulatory requirements, GSK CH may 
conduct a quality assurance assessment and/or audit of the site records, and the regulatory 
agencies may conduct a regulatory inspection at any time during or after completion of the 
study.  
In the event of an assessment, audit or inspection, the investigator (and institution) must agree 
to grant the advisor(s), auditor(s) and inspector(s) direct access to all relevant documents and 
to allocate their time and the time of their staff to discuss the conduct of the study, any 
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findings/relevant issues and to implement any corrective and/or preventative actions to address 
any findings/issues identified. 
The investigator(s) will notify GSK CH or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with GSK CH 
or its agents to prepare the study site for the inspection and will allow GSK CH or its agent, 
whenever feasible, to be present during the inspection. The investigator will promptly apply 
copies of the inspection finding to GSK CH or its agent. Before response submission to the 
regulatory authority, the investigator will provide GSK CH or its agents with an opportunity to 
review and comment on responses to any such findings.  
The sponsor will be available to help investigators prepare for an inspection. 
13.3 
Regulatory and Ethical Considerations 
13.3.1 
Institutional Review Board/ Ethics Committee  
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, investigator brochure/safety statement 
(including any updates) and other relevant documents, e.g. recruitment advertisements, if 
applicable, from the IRB/EC. All correspondence with the IRB/EC should be retained in the 
investigator file. Copies of IRB/EC approvals should be forwarded to GSK CH prior to the 
initiation of the study, and also when subsequent amendments to the protocol are made. 
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects. In that 
event, the investigator must notify the IRB/EC and GSK CH in writing immediately after the 
implementation. 
13.3.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol and legal and regulatory 
requirements, as well as the general principles set forth in the International Ethical Guidelines 
for Biomedical Research Involving Human Subjects (Council for International Organizations 
of Medical Sciences 2002), International Ethical Guidelines for Health-Related Research 
Involving Humans (Council for International Organizations of Medical Sciences, 2016), 
guidelines for GCP (ICH 1996 and revision 2), and the Declaration of Helsinki (World Medical 
Association 2013).  
In addition, the study will be conducted in accordance with the protocol, the ICH guideline on 
GCP, and applicable local regulatory requirements and laws. 
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13.3.3 
Subject Information and Consent 
All parties will ensure protection of subject personal data and will not include subject names or 
other identifiable data in any reports, publications, or other disclosures, except where required 
by laws.  
When study data are compiled for transfer to GSK CH and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by GSK CH in order to de-identify study subjects. The use of 
initials should be avoided. 
The study site will maintain a confidential list of subjects who participated in the study, linking 
each subject’s numerical code to his or her actual identity. In case of data transfer, GSK CH 
will maintain high standards of confidentiality and protection of subjects’ personal data 
consistent with applicable privacy laws. 
The informed consent documents must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws. 
The informed consent documents used during the informed consent process must be reviewed 
and approved by the sponsor, approved by the IRB/EC before use, and available for inspection. 
The investigator must ensure that each study subject, is fully informed about the nature and 
objectives of the study and possible risks associated with participation.  
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed. The investigator will 
retain the original of each subject's signed informed consent document. 
13.3.4 
Subject Recruitment  
Advertisements approved by IRBs/ECs and investigator databases may be used as recruitment 
procedures. Use of ethics committee approved, generic, prescreening questionnaire to assess 
basic subject characteristics to determine general eligibility for this study is allowed. This 
generic questionnaire may be used by sites as a phone script and/or to review internal databases 
to identify subjects.   
GSK CH will have an opportunity to review and approve the content of any study recruitment 
materials directed to potential study subjects before such materials are used.  
13.3.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP  
Within GSK CH a serious breach is defined as a breach likely to affect to a significant degree 
the safety and rights of a subject or the reliability and robustness of the data generated in GSK 
CH-sponsored human subject research studies.  
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In the event of any prohibition or restriction imposed (i.e., clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, GSK CH should be informed immediately.  
In addition, the investigator will inform GSK CH immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of any 
serious breaches of this protocol or of ICH GCP that the investigator becomes aware of. 
13.4 
Posting of Information on Publicly Available Clinical Trial 
Registers 
Study information from this protocol will be posted on publicly available clinical trial registers 
before enrollment of subjects begins in accordance with applicable GSK CH processes. 
GSK intends to make anonymized subject-level data from this trial 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 trial participants are 
used to maximum effect in the creation of knowledge and understanding 
13.5 
Provision of Study Results to Investigators 
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 CH site or other mutually-agreeable location. 
GSK CH will also provide the investigator with the full summary of the study results. The 
investigator is encouraged to share the summary results with the study subjects, as appropriate. 
The procedures and timing for public disclosure of the results summary and for development of 
a manuscript for publication will be in accordance with GSK CH Policy. 
A manuscript will be progressed for publication in the scientific literature if the results provide 
important scientific or medical knowledge. 
13.6 
Records Retention 
Following closure of the study, the investigator must maintain all site study records (except for 
those required by local regulations to be maintained elsewhere), in a safe and secure location.   
The records (study/ site master file) must be maintained to allow easy and timely retrieval, when 
needed (e.g. for a GSK CH audit or regulatory inspection) and must be available for review in 
conjunction with assessment of the facility, supporting systems, and relevant site staff. 
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Where permitted by local laws/regulations or institutional policy, some or all of these records 
can be maintained in a format other than hard copy (e.g. microfiche, scanned, electronic); 
however, caution needs to be exercised before such action is taken.  
The investigator must ensure that all reproductions are legible and are a true and accurate copy 
of the original and meet accessibility and retrieval standards, including re-generating a hard 
copy, if required. Furthermore, the investigator must ensure there is an acceptable back-up of 
these reproductions and that an acceptable quality control process exists for making these 
reproductions. 
The investigator must assure that the subject’s anonymity will be maintained. On CRFs or other 
documents submitted to GSK CH, subjects should not be identified by their names or initials, 
but by an identification code. The investigator should keep a separate log of subjects’ codes, 
names and addresses. Documents not for submission to GSK CH, e.g. subjects’ written consent 
forms, should be maintained by the investigator in strict confidence. 
Records and documents, including signed ICF, pertaining to the conduct of this study must be 
retained by the investigator for 25 years, from the issue of the final Clinical Study Report (CSR) 
or equivalent summary, unless local regulations or institutional policies require a longer 
retention period. The minimum retention time will meet the strictest standard applicable to that 
site for the study, as dictated by any institutional requirements or local laws or regulations, GSK 
CH standards/procedures, and/or institutional requirements.   
No study document should be destroyed without a prior written agreement between GSK CH 
and the investigator. The investigator must notify GSK CH of any changes in the archival 
arrangements, including, but not limited to, archival at an off-site facility or transfer of 
ownership of the records in the event the investigator is no longer associated with the site. 
13.7 
Conditions for Terminating the Study  
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or study product safety problems, or at the discretion of GSK 
CH. In addition, GSK CH retains the right to discontinue development of esomeprazole 
formulation at any time. 
If a study is prematurely terminated, GSK CH will promptly notify the investigator. After 
notification, the investigator must promptly contact all participating subjects and should assure 
appropriate therapy/ follow-up for the subjects. As directed by GSK CH, all study materials 
must be collected and all CRF’s completed to the greatest extent possible. Where required by 
the applicable regulatory requirements, GSK CH should inform the regulatory authority(ies) 
and the investigator should promptly inform the IRB/EC and provide the IRB/EC a detailed 
written explanation of the termination or suspension.  
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If the IRB/EC terminates or suspends its approval/favorable opinion of a trial, the investigator 
should promptly notify the GSK CH and provide GSK CH with a detailed written explanation 
of the termination or suspension. 
Upon completion or premature discontinuation of the study, the GSK CH monitor will conduct 
site closure activities with the investigator or site staff, as appropriate, in accordance with 
applicable regulations including GCP, and GSK CH Standard Operating Procedures. 
14 
REFERENCES 
1. Hatcher RA, Trussell J, Nelson AL, Cates W Jr, Stewart F, Kowal D, editors. 
Contraceptive Technology. 19th edition. New York: Ardent Media, 2007(b): 28. Available 
on request 
2. ICH Topic E6 (R2) Guideline for Good Clinical Practice, Nov 2016. 
3. World Medical Association Declaration of Helsinki, 64th General Assembly, Fortaleza 
2013. 
4. [Health Canada Guidance document, Comparative Bioavailability Standards: 
Formulations Used for System Effects July 2018]  
5. [Health Canada Guidance document, Conduct and Analysis of Comparative 
Bioavailability Studies September 2018] 
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15 
APPENDICIES 
15.1 
ABBREVIATIONS 
The following is a list of abbreviations that may be used in the protocol. 
Table 15-1 
Abbreviations 
Abbreviation 
Term 
λz 
terminal elimination rate constant 
Ab 
antibody 
AE 
adverse event 
Ag 
antigen 
ALP 
alkaline phosphatase 
ALT 
alanine transaminase 
AMIS 
analytical methodology information sheet 
ANOVA 
analysis of variance 
AST 
aspartate transaminase 
AUC0-t 
area under the concentration-time curve from time 0 to the last measurable 
sampling time point, t 
AUC0-inf 
area under the concentration-time curve from time 0 to infinity 
%AUCex 
percentage of AUC0-inf obtained by extrapolation 
AZ 
AstraZeneca 
BDR 
blinded data review 
BLOQ 
below the level of quantification 
BMI 
body mass index 
BP 
blood pressure 
BPM 
beats per minute 
BT 
body temperature 
BUN 
blood urea nitrogen 
CG 
Catalent Guayama 
CI 
confidence interval 
CK 
creatine kinase 
Cmax 
peak or maximum observed concentration 
CPL 
clinical project lead 
CRF 
case report form 
CRO 
clinical research organization 
CSR 
clinical study report 
CTA 
clinical trial application 
CV 
coefficient of variation 
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Abbreviation 
Term 
CYP 
cytochrome P450 
DIN 
drug identification number 
DM 
data management 
EC 
ethics committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EDTA 
edetic acid (ethylenediaminetetraacetic acid) 
EudraCT 
European Clinical Trials Database 
FDA 
Food and Drug Administration (United States) 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GERD 
gastroesophageal reflux disease 
GGT 
gamma-glutamyl transpeptidase 
HBcAb 
hepatitis B core antibody 
HBsAg 
hepatitis B surface antigen 
hCG 
human chorionic gonadotropin 
HCV Ab 
hepatitis C virus antibody 
HIV 
human immunodeficiency virus 
IB 
investigator’s brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IgG 
immunoglobulin G  
IgM 
immunoglobulin M  
IND 
investigational new drug  
IRB 
institutional review board 
IUD 
intrauterine contraceptive device 
K2EDTA 
dipotassium ethylene diamine tetraacetic acid 
LSM 
least-squares mean 
MedDRA 
Medical Dictionary for Regulatory Activities 
MDMA 
3,4- methylenedioxymethamphetamine 
N/A 
not applicable 
ND 
not detectable 
PCP 
phencyclidine 
PCR 
polymerase chain reaction 
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Abbreviation 
Term 
PI 
personal information 
PK 
pharmacokinetics 
PR 
pulse rate 
QTc 
corrected QT 
RBC 
red blood cell 
RR 
respiratory rate 
SAE 
serious adverse event 
SAP 
statistical reporting and analysis plan 
SOC 
system organ class 
SOP 
standard operating procedure 
SRDS 
single reference safety document 
SUSAR 
suspected unexpected serious adverse reaction 
T1/2 
terminal half-life 
TBC 
to be confirmed 
TEAE 
treatment emergent adverse event 
TFL 
tables, figures and listings 
THC 
tetrahydrocannabinol 
Tmax 
time to reach maximum concentration 
UK 
United Kingdom 
ULN 
upper limit of normal 
US 
United States 
WBC 
white blood cell 
WHO 
World Health Organization 
WHO DD 
WHO drug dictionary 
 
