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

Brief summary:
The objective of the study is to compare the bioequivalence of a New Paracetamol Oral Suspension 24 milligram/milliliter (mg/ml) with that of an already approved Paracetamol (24 mg/ml) Oral Suspension (Panadol Baby \& Infant) when administered to healthy volunteers under fasting condition. Pharmacokinetic parameters will be calculated from plasma concentration data. The rate and extent of absorption of the formulations will be compared.

Detailed description:
This will be a 2-arm, single center, single dose, open-label, randomized, two-sequence, two period crossover, bioequivalence study in healthy adult participants. Participants will be screened for eligibility within 15 days prior to dosing. Participants will receive each of the two study treatments in fasted state during a 6-day (5-overnight stay) residential period at the study site. Participants will receive both treatment regimens in a randomized order with a 72-hour washout period between each dose. During each treatment period, a total of 21 blood samples will be collected which will include a pre-dose blood sample 1 hour before dosing and 20 post-dose blood samples at 5, 10, 20, 30, 40, 50, 60, 80, 90, 120, 150, 180 minutes, 4, 5, 6, 8, 10, 12, 14, 16 hours, for bioanalytical analyses of paracetamol.

Arms:
arm 1: Participants will receive a single oral dose of either New Paracetamol Oral Suspension (24 mg/ml) or Panadol B\&I Oral Suspension (24 mg/ml paracetamol) on Day 1 (Period 1) and Day 4 (Period 2) under fasting conditions as per the randomization schedule. A wash out period of at least 72-hour will be maintained between each treatment period. arm 2: Participants will receive a single oral dose of either New Paracetamol Oral Suspension (24 mg/ml) or Panadol B\&I Oral Suspension (24 mg/ml paracetamol) on Day 1 (Period 1) and Day 4 (Period 2) under fasting conditions as per the randomization schedule. A wash out period of at least 72-hour will be maintained between each treatment period

Interventions: intervention 1: New Paracetamol Oral Suspension (24 mg/ml) intervention 2: Panadol B&I Oral Suspension (24 mg/ml paracetamol)
Intervention descriptions: intervention 1: After an overnight fasting for at least 10 hours, New Paracetamol Oral Suspension (24 mg/ml) in a volume of 42 ml will be administered orally via a single use syringe by a trained study person to the study participants as per the randomization schedule in each period. intervention 2: After an overnight fasting for at least 10 hours, Panadol B\&I Oral Suspension (24 mg/ml paracetamol) in a volume of 42 ml will be administered orally via a single use syringe by a trained study person to the study participants as per the randomization schedule in each period.

Protocol document:
Prot_000.pdf: 
GSK Consumer Healthcare 
Clinical Protocol 
Protocol Number: 215262  
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 v6.0 
Page 1 of 85 
CLINICAL PROTOCOL 
A RANDOMIZED, OPEN LABEL, SINGLE CENTER, SINGLE DOSE, 
TWO PERIOD, TWO SEQUENCE, CROSSOVER BIOEQUIVALENCE 
STUDY OF PARACETAMOL IN A NEW PEDIATRIC PARACETAMOL 
ORAL SUSPENSION COMPARED TO A MARKETED PARACETAMOL 
ORAL SUSPENSION (PANADOL BABY & INFANT) IN HEALTHY 
ADULT SUBJECTS 
Protocol Number: 
215262 
Quinta Study Number: 
811/20 
Compound/Product Name: 
Paracetamol 24mg/mL Strawberry oral 
suspension  
United States (US) Investigational 
New Drug (IND) Number: 
Not applicable 
European Clinical Trials Database 
(EudraCT) Number: 
2021-000900-40 
Other Regulatory Agency Identified 
Number: 
Not applicable 
Phase: 
Phase I 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0
This document contains confidentiality statements that are not relevant for this publicly
available version


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 2 of 85 
 
Sponsor Information 
Sponsor Name & Legal Registered 
Address 
 
GlaxoSmithKline Consumer 
Healthcare (UK) Trading Limited 
980 Great West Road, Brentford, 
Middlesex, TW8 9GS, United Kingdom 
 
Sponsor Contact Details 
 
GlaxoSmithKline Consumer 
Healthcare (GSKCH) 
St Georges Avenue,  
Weybridge,  
KT13 0DE, United Kingdom  
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 3 of 85 
Document History 
Document 
Version Summary of Changes  
Original protocol 
1.0 
Not applicable (N/A) 
Amendment 1 
2.0 
• Tests name in footnotes of Table 1-1 Schedule 
of Activities are made consistent with Table 9-
1 Laboratory Tests. 
• Volume of fluids (water and soup) in Table 1-2 
Schedule for all Study Periods are made 
consistent with Table 9-2 Example Standard 
Meal Composition. 
• Schedule of physical examination in Table 1-2 
Schedule for all Study Periods is made 
consistent with Section 8 Study Period. 
• Sponsor name & legal registered address in 
Sponsor Information section is made consistent 
with contracting documents. 
Amendment 2 
3.0 
• Added Schedule of Activities and Study 
Schedule tables to Section 4.1 
• Added exclusion criterion to exclude subjects 
with anemia 
• Added definition of non-childbearing potential 
• Additional editorial changes 
Amendment 3 
4.0 
• Increase minimum weight for inclusion to 60 kg 
• Section 7.1 add consideration that subjects with 
emesis shortly prior to administration may be 
withdrawn 
Amendment 4 
5.0 
• Section 1.1 Key Subject Selection Criteria, 
           weight for inclusion changed to 60 kg 
 
• Exclusion Criteria #10 change to reflect wording 
           change from “more than one” to “one or more” 
Amendments incorporate all revisions to date, including amendments made at the request of 
country health authorities, institutional review boards/ethics committees (IRBs/ECs), etc.   
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 4  of 8 5  
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 me nt t o c o nd uct t he st u d y i n c o m plia nce wit h t he 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 nt er nati o n al C o nfere n ce o n Har m o nizati o n  G o o d 
Cli nical Practice (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 verall st u d y c o n d uct. I a gree t o perso nall y c o n d uct 
or s u per vise t he d escri be d st u d y.  
•  I a gree t o e ns ur e t hat all ass ociates, c ollea g ues 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 me d a b o ut t heir o bli gati o ns. Mec ha nis ms are i n place t o e ns ure site staff 
recei v es all a p pr o priate i nf or mati 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 nce wit h t he la ws a n d re g ulati o ns of t he c o u ntr y 
i n w hic h t he researc h is c o n d ucte d a n d t he Declarati o n of Helsi n ki. 
 
I n v esti gat or Na me: 
 
I n v esti gat or Q ualificati o ns:  
M. D., P h. D.  
I n v esti gat or Si g nat ure: 
Date of Si g nat ure/ A gree me nt:  
 
 
 
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P P D


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 5 2 6 2   
 
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 6. 0  
Pa ge 5  of 8 5  
S P O N S O R SI G N A T U R E S  
 
 
A R A N D O MI Z E D, O P E N L A B E L, SI N G L E C E N T E R,  SI N G L E D O S E, T W O 
P E RI O D, T W O S E Q U E N C E , C R O S S O V E R BI O E Q UI VA L E N C E S T U D Y O F 
P A R A C E T A M O L I N 
A 
N E W  P E DI A T RI C 
P A R A C E T A M O L 
O R A L 
S U S P E N SI O N C O M P A R E D T O A  M A R K E T E D P A R A C E T A M O L  O R A L 
S U S P E N SI O N ( P A N A D O L B A B Y 
& I N F A N T) I N 
H E A L T H Y 
A D U L T 
S U BJ E C T S  
 
 
S p o ns or Pr ot oc ol N u m ber:  
 
2 1 5 2 6 2  
Q ui nt a St u d y N u m ber:  
 
8 1 1/ 2 0  
E u dr a C T n u m ber : 
2 0 2 1 -0 0 0 9 0 0 -4 0  
I here b y decl are t h at I h a ve re vie we d t his st u d y pr ot oc ol  
 a n d t h at I a p pr o ve its c o nte nt  
 
 
Vice Presi de nt,  Cli nical De vel o p me nt ,  
G S K C H  
 
 
 
 
 
 
Date  
(S p o ns or’s Re prese nt ati ve ) 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
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P P D
P P D
P P D


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 6 of 85 
Table of Contents 
Sponsor Information ............................................................................................................ 2 
Document History ............................................................................................................... 3 
Principal Investigator Protocol Agreement Page ................................................................ 4 
Table of Contents ................................................................................................................ 6 
CONTACT INFORMATION .................................................................................................. 11 
1 
PROTOCOL SUMMARY ................................................................................................ 13 
1.1 
Synopsis ................................................................................................................. 13 
1.2 
Schedule of Activities ............................................................................................ 22 
2 
INTRODUCTION ............................................................................................................. 27 
2.1 
Study Rationale ...................................................................................................... 27 
2.2 
Background ............................................................................................................ 27 
2.3 
Benefit/Risk Assessment ....................................................................................... 28 
2.4 
Mechanism of Action/Indication ........................................................................... 28 
3 
STUDY OBJECTIVES AND ENDPOINTS .................................................................... 28 
4 
STUDY DESIGN .............................................................................................................. 29 
4.1 
Overall Design ....................................................................................................... 29 
4.2 
Scientific Rationale for Study Design ................................................................... 34 
4.3 
Justification for Dose ............................................................................................. 34 
4.3.1 
Medications and Treatment ................................................................... 34 
4.4 
End of Study Definition ......................................................................................... 35 
5 
STUDY POPULATION .................................................................................................... 35 
5.1 
Type and Planned Number of Subjects ................................................................. 35 
5.2 
Inclusion Criteria ................................................................................................... 35 
5.3 
Exclusion Criteria .................................................................................................. 36 
5.4 
Randomization Criteria .......................................................................................... 39 
5.5 
Lifestyle Considerations ........................................................................................ 39 
5.5.1 
Meals and Dietary Restrictions ............................................................. 39 
5.5.2 
Alcohol, Caffeine and Tobacco............................................................. 39 
5.5.3 
Activity .................................................................................................. 40 
5.5.4 
Contraception ........................................................................................ 40 
5.6 
Screen Failures....................................................................................................... 41 
5.7 
Sponsor’s Qualified Medical Personnel ................................................................ 41 
5.8 
Rater/Clinical Assessor Qualifications .................................................................. 41 
6 
STUDY PRODUCTS ........................................................................................................ 41 
6.1 
Study Product Supplies .......................................................................................... 42 
6.1.1 
Dosage Form and Packaging ................................................................. 44 
6.1.2 
Preparation and Dispensing................................................................... 44 
6.2 
Administration ....................................................................................................... 45 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 7 of 85 
6.2.1 
Medication/Dosing Errors ..................................................................... 45 
6.2.2 
Overdose ............................................................................................... 45 
6.3 
Investigational/Study Product Storage .................................................................. 46 
6.4 
Investigational/Study Product Accountability ....................................................... 46 
6.4.1 
Destruction of Investigational/Study Product Supplies ........................ 47 
6.5 
Blinding and Allocation/Randomization ............................................................... 47 
6.6 
Breaking the Blind ................................................................................................. 47 
6.7 
Compliance ............................................................................................................ 48 
6.8 
Concomitant Medication/Treatment(s) .................................................................. 48 
6.9 
Rescue Medication................................................................................................. 48 
7 
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL. ........................................................................ 48 
7.1 
Subject Discontinuation/Withdrawal ..................................................................... 48 
7.2 
Lost to Follow up ................................................................................................... 49 
8 
STUDY PROCEDURES ................................................................................................... 50 
8.1 
Screening ............................................................................................................... 50 
8.1.1 
Informed Consent .................................................................................. 50 
8.1.2 
Demographics ....................................................................................... 51 
8.1.3 
Medical History ..................................................................................... 51 
8.1.4 
Prior Medication/Treatment .................................................................. 51 
8.1.5 
Physical Examination ............................................................................ 51 
8.1.6 
Height and Weight ................................................................................ 51 
8.1.7 
Vital Signs ............................................................................................. 51 
8.1.8 
Body Temperature ................................................................................. 51 
8.1.9 
Screening Procedures ............................................................................ 51 
8.1.10 
Inclusion/Exclusion Criteria ................................................................. 52 
8.1.11 
Subject Eligibility ................................................................................. 52 
8.2 
Study Period .......................................................................................................... 52 
8.2.1 
Day -1 .................................................................................................... 52 
8.2.2 
Day 1 ..................................................................................................... 53 
8.2.3 
Day 2 ..................................................................................................... 53 
8.2.4 
Washout................................................................................................. 54 
8.2.5 
Day 4 ..................................................................................................... 54 
8.2.6 
Day 5 ..................................................................................................... 55 
8.3 
End of Study /Day 5 .............................................................................................. 55 
8.4 
Follow-up Visit ...................................................................................................... 55 
9 
STUDY ASSESSMENTS ................................................................................................. 55 
9.1 
Screening Assessments .......................................................................................... 56 
9.2 
Efficacy Assessments ............................................................................................ 56 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 8 of 85 
9.3 
Safety and Other Assessment ................................................................................ 56 
9.3.1 
Laboratory Tests.................................................................................... 56 
9.3.2 
Pregnancy Testing ................................................................................. 58 
9.3.3 
Physical Examination ............................................................................ 58 
9.3.4 
Height, Weight and BMI ....................................................................... 58 
9.3.5 
Blood Pressure and Pulse Rate .............................................................. 59 
9.3.6 
Respiratory Rate .................................................................................... 59 
9.3.7 
Body Temperature ................................................................................. 59 
9.3.8 
COVID-19 Test ..................................................................................... 59 
9.3.9 
Electrocardiogram ................................................................................. 60 
9.3.10 
Virology ................................................................................................ 60 
9.3.11 
Urine illicit drug screen ......................................................................... 61 
9.3.12 
Urine cotinine level ............................................................................... 61 
9.3.13 
Alcohol test ........................................................................................... 61 
9.4 
Standard Meals ...................................................................................................... 61 
9.5 
Pharmacokinetics (PK) .......................................................................................... 62 
9.5.1 
Plasma for Analysis of Paracetamol ..................................................... 62 
9.5.2 
Sample Handling ................................................................................... 63 
9.6 
Blood Volume ........................................................................................................ 63 
10 ADVERSE EVENT AND SERIOUS ADVERSE EVENTS ........................................... 64 
10.1 
Definition of an Adverse Event (AE) .................................................................... 64 
10.2 
Definition of a Serious Adverse Event (SAE) ....................................................... 65 
10.3 
Time Period and Frequency for Collecting AE and SAE Information .................. 66 
10.4 
Reporting Procedures............................................................................................. 66 
10.4.1 
Reporting of an Adverse Event ............................................................. 67 
10.4.2 
Reporting of a Serious Adverse Event .................................................. 67 
10.5 
Evaluating Adverse Events .................................................................................... 68 
10.5.1 
Assessment of Intensity ........................................................................ 68 
10.5.2 
Assessment of Causality- ...................................................................... 68 
10.6 
Follow-up of AEs and SAEs.................................................................................. 69 
10.7 
Withdrawal Due to an Adverse Event ................................................................... 70 
10.8 
Regulatory Reporting Requirements for SAEs...................................................... 70 
10.9 
Pregnancy .............................................................................................................. 70 
10.9.1 
Time Period for Collecting Pregnancy Information.............................. 70 
10.9.2 
Action to be Taken if Pregnancy Occurs .............................................. 70 
11 DATA MANAGEMENT .................................................................................................. 71 
11.1 
Case Report Form .................................................................................................. 72 
11.2 
Data Handling ........................................................................................................ 72 
11.2.1 
Data Queries .......................................................................................... 72 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 9 of 85 
11.3 
Processing Patient Reported Outcomes ................................................................. 73 
11.4 
External Data ......................................................................................................... 73 
11.5 
Subject Cards ......................................................................................................... 73 
11.6 
Subject Data Forms................................................................................................ 73 
12 STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................. 73 
12.1 
Sample Size Determination ................................................................................... 73 
12.2 
Populations for Analysis ........................................................................................ 74 
12.3 
Statistical Analyses ................................................................................................ 74 
12.3.1 
Primary Analysis(es) ............................................................................. 74 
12.3.2 
Secondary Analysis(es) ......................................................................... 75 
12.3.3 
Safety Analysis(es)................................................................................ 76 
12.3.4 
Exclusion of Data from Analysis .......................................................... 76 
12.3.5 
Demographic and Baseline Characteristics ........................................... 77 
12.3.6 
Study Drug/Product Compliance and Use of Other Therapies ............. 77 
12.3.7 
Handling of Dropouts and Missing Data .............................................. 77 
12.3.8 
Interim Analysis .................................................................................... 77 
13 STUDY GOVERNANCE CONSIDERATIONS.............................................................. 77 
13.1 
Quality Control ...................................................................................................... 77 
13.2 
Quality Assurance .................................................................................................. 78 
13.3 
Regulatory and Ethical Considerations ................................................................. 78 
13.3.1 
Institutional Review Board/ Ethics Committee..................................... 78 
13.3.2 
Ethical Conduct of the Study ................................................................ 78 
13.3.3 
Subject Information and Consent .......................................................... 79 
13.3.4 
Subject Recruitment .............................................................................. 79 
13.3.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP ............................................................................................... 79 
13.4 
Posting of Information on Publicly Available Clinical Trial Registers ................. 80 
13.5 
Provision of Study Results to Investigators ........................................................... 80 
13.6 
Records Retention .................................................................................................. 80 
13.7 
Conditions for Terminating the Study ................................................................... 81 
14 Facilities ............................................................................................................................ 81 
15 Competent Authority and Ethics Committee .................................................................... 82 
16 Insurance............................................................................................................................ 82 
17 REFERENCES .................................................................................................................. 82 
18 APPENDICIES.................................................................................................................. 83 
18.1 
ABBREVIATIONS ............................................................................................... 83 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 10 of 85 
List of in text tables 
Table 1-1 
Schedule of Activities ........................................................................... 23 
Table 1-2  
Schedule for all Study Periods .............................................................. 25 
Table 3-1 
Study Objectives and Endpoints ........................................................... 28 
Table 4-1 
Schedule of Activities ........................................................................... 30 
Table 4-2 
Timing Schedule for All Study Periods ................................................ 32 
Table 6-1 
Investigational/Study Product Supplies ................................................ 43 
Table 6-2 
Sundry Items ......................................................................................... 44 
Table 9-1 
Laboratory Tests.................................................................................... 57 
Table 9-2  
Example Standard Meal Composition .................................................. 62 
Table 9-2 
Blood Volume ....................................................................................... 63 
Table 18-1 
Abbreviations ........................................................................................ 83 
 