 
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Si g nat ure Pa ge f or  2 1 8 2 4 6 T M F- 2 1 8 1 0 6 v 1. 0
Si g nat ure Pa ge f or T M F- 2 1 8 1 0 6 v 1. 0
Reas o n f or si g ni n g: A p pr o ve d
Na me: 
R ole: A
nat ure: 
Reas o n f or si g ni n g: A p pr o ve d
Na me: 
R ole: A
nat ure: 
Reas o n f or si g ni n g: A p pr o ve d
Na me: 
R ole: A
nat ure: 
2 1 8 2 4 6 | Pr ot oc ol A me n d me nt  1 4 Mar 2 0 2 2 | T M F- 2 1 8 1 0 6 | 1. 0
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D

SAP_001.pdf: 
Statistical A n al ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 1 of 3 2 
N otice of C o nfi de ntial a n d Pr o prietar y I nf or mati o n: 
T he  i nf or mati o n  c o ntai ne d  i n  t his  d oc u me nt  is  c o nfi de ntial  bel o n gi n g  t o  G S K  C o ns u mer  
Healt hcare.  Acce pta n ce  of  t his  d oc u me nt  c o nstit utes  a gre e ment  b y  t he  reci pie nt  t hat  n o  
i nf or mati o n c o ntai ne d h erei n will be p u blis he d or discl ose d wit h o ut pri or writte n a ut h orizati o n 
fr o m a n official of G S K C o ns u mer Healt hcare . H o we ver, t his d oc u me nt ma y be discl ose d t o 
a p pr o priate I nstit uti o nal Re vie w B oar d a n d Et hics C o m mittees or d ul y a ut h orize d re pres e ntati ves 
of  a  n ati o nal  re g ul at or y  a ut h orit y  u n der  t he  c o n diti o n  t hat  t he y  are  re q ueste d  t o  kee p  it  
c o nfi de ntial. I n t he e ve nt of a n act u al or s us pecte d breac h of t his o bli gati o n, 
 
s h o ul d be n otifie d pr o m ptl y. 
St atistic al A n al ysis  Pl a n 
S p o ns or N a me: G S K  Co ns u mer He alt hc are  
Pr ot oc ol N u m ber:  2 1 8 2 4 6 
Pr ot oc ol T itle: A ra n d o mize d, si n gle bl i n d, si n gle ce nter, si n gle d os e, t w o pe ri o d, t w o se q ue n ce 
cr oss o ver bi oe q ui v ale nce st u d y of es o me praz ole 2 0 m g dela ye d- releas e ca ps ules (Catale nt,  
G ua ya ma)  c o m par e d to  the  es o me pr az ole 2 0 mg  dela ye d-release ca ps ules (Ne xi u m  2 4 HR , 
Astra Ze neca S ö dertälje) in healt h y a d ult su bjects u n der fasted c o n diti o ns 
P r ot oc ol V ersi o n a n d D ate: 1. 0, 2 5- N o v- 2 0 2 1 
 Pr oject  C o d e:  
 
A ut h or: 
, Se ni or Bi ost atistici a n 
T his d oc u me nt c o ntai ns c o nfi de ntialit y state me nts t hat are n ot rele va nt f or t his p u blicl y a vaila ble 
versi o n.
P P D
P P D
P P D
P P D
C CI
C CI
C CI


Statis tical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 2 of 3 2 
R e visi o n Hist or y 
Versi o n 
# 
D ate ( D D -M m m -
Y Y Y Y)  
D oc u me nt O w ner  
Re visi o n S u m m ar y 
0. 1  
1 1 -Fe b -2 0 2 2
 
I nitial Versi o n 
0. 2  
0 1 -Mar -2 0 2 2
 
A d dress C o m me nts  
1. 0  
1 1 -Mar -2 0 2 2
 
Fi nalize S A P  
P P D
P P D
P P D
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 3 of 3 2 
 
Si g n at ure A p pr o v als  
I c o nfir m t hat I h a ve r e vie we d t his d oc u me nt a n d a gree wit h t he c o nte nt. 
 
 A p pr o v al  
, Sr. Bi ostatisticia n  
 
 
Na me, Title  
Lea d Bi ostatisticia n  
 Si g nat ure  
 Date ( D D -M m m -
Y Y Y Y)  
 
Pri nci pal Statisticia n  
  
  
Na me, Title  
S e ni or Re vie wi n g Bi ostatisticia n  
 
 Si g nat ure  
 Date ( D D -M m m -
Y Y Y Y)  
, P har mac o ki net icist 
  
 
Na me, Title  
Lea d P har mac o ki neticist  
 
 Si g nat ure  
 Date ( D D -M m m -
Y Y Y Y)  
 Sr Me dical Writer  
 
  
Na me, Ti tle 
Lea d Me dical Writer  
 
 Si g nat ure  
 Date ( D D -M m m -
Y Y Y Y)  
G S K  C H A p pr o v al  
, Ma na g er Bi ostatistics 
  
 
Na me, Title  
S p o ns or C o ntact 
 
  
 Si g nat ure  
 
 
 
 
 
  
 Date ( D D -M m m -
Y Y Y Y)  
 
 
 
 
 
 
 
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 4 of 3 2 
 
T a ble of C o nte nts  
Re visi o n Hist or y ................................................................................................................. 2 
Si g nat ure A p pr o vals ........................................................................................................... 3 
Ta ble of C o nte nts ............................................................................................................... 4 
1.  
Gl os sar y of A b br e viati o ns ........................................................................................... 7 
2.  
P ur p ose ........................................................................................................................ 9 
2. 1  
Res p o nsi bilities  ........................................................................................................ 9 
2. 2  
Ti mi n g s of A nal yses ................................................................................................ 9 
3.  
St u d y O bjecti ves ........................................................................................................ 1 1  
3. 1  
Pri mar y o bjecti ve  ................................................................................................... 1 1 
3. 2  
Se c o n dar y o bjecti ve ............................................................................................... 1 1  
3. 2. 1  
P K o bjecti ve ................................................................................................... 1 1  
3. 2. 2  
Safet y o bjecti ve  .............................................................................................. 1 1 
4.  
E n d p oi nts ................................................................................................................... 1 1  
4. 1  
P har mac o ki netic E n d p oi nts ................................................................................... 1 1  
4. 2  
Safet y E n d p oi nts .................................................................................................... 1 2  
5.  
St u d y Desi g n ............................................................................................................. 1 3  
5. 1  
S u bject Selecti o n  ................................................................................................... 1 3 
5. 2  
Deter mi nati o n of Sa m ple Size  ............................................................................... 1 3 
5. 3  
Ra n d o mizati o n a n d Bli n di n g ................................................................................. 1 3  
5. 3. 1  
Ra n d o mizati o n ............................................................................................... 1 3  
5. 3. 2  
Bli n di n g.......................................................................................................... 1 4  
5. 4  
S u bject Wit h dra wal  ............................................................................................... 1 4 
6.  
A nal ysis P o p ulati o ns a n d Sets ................................................................................... 1 5  
6. 1  
Scree ne d P o p ulati o n .............................................................................................. 1 5  
6. 2  
Safet y P o p ulati o n ................................................................................................... 1 5  
6. 3  
P har mac o ki netic P o p ulati o n .................................................................................. 1 5  
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 5 of 3 2 
 
6. 4  
P har mac o ki netic A n al ysis Set  ............................................................................... 1 5 
7.  
Ge neral As pects f or Statistical A nal ysis  ................................................................... 1 5 
7. 1  
Ge ner al Met h o ds  .................................................................................................... 1 5 
7. 2  
S u m mar y Statistics  ................................................................................................ 1 6 
7. 3  
Ke y Defi niti o ns ...................................................................................................... 1 7  
7. 4  
Ha n dli n g of Dr o p o uts a n d Missi n g Data ............................................................... 1 7  
8.  
De m o gra p hic, Ot her Bas eli ne C haracteristics a n d Me dicati o n  ................................. 1 9 
8. 1  
I n cl usi o n a n d E xcl usi o n Criteria ........................................................................... 1 9 
8. 2  
De m o gra p hics a n d B o d y Meas ure me nts ............................................................... 1 9  
8. 3  
Me dical Hist or y  ..................................................................................................... 1 9 
8. 4  
Uri ne Dr u g Scree n, Uri n e C oti ni ne Test, a n d Alc o h ol breat h test ........................ 1 9  
8. 5  
Vir ol o g y ................................................................................................................. 1 9  
8. 6  
Pre g na nc y T esti n g a n d F ollicle Sti m ulati n g H or m o ne ( F S H) Le vels ................... 2 0  
8. 7  
C O VI D - 1 9 Testi n g ................................................................................................ 2 0 
8. 8  
Electr ocar di o gra m .................................................................................................. 2 0 
8. 9  
Pri or a n d C o nc o mita nt M e dicati o ns ...................................................................... 2 0 
8. 1 0  St u d y Dr u g A d mi nistrati o n ................................................................................... 2 2  
8. 1 1  S u bject Dis p ositi o n  ................................................................................................ 2 2 
9.  
P har mac o ki netic A n al yses ......................................................................................... 2 3 
9. 1  
Ha n dli n g of C o nce ntrati o ns  Bel o w t he L o wer Li mit of Q ua ntificati o n ( B L O Q), 
N o Re p orta ble C o nce ntrati o n Val ues, a n d Missi n g Data ...................................... 2 3  
9. 2  
Ha n dli n g  of  t h e  Differ e n ce  b et wee n  t he  Sc he d ule d  a n d  t h e  A ct ual  Sa m pli n g  
Ti mes  ..................................................................................................................... 2 3 
9. 3  
P K Sa m pli n g Sc he d ule .......................................................................................... 2 3  
9. 4  
Plas ma P har ma c o ki netic Para meters  ..................................................................... 2 4 
9. 5  
Statistical A nal yses  ............................................................................................... 2 5 
9. 6  
Assess me nt of Bi oe q ui vale nce .............................................................................. 2 5  
9. 6. 1  
Gr o u p Eff ect A nal ysis.................................................................................... 2 5  
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 6 of 3 2 
 
1 0.  
Safet y  ......................................................................................................................... 2 6 
1 0. 1  A d verse E v e nts  ...................................................................................................... 2 6 
1 0. 2  Cli nical La b orat or y Par a meters  ............................................................................. 2 8 
1 0. 3  Vital Si g n Meas ure me nts  ....................................................................................... 2 8 
1 0. 4  P h ysical E xa mi nati o n  ............................................................................................ 2 9 
1 1.  
C ha n ges fr o m t he Pr ot oc ol ........................................................................................ 2 9  
1 2.  
Refere n ce List  ............................................................................................................ 3 0 
1 3.  
Q ualit y C o ntr ol .......................................................................................................... 3 1  
1 4.  
A p pe n dices ................................................................................................................ 3 2  
 
 
 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 7 of 3 2 
 
1.  
Gl oss ar y of A b bre vi ati o ns 
A b bre viati o n  
Descri pti o n  
λ z 
T he ter mi nal eli mi nati o n rate c o nsta n t 
A bs  
a bs ol ute 
A E  
a d verse e ve nt  
A L T  
ala ni ne tra ns a mi nase  
A S T  
as partate tr a nsa mi nase  
A U C  
area u n d er t he c ur ve  
A U C 0 -t 
area u n d er t he c o nce ntrati o n ‑ti me c ur ve fr o m ti me 0 t o t he ti me of t he 
last meas ura ble s a m pli ng ti me p oi nt, t   
A U C 0 -i nf 
area u n d er t h e c o nce ntrati o n ti me c ur ve fr o m ti me 0 t o i nfi nit y 
A Z  
Astra Ze neca  
B D R  
bli n d e d data re vie w  
B L O Q  
bel o w t he l o wer li mit of q ua ntificati o n   
B MI  
b o d y mass i n de x  
B P  
bl o o d press ure  
B U N  
b l o o d urea nitr o ge n 
C G  
Catale nt  G ua ya ma  
CI  
c o nfi de nce i nter val  
C ma x  
p ea k or ma xi m u m o bser v e d c o nce ntrati o n  
C R F  
case r e p ort f or m  
C S R  
cli nical st u d y re p ort  
E C  
et hics c o m mittee 
E C G  
electr ocardi o gr a m  
e C R F 
Electr o nic Case Re p ort F or m  
F S H  
f ollicle sti m ulati n g h or m o ne 
G C P  
G o o d Cli nica l Practice 
G G T  
ga m ma gl uta m yl tra ns pe pti dase  
HI V  
h u ma n i m m u n o deficie nc y vir us  
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 8 of 3 2 
 