 
 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 1 5 2 6 2   
 
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  
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Pr o pert y of G S K C o ns u mer Healt hcare  - C o nfi de ntial   
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Pr ot oc ol N u m ber : 2 1 5 2 6 2   
 
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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  
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S y n o p si s  
Na me of S p o ns or  
Gla x o S mit h Kli ne C o ns u mer Healt hcare ( G S K C H)  
St u d y Title  
A Ra n d o mize d, O pe n La bel, Si n gle Ce nter, Si n gle d ose, T w o Peri o d, T w o 
Se q ue nce, Cr oss o v er Bi o e q ui vale nce  St u d y of Paraceta m ol i n a n e w Pe di atric  
Paracet a m ol  Oral  S us pe nsi o n C o m pare d t o a 
Mar kete d Paracet a m ol O ral 
S us pe nsi o n ( Pa n a d ol Ba b y  & I nfa nt ) i n Health y A d ult S u bjects  
S h ort Title  
A bi oe q ui vale nce st u d y of a ne w paraceta m ol oral s us pe nsi o n c o m pare d t o t he 
mar kete d paraceta m ol oral s us pe nsi o n ( Pa na d ol Ba b y a n d I nfa nt , a b bre vi ate d 
Pa na d ol B &I ). 
St u d y 
I d e ntificati o n  
E u dra C T N o.: 2 0 2 1 -0 0 0 9 0 0 -4 0  
S p o ns or’s  Pr ot oc ol N o.: 2 1 5 2 6 2    
 
Site  
 
 
Cli nical P hase  
P hase I ( Bi oe q ui vale nce)  
St u d y O bjecti ves  
T he pri m ar y o bjecti ve is:  
•  T o de m o nstrate bi oe q ui v ale nce of paraceta m ol i n a ne w p araceta m ol 
oral s us pe nsi o n v ers us a mar kete d paraceta m ol 
oral s us pe nsi o n 
(Pa na d ol B &I )  
T he sec o n d ar y o bjecti v e is:  
•  Assess t he p har mac o ki n etic pr ofile of  ne w a n d mar kete d paraceta m ol 
oral s us pe nsi o n  
St u d y Desi g n  
T his is a 2 -ar m, si n gl e ce nter, si n gle d os e, o p e n -la bel, ra n d o mize d, t w o-
se q ue nce, t w o-p eri o d cr oss o ver, bi oe q ui val e nce st u d y i n healt h y a d ult s u bjects, 
se parat e d b y o ne  was h -o ut peri o d of at least 7 2 h o urs . 
St u d y M e dicati o n  
Test:  
Na me:  
N e w paraceta m ol oral s us pe nsi o n 
Acti ve i n gre die nt:  
Paracet a m ol  
D osa ge f or m:  
O ral s us pe nsi o n 
Stre n gt h:  
2 4 m g/ ml paraceta m ol  
D ose:  
4 2 m L ( 1 g p araceta m ol)  
R o ute of a d mi nistrati o n:  
O ral 
M A H:  
G S K C H, Fi nla n d   
Ma n ufact ur er:  
G S K C H,  N y o n , S witzerl a n d  
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
P P D
P P D


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 14 of 85 
Reference: 
Name: 
Marketed paracetamol oral suspension (Panadol 
B & I, Marketed as Panadol pro děti jahoda 
perorální suspenze) 
Active ingredient: 
Paracetamol 
Dosage form: 
Oral suspension 
Strength: 
24 mg/ml paracetamol Dose: 
42 
mL 
(1g 
paracetamol) 
Route of administration: 
Oral 
Strength: 
24 mg/ml paracetamol 
MAH: 
GSKCH, Czech Republic 
Manufacturer: 
Farmaclair (a contract manufacturing organization, 
under GSKCH), France  
Source market: 
Czech Republic 
Dose 
Single oral dose of Test Product (new paracetamol oral suspension) or 
Reference Product (Panadol B & I) will be administered to all subjects in each 
study period. The administration will proceed according to the randomization 
schedule. 
Number of Subjects Approximately 110 subjects will be screened to randomize approximately 37 
healthy adult subjects to ensure at least 31 evaluable subjects complete the 
entire study. In addition, two (2) overnight stand-by subjects will be confined 
until the first dosing as a reserve for pre-dose dropouts. 
Subjects Evaluated All randomized subjects who complete the two periods and who have no major 
protocol deviations concerning pharmacokinetics. Subjects with baseline* 
paracetamol concentration > 5% of the individual Cmax for either period will be 
excluded from PK population. 
*Baseline is defined as the last available value before dosing.  
Key 
Subject 
Selection Criteria 
Approximately 37 healthy adult males and female ≥ 18 and ≤ 45 years of age 
(on the day of Informed Consent), with body-mass index (BMI) ≥ 18.5 and ≤ 
30 kg/m2 and body weight above 60 kg (on the day of screening). 
Sampling Schedule Blood will be sampled regularly at scheduled times for 16 hours post-dose. 
Blood collections will be performed prior to the administration of study 
medication (-1.00) and 5, 10, 20, 30, 40, 50, 60, 80, 90, 120, 150, 180 minutes , 
and  4.00, 5, 6, 8, 10, 12, 14 and 16 hours after drug administration. Total 
number of blood collections in each Study Period will be 21.  
Inclusion Criteria 
1. Subject provision of a 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. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 1 5  of 8 5  
2.  S u bject is m ale or fe male  
3.  S u bject is 1 8 t o 4 5  years of a ge i ncl usi ve, at t he si g ni n g of t he i nf or me d c o nse nt.  
4.  A s u bject w h o is willi n g a n d a ble t o c o m pl y wit h sc he d ule d visits, treat me nt pla n, la b orat or y 
tests, st u d y restricti o ns a n d ot her st u d y pr oce d ures. 
5.  A s u bject  i n g o o d ge neral a n d me ntal healt h wit h, i n t he o pi ni o n of t he i n vesti gat or or me dicall y 
q ualifie d  desi g nee, as det er mi ne d b y me dical e val uati o n, i ncl u di n g me dical hist or y, f ull p h ysical 
e x a mi nati o n, i ncl u di n g bl o o d press ur e a n d p uls e rate meas ure m e nt, 1 2 -lea d E C G or cli nical 
la b orat or y tests 
6.  A s u bject wit h a B o d y M ass I n de x ( B MI) of 1 8. 5  t o 3 0 k g/ m 2; a n d a t otal b o d y wei g ht >6 0  k g  
7.  Fe male s u bjects of c hil d beari n g p ote ntial a n d at ris k f or pre g na nc y m ust a gree t o use a hi g hl y 
effecti ve met h o d of c o ntrace pti o n t hr o u g h o ut t h e st u d y a n d f or 7 da ys after t he last d os e of 
assi g ne d treat me nt.  Fe male s u bjects w h o are n ot of c hil d beari n g p ote ntial 
m ust 
meet 
re q uire me nts i n 
 
8.  S u bject wit h t w o c o nsec uti ve ne gati ve tests f or acti ve C O VI D -1 9 , se p arat e d b y > 2 4 h o urs. 
9.  Czec h cit ize ns hi p 
E xcl usi o n Criteri a  
1.  A s u bject w h o is a n e m pl o yee of t he i n vesti gati o n al site, eit her directl y i n v ol ve d i n t he c o n d uct 
of t he st u d y or a me m ber of t heir i m me diate fa mil y; or a n e m pl o yee of t h e i n vesti gati o nal site  
ot her wise s u per vise d b y t he i n vesti gat or; or, a G S K C H e m pl o yee directl y i n v ol ve d i n t he 
c o n d uct of t he st u d y or a me m ber of t heir i m me diate fa mil y.  
2.  A s u bject w h o h as partici pate d i n ot her st u dies (i ncl u di n g n o n -me dici nal st u dies) i n v ol vi n g 
i n vesti gati o nal pr o d uct(s) wit hi n 3 0 da ys b ef ore d osi n g.  
3.  A s u bject wit h , i n t he o pi ni o n of t he i n vesti gat or or me dicall y q ualifie d  d esi g nee,  a n ac ute or 
c hr o nic me dical or ps yc hiatric c o n diti o n or la b orat or y a b n or m alit y t hat ma y i ncreas e t he ris k 
ass ociate d wit h st u d y p a rtici pati o n or i n vesti gati o nal pr o d uct a d mi nistrati o n or ma y i nterfere 
wit h t he i nter pretati o n of st u d y res ults a n d, i n t he j u d g me nt of t h e i n vesti gat or or me di call y 
q ualifie d desi g nee, w o ul d ma ke t he s u bject i na p pr o priate f or e ntr y i nt o t his st u d y.  
4.  A s u bj ect w h o is pre g na nt as c o nfir me d b y a p ositi ve h C G la b orat or y test or i nte n di n g t o bec o me 
pre g na nt o ver t he d urati o n of t he st u d y.  
5.  A s u bject w h o is breastfee di n g.  
6.  A s u bject wit h k n o w n or s us pecte d i nt olera nce or h y perse nsiti vit y t o t he st u d y m aterials ( or 
cl osel y relate d c o m p o u n ds) or a n y of t heir state d i n gre di e nts. T his i ncl u des paraceta m ol a n d 
e x ci pie nts i n t he pr o d ucts e. g. s or bit ol, maltit ol gl ycer ol etc.  
7.  A s u bject u n willi n g or u na ble t o c o m pl y wit h Lifest yl e C o nsi derati o ns  (Secti o n 5. 5  of pr ot oc ol) 
de scri be d i n t his pr ot oc ol. 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
C CI


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 16 of 85 
8. Diagnosis of long QT syndrome or QTc > 450 msec for males and > 470 msec for females at 
screening. 
9. A subject with 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.  
10. 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) or urea (≥8.9 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 one or more of the following lab value deviations 
are found: 1) AST/SGOT (≥ 1.2 ULN), ALT/SGPT (≥ 1.2 ULN), 2) GGT (≥ 1.2 ULN), ALP 
(≥ 1.2 ULN), 3) bilirubin (≥ 1.2 ULN) or CK (≥ 3 ULN); 
• Evidence of urinary obstruction or difficulty in voiding at screening. 
• History or clinical evidence at screening of pancreatic injury or pancreatitis 
11. A subject with history of regular 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 
12. 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) 
13. Positive results in any of the virology tests for HIV-Ab, HCV-Ab, HBsAg and HBc-Ab (IgG + 
IgM)  
14. 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. 
15. 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 
16. A subject who has previously been enrolled in this study. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 17 of 85 
17. A subject who, in the opinion of the investigator or medically qualified designee, should not 
participate in the study 
18. Use of any medication (including over-the-counter medications, vitamins, herbal remedies, 
dietary supplements) within 2 weeks prior to admission to the unit 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: 
a. systemic contraceptives and hormone replacement therapy, as long as female subject is on 
stable treatment for at least 3 months and continues treatment throughout the study; 
b. occasional use of ibuprofen 200 mg (up to 1200 mg daily) or equivalent analgesic 
19. 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. 
20. Sitting blood pressure after a minimum of 5 minutes of rest is out of the range of 90-140 mmHg 
for systolic BP and/or 60-90 mmHg for diastolic BP and/or heart rate out of the range of 50-100 
bpm during the screening procedure. 
21. Body temperature is consistently out of the range of 35.4-37.3°C at screening, at check-in or 
during the study. 
22. Anemia, defined as level of hemoglobin in women below 120 g/L and in men below 130 g/L at 
screening 
23. Clinically relevant chronic or acute infectious illnesses or febrile infections within 2 weeks prior 
to screening till admission to the unit 
24. A subject with a positive urine drug screen, alcohol breath test at screening and on day of 
admission to the unit 
25. Smokers, defined as the use of tobacco products during the 3 months prior to screening till 
admission to the unit or a positive urine cotinine test at screening 
26. Performance of strenuous physical exercise (body building, high performance sports) from 2 
weeks prior to admission to the unit 
27. Donation or loss of at least 500 mL of blood within 90 days or any donation of plasma or platelets 
from 2 weeks prior to admission to the unit 
28. Getting a tattoo, body piercing or any cosmetic treatment involving skin penetration within 90 
days before the screening till admission to the unit, unless evaluated by Investigator as non-
significant for inclusion in the study 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 18 of 85 
29. Subject with signs and symptoms suggestive of COVID-19 (i.e. fever, cough, etc.)1 from 2 weeks 
prior to screening till admission to the unit 
30. Subject with known COVID-19 positive contacts in the past from 2 weeks prior to screening till 
admission to the unit 
31. Subjects who were hospitalized for COVID-19 related reasons 
Screening  
Medical history, physical examination, COVID-19 test, 12-lead ECG, clinical 
chemistry, urinalysis, haematology, viral serology, blood pregnancy test for 
females, urinary drug screen, measurement of height and weight (includes 
calculation of BMI), coagulation, serum FSH if applicable, vital signs 
measurement, body temperature, alcohol breath test, urinary cotinine test. 
Total 
Blood 
Volume Taken 
+ 11.5 mL for screening 
+ 21 (samples) x 2 (study periods) x 2 mL = 84 mL 
+ 20 (catheter purge) x 2 (study periods) x 2 mL = 80 mL 
+ 11.5 mL at end of study visit  
= 187 mL of blood in total 
About 20 mL of blood can be additionally withdrawn if repeated laboratory 
tests will be required during screening or follow-up. If one or more blood 
collections must be repeated during the study, it may be necessary to withdraw 
additional amount of blood. The reason for such additional blood collections 
must be justified by Investigator. 
Vital Signs (Blood 
pressure, heart rate, 
respiratory rate) 
 
Body temperature 
Vital signs will be monitored during screening procedures, check-in, prior to 
dosing (-1.00) and at 2.00, 4.00, 12 and 24 hours after IMP administration in 
each Study Period, every day during the subjects’ stay in clinical unit (including 
at -12:00 hour before second dose) and at exit examination.  
Body temperature will be measured during screening, check-in, twice a day 
during the subjects’ stay in clinical unit, and at exit examination. 
Query on AE 
Query on AE will be performed during check-in and every day during 
hospitalization.  
Exit Procedures 
Physical examination, measurement of body mass, vital signs, body 
temperature, COVID-19 test, and the same hematology, coagulation, urinalysis 
and clinical chemistry tests as the screening ones except for the HBsAg, HCV, 
HIV tests, serum FSH, urinary drug abuse test, cotinine test and alcohol breath 
test and pregnancy test for women. 
                                                 