A b bre viati o n  
Descri pti o n  
I C F 
i nf or me d c o nse nt f or m 
I C H 
I nter nati o nal C o nfere nce o n Har m o nizati o n  
I E C 
I n d e pe n de nt Et hics C o m mittee 
I R B 
i nstit uti o nal re vie w b oar d 
M C H  
Mea n c or p us c ular h e m o gl o bi n  
M C H C  
Mea n c or p us c ular h e m o g l o bi n c o nce ntrati o n 
M C V  
Mea n c or p us c ula r v ol u m e 
Me d D R A  
me dical Dicti o nar y f or R e g ulat or y Acti vities  
N/ A  
n ot a p plica bl e 
P C R  
p ol y merase c h ai n reacti o n  
P K  
p har mac o ki netics  
P R  
p ulse rate  
P T  
preferre d t er m  
Q C  
q uali t y c o ntr ol 
R B C  
re d blo o d cell  
S A E  
seri o us a d vers e e v e nt 
S A P  
statistical a nal ysis pla n 
S D  
Sta n dar d de viati o n  
S O C  
s yste m or ga n class 
S O P  
sta n dar d o per ati n g pr oce d ure 
t½   
ter mi nal half -life 
T L Fs  
ta bles, listi n gs a n d fi g ures 
T H C  
tetra h y dr oca n na bi n ol  
tma x  
ti me t o reac h ma xi m u m c o nce ntrati o n 
W B C  
w hite bl o o d cell  
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 9 of 3 2 
 
2.  
P ur p ose  
T he p ur p ose of t his statistical a nal ysis pla n ( S A P) is t o e ns ure t hat t he data listi n gs, s u m mar y 
ta bles, a n d fi g ures w hic h will be pr o d uce d, a n d t he statistical met h o d ol o gies t hat will be use d, 
are c o m plete a n d a p pr o priate t o al l o w vali d c o ncl usi o n re gar di n g t he st u d y o bjecti ves. Safet y  a n d 
p har mac o ki netic ( P K)  a n al yses will all be descri b e d.  
T his S A P is base d o n t he f oll o wi n g d oc u me nts: 
•  Pr ot oc ol  N o.  2 1 8 2 4 6 ,  Versi o n  1. 0 d ate d 2 5- N o v - 2 0 2 1 (
 Pr oject  N o.  
 
•  Electr o nic Case Re p ort F or m (e C R F) Draft  1. 0, d ate d 1 0-Fe b - 2 0 2 2  
T he pla n ma y c ha n ge d u e t o u nf ores ee n ci rc u mst a nces a n d a n y c ha n ges ma de aft er t he pla n has 
bee n fi nalize d will be d oc u me nte d. If a d diti o nal a nal yses are re q uire d t o  s u p ple me nt t he pla n ne d 
a nal yses d escri be d i n t he S A P, t he c h a n ges a n d j ustificati o n f or t h e c ha n ges will be o utli ne d i n 
t he cli nical st u d y r e p ort ( C S R). N o c ha n g e will be ma de wit h o ut pri or a p pr o val of t he st u d y 
s p o ns or.  N o  re visi o n  t o  t he  S A P  is  re q uire d f or  c ha n ges  w hic h  d o  n ot  affect  t he  statistical  
a nal ysis met h o ds, defi niti o ns, or r ules defi ne d i n t his d oc u me nt.  
W he n  a p plica bl e ,  all  met h o d ol o gies  a n d  relate d  pr ocesses  will  be  c o n d ucte d  acc or di n g  t o  
 Sta n dar d O perati n g Pr oce d ures ( S O Ps) a s a p pr o priate. S h ells f or all statistical 
ta bles, listi n gs, a n d fi g ures ref err e d t o i n t his S A P will be dis pla ye d i n a se parate d o c u me nt. 
2. 1  
Res p o nsi bilities  
 will perf or m t he statistical a nal yses a n d are res p o nsi ble f or t he pr o d ucti o n a n d 
q ualit y c o ntr ol of all ta bles, listi n gs a n d fi g ures ( T L Fs) a n d P K a nal ysis. 
2. 2  
Ti mi n gs of A n al yses 
N o I nteri m a nal ysis is pla n ne d f or t his st u d y. 
Dr y -r u n A n al ysis: 
A Dr y -r u n a nal ysis is pla n ne d f or t his st u d y usi n g d u m m y or a vaila ble data bef ore d ata bas e 
s oftl oc k. T his dr y-r u n a nal ysis will i ncl u de a set of all u ni q ue ta bles, fi g ures, a n d listi n gs a n d ar e 
de n ote d i n t he acc o m pa n yi n g S A P S hells.  
Bli n de d Data Re vie w ( B D R):  
After c o m pleti o n of d ata base s oftl oc k, a B D R will be c o n d ucte d. T h e details of t he B D R will be 
c o m pile d i n a se par ate d o c u me nt. T he p ur p ose of t he B D R is t o assi g n t he st u d y p o p ulati o ns 
o utli ne d i n Secti o n 6  of t his S A P. As t his st u d y is si n gle bli n d, t he ter m “ bli n d” is use d t o de n ote 
t hat t he p o p ulati o n deter mi nati o n will be d o ne wit h o ut res pect t o treat me nt.  
T o pli ne T L F s: 
After c o m pleti o n of d ata bas e har dl o c k, a s u bset of all T L F s wil l be ge n erat e d i nte n de d t o 
i de ntif y ke y res ults of t he st u d y (i.e. bi oe q ui vale nce a n d safet y).   
P P D
P P D
P P D
P P D
C CI
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 1 0 of 3 2 
 
Fi nal A nal ysis:  
T he  fi nal a nal ysis of s afet y a n d P K is pla n ne d t o b e c o m plete d after c o m pleti o n of T o pli ne T L Fs . 
T h e fi nal a n al ysis will i ncl u de t he T o pli n e T L F.  
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 1 1 of 3 2 
 
3.  
St u d y O bjecti ve s 
3. 1  
Pri m ar y o bjecti ve   
•  De m o nstrate t he bi oe q ui vale nce of es o me praz ole 2 0 m g dela ye d -releas e ca ps ules 
fr o m Catalent G ua ya ma ( C G) c o m pare d t o es o me praz ol e 2 0 m g dela ye d -releas e 
ca ps ules fr o m Astr a Ze n eca S ö dertälje ( A Z) u n d er faste d c o n diti o ns. 
3. 2  
Sec o n d ar y o bjecti ve  
3. 2. 1  
P K o bjecti ve 
•  Assess t he p har mac o ki netic pr ofile 
3. 2. 2  
S afet y  o bjecti ve  
•  Assess t he safet y pr ofile (l ocal a n d s ys te mic) of b o t h pr o d ucts 
4.  
E n d p oi nts  
4. 1  
P h ar m ac o ki netic  E n d p oi nt s 
o  Pri mar y  
•  C ma x  ( T he  ma xi m u m  o bser ve d  p ost-d ose  c o nce ntrati o n;  o b tai ne d  wit h o ut  
i nter p olati o n) 
•  A U C 0-t  (T he area u n der t he plas ma c o n ce ntrati o n vers us ti me c ur ve calc ulate d 
fr o m ti me 0 t o t he last meas ura ble sam pli n g ti me p oi nt, t, c o m p ute d usi n g t he 
li near tra p ez oi dal r ule) 
o  Sec o n dar y  
•  A U C 0- i nf  (T he area u n der t he plas ma c o nce ntrati o n vers us ti me c ur ve calc ulate d 
fr o m ti me 0 t o i nfi nit y A U C0- i nf = A U C 0-t + C(t)/ λ z w here C(t) is t he c o nce ntrati o n 
at t he last meas u rabl e sa m pli n g ti me p oi nt a n d λ z is t he ter mi nal eli mi nati o n rate 
c o nsta nt) 
•  % A U C
e x  (Perce nta ge of A U C 0- i nf  o btai ne d b y e xtra p o lati o n, calc ulate d as ( 1－
[ A U C0- t / A U C0- i nf] ) × 1 0 0) 
•  λ z (T he ter mi nal el i mi nati o n rate c o nsta nt c o m p ute d as t he sl o pe of the re gress i on 
li ne  of  l n  ( C(t))  o n  ti me.  T he  re gressi o n  s h o ul d  ge nerall y  i n v ol ve  at  least  3  
c o nsec uti ve meas ura bl e c o nce nt rati o ns t hat decrease o ver ti me ) 
•  tma x  ( T he ti me of t he ma xi m u m o bser ve d p ost-d ose c o nce ntrati o n) 
•  t1/ 2 ( T he eli mi nati o n half-life c o m p ute d as t1/ 2 = l n( 2)/ λz) 
All P K para meters, calc ulate d usi n g plas ma  c o nce ntrati o n data, are referre d  t o i n Secti o n  a n d 9. 4 . 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 1 2 of 3 2 
 
4. 2  
S afet y  E n d p oi nts  
Safet y  will be assesse d b y : 
•  M o nit ori n g a n d rec or di n g of a d vers e e ve nts 
•  P h ysical e xa mi nati o n  
•  Vital si g ns   
•  La b orat or y tests 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
 Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 1 3 of 3 2 
 
5.  
St u d y Desi g n  
T h is is a si n gle ce nter, si n gle d ose, si n gle- bli n d, ra n d o mize d, t w o- se q u e nce, t w o- peri o d 
cr oss o ver, bi oe q ui v ale nce st u d y i n healt h y a d ult s u bjects wi t h at least a 7-d a y was h o ut peri o d. 
T he st u d y is i nte n de d t o d ose i n m ore t ha n o ne gr o u p; all gr o u ps will be d ose d at t he sa me 
cli nical site a n d t he sa me pr ot oc ol re q uire m e nts a n d pr oce d ures will be f oll o we d wit hi n eac h 
gr o u p. 
S u bjects will be ra n d o ml y  assi g ne d t o o ne of 2 treat me nt se q ue nces a n d re cei ve a si n gle d ose of 
o ne of t he f oll o wi n g treat me nts i n eac h peri o d f oll o wi n g a cr oss o ver desi g n:  
Treat me nt A: es o me praz ole 2 0 m g ca ps ules fr o m C G i n t he faste d state ( T est)  
Treat me nt B: es o me pr az ole 2 0 m g  caps ules fr o m A Z i n t he faste d state ( Refere nce). 
5. 1  
S u bject Selecti o n  
H ealt h y n o n-s m o ki n g a d ult s u bjects bet wee n the a ge s of 1 8 t o 5 5 y ears of a ge, i n cl usi ve, at t h e 
si g ni n g of i nf or me d c o nse nt wit h  a B o d y Mass I n de x ( B MI) bet wee n  1 8. 5 t o 3 0 k g/ m2 a n d a t otal 
b o d y wei g ht ≥  5 0. 0  k g f or  males  a n d  ≥  4 5. 0  k g f or fe males are t o b e i ncl u de d i n t his st u d y. 
Detail  all of t he  i ncl usi o n a n d e xcl usi o n criteria m a y be f o u n d i n st u d y pr ot oc ol, S ecti o ns 5. 2 a n d 
5. 3. 
5. 2  
Deter mi n ati o n of S a m ple Size  
A s ufficie nt n u m ber of s u bject s will be s c ree ne d t o ra n d o mize a p pr o xi matel y 4 9 t o e ns ure at 
least 4 1 e val ua ble s u bj ects c o m plete t he e ntire st u d y.  
Acc or di n g t o pre vi o us G S K C H st u d y 
 