 
1 as defined by WHO or local guidance 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 1 9  of 8 5  
Sc he d ule 
of 
t he 
E ve nts  
See Ta ble 1 -1  Sc h e d ule of Acti vities  
Cli nical Pr oce d ures 
d uri n g 
C o nfi ne me nt  
See Ta ble 1 -2 Sc h e d ule f or all St u d y Peri o ds  
Was h o ut  
At least 7 2  h o urs  bet wee n t he d oses  
Sa m ple Ha n dli n g  
See Sa m ple Ha n dli n g Ma n ual  
St ora ge of Sa m ples  Plas ma sa m ples will be st ore d at te m perat ure ≤ -2 0° C.  
A nal ytical Met h o d  T he Bi oa nal ytical La b orat or y of 
 will a nal yz e 
plas ma  sa m ples usi n g v ali date d met h o d. 
T he l o wer li mit of q ua ntificati o n ( L L O Q):  
•  P aracet a m ol   
 
 
0. 2 5 µ g/ m L of plas ma  
P har mac o ki netic 
Para meters 
E val uate d  
A U C 0 -tlast, tma x , C ma x , A U C 0 -i nf, % A U C
e x, λ z 
Pri mar y e n d p oi nts  •  A U C 0 -tlast (T he area u n der t he pl as ma c o n ce ntr ati 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 sa m pli n g ti me p oi nt, t, 
c o m p ute d usi n g t he li near tra pez oi dal r ule)   
•  tma x  ( T he ti me of t he ma xi m u m obser ve d p ost -d ose c o nce ntrati o n)  
•  C ma x ( T he ma xi m u m o bser ve d p ost-d ose c o nce ntr ati o n)  
Sec o n dar y  
e n d p oi nts  
•  A U C 0 -i nf ( T he area u n d er t he plas ma c o nce ntr ati 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 C 0 -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 h e l ast meas ura ble sa m pli n g ti me p oi nt a n d λz is t he 
ter mi nal eli mi nati o n rate c o nsta nt) 
•  % A U C
e x ( Perce nt a ge of A U C0 -i nf o btai ne d b y e xtra p olati o n, calc ulate d as 
( 1－ [ A U C0 -t / A U C0 -i nf]) × 1 0 0) 
•  λ z ( T h e ter mi nal eli mi nati o n rate c o nsta nt c o m p ute d as t he sl o pe of t he 
re gressi o n li ne of l n ( C(t)) o n ti me. T he re gressi o n s h o ul d ge n erall y i n v ol ve 
at least 3 c o nsec uti ve meas ura ble c o nce ntr ati o ns t hat decrease o v er ti me)  
C o m paris o n of Test 
a n d  
Refere nce 
Pr o d ucts  
•  T he rati o of t he ge o metri c least s q uare mea ns b et wee n t he test a n d 
refere nce a n d its 9 0 % c o nfi de nce i nter vals ( CIs) of A U C 0 -tlast a n d C ma x  
will be calc ulate d.   
•  Me dia n differe n ces bet w ee n t he test a n d refere n ce a n d its 9 0 %  CI  of t ma x 
will be calc ulate d. 
T his st u d y will be c o nsi d ere d s u ccessf ul if bi oe q ui vale nce b et wee n treat me nts 
c o ncl u des t hat t he 9 0 % CIs f or t he rati o of t he mea ns of A U C 0 -tlast a n d C ma x  of 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
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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 5 2 6 2   
 
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 6. 0  
Pa ge 2 0  of 8 5  
t he paraceta m ol pr ofiles lie c o m pletel y wit hi n t he ra n ge 0. 8-1. 2 5 , a n d if t here 
is n o differe n ce bet w ee n t he t w o treat me nts i n ter ms of tma x . 
 
S h ort Titl e:   
A bi oe q ui vale n ce  st u d y of a n e w p araceta m ol oral s us pe nsi o n 2 4 m g/ ml c o m pare d t o  t h e 
mar kete d paracet a m ol oral s us pe nsi o n ( Pa na d ol Ba b y a n d I nfa nt  2 4 m g/ ml ) i n healt h y a d ult 
s u bjects. 
B a c k gr o u n d a n d R ati o n al e : 
Paracet a m ol 2 4 m g/ ml Stra w berr y oral s us pe nsi o n is a ne wl y de vel o p e d 
 
 f or m ulati o n w hic h is e x pecte d t o re place t he e xisti n g p araceta m ol  2 4  m g/ ml  
oral s us pe nsi o n ( Pa na d ol B &I) f or p e diatric use. A c o m parati ve diss ol uti o n st u d y has bee n 
perf or me d , w h os e res ults c o nfir m e d t hat Pa na d ol B &I a n d ne w p araceta m ol s us pe nsi o n ha ve 
si milar i n vitr o release c haract eristics. 
 
 
. I n or der t o s u p p ort t he Mar keti n g A ut h orizati o n A p plicati o n of t he ne w 
oral s us pe nsi o n i n t he sa me i n dicati o ns, bi oe q ui vale nce s h o ul d be de m o nstrate d wit h t he 
a p pr o ve d p araceta m ol ( 2 4 m g/ ml)  oral s us pe nsi o n ( Pa na d ol B &I). 
O bj e cti v e s a n d E n d p oi nt s : 
O bj e cti v e( s)  
E n d p oi nt( s)  
Pri m ar y   
•  
T o 
de m o nstrate  bi oe q ui vale nce  of 
paraceta m ol i n  a ne w paraceta m ol oral 
s us pe nsi o n  
vers us 
a 
mar kete d 
paraceta m ol oral s us pe nsi o n (Pa na d ol 
B &I )  
•  A U C 0 -tlast (T he area u n d er t he plas ma 
c o nce ntr ati 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 sa m pli n g ti me p oi nt, t, 
c o m p ute d usi n g t he li near tra pez oi dal 
r ule)  
•  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)  
•  C ma x  ( T he 
ma xi m u m o bser ve d p ost-
d ose c o nce ntrati o n)  
S e c o n d ar y  
•  Assess t he p har mac o ki n etic pr ofile of  
ne w a n d 
mar kete d paraceta m ol oral 
s us pe nsi o n  
•  A U C 0 -i nf ( T he area u n d er t he plas ma 
c o nce ntr ati 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 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 m e 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 nt a ge 
of 
A U C0 -i nf 
o btai ne d b y e xtra p olati o n, calc ulate d 
as ( 1－ [ A U C0 -t / A U C0 -i nf]) ×1 0 0)  
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
C CI
C CI


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Protocol Number: 215262  
 
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May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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• 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) 
Safety 
Assess the safety profile of both products  
• AEs (Adverse events), vital signs and 
clinical safety laboratory test results 
Study Design: 
This will be a 2-arm, single center, single dose, open-label, randomized, two-sequence, two-
period crossover, bioequivalence study in healthy adult subjects. 
Subjects will be screened for eligibility within 15 days prior to dosing. Subjects will receive 
each of the two study treatments in fasted state during a 6-day (5-overnight stay) residential 
period at the study site. Subjects will receive each treatment in a randomized order with a 
washout period of at least 72-hour between doses. During each treatment period, subjects will 
provide a pre-dose blood sample 1 hour before dosing and 20 post-dose blood samples at 5, 10, 
20, 30, 40, 50, 60, 80, 90, 120, 150, 180 minutes, 4, 5, 6, 8, 10, 12, 14, 16 hours, for bioanalytical 
analyses of paracetamol. 
Study Products: 
 
Test Product 
Reference Product 
Product 
New 
paracetamol 
oral 
suspension  
(24 mg/ml paracetamol) 
Panadol B&I 
(24 mg/ml paracetamol) 
Dose 
42 mL (1g paracetamol) 
42 mL (1g paracetamol) 
Route of administration 
Oral 
Oral 
Marketing Authorization 
Holder & Source market  
GSKCH, Finland 
GSKCH, Czech Republic (CZ) 
Type and Planned Number of Subjects: 
Approximately 110 subjects will be screened to randomize approximately 37 healthy adult 
subjects to ensure at least 31 evaluable subjects complete the entire study. In addition, two (2) 
overnight stand-by subjects will be confined until the first dosing as a reserve for pre-dose 
dropouts. 
Statistical Methods: 
The bioequivalence between a new paracetamol oral suspension (Test) and the marketed 
paracetamol oral suspension (Panadol B&I) (Reference) in fasted state will be assessed on the 
PK population:  
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• If the 90% confidence intervals (CIs) for the ratio of the means of the primary 
pharmacokinetic parameters, AUC0-tlast and Cmax of the paracetamol profiles lie 
completely within the range 0.8-1.25.  
• If there is no difference between the two treatments in terms of tmax.  
An Analysis of Variance (ANOVA) model will be fitted to the log-transformed PK variables 
(AUC0- tlast and Cmax), as the dependent variable, and treatment, period, sequence and subject 
nested within sequence as fixed effects. For each pairwise comparison, only the data from the 
two corresponding treatments will be included in the model. The presence of a statistically 
significant sequence effect will be noted, and its implications will be discussed. Least squares 
estimate of treatment effects will be calculated and a 90% confidence interval (CI) for the 
treatment difference will be computed. The treatment difference and its CI will be exponentiated 
to obtain the ratio of the geometric least square means between the test and reference and its CI. 
Bioequivalence will be determined if the 90% CI for the treatment geometric least square mean 
ratio lies completely within the range 0.80 – 1.25.  
tmax will be analyzed nonparametrically using Wilcoxon signed-rank test. Median of differences 
between treatments will be presented with 90% CI for the median difference based on a method 
by Hodges and Lehman based on PK population. 
AUC0-inf will be analyzed using the same ANOVA model method as for AUC0-tlast and Cmax. 
%AUCex and λz will be summarized for each treatment using descriptive statistics same as for 
the primary PK parameters. 
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.
 
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Table 1-1 
Schedule of Activities 
Procedure/Assessment 
Screening 
Confinement Period1 at Clinical Research Unit 
Check-
in 
Period 1 
Washout2 
 
Period 2 
Early 
Discontinuation 
or End of study3 
Day -15 to 
Day -2 
Day 
 -1 
Day 
1 
Day 
2 
Day 
4 
Day 
5 
Day 5 
Informed Consent 
X 
 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Current/Prior/Concomitant 
Medication Review 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
 
X 
 
 
X 
 
X 
Height  
X 
 
 
 
 
 
 
 
Weight 
X 
 
 
 
 
 
 
X 
Vital signs4 
X 
X 
X 
X 
X 
X 
X 
X 
Body temp check5 
X 
X 
X 
X 
X 
X 
X 
X 
COVID19 test6 
X 
X 
 
 
 
 
 
X 
12-lead ECG 
X 
 
 
 
 
 
 
 
Pregnancy test (in females) 
X7 
X8 
 
 
X8 
 
 
 
Blood sample collection for 
biochemistry9, hematology 
and coagulation 10  
X 
 
 
 
 
 
 
X11 
Virology 
X 
 
 
 
 
 
 
 
Urine sample collection for 
urine analysis12  
X 
 
 
 
 
 
 
X 
Urine illicit drug screen13 
X 
X 
 
 
 
 
 
 
Urine cotinine test 
X 
X 
 
 
 
 
 
 
Alcohol screen 
X 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X14 
 
 
 
 
 
 
Continued eligibility15 
 
 
X 
X 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
 
Study product administration 
 
 
X 
 
 
X 
 
 
Blood sample collection for 
PK parameters16 
 
 
X 
X 
 
X 
X 
 
AE17 Review 
X 
X 
X 
X 
X 
X 
X 
X 
Study conclusion  
 
 
 
 
 
 
 
X 
Abbreviations: PK= Pharmacokinetic, AE= Adverse events 
                                                 
 
1 Evening of the day prior to dosing until when end of study procedures are completed 
 
 
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2 There will be a 72-hour washout scheduled between each dose administered 
3 These assessments are also to be conducted for subjects who discontinue study drug. These assessments will 
occur before discharge, on study Day 5 
4 Vital Signs- includes systolic and diastolic blood pressures, heart rate and respiratory rate measurement. Pre-
treatment measurements (i.e. day 1 and day 4) of vitals will happen 1 hour before the scheduled drug administration 
with allowance up to +50 minutes from the scheduled time but must be measured before intravenous catheter 
insertion. Post treatment measurement will take place at 2.00, 4.00 and 12.00 and 24.00 hours after dosing. 
Additional measurements will be performed for medical reasons if necessary. 
5 Based on the actual epidemiologic situation, body temperature will be measured in all subjects in the morning 
and in the evening during the stay at the clinical unit. 
6 For detection of COVID-19, test/s are to be performed as follows: 
• 
At screening visit- RT PCR test is to be done. 
• 
At check-in and early discontinuation or end of study- Antigen test is to be done. 
• 
At any time during residential period in study, when subjects report symptoms suggestive of COVID-19, 
subject will be isolated and antigen test is to be done. If test result is negative, isolate the subject in unit and 
conduct RT PCR. If test result is positive, conduct RT PCR test and discharge the subject for further 
management. Further details in Section 9.3.8: COVID-19 test. 
7 Blood pregnancy test 
8 Urine pregnancy test. 
9 Urea, Creatinine, Glucose (Fasting), Calcium, Magnesium, Sodium, Potassium, Chloride, Aspartate 
aminotransferase (AST), Alanine transaminase (ALT), Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, 
Alkaline phosphatase (ALP), Uric acid, Albumin, Total Protein, Creatine Kinase, Gamma-glutamyl transferase 
(GGT), Cholesterol and Follicle-stimulating hormone (FSH) 
10  Hemoglobin, Hematocrit, Red blood cells (RBC), Mean corpuscular volume (MCV), Mean corpuscular 
hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), Platelets, White blood cells (WBC), 
Absolute counts of Neutrophils, Eosinophils, Monocytes, Basophils, Lymphocytes and prothrombin time (PT)/ 
international normalized ratio (INR) 
11 No FSH, HIV, HBsAg and Hepatitis C tests will be performed. 
12 pH, Glucose, Protein, Blood, Ketones, Nitrites, Urobilinogen, Bilirubin, Specific Gravity, Hemoglobin and 
Microscopy (RBC, WBC, squamous epithelial cells, transitional epithelial cells and casts). 
13  Amphetamine (AMP), barbiturates (BAR), benzodiazepines (BZO), cocaine (COC), ecstasy (MDMA), 
methamphetamine (MET), morphine (MOR), methadone (MTD), tricyclic antidepressants (TCA), and 
cannabinoids (THC) 
14 Only applicable to inclusion/exclusion criteria which are required to be re-confirmed before check-in as specified 
in section 5.2 and 5.3 
15 Continued eligibility is to be determined based on Subject Discontinuation/Withdrawal criteria (Section 7.1), as 
applicable on the day of assessment 
16 Pre-dose (-1 hour) and 5, 10, 20, 30, 40, 50, 60, 80, 90, 120, 150, 180 minutes, 4, 5, 6, 8, 10, 12, 14, 16 hours 
post-doses 
17 Adverse Events (AEs) and therefore all Serious Adverse Events (SAEs) will be collected immediately after a 
subject consents to participate in the study by the completion of the Informed Consent Form (ICF). 
 
 
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Protocol Number: 215262  
 
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Table 1-2  
Schedule for all Study Periods 
Day 
Absolute 
Time1 
Relative 
Time 
Blood 
sample 
No. 
Drug 
Admin. 
Vital Signs2 
& Temp.3 
AE4 Check 
Others 
Fluids 
 (mL) 
Standard. 
Food 
Day 
-1 
Until 
19:00 
(Check-in) 
-12.00 
  
 
Vital Signs & 
Temp.  
AE Check 
Check-in5 
No limit 
 
20:30 
-10.50 
  
 
  
  
 
200 
(water) 
Dinner6 
Day 1 
 
Period 1 
06:00 
-1.00 
1 
 
Vital Signs & 
Temp. 
AE Check 
i.v. catheter 
insertion 
2007 (water) 
No intake 
07:00   
0.00 
  
X 
  
  
 
No intake 
 
07:05 
0.08 
2 
 
 
 
 
07:10 
0.17 
3 
 
 
 
 
07:20 
0.33 
4 
 
 
 
 
07:30 
0.50 
5 
 
 
 
 
07:40 
0.67 
6 
 
 
 
 
07:50 
0.83 
7 
 
 
 
 
08:00 
1.00 
8 
 
 
 
 
Only water 
08:20 
1.33 
9 
 
 
 
 
08:30 
1.50 
10 
 
 
 
 
09:00 
2.00 
11 
 
Vital Signs 
AE Check 
 
09:30 
2.50 
12 
 
 
 
 
10:00 
3.00 
13 
 
 
 