 
 it is esti mate d a s am ple of 4 1 s u b jects will pr o vi de at least 
9 0 % p o wer t o esta blis h bi oe q ui vale nce. C o nsi deri n g a dr o p o ut disc o nti n uati o n rate of 1 5 %, 
a p pr o xi matel y 4 9 s u bjects will nee d  t o be e nr olle d.  
5. 3  
R a n d o miz ati o n a n d Bli n di n g  
5. 3. 1  
R a n d o miz ati o n 
Ra n d o mizati o n will occ ur pri o r t o first d osi n g. Si nce e nr oll me nt i nt o t he st u d y is base d o n t he 
res ults of i ncl usi o ns/e xcl usi o n a n d Ra n d o mizati o n is pri or t o d osi n g, it is p ossi ble t hat a s u bject 
is e nr olle d i n t he st u d y, b ut n ot ra n d o mize d. He nce, ra n d o mizati o n will be c o nsi dere d t he ti me at 
w hic h t he s u bject i de ntifier is assi g ne d t o a s u bject w hic h is tie d t o a ra n d o mize d treat me nt 
se q ue nce. 
C o m p uter ge nerat e d ra n d o mizat i on sc he d ules will be  pre pare d pri or t o t he start of t he st u d y. T he 
sc he d ules will be g e ner ate d t hr o u g h t he statistical a nal ysis s yste m ( S A S) s oft ware, v ersi o n 9. 4. 
Bl oc k ra n d o mizati o n will be use d.  S u bjects will be ra n d o ml y assi g ne d a 3- di git s u bject n u m b er 
P P D
C CI
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 1 4 of 3 2 
 
be gi n ni n g wit h 0 w it h t he last t w o n u m bers bei n g 0 1- 6 0. 
5. 3. 2  
Bli n di n g  
Bli n di n g is re q uire d as per Ca na dia n re g ul ati o n. T his will be a si n gle- bli n d st u d y. 
 will pr o vi de a ra n d o mizati o n sc he d ule t o t he i n vesti gat or a n d, i n acc or d a nce wit h 
t he ra n d o mizati o n n u m bers, t he s u bject will recei v e t he st u d y treat me nt re gi me n assi g ne d t o t he 
c orres p o n di n g r a n d o miz ati o n n u m ber. 
Tr eat me nts will be pr o vi de d i n a bli n d ma n ner. Pers o n nel i n v ol ve d i n t he c ollecti o n, m o nit ori n g, 
re visi o n, or e val uati o n of a d verse e ve nts, pers o n nel of t he bi oa nal ytical de p art me nt, a n d 
pers o n nel w h o c o ul d h a v e a n i m pact o n t he o utc o me o f t he st u d y, i ncl u di n g G S K/
 
statisticia ns, pr o gra m mers, scie ntists, D M st u d y ma na gers, cli nical st u d y tea m e xce pt Gl o b al 
s u p pl y, a n d 
 P K anal yst, will n ot ha ve pri or access t o t he ra n d o mizati o n c o de. 
5. 4  
S u bject Wit h dr a w al  
A s u bject ma y w ith dra w fr o m t he  st u d y at a n y ti me at his or her o w n re q u est or ma y be 
wit h dra w n at a n y ti me at t he discreti o n of t he i n vesti gat or or s p o ns o r f or safet y, be ha vi oral 
reas o ns, or t he i n a bilit y of t he s u bject t o c o m pl y wit h t he pr ot oc ol re q uire d sc he d ule of s t ud y 
visits or p r oce d ures. 
T he f oll o wi n g circ u msta nces re q uir e disc o nti n uati o n of st u d y pr o d uct a n d/ or pre mat ure s u bject 
wit h dra wal:  
•  Pr ot oc o l vi olati o n t hat ma y i mpact t he s u bject’s s afet y  
•  P ositi ve test f or C O VI D - 1 9, c o n d ucte d d uri n g t he st u d y, at ti mes dee me d 
necessar y b y I n vesti gat or  
•  E mesis wit hi n 5 h o urs p ost d osi n g 
•  Diarr hea ( defi ne d as o n e e pis o de of l o ose st o ols) wit hi n 1 0 h o ur p ost d osi n g 
•  Wit h dra wal of i nf o r med c o nse nt  
•  S u bject l ost t o f oll o w - u p 
•  U n bli n di n g of t he s u bject 
•  Pre g na nc y  
If a s u bject is disc onti n ue d or pre mat urel y wit h dra ws fr o m t he st u d y, t he reas o n(s) f or 
disc o nti n uati o n or wit h dra wal a n d t he ass ociate d d ate m ust be d oc u me nte d i n t he rele va nt 
secti o n(s) of t he C R F. Wit h dra wal d ue t o A Es s h o ul d be disti n g uis he d fr o m wit h dra wal d ue t o 
ot he r caus es, acc or di n g t o t he defi niti o n of a n A E n ote d earlier, a n d rec or d e d o n t he a p pr o priat e 
A E C R F pa ge. 
P P D
P P D
P P D
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 1 5 of 3 2 
 
6.  
A n al ysis P o p ul a ti o ns a n d Sets  
S u bjec ts w h o de viate fr o m t he pr ot oc ol will be i d e ntifie d a n d e xcl u de d fr o m t he p har mac o ki netic 
a nal yses as a gr ee d b y t he bio statisticia n a nd me dical dire ct or or d esi g nee. E xcl usi o n of a n y dat a 
fr o m t he a nal yses will be deter mi ne d d uri n g a B D R meeti n g pri or t o d ata b ase l oc k. A n y re as ons 
f or e xcl usi o n fr o m a n a n al ysis p o p ulati o n will be liste d, if a p plica ble. 
T he a nal ysis of saf et y para meter s will be base d o n t he Safet y P o p ulati o n detaile d i n Secti o n  6. 2 . 
S u m m aries statistics of P K (c o n ce ntrati o n a n d para meters ) will be bas e d o n t he P K A nal ysis Set 
detaile d i n Secti o n 6. 4 . All c ollecte d da ta will be i ncl u de d i n t he listi n g, i ncl u di n g a n y data 
ca pt ure d a n d e nte re d int o t he data base of scree n fail ures.  
6. 1  
S cree ne d  P o p ul ati o n 
T he S cree ne d   Po p ulati o n is defi ne d as all w h o were scree n e d t o p ote ntial recei ve at least o ne 
d ose of t he st u d y me dicati o n. Listi n gs w hic h i ncl u de s cree n fail ure s u bjects o r eli gi ble s u bjects 
w h o  we r e n ot ra n d o mize d will use d t he Scree n e d P o p ulati o n. 
6. 2  
S afet y P o p ul ati o n 
T he S afet y P o p ulati o n is defi ne d as all ra n d o mize d s u bjects wh o recei ve at least o ne d ose o f 
st u d y me dicati o n. T he Safet y P o p ulati o n will be use d f or all listi n gs u nl ess state d ot her wise. 
6. 3  
P h ar m ac o ki netic  P o p ul ati o n 
T he P K p o p ulati o n is defi ne d as all ra n d o mize d s u bjects w h o ha ve at least o ne p ost- d ose 
c o nce ntr ati o n  val ue, a n d w h o ha ve n o maj or pr ot oc ol de viati o ns c o ncer ni n g p har mac o ki netics. 
T he P K p o p ulati o n wi ll be use d t o list all c o nce ntrati o n data f or e ver y s u bject. 
6. 4  
P h ar m ac o ki ne tic A n al ysis Set  
T he f oll o wi n g P K a nal ysis set is defi ne d t o a d dress t he P K o bjecti ves a n d f urt her P K 
c o nsi derati o ns wit hi n t his st u d y : 
P K a nal ysis set i ncl u des all s u bjects of t he  P K  p o p ulati o n w h o c o m plete b ot h treat me nt peri o ds, 
a n d f or w hic h t h e relev a nt P K para meters (at least A U C 0-t or C ma x ) ca n be deri ve d. S u bjects wit h 
baseli ne c o nce ntrati o n > 5 % of t he i n di vi d ual C ma x  f or eit her peri o d will be e xcl u de d fr o m t he P K 
a nal ysis set.  T hi s a nal ysis set will be use d i n s u m maries, t he pri mar y P K a nal ysis, a n d t h e 
sec o n dar y PK a nal ysis.  
7.  
Ge ner al As pects f o r St atistic al A n al ysis  
7. 1  
Ge ner al Met h o ds  
S A S ®  f or Wi n d o ws, Release 9. 4 ( S A S®  I nstit ute I n c., Car y, N C, U S A) s oft ware will be use d t o 
pe rf or m all dat a a nal ys es.  
U nless ot her wise state d, all listi n gs will  be s ort e d b y s u bject n u m ber a n d assess me nt date/ti me , 
w he n a p plica bl e.  
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 1 6 of 3 2 
 
T he f oll o wi n g la bels f or treat me nt will be us e d o n all ta b ulati o ns w here t he res ults are dis pla y e d 
b y treat me n t, i n t he f ollo wi n g or der: 
•  E s o me praz ole C G ( Test) [A]  
•  E s ome praz ole A Z ( Ref er e nce) [B]  
7. 2  
S u m m ar y St atistics  
U nless  ot her wise  state d,  c o nti n u o us  varia bles  will  be  s u m marize d  usi n g  t he  n u m ber  of  
o bser vati o ns ( n), a n d t h e statistics arit h metic m ea n, sta n d ar d de viati o n  ( S D) , ge o metric   mea n, 
c oeffi cie nt of variati o n  ( C V %), me dia n, mi ni m u m, a n d ma xi m u m. Th e mi ni m u m a n d  ma xi m u m 
val ues  will  be  prese nte d  t o  t he  sa me  n u m ber  of  deci ma l  places  as  rec or d e d  i n  t he  C R F,  
arit h metic mea n a n d m e dia n will be prese nte d t o o ne m ore dec i mal place t ha n t h e ra w d ata a n d 
t he S D will be pr ese nte d t o t w o m ore deci mal places  t han t he ra w data. C ate g orical v aria bles will 
be s u m marize d wit h fre q ue nc y c o u nts a n d perce nta ges. Perce nta g es  ( ot her t ha n P K para meters ) 
will be  r o u n d e d t o o n e d eci mal place, wit h t he d e n o mi nat or bei n g t he n u m ber of s u bjects i n t he 
rele vant p o p ulati o n, u nless ot her wise state d. 
F or  t he plas ma P K da ta, t he data will be r o u n de d t o t w o deci mal places in t he listi n gs . T he 
f oll o wi n g r ules will be a p plie d t o f oll o wi n g sit uati o ns: 
•  λ z data:  Prese ntati o n of data i n listi n gs a n d calc ulate d mea ns (ari t h metic a n d ge o metric), 
mi ni m u m,  a n d  ma xi m u m  - r o u n de d  off  t o  4 deci mal  di gits.  Calc ulate d  S D  will  be  
prese nte d t o 5 deci mal places.  
•  P har mac o ki netic p ar a meters r elate d t o ti me s uc h as T ma x , Kel L o wer , a n d Kel U p per m ust be 
re p orte d wit h t he sa m e precisi o n as t he act ual s a m pli n g ti me: r o u n de d off t o 3 deci mal 
di gits.  T his  a p plies  t o  prese ntati o n  i n  listi n gs  a n d  calc ulat e d  mea ns  (arit h metic  a n d  
ge o metric), mi ni m u m, a n d ma xi m u m . S D will be prese nte d t o 4 deci mal places. 
•  C o nce ntrati o n data as well as C ma x : re porte d as t he y a p pear i n t he c orres p o n di n g dataset. 
N ote: t hese r ules are o nl y i nte n de d as a g ui de a n d ma y be c h a n ge d b ase d o n a v aila ble d ata f or 
t he st u d y a n d are n ot mea nt t o o verri d e t he nu m b er of d eci mal places i n t h e data us e d as i n p ut f or 
a nal ysis. T he f ull  u nr o u n de d precisi o n will  be use d f or all  calc ulati o n pri or t o r o u n di n g f or 
dis pla y as a p plica ble.  
S u m mar y statistics i ncl u d i n g t he ge o metric mea n will be dis pla ye d t o t he sa me n u m ber of 
deci mal places as t he arit h metic mea n a n d t he  c oefficie nt of variati o n ( C V) ( %) will be r o u n d e d 
t o 1 deci mal place.   
O nl y data fr o m n o mi nal pr ot oc ol sc he d ul e d visits will be i ncl u d e d i n t he s u m mar y ta bles. D ata 
fr o m u nsc he d ule d visits will n ot be i ncl u de d i n t he s u m mar y ta bles  b ut will be i ncl u de d i n t he 
listi n gs. 
All  assess me nts will be prese nte d i n t he listi n gs.  
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 1 7 of 3 2 
 