 
11:00 
4.00 
 
14 
 
Vital Signs 
AE Check 
 
530 (water 
and soup) 
Lunch  
12:00 
5.00 
15 
 
 
 
 
Only water 
No intake 
13:00 
6.00 
16 
 
  
  
 
Only water 
No intake 
15:00 
8.00 
17 
 
 
 
 
200 
(water) 
Snack 
17:00 
10.00 
18 
 
 
 
Physical 
examination 
Only water 
No intake 
19:00 
12.00 
19 
 
Vital Signs& 
Temp. 
AE Check 
 
200 
(water) 
Dinner 
21:00 
14.00 
20 
 
 
 
 
Only water 
No intake 
23:00 
16.00 
21 
 
 
 
i.v. catheter 
removal 
Only water 
No intake 
Day 2 
Wash-
out 
07:00 
24.00 
 
 
Vital Signs & 
Temp. 
AE Check 
 
Only water 
No intake 
8:30 
 
 
 
 
 
 
Only water 
Breakfast 
13:00 
 
 
 
 
 
 
530 (water 
and soup) 
Lunch 
                                                 
 
1 Absolute time is valid for subject No. 01. The activities in consecutive subjects follow in 2-minute intervals. 
2 Vital Signs – includes systolic and diastolic blood pressures, heart rate and respiratory rate measurement. 
3 Body temperature  
4 AE – Adverse Events. 
5 Drug screening from urine, urine pregnancy test (in females), alcohol breath test, cotinine test, body temperature, protocol 
restrictions compliance check 
6 Consumption of dinner must be finished 30 minutes after serving. 
7 The 200 mL of water has to be consumed completely. 
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Day 
Absolute 
Time1 
Relative 
Time 
Blood 
sample 
No. 
Drug 
Admin. 
Vital Signs2 
& Temp.3 
AE4 Check 
Others 
Fluids 
 (mL) 
Standard. 
Food 
17:00 
 
 
 
 
 
 
Only water 
Snack 
20:30 
 
 
 
Temp. 
 
 
Only water 
Dinner 
Day 3 
Wash-
out 
07:00 
 
 
 
Temp. 
 
 
Only water 
No intake 
8:30 
 
 
 
 
 
 
Only water 
Breakfast 
13:00 
 
 
 
 
 
 
 530 
(water and 
soup) 
Lunch 
17:00 
 
 
 
 
 
 
Only water 
Snack 
19:00 
-12.00 
 
 
Vital Signs & 
Temp. 
AE Check 
 
Only water 
No intake 
20:30 
-10.50 
  
 
  
  
 
Only water 
Dinner6 
 
Day 4 
 
Period 2 
06:00 
-1.00 
1 
 
Vital Signs & 
Temp. 
AE Check 
i.v. catheter 
insertion 
2007 (water) 
 
 
 
 
 
 
 
 
 
No intake 
07:00 
0.00 
  
X 
  
  
 
No intake 
07:05 
0.08 
2 
 
 
 
 
07:10 
0.17 
3 
 
 
 
 
07:20 
0.33 
4 
 
 
 
 
07:30 
0.50 
5 
 
 
 
 
07:40 
0.67 
6 
 
 
 
 
07:50 
0.83 
7 
 
 
 
 
08:00 
1.00 
8 
 
 
 
 
Only water 
08:20 
1.33 
9 
 
 
 
 
08:30 
1.50 
10 
 
 
 
 
09:00 
2.00 
11 
 
Vital Signs 
AE Check 
 
09:30 
2.50 
12 
 
 
 
 
10:00 
3.00 
13 
 
 
 
 
11:00 
4.00 
 
14 
 
Vital Signs 
AE Check 
 
530 (water 
and soup) 
Lunch  
12:00 
5.00 
15 
 
 
 
 
Only water 
No intake 
13:00 
6.00 
16 
 
  
  
 
Only water 
No intake 
15:00 
8.00 
17 
 
 
 
 
200 
(water) 
Snack 
17:00 
10.00 
18 
 
 
 
Physical 
examination 
Only water 
No intake 
19:00 
12.00 
19 
 
Vital Signs & 
Temp. 
AE Check 
 
200 
(water) 
Dinner 
21:00 
14.00 
20 
 
 
 
 
Only water 
No intake 
23:00 
16.00 
21 
 
 
 
i.v. catheter 
removal 
Only water 
No intake 
 
Day 5 
Check-
out 
07:00 
24.00 
 
 
Vital Signs & 
Temp. 
AE Check 
Check-out 
 
 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 2 7  of 8 5  
2  
I N T R O D U C TI O N 
2. 1  
St u d y R ati o n al e  
T he refere nce pr o d uct Pa na d ol B &I is re gistere d i n m ore t h a n  1 1 0 c o u ntries  w orl d -wi de wit h 
n o n -prescri pti o n stat us ( o ver t he c o u nter ( O T C)) gra nte d i n a b o ut  8 0 c o u ntries . It is i n dicate d 
t o re d uce: 
A. mil d -t o-m o derate pai n i ncl u di n g:  
- 
t o ot h e xtracti o n 
- 
t o ot hac he 
- 
hea dac he  
- 
s ore t hr oat r elate d t o t he i nfla m mati o n of t he u p per res pirat or y tract 
B.  fe ver acc o m pa n yi n g fl u, c ol d, ac ute i nfla m mati o n of t he u p per res pirat or y a n d i nfecti o us 
diseases i n c hil dre n, s u c h as measles, r u bella, c hi c ke n p o x, scarlet fe v er a n d m u m ps a n d t o 
re d uce ele vat e d te m perat ures after vacci nati o n. 
A ne w  p araceta m ol oral s us pe nsi o n f or m ulati o n has bee n de v el o pe d b y Gla x o S mit h Kli ne 
C o ns u mer Healt hcare ( G S K C H).  
I n or der t o s u p p ort t he M ar keti n g A ut h orizati o n A p plicati o n of t he ne w oral s us pe nsi o n i n t he 
sa me i n dicati o ns, bi oe q ui vale nce s h o ul d be d e m o nstrate d wit h t he a p pr o ve d pa raceta m ol 
( 2 4 m g/ ml) oral s us pe nsi o n (Pa na d ol B &I). T h e pr o p ose d paraceta m ol oral s us pe nsi o n will  ha ve 
t he sa me i n dicati o ns as t he a p pr o ve d P a na d ol B &I . 
2. 2  
B a c k gr o u n d  
Paracet a m ol is o ne of t he m ost c o m m o nl y us e d n o n -prescri pti o n a nal gesic  me dicati o ns. Use of 
pe diatric f or m ulati o ns of paraceta m ol is es peciall y  wi des prea d f or t he ma na ge me nt of fe ver a n d 
t o relie ve mil d t o m o derate ac hes a n d pai ns d u e t o c o m m o n c ol d, i nfl ue n za, hea dac he, s ore 
t hr oat, t o ot hac hes a n d ot her i n dicati o ns. T h e safet y of s h ort -ter m use of paraceta m ol i n t h e 
pe diatric  p o p ulati o n is w ell esta blis he d. A vaila bilit y of t he me dicati o n as a li q ui d  f or m ulati o n 
ma kes it eas y t o a d mi nister i n c hil dre n a n d pr o m otes c o m plia nce.  
G S K C H  c hil dre n’s li q ui d paraceta m ol is c urre ntl y mar kete d u n d er t he p ort f oli o of Pa na d ol B &I . 
 