7. 3  
Ke y Defi niti o ns  
St u d y Da y: 
St u d y da y will be calc ulate d usi n g first  st u d y dr u g a d mi nistrati o n  (eit her Test or Refere nce) dat e 
as t he ref er e nce d ate. If t he date o f i nterest occ urs o n or after t h e first st u d y dr u g a d mi nistrati o n 
date, st u d y da y will be calc ulate d as ( date of i nterest – first st u d y dr u g a d mi nistrati o n date) + 1. 
If t he date of i nterest occ urs pri or t o t he first st u d y dr u g a d minist rati o n date, st u d y d ay will be 
calc ulate d as ( d ate of i nterest – f irst st u d y dr u g a d mi nistrati o n date). T here will be n o st u d y da y 
0. 
Pri or  me dicati o n : 
Me dicati o n/treat me nts  t a ke n  wit hi n  9 0  da ys  of  si g ni n g  t he  i nf or me d  c o nse nt  f or m  will  be  
d oc u me nte d as a pri or m e dicati o n/tre at me nt. 
C o nc o mita nt me dicati o n : 
Me dicati o ns/tr eat me nts ta ke n after t he first st u d y dr u g a d mi nistrati o n will be d oc u me nte d as 
c o nc o mita nt me dicati o n/treat me nts .  
Treat me nt: Tr eat me nt is assi g ne d as t he last recei ve d treat me nt, e xce pt  i n t he cas e of pre- d ose 
meas ure me nts. A n y n o n -a d vers e e ve nt  assess me nt  occ urri n g  o n  t he sa me cale n d ar date as  a  
gi ve n treat me nt bef ore d osi n g w o ul d be attri b ute d t o t he sa me treat me nt gi ve n o n t hat cale n dar 
da y. If n o treat me nt was a p plie d o n t he sa m e cal e n dar da y t h e n a n y m eas ure me nts pre -d ose will 
n ot be s u m marize d b y tr e at me nt. Ad v erse e ve nts will be s u m mari ze d o nl y b y t he l ast recei ve d 
treat me nt. 
Hei g ht: 
Hei g ht (i n c m) = h ei g ht (i n i nc hes) * 2. 5 4 
Wei g ht:  
Wei g ht (i n k g) = w ei g ht (i n l bs) * 0. 4 5 3 6 
B MI:  
B MI ( k g/ m 2) = Wei g ht( k g)/[ Hei g ht( m)2] 
7. 4  
H a n dli n g of Dr o p o uts a n d Missi n g D at a  
All d ata fr o m s u bjects w h o wit h dra w fr o m t he st u d y will be i ncl u de d i n t he  s u m maries u p t o t he 
ti me of wit h dra wal. 
F or safet y,  
•  If a n A E is rec or de d wit h a n o nset date c orres p o n di n g t o a st u d y dr u g a d mi nistrati o n 
da y, b ut t he ti me is missi n g, t he n t he  A E wil l be assi g ne d t o t he act ual treat me nt wit h 
st u d y dr u g a d mi nistrati o n t hat da y a n d c o nsi dere d treat me nt-e mer ge nt.  
•  If a n A E is rec or de d wit h a n o nset d ate t h at d o es n ot c orres p o n d to  a st u d y dr u g 
a d mi nistrati o n  da y, b ut t he ti me is missi n g, t he n t he A E will be assi g ne d t o act ual 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 1 8 of 3 2 
 
treat me nt  t hat  c o vers  t he  A E  o nset  da y  a n d  c o nsi dere d  treat me nt-e mer ge nt  if  
a p pr o priate. 
•  If a n A E is rec or de d wit h a n o nset date w here d a y a n d ti me are b ot h miss i n g, t he n t he 
A E  all ocati o n  t o  a  treat me nt  will  be  d o ne  o n  a  case  b y  case   basis  c o nsi deri n g  
a vaila ble  i nf or mati o n  ( e. g.  A E  o nset  date,  A E  e n d  date,  A E  c o m me nts,  s u bject  
dis p ositi o n) i n ra w data. It will be c o nsi d ere d treat me nt- e mer g e nt if a p pr o priate.  
•  Miss i n g  data  are  re pres e nte d  o n  s u bject  listi n gs  as  eit her  a  h y p he n  (“-”)  with  a  
c orres p o n di n g  f o ot n ote  (“ - =  u n k n o w n  or  n ot  e val uate d ”),  or  as  “ N/ A ”,  wit h  t he  
f o ot n ote “ N/ A = n ot a p plica ble”, w hi c he ver is a p pr o priate 
•  Dates t hat are missi n g b eca use t he y ar e  n ot a p plica ble f or t he s u bject are o ut p ut as 
“ N/ A”, u nless ot her wise s pecifie d.  
F or P K  a nal ysis, o nl y o bser ve d c o n ce ntrati o n data will be use d i n t he data a nal ysis e xce pt f or 
c o nce ntr ati o n val ues B L Q as descri be d i n Sect i o n 9. 1 a n d Secti o n 9. 2 . No atte m pt will be ma de 
t o e xtra p olate or i nter p olate esti mates f or missi n g data. 
 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 1 9 of 3 2 
 
8.  
De m o gr a p hic, Ot her B aseli ne C h ar acteristics a n d Me dic ati o n  
8. 1  
I ncl usi o n a n d E xcl usi o n Criteri a  
All rec or de d i ncl usi o n/e xcl usi o n criteria stat us will be prese nt e d i n a  data listi n g . Eac h s u b ject’s 
i ncl usi o n or e xcl usi o n fr o m eac h p o p ulati o n will als o be prese nt e d i n a dat a listi n g. 
8. 2  
De m o gr a p hics a n d B o d y Me as ure me nts  
T he  de m o gr a p hic  c har acteri stics  will  c o nsist  of  a ge  ( years),  s e x  (fe male  or  mal e),  et h nicit y  
( His pa nic or Lati n o, N ot  His pa n ic  or Lati n o, N ot  Re p orte d, a n d U n k n o w n), race ( A merica n 
I n dia n or Alas ka Nati ve, Asia n, Blac k or Afri ca n A merica n, N ati ve Ha w aiia n or Ot her Pacific 
Isla n d er, W hite, M ulti ple, Ot her , N ot Re p orte d, a n d U n k n o w n). T he b o d y m eas ure me nts c o nsist 
of hei g ht (c m), weig ht ( k g), a n d b o d y mass i n de x ( B MI) ( k g/ m 2).  
Descri pti ve  statistics  (n,  mea n,  S D,  Mi n,  me dia n, 
a n d  Ma x)  will  be  calc ulate d  f or  b o d y 
meas ure me nts  usi n g t he last res ults o btai ne d pri or t o first st u d y dr u g a d mi nistrati o n . Fre q ue n c y 
c o unts  a n d  perce n ta g es  will  be  ta b ulate d  f or  cate g orical  varia bles. All 
de m o gra p hic 
c haracteristics will be s u m marize d o verall a n d liste d b y s u bject f or t h e Safet y P o p ulati o n a n d PK 
P o p ulati o n. If  t he  Safet y  P o p ulati o n a n d  P K  P o p ulati o n are  t he  sa me,  t he  ta ble  f or  t he  P K 
P o p ula tio n will n ot be ge nerate d. 
8. 3  
Me dic al Hist or y  
Details of rele va nt me dical a n d s ur gical hist or y i n t he last 5 years, i ncl u di n g aller gies or dr u g 
se nsiti vit y will be rec or d e d. T his data will be i ncl u de d i n a d ata listi n g . A n y a b n or mal fi n di n gs 
fr o m t he ph ysica l e x a m occ urri n g b ef ore t he first st u d y dr u g a d mi nistrati o n will be i ncl u de d i n 
t he Me dical Hist or y. T he  Me dical Dicti o nar y f or Re g ulat or y   Acti vities ( Me d D R A ® ) Versi o n  
2 4. 1 will be use d t o classif y all me dical hist or y fi n di n gs b y S yste m Or ga n Class ( S O C) a n d 
P referre d Ter m ( P T). 
8. 4  
Uri ne Dr u g Scree n, Uri ne C oti ni ne Test,  a n d Al c o h ol bre at h test  
A uri ne dr u g scree n will be perf or me d at s cree ni n g a n d Da y - 1 of eac h peri o d. Testi n g i ncl u des: 
A m p heta mi ne , Met ha m p heta mi ne , Bar bit urates , B e nz o diaz e pi ne, c o cai ne, 
3, 4 ‑met h yle ne di o x y met h a m p heta mi ne, Met ha d o n e, O piate, P he nc y cli di ne, a n d 
Tetra h y dr o ca n na bi n ol.  
A uri ne c oti ni ne test will be perf or m e d at scree ni n g a n d Da y - 1 of eac h peri o d. 
A n alc o h ol breat h test will be perf or me d at scree ni n g a n d Da y - 1 of eac h p eri o d. 
T h e uri ne  dr u g scree n , uri ne c oti ni ne test, a n d  alc o h ol breat h test a n d restri cti o n assess me nts will 
be prese nt e d i n se par ate listi n gs.  
8. 5  
Vir ol o g y 
Vir us ser ol o g y will be perf or me d at scree ni n g  f or He patitis B S urface A nti ge n , He patitis B C ore 
A nti b o d y, He pa titis C Vir us A nti b o d y, HI V A nti ge n/ A nti b o d y . Fi n di n gs fr o m Vir ol o g y res ults 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 2 0 of 3 2 
 
will be i ncl u de d i n a data listi n g.  
8. 6  
Pre g n a nc y Testi n g  an d F ollicle S ti m ul ati n g H or m o ne  ( F S H) Le vels 
F or all fe male s u bjects of c hil d beari n g p ote ntial, a uri ne pre g na nc y te st, will be perf or me d at 
scree ni n g a n d e n d of st u d y a n d a ser u m pre g na nc y test will be perf or me d o n Da y -1 of eac h 
peri o d. Res ults will be  obtai ne d pri or t o d osi n g d uri n g eac h peri o d . A ne g ati ve pre g na n c y res ult 
is re q uire d bef ore t h e s u bject ma y recei ve th e i n vesti gati o nal pr o d uct. Pre g na nc y tests will als o 
be  d o ne  w h e ne ver  o ne  me nstr ual  c ycle  is  miss e d  d uri n g  t he  acti ve  st u d y  peri o d  ( or  w h e n  
p ote ntial pre g na n c y is o t her wise s us pecte d). Pre g na nc y tests ma y als o b e re peate d as per re q u est 
of I R Bs/ E Cs or if re q uire d b y l ocal re g ulati o ns. 
F S H will be perf or me d at t he   scr ee ni n g visit f or  fe males w h o ha ve b ee n a me n orr h o eic f or 12 
m o nt hs. 
Res ults fro m t he p re g na n c y testi n g a n d F S H Le v els  will be liste d , se paratel y. 
8. 7  
C O VI D - 1 9 Testi n g  
Nasal/ Nas o p har y n geal s wa b will b e c ollecte d t o test f or C O VI D-1 9 usi n g P C R or a nti ge n test , at 
scree ni n g,  Da y  - 1 of  eac h  p eri o d , at Da y  2  of  Peri o d  1 , d u rin g  t he  was h o ut  peri o d,  earl y 
disc o nti n uat i o n or e n d of st u d y, a n d at a n y ti me d uri n g resi de ntial peri o d i n t he st u d y w he n 
s u bjects rep ort s y m pt o ms s u g gesti ve of C O VI D ‑1 9. A listi n g i ncl u di n g all res ults fr o m C O VI D -
1 9 testi n g will be create d.  
8. 8  
Electr oc a r di o g r a m  
A sta n dar d 1 2 -lea d E C G will be perf orme d at scree ni n g. Res ults of a n y cli nicall y si g nifica nt 
a b n or malities s h o ul d be re p orte d i n  t he C RF. Cli nicall y si g nifica nt a b n or malities s h o ul d als o be 
rec or d e d o n t he A d v erse E ve nt C R F. All fi n di n gs will be liste d. 
8. 9  
Pri or a n d C o nc o mit a nt Me dic ati o ns  
C o nc o mita nt me dicati o n use will be rec or de d fr o m t he ti me t he s u bject si g ns t he I C F u ntil t h e 
E O S visit . S u bjects will a bstai n fr o m all c o nc o mita nt treat me nts, e xce pt f or c o ntrace pti ves a n d 
h or m o ne re pl ace m e nt t hera p y,   an d t h ose us e d f or t he treat me nt of a d ver se e v e nts u nless t he y 
je o par dize t h e i nte grit y of t he st u d y.  
C o nc o mita nt me dicati o ns will b e c o de d  usi n g t he W orl d Healt h Or ga nizati o n Dr u g Dicti o nar y 
(W H O  D D ), Versi o n B 3, Mar 2 0 2 1  or later . D ata as rec or de d i n t he C R F (i.e. wit h i nc o m plete 
dates) will b e liste d. F or t he p ur p os e of i n clusi o n i n Pri or a n d c o nc o mit a nt me dicati o n ta bl es, 
i nc o m plete me dicat i o n start a n d st o p dates o n C R F will be i m p ute d as f oll o ws: 
•  If t he sto p d ate is i nc o m plete, t he f oll o wi n g r ules will be a p plie d:  
o  Missi n g da y: Ass u me t he last da y of t he m o nt h; 
o  Missi n g da y, m o nt h, a n d year: Ass u me t hat t he me dicati o n is c o nti n ui n g; 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 2 1 of 3 2 
 
o  I n t he case of t he deat h of a s u bject, a n d if t he i m p ute d e n d date is after th e  date of deat h, 
t he e n d date will be i m p ute d as t he date of deat h. 
•  If t he st o p date is i nc o m plete, i m p ute d e n d date will be use d i nstea d of re p orte d e n d date 
•  If t he start dat e is i nc o m plete, t he f oll o wi n g r ules will be a p plie d: 
o  Missi n g da y: Ass u me t he fi rst da y of t he m o nt h; 
•  H o we ver, if t he partial date a n d t he date of dr u g a d mi nistrati o n lie wit hi n t he sa me m o nt h 
a n d year a n d t he date of dr u g a d mi nistrati o n is n o t after t he st o p date of t he me dicati o n, set t o 
t he date of dr u g a d mi nistrati o n. Ot her wise, s et t o st o p date of t he me dicati o n.  
o  Missi n g da y a n d m o nt h: Ass u me Ja n uar y 1
st. 
•  H o we ver, if t he partial date a n d t h e date of dr u g a d mi nistrati o n lie wi thi n t he sa me year a n d 
t he date of dr u g a d mi nistrati o n is n ot after t he st o p  date of t he me dicati o n, set t o t he date of 
dr u g a d mi nistrati o n. Ot her wise, s et t o st o p date of t he me dicati o n. 
o  Missi n g da y, m o nt h, a n d year:   Ass u me date of dr u g  a d mi nistrati o n if it’s n ot after t he 
st o p date f or t he me dicati o n. Ot her wise, set t o  st o p date f or t he m e dicati o n.  
F or t h e missi n g da y i m p utati o n, t he f oll o wi n g e xa m ples s h o ul d be use d f or refere nce: 
•  E xa m ple 1:  
Me dicati o n start: U N J UN 2 0 1 9 
Me dicati o n e n d: 2 0 O C T 2 0 1 9 
Date of a d mi nistrati o n: 1 6 O C T 2 0 1 9 
Me dicati o n start i m p ute d: 0 1J U N 2 0 1 9 
Ta b ular r es u lts: C o nc o mita nt 
•  E x a mple 2:  
Me dicati o n start: U N O C T 2 0 1 9 
Me dicati o n e n d: 2 0 O C T 2 0 1 9 
Date of a d mi nistrati o n: 1 6 O C T 2 0 1 9 
Me dicati o n start i m p ute d: 1 6 O C T 2 0 1 9 
Ta b ular r es u lts: C o nc o mita nt 
•  E xa m ple 3:  
Me dica ti o n start: U N O C T 2 0 1 9 
Me dicati o n e n d: 2 0 O C T 2 0 1 9 
Date of a d mi nistrati o n: 2 4 O C T 2 0 1 9 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 2 2 of 3 2 
 
Me dicati o n start i m p ut e d: 2 0 O C T 2 0 1 9 
Ta b ular  r esu lts: Pri or  
Relati ve start da y or e n d  da y wit h res p ect t o t he d ose date of t h e st u d y dr u g a dmi nistrati o n  will 
n ot be calc ulate d if t he m e dicati o n star t date or e n d date is i nc o m plete . 
All pri or a n d c o nc o mita nt me dicati o ns will be prese nte d i n data listi n gs. 
8. 1 0  St u d y Dr u g A d mi nistr ati o n  
T he  st u d y  dr u g  a d mi nistrati o n  details  i ncl u di n g  date  a n d  ti me  o f  a d mi nistrati o n, Treat me nt  
Descri pti o n  (fre q ue n c y, r o ute, f or m ulati n g, d ose ( u nits)), Fasti n g stat us at ti me of a d mi nistrati o n,  
a n d if a me dicati o n/ d osi n g err or o ccu rre d w ill be liste d b y S u bject.  
8. 1 1  S u bj ect Dis p ositi o n 
T he  n u m ber  of  s u bj ects  scree ne d,  e nr olle d, s u bjects  n ot  ra n d o mize d (a n d  reas o n),  s u bjects  
ra nd o mize d i n Peri o d 1 or 2 (i n cl u di n g n u m ber of s u bject starti n g, c o m pleti n g peri o d , a n d n ot 
c o m pleti n g  (a n d r eas o n))  will  be  ta b ulate d  f or  t he  safety  p o p ulati o n.  Me dicati o n  err ors  a n d  
reas o n f or disc o nti n uati o n f or i n di vi d ual s u bjects will be liste d a n d s u m marize d.  
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 2 3 of 3 2 
 
9.  
P h ar m ac o ki netic A n al yses  
All plas ma c o nce ntrat io n a n d P K para meter  s u m maries a n d a n al ysis will be c o n d ucte d on t he P K 
A nal ysis Set . All co nce ntrati o n a n d P K data will be liste d  o n t he P K p o p ulati o n . T his i ncl ude s 
a n y data f or s u bjects w h o are n ot i ncl u de d i n t h e a nal ysis ( e.g. s u bjects wit h dra w n fr o m t he st u d y 
d ue t o a d verse e ve nts) . T he listi n g f or plas ma c o nce ntrati o n will i ncl u d e pla n ne d ti me p oi nt, 
sa m ple c ollecti o n ( yes or n o), d ate a n d ti mes of c ollecti o n,  an d t he calc ulate d ti me de viat i o ns 
fr o m t he pla n ne d ti me p oi nt.   
9. 1  
H a n dli n g of C o nce ntr ati o ns  Bel o w t he L o wer Li mit of Q u a ntific ati o n ( B L O Q), N o 
Re p ort a ble C o nce nt r ati o n V al ues , a n d Mi ssi n g D at a 
F or t he a nal ysis of all i n di vi d ual plas ma c o nce ntrati o ns a n d a ll sec o n d ar y P K para meter, all 
c o nce ntr ati o n B L O Q  val ues  t hat  occ ur bef ore t he  first  meas urab le c o nce ntrati o n  (i.e.  n o n -
B L O Q) will be treate d as zer o ( 0). A n y B L O Q val ues a fter  th e first meas ura ble   c o nce ntrati o n 
will  be  treate d  as  “ N ot  Detecta ble”  ( N D) , w hi c h  will  be  s h o w n  as  missi n g  f or  plas ma  P K 
c o nce ntr ati o ns a n d P K para meter esti mat i o n.  
Sa m ples wit h i n vali d c o nce ntrati o n ( d ue t o bi oa nal ytical or cli nical iss ue)  wil l b e re place d b y 
“ 0. 0 0” w h e n it occ urs pri or t o st u d y dr u g a d mi nistrati o n . Ot her wise, the y will be set t o missi n g 
f or ta b ulati o n, gra p hical re pr ese ntati o n a n d calc ulati on  p ur p oses if it occ urs after st u d y dr u g 
a d mi nistrati o n .  
List i n gs will s h o w t he act ual val ue of c o nce ntrati o n at t he ti me p oi nt. T he val ue of B L O Q will be 
dis pla ye d as a p pl ica bl e i n t he listi n gs. 
If a n y c o nce ntrati o n dat a is missi n g or de viates fr o m t he pla n ne d ti me of c ollecti o n, t he n t he 
p har mac o ki neticist ma y calc ulate t he P K p ara m eters u sin g t he a vaila ble d ata.  
9. 2  
H a n dli n g of t he Differe nce b et wee n t he Sc he d ule d a n d t he Act u a l S a m pli n g Ti mes 
T he act ual cl oc k ti me f or st u d y dr u g a d mi nistrati o n a n d eac h c o llecti o n ti me f or t he P K sa m ples 
will  be  r ec or d e d.  F or  all  sa m pli n g  ti mes,  t he  act ual  s a mpli n g  ti mes  relati ve  t o  st u d y  dr u g  
a d mi nistrati o n  will be calc ulate d as t he differe nc e bet wee n  t he act ual cl oc k ti me of sa m pli n g a n d 
t he act ual cl oc k ti me of st u d y dr ug a d mi nistrati o n . T he act ual p ost-d ose sa m pli n g ti me s relati ve 
t o st u d y dr u g a d mi nistratio n e x presse d i n h o urs a n d r o u n de d off t o t hree deci mal di gits will be 
use d t o calc ula te t he P K para meters, e x ce pt f or pre- d ose sa m ples occ urri n g pri or t o st u d y dr u g 
a dmi ni strati o n, w hic h will al wa ys be re p orte d as zer o ( 0. 0 0 0), re g ar dless of t he ti me diffe ren ce. 
Sc he d ule d  sa m pli n g  ti mes  ( pres e nte d  as  3  n u m bers  [i.e.  0. 5 0,  0. 7 5,  1. 0 0  or  2 4. 0]) will  be  
prese nte d i n c o nce ntr ati o n ta bles a n d mea n gra p hs, w hile act ual sa m pli n g t i mes will be prese nte d 
i n t he i n di vi d ual gra p hs. 
9. 3  
P K S a m pli n g  Sc he d ule  
Bl o o d sa m ples w ill be c ollecte d fr o m eac h s u bject d uri n g t his st u d y f or t he deter mi nati o n of t he 
P K of es o me praz ole. 
P K b l o o d sa m ples of es o me praz ole will be dra w n acc or di n g t o t he f oll o wi n g sc he d ule: 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 2 4 of 3 2 
 
Pre -d ose ( wit h i n 1 h o ur bef ore st u d y dr u g a d mi nistrati o n) a n d at 0. 5-, 0. 7 5- , 1-, 1. 2 5-, 1. 5-, 1. 7 5-
, 2-, 2. 2 5-, 2. 5-, 2. 7 5-, 3-, 3. 5-, 4-, 4. 5-, 5-, 5. 5-, 6- , 8-,  1 0-, 1 2-, 1 6-, a n d 2 4- h o urs f ollo wi n g 
d osi n g i n eac h tr eat me nt peri o d . T he ti me t olera nce wi n d o w f or bl o o d sa m ples will be ± 1 mi n ute 
f or all sa m ples c ollecte d before 8 h o urs p ost- d ose a n d ± 3 mi n utes f or s u bse q ue nt sa m ples. 
Sa m ples o btai ne d o utsi de t he pre- d e fi ne d ti me wi n d o ws will n ot be ca pt ure d as a pr ot oc ol 
de viati o n, as l o n g as t he e xact ti me of t he s a m ple c ollecti o n is n ote d o n t he s o urce d oc u m e nt a n d 
data  c ollecti o n t o ol (e. g. C R F). 
9. 4  
Pl as m a  P h ar m ac o ki netic P ar a meters  
Pl as ma c o nce ntrati o ns fr o m  es o me prazole  will b e use d t o calc ulate the f oll o wi n g P K para meters 
b y sta n dar d n o n- c o m part me ntal met h o ds: 
P K Para meter  
Defi niti o n  
Pri mar y P K Para meters  
A U C 0-t 
Area  u n d er t he plas ma c o nce ntrati o n vers us ti m e cur ve fr o m ti me zer o t o 
time t, w here t is t he ti me of t he last meas ura ble plas ma c o nc entrati o n of 
es o me praz ole, c o m p ute d usi n g  t he li near tra pez oi d al r ule  
C ma x  
T he  ma xi m u m  o bser v e d  p ost -d ose  c o n ce ntrati o n;  o bt ai ned  wit h o ut  
i nter p olati o n 
Se c o ndar y P K Para meters  
A U C 0- i nf 
Are a un der t he plas ma c o nce ntrati o n v ers us ti me c ur ve calc ul ate d fr o m ti me 
zer o t o i nfi nit y. A U C 0- i nf = A U C 0-t + C(t)/ λ z w here C(t) is t he c o n ce ntrati o n 
at t he last meas ura ble s a m pli n g ti me p oi nt an d λ z is t he ter mi nal eli mi nati o n 
rate c o nsta nt 
% A U C
e x 
Perce n ta ge of A U C 0- i nf o btai ne d b y e xtra p olati o n, calc ulate d as ( 1 －[ A UC 0- t 
/ A U C0- i nf] ) × 1 0 0 
tma x  
T i me of t he max i m u m o bser ve d p ost-d ose c o nce ntrati o n  
t½  
E li mi nati o n half-life c o m p ute d as t1/ 2 =  l n(2)/ λ z 
λ z 
T er mi nal eli mi nati o n rate c o nsta nt c o m p ute d as t he sl op e of t he re gressi o n 
li ne of l n ( C(t)) o n ti me. T he re gressi on s h o ul d g e nerall y i n v ol ve at least 3 
c o nsec uti ve meas ura ble c o nce ntrati o ns t hat decrease o ver ti me. 
T he a dj uste d c oeffici e nt   of deter mi nati o n ( R 2 a dj uste d) i n ge neral s h o ul d be greater t ha n 0. 8 0. 
All t he deri ve d p ara m eters ( e. g., λ z, t½ , A U C0- i nf) will be fla g g e d acc or di n gl y f or e xcl usi o n fr o m 
s um mar y statistics a n d statistical m o deli n g as a p pr o priate . T h e ti me p oi nt w here l n -li near λ z 
calc ulati o n be gi ns ( λ z l o wer), t he act ual sa m pli n g ti me of t he last q ua ntifia ble c o nce ntrati o n use d t o 
esti mate t he λ z (λ z u p per) as well as t he R 2 a dj uste d f or t he l n-li near re gressi o n f or t he calc ulati o n 
of t he eli mi nati o n rate c o nsta nt calc ulat i o n will be re p orte d. 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 2 5 of 3 2 
 
9. 5  
St atistic al  A n al yses  
T he f oll o wi n g statistical a nalys is wi ll be base d o n t he P K A nal ysis Set. 
I n di vi d ual  plas ma  c o nce ntrati o ns  will  be  s u m marize d  de scri pti vel y  at  eac h  ti me  p oi nt;  t he 
c o nce ntr ati o n vs. ti me pr ofile will be  gra p h e d  b y f or m ulati o n f or i n di vi d ual s u bjects a n d f or t he 
arit h metic mea n ( ± S D) o n b ot h ori gi nal a n d l o garit h mic scales f or t he safet y p o p ulati o n. F or eas e 
of pres e ntati o n, act u al a n d sche d ule d s a m pli n g ti mes will  be use d t o pres e nt res ults f or i n di vi d ual 
a n d mea n fi g ur es res p ecti vel y. I n di vi d ual s u bject data will als o be liste d. 
T he P K para meters ( A U C 0-t, a n d C ma x ) will be s u m marize d f or each treat me nt b y descri pti ve 
statistics. 
T h e P K para m eters ( A U C 0- i nf, % A U C
e x, λ z, tma x , a n d t1/ 2) will be s u m marize d f or eac h treat me nt 
usi n g descri pti ve statistics sa me as f or t h e pri mar y P K para meters.  
9. 6  
Assess m e nt of Bi oe q ui v ale nce  
T he pri mar y o bjecti ve will be e val uate d bas e d o n t he f oll o wi n g c o m paris o n: 
E s o me praz ole C G ( Test)  ver s us es o me praz ole A Z ( Refere n ce) , i n ter ms o f eso me p raz ole A U C 0-t 
a n d C ma x . 
A li near mi xe d effects m o del will be fit te d t o t he l o g-tra nsf or me d P K varia bles ( A U C0-t or Cma x ), 
as t he de pe n d e nt varia bl e, a n d treat me nt, se q u e nce, a nd peri o d as fi xe d effects. S u bject neste d  
wit hi n se q ue nce will be a ra n d o m e ff ect. L east s q u ares esti mates of treat me nt effects will be  
calc ulate d a n d a 9 0 % c o nfi de nce i nter val ( CI) f or t he treat me nt differe n ce will be c o m p ute d.  T he 
treat me nt differe nce an d its CI will be e x p o ne ntiate d t o o btai n t he rati o of t he ge o metric mea n s 
b et wee n t he t est a n d refere nce pr o d ucts  (test/refere nce) a n d its CI. 
Bi oe q ui vale nce will be d eclar e d f or A U C 0-t if t he 9 0 % 2-si de d CI f or t h e rati o lies c o m pletel y 
wit hi n t he ra n ge of 0. 8- 1. 2 5 a n d f or C ma x  if th e p oi nt esti mate f or t he rati o  lies c o m pletel y wi t hi n 
t he ra n ge of 0. 8- 1. 2 5. N o f urt her a dj ust me nts f or m ulti plicit y of t he c o- pri mar y e n d p oi nts are 
necessar y as b ot h e n d p oi nts m ust be met i n or der t o ac hie ve st u d y s uccess. 
T h e SA S c o de f or t he a n al ysis m o del will f oll o w t he f or mat gi ve n b el o w  (T h e i np ut varia bles ( or 
datasets) are de pi cte d i n sla nte d re d te xt a n d h a ve bee n gi ve n ge n eric n a mes).  
9. 6. 1  
Gr o u p Effect A n al ysis  
T his st u d y is pla n ne d t o d ose i n m ore t ha n 1 g r o u ps. T he gr o u p effect will b e a d de d t o t he m o del 
P P D
C CI
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 2 6 of 3 2 
 
as descri be d i n Secti o n 9. 6  base d o n t he f oll o wi n g criteria: 
•  If t he t w o gr o u ps are d os e d m ore t ha n 4 w ee ks ( 2 8 da ys) a part t he gr o u p 
a. All s u bjects ha ve bee n r ecr uite d fr o m t he sa me e nr o ll me nt p o ol (T he e nr oll me nt 
p o ol will be c o nsi dere d t he sa me if all s u bjects fr o m t he s ec o n d gr o u p are n ot 
scree n e d aft er d osi n g of t he first gr o u p). 
b.  All s u bjects ha ve si milar de m o gra p hics.  
c. T he cli nical st u d y ta kes place at o n e site. 
d.  All e nr olle d s u bjects  are ra n d o ml y assi g ne d treat me nt gr o u ps at st u d y o utset. 
Beca use t his is a si n gle ce nter st u d y wit h well -d efi ne d e nr oll me nt criteria f or s u bject i n res p ects 
t o de m o gra p hics, p oi nts B a n d C are met b y defi niti o n of t he st u d y. A si ngle ra n d o mizati o n was 
als o pr o vi de d  f or  all  s u bjects  bef ore  a n y  d osi n g f or  th e  st u d y  was  perf or me d,  i ncl u di n g  4 9  
s u bjects.  If  a d diti o nal  r a n d o mizati o n  is  re q uire d  after  d osi n g  2  gr o u ps  d ue  t o  a  lar ger  t ha n  
e x pecte d dr o p o ut rate, t his p oi nt will n ot be met a n d t he effect of gr o u p w o ul d be i ncl u de d i n t he 
statistical m o del. Other w ise, t he pri mar y criteria f or t he decisi o n of a d di n g t he gr o u p effect will 
be base d o n t he ti me bet wee n t he t w o gr o u ps a n d t he scree ni n g peri o d of all s u bjects.  
If t he gr o u p effect is deter mi ne d t o be necessar y, t he f oll o wi n g fi xe d ter ms will be inc l ude d  i n 
t he m o del: gr o u p, se q u e nce, gr o u p b y se q ue n ce, peri o d wit hi n gr o u p, a n d  treat me nt .  Th e rati o 
a n d 9 0 % CI will be cal c ulate d f or A U C 0-t a n d Cma x  as a p plica ble. 
T he S A S c o de f or t he a n al ysis m o del will f oll o w  t he f or mat gi ve n bel o w ( T he i n p ut varia bles ( o r 
d atasets) are de pi cte d i n sla nte d re d te x t a nd h a ve bee n gi ve n ge n eric n a mes).  
1 0.  
S afet y  
All safet y a nal yses will be base d o n t he Safet y P o p ulati o n. Safet y wil l be assesse d o n t he basis of  
a d verse e ve n t ( A E), cli ni cal la b orat or y data, vital si g ns, a n d ph ysical e xa mi nati o n. 
1 0. 1  A d verse E ve nts  
T he assess me nt of s afet y will be base d o n t he fre q ue nc y a n d se v erit y of A Es t hat are c ollecte d 
i m me diatel y after a s u bj ect pr o vi des c o nse nt t o partici pate i n t he st u d y b y t he c o m pleti o n 
(si g nat ure) of th e I C F a n d u ntil 5 da ys f oll o wi n g last a d mi nistrati o n of t he st u d y pr o d uct. 
Treat me nt -e mer ge nt  A Es  ( T E A Es)  a n d  n o n -T E A Es will  be  liste d   b y s u bject a n d  treat me nt . 
P P D
C CI
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 2 7 of 3 2 
 
T E A Es will be   defi ned as  a n y A Es t hat first occ urs o n or after t he dat e a n d ti me of first dr u g 
a d mi nistrati o n. A n y A E t hat first occ urs pre -d ose b ut w orse ns i n se verit y after t he first st u d y 
dr u g a d mi nistrati o n  will als o be c o nsi dere d   a T E A E. N o n -T E A Es are t h ose t ha t occ u r pri or t o 
t he first a d mi nistrati o n of t he st u d y me di cati o n a n d res ol ve d pri or t o st u d y dr u g a d mi nistrati o n or 
t hat first occ ur pri or t o t he first st u d y dr u g a d mi nistrati o n b ut d o n ot w orse n i n se v erit y aft er 
st u d y  dr u g  a d mi nistrati o n. A Es  will  be  ca pt ur e d  d uri n g  t he  st u d y  u ntil  st u d y  exit. All  A Es 
(seri o us a n d n o n-seri o us) will b e f oll o we d u ntil res ol uti o n, u ntil t he c o n diti o n sta bilizes, u ntil t he 
e ve nt is ot her wise e x pl ai ne d, or u ntil t he s u bject is l ost t o f oll o w- u p. . 
A d verse e ve nts will be c o de d usi n g t he Me d D R A
®  dicti o nar y V ersi o n 2 4. 1. T he i nci de nce o f 
A Es will be ta b ulate d  (f or eac h treat me nt ) after gr o u pi n g b y preferre d ter m wit hi n S yste m Or ga n 
Class ( S O C). A E s will be s u m marize d as t he n u m ber a n d perce nta ge of s u bjects ha vi n g a n y A E, 
a n A E b y S O C, a n d A E b y preferr e d ter m wit hi n S O C.  Treat me nt -e mer ge nt A Es will als o be 
s u m marize d b y S O C, P T, a n d ma xi m u m se verit y. T he s u bset of A Es s us pecte d of a relati o ns hi p 
t o st u d y dr u g a d mi nistrati o n (relate d: pr o b a ble, p ossi ble, re m ote, or n ot relate d: u nrel ate d) will 
be s u m marize d  si milarl y. All A Es will als o be ta b ulate d b y se verit y ( mil d, m o derate, or s e vere). 
A Es will be assi g ne d t o t he treat me nt a d mi nistere d i m me diately pri or t o t he o nset. A d vers e 
e ve nts d ue t o C O VI D- 1 9, if a n y, will be liste d a n d ta b ula te d se paratel y. 
 
T he  rel ati ons hi p of T E A Es will be classifie d acc or di n g t o t he st u d y pr ot oc ol as u n relate d  or 
relate d (re m ote, p ossi ble , or pr o b a ble) t o es o me praz ole. T h e s e verit y of T E A Es will be classifie d 
acc or di n g t o t he st u d y pr ot oc ol as mil d, m o derat e or se vere. 
I n ci de nce of s ubjects w h o e x perie nce d T E A Es  (fre q ue nc y a n d t he perce nta ge of s u bjects) will be 
prese nte d f or eac h treat me nt a n d o ver all b y: 
•  O verall s u m ma r y of T E A Es; 
•  T E A Es b y S O C  
•  T E A Es b y S O C a n d P T; 
•  T E A Es b y S O C , P T , a n d se verit y; 
•  T E A E s by S O C, P T, a n d relati o ns hi p t o t he st u d y dr u g; 
All A Es will be liste d.  A E’s t hat are seri o us, lea di n g t o deat h, lea di n g t o st u d y  disc o nti n uati o n, 
or Treat me nt E mer ge nt will be fla g ge d.   
F or t he p ur p ose of i ncl usi o n i n T E A E ta bles, t he C R F  q uesti o n “ O ns et Date a n d Ti me” o n 
“ A d vers e E ve n ts” pa g e will be c o m pare d t o t he date a n d ti me of st u d y dr u g a d mi nistrati o n, if t he 
a ns wer is n ot a v aila ble, t he i m p ute d A E o ns et date will be us e d. I n c o m plete A E o nset a n d e n d 
dates will be i m p ute d si milar t o t h ose r ul es as presente d i n Secti o n 8. 9 . A d diti o nal rules are as 
f oll o ws: 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 2 8 of 3 2 
 
If a n A E is rec or de d wit h a n o nset date c orres p o n di n g t o a st u d y dr u g a d mi nistrati o n  da y, b ut t he 
ti me is missi n g, t he n t he A E will be assi g ne d t o t he treat ment as a T E A E.  
If a n A E is rec or de d wit h a n o nset date t hat d oes n ot c orres p o n d t o t he st u d y dr u g a d mi nistrati o n  
da y, b ut t he  time is missi n g, t he n t he A E will be assi g ne d t o t he treat me nt as a T E A E if A E o nset 
date is after st u d y dr u g a d mi nistrati o n da te. 
If a n A E is rec or de d wit h a n o nset date w here da y a n d ti me are b ot h missi n g, t he n t he A E 
allocati o n t o t he treat me nt will be  d one o n a case b y case basis c o nsi deri n g a vaila ble i nf or mati o n 
(e. g., A E e n d d ate, A E c o m me nts, s u bject dis p ositi o n). 
1 0. 2  Cli ni c al L a b or at or y P ar a m eters  
La b orat or y a nal yses of bl o o d a n d uri ne sa m ples will be perf or me d b y t h e l o cal la b orat ory. 
T he f oll o wi n g cli ni cal la b orat or y assess me nts will be perf or m e d:  
C he mistr y:  
Sta n dar d ser u m ch e mistr y will be c ollecte d. T hes e i ncl u de: 
Al b u mi n, A L P,  A L T, A S T, Calci u m, C hl or ide, Creati ne ki nase, Creati ni ne, 
G G T,  Gl uc ose,  P h os p h or us,  P otassi u m,  S o di u m,  T otal  bilir u bi n,  T ot al 
pr otei n, Urea ( B U N) 
He mat ol o g y:  
Sta n dar d bl o o d He mat ol o g y  will be c ollecte d. T h ese i ncl u de:  
He mat ocrit , He m o gl o bi n, Pla telet c ou nt, R B C c o u nt, W B C c o u nt a n d 
differe ntial  ( Bas o p hils, E osi n o p hils, L y m p h oc ytes, M o n oc ytes, a n d 
Ne utr o p hils ) 
Uri nal ysis:  
St an d ar d Uri nal ysis will be c ollecte d. T his i ncl u d es : 
Bilir u bi n , Bl o o d ( occ ult), C ol or a n d a p peara nce, Gl uc ose, Ket o nes , 
Le u k o cyte  est eras e, Nitrite , p H , Pr ote in , S pecific gra vit y , a n d Ur o bili n o ge n  
L ocal 
Uri nal ysis 
( Micr osc o pic) 
Uri ne sa m ples f or Micr os co pi c ins pecti o n will be perf or me d  o nl y  i n t he 
e ve nt of a b n or mal fi n di n gs . T his will i ncl u de: 
Le u k oc ytes, Er yt hr o c ytes , E pit helial cells, a n d t he res ults, i nter pretati o n, a n d 
cli nical si g nifica nce of ( Bacteria, M uc us, or ot her) 
Cli nical  la b orat or y  testi n g  ( he ma t ol o g y,  che mistr y,  a n d  uri nal ysis)  will  be  perf or m e d  at  
scree ni n g a n d at t he E n d of St u d y visit. 
C li nical lab orat or y val ue s wi ll be fla g ge d as eit her hi g h o r l o w base d o n t he  refere n ce ra n g es 
pr o vi de d b y t he l ocal la b orat ories f or eac h la b orat or y para m eter. 
I n di vi d ual cli nical la b orat or y res ults a n d refere nce ra n ges will be prese nte d i n data listi n gs . 
1 0. 3  Vit al Si g n  Me as ure m e nts  
V ital si g ns meas ure me nts will i nclu de s yst olic a n d diast olic bl o o d press ures ( B Ps), p ulse rate  
( P R), res pirat or y r ate ( R R), a n d oral  b o d y te m perat ure ( BT) . 
Vital si g n meas ure me nts will be perf or me d at scree ni n g, B T o n Da y -1 of eac h p eri o d,   Da y 1 
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 2 9 of 3 2 
 
( wit hi n  1  h o ur  bef ore  dr u g  a d mi nistrati o n) of  eac h  tre atme nt  peri o d , B T  o n  Da y  2  of  eac h  
treatme nt peri o d ( N ote: oral b o d y te m perat ure perf or me d o n D a y 2 of Peri o d 2 ca n be use d as t he 
oral b o d y te m per at ure r e q uire d at E n d of St u d y), a n d at t he e n d of St u d y Visit. 
V ital si g ns will be s u m marize d b y ti me- p oi nt ( Overall) . S u m mar y statistics will i ncl ude mea n, 
S D , mi ni m u m, me dia n, a n d ma xi m u m. N o i n fere ntial statistics will be prese nte d. D ata will be 
liste d wit h a b n or mal val ues fla g ge d. 
1 0. 4  P h ysic al E x a mi n ati o n 
A f ull p h ysical e xa mi nati o n will be perf or me d  at scree ni ng. A brief p h ysical e xa mi nati o n  will be 
perf or me d o n Da y - 1 of eac h peri o d a n d t he E n d of St u d y visit. 
A f ull p h ysical e xa mi na ti o n will i ncl u de hea d, ears, e yes, n os e, m o ut h, s ki n, heart a n d l u n g 
e xa mi nati o ns, l y m p h n o d es, gastr oi ntesti nal, m usc ul os keletal, vasc ul ar a n d ne ur ol o gical s yste ms. 
A b rief p h ysical e xa mi nati o n will be f oc us e d o n g e n eral a p peara nce, heart  ( Car di o vasc ular), a n d  
l u n g (Res pirat or y ) fi n di n gs, as well as t o war ds s u bject re p ort e d s y m pt o ms. 
A n y   u nto war d fi n di n gs i de ntifie d o n p h ysical e xa ms c o n d ucte d after t he a d mi nistrati o n of  t he 
first stu d y dr u g a d mi nistrati o n  will be ca p t ure d as a n a d verse e v e nt, if t h ose fin di n gs meet  t he 
defi niti o n of a n a d verse e ve nt. 
1 1.  
C h a n ges fr o m t he Pr ot oc ol 
T he f oll o wi n g t e xt fr o m t he pr ot oc ol was i n cl u d e d  b y err or a n d was n ot c o nsi dere d f or t his S A P  
as baseli ne c orrecti o ns f or plas ma c o nce ntrati o n s is n ot pla n ne d: 
“Missi n g val ues of λ
z ca n be esti mate d fr o m t he s u bject’s λ z val ue fr o m t he ot her treat me nt. If a 
λ z val ue ca n n ot be cal c ulate d fr o m t he o t her treat me nt, t he n t he λz will be o btai ne d fr o m t he 
treat me nt mea n v al ue f or s u bjects wit h n o n-missi n g val ues of λ z i n t he peri o d i n w hic h it is n ot 
a vaila ble. T his esti mate d λ z ca n be use d t o calc ulat e ot her λ z de pe n de nt varia bles. T his λ z val ue 
deri vat i o n is o nl y a p plie d f or pre- d ose c o n ce ntrati o n a dj ust me nts.”.
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 3 0 of 3 2 
 
1 2.  
Refere nce List  
N o ne 
•   
P P D
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 3 1 of 3 2 
 
1 3.  
Q u alit y C o ntr ol 
S A S pr o gra ms are de vel o pe d t o pr o d u ce o ut p u ts s uc h as a nal ysis d ata sets, s u m mar y ta bles, data 
listi n gs, fi g ures or statistical a nal yses. T h ese will be de vel o pe d a n d u n der g o q ualit y c o ntr ol as 
per S O Ps  
 a n d  
 
P P D
C CI
C CI
C CI
C CI


Sta tistical A nal ysis Pla n 
G S K C o ns u mer Healt hcare 
Pr ot oc ol 2 1 8 2 4 6 ( Pr oject  
 
T his d oc u me nt is c o nfi de nt ial. 
Versi o n: Draft 1. 0 1 1- Mar - 2 0 2 2 
C o ntr olle d D oc u m e nt I D:  
, Effecti ve Date 2 9-J ul- 2 0 1 9 
Fili n g re q uire me nts: T M F  
Pa ge 3 2 of 3 2 
 
1 4.  
A p p e n dices 
N o ne 
P P D
C CI
C CI