 
  
 
 
 
 
 
 
 
 
 A c o m parati ve 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
C CI
C CI


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Protocol Number: 215262  
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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dissolution study has been performed to confirm that both products show similar in vitro release 
characteristics. 
Paracetamol can be considered as highly permeable drug. Like BCS class I drugs, their 
bioavailability is unlikely to be affected by any change of small intestine transit time caused by 
sorbitol/ maltitol or any other critical excipients  
2.3 
Benefit/Risk Assessment  
Complete information for this paracetamol oral suspension may be found in the single reference 
safety document (SRSD), which for this study is the Summary of Products Characteristics 
(SmPC) for Czech Republic. 
2.4 
Mechanism of Action/Indication 
Paracetamol is an analgesic and antipyretic without anti-inflammatory effect and with good 
gastrointestinal tolerability. It is suitable for adults and in pediatrics. The mechanism of action 
is likely to be similar to that of acetylsalicylic acid and is dependent on the inhibition of 
prostaglandins primarily in the central nervous system.  
3 
STUDY OBJECTIVES AND ENDPOINTS 
Table 3-1 
Study Objectives and Endpoints 
Objective(s) 
Endpoint(s) 
Primary  
• 
To demonstrate the bioequivalence of 
paracetamol in a new paracetamol oral 
suspension 
versus 
the 
marketed 
paracetamol oral suspension (Panadol 
B&I)  
• AUC0-tlast (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)  
• tmax (The time of the maximum 
observed post-dose concentration) 
• Cmax (The maximum observed post-
dose concentration) 
Secondary 
• Assess the pharmacokinetic profile of 
new and the marketed paracetamol oral 
suspension  
• 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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• 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) 
Safety 
Assess the safety profile of both products  
• AEs, vital signs and clinical safety 
laboratory test results 
This study will be considered successful if bioequivalence between the new and the currently 
marketed paracetamol oral suspension concludes that the 90% CIs for the ratio of the means of 
the primary pharmacokinetic parameters AUC0-tlast and Cmax of the paracetamol profiles lie 
completely within the range 0.8-1.25, and if there is no difference between the two treatments 
in terms of tmax. 
4 
STUDY DESIGN  
4.1 
Overall Design 
This will be a 2-arm, single center, single dose, open-label, randomized, two-sequence, two-
period crossover, bioequivalence study in healthy adult subjects. Subjects will be screened for 
eligibility within 15 days prior to dosing. Subjects will receive each of the two study treatments 
in fasted state during a 6-day (5-overnight stay) residential period at the study site. Subjects will 
receive both treatment regimens in a randomized order with a 72-hour washout period between 
each dose. During each treatment period, subjects will provide a pre-dose blood sample 1 hour 
before dosing and 20 post-dose blood samples at 5, 10, 20, 30, 40, 50, 60, 80, 90, 120, 150, 180 
minutes, 4, 5, 6, 8, 10, 12, 14, 16 hours, for bioanalytical analyses of paracetamol. The schedule 
of activities table (Table 4-1) provides an overview of the subject visits and study procedures. 
Table 4-2 provides an overview of the PK sampling scheme during the study. 
Figure 4-1 Study design 
Screening 
Period 1 
Washouta 
Period 2 
End of study 
visit 
Day -15 to -2 
Day -1 to 2 
Day 1b-3 
Day 4-5 
Day 5 
a: Washout period of at least 72 hours between the doses. 
b: Begins post administration of first dose 
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Table 4-1 
Schedule of Activities 
Procedure/Assessment 
Screening 
Confinement Period1 at Clinical Research Unit 
Check-
in 
Period 1 
Washout2 
 
Period 2 
Early 
Discontinuation 
or End of study3 
Day -15 to 
Day -2 
Day 
 -1 
Day 
1 
Day 
2 
Day 
4 
Day 
5 
Day 5 
Informed Consent 
X 
 
 
 
 
 
 
 
Demographics  
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
Current/Prior/Concomitant 
Medication Review 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
 
X 
 
 
X 
 
X 
Height  
X 
 
 
 
 
 
 
 
Weight 
X 
 
 
 
 
 
 
X 
Vital signs4 
X 
X 
X 
X 
X 
X 
X 
X 
Body temp check5 
X 
X 
X 
X 
X 
X 
X 
X 
COVID19 test6 
X 
X 
 
 
 
 
 
X 
12-lead ECG 
X 
 
 
 
 
 
 
 
Pregnancy test (in females) 
X7 
X8 
 
 
X8 
 
 
 
Blood sample collection for 
biochemistry9 hematology 
and coagulation 10 
X 
 
 
 
 
 
 
X11 
Virology 
X 
 
 
 
 
 
 
 
Urine sample collection for 
urine analysis12 
X 
 
 
 
 
 
 
X 
Urine illicit drug screen13 
X 
X 
 
 
 
 
 
 
Urine cotinine test 
X 
X 
 
 
 
 
 
 
Alcohol screen 
X 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X14 
 
 
 
 
 
 
Continued eligibility15 
 
 
X 
X 
X 
X 
X 
X 
Randomization 
 
X 
 
 
 
 
 
 
Study product administration 
 
 
X 
 
 
X 
 
 
Blood sample collection for 
PK parameters16 
 
 
X 
X 
 
X 
X 
 
AE17Review 
X 
X 
X 
X 
X 
X 
X 
X 
Study conclusion  
 
 
 
 
 
 
 
X 
1 Evening of the day prior to dosing until when end of study procedures are completed 
2 There will be a 72-hour washout scheduled between each dose administered 
                                                 
 
 
 
 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 31 of 85 
3 These assessments are also to be conducted for subjects who discontinue study drug. These assessments will occur before 
discharge, on study Day 5 
4 Vital Signs- includes systolic and diastolic blood pressures, heart rate and respiratory rate measurement. Pre-treatment 
measurements (i.e. day 1 and day 4) of vitals will happen 1 hour before the scheduled drug administration with allowance up 
to +50 minutes from the scheduled time but must be measured before intravenous catheter insertion. Post treatment 
measurement will take place at 2.00, 4.00 and 12.00 and 24.00 hours after dosing. Additional measurements will be performed 
for medical reasons if necessary. 
5 Based on the actual epidemiologic situation, body temperature will be measured in all subjects in the morning and in the 
evening during the stay at the clinical unit. 
6 For detection of COVID-19, test/s are to be performed as follows: 
• 
At screening visit- RT PCR test is to be done. 
• 
At check-in and early discontinuation or end of study- Antigen test is to be done. 
• 
At any time during residential period in study, when subjects report symptoms suggestive of COVID-19, subject will be 
isolated and antigen test is to be done. If test result is negative, isolate the subject in unit and conduct RT PCR. If test 
result is positive, conduct RT PCR test and discharge the subject for further management. Further details in Section 9.3.8: 
COVID-19 test. 
7 Blood pregnancy test 
8 Urine pregnancy test. 
9Urea, Creatinine, Glucose (Fasting), Calcium, Magnesium, Sodium, Potassium, Chloride, Aspartate aminotransferase (AST), 
Alanine transaminase (ALT), Direct Bilirubin, Indirect Bilirubin, Total Bilirubin, Alkaline phosphatase (ALP), Uric acid, 
Albumin, Total Protein, Creatine Kinase, Gamma-glutamyl transferase (GGT), Cholesterol and Follicle-stimulating hormone 
(FSH) 
10 Hemoglobin, Hematocrit, Red blood cells (RBC), Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), 
mean corpuscular hemoglobin concentration (MCHC), Platelets, White blood cells (WBC), Absolute counts of Neutrophils, 
Eosinophils, Monocytes, Basophils, Lymphocytes and prothrombin time (PT)/ international normalized ratio (INR) 
11 No FSH, HIV, HBsAg and Hepatitis C tests will be performed. 
12 pH, Glucose, Protein, Blood, Ketones, Nitrites, Urobilinogen, Bilirubin, Specific Gravity, Hemoglobin and Microscopy 
(RBC, WBC, squamous epithelial cells, transitional epithelial cells and casts). 
13 Amphetamine (AMP), barbiturates (BAR), benzodiazepines (BZO), cocaine (COC), ecstasy (MDMA), methamphetamine 
(MET), morphine (MOR), methadone (MTD), tricyclic antidepressants (TCA), and cannabinoids (THC) 
14 Only applicable to inclusion/exclusion criteria which are required to be re-confirmed before check-in as specified in section 
5.2 and 5.3 
15 Continued eligibility is to be determined based on Subject Discontinuation/Withdrawal criteria (Section 7.1), as applicable 
on the day of assessment 
16 Pre-dose (-1 hour) and 5, 10, 20, 30, 40, 50, 60, 80, 90, 120, 150, 180 minutes, 4, 5, 6, 8, 10, 12, 14, 16 hours post-doses 
17 Adverse Events (AEs) and therefore all Serious Adverse Events (SAEs) will be collected immediately after a subject 
consent to participate in the study by the completion of the Informed Consent Form (ICF). 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 32 of 85 
Table 4-2 
Timing Schedule for All Study Periods 
Day 
Absolute 
Time1 
Relative 
Time 
Blood 
sample 
No. 
Drug 
Admin. 
Vital Signs2 
& Temp.3 
AE4 Check 
Others 
Fluids 
 (mL) 
Standard. 
Food 
Day 
-1 
Until 
19:00 
(Check-in) 
-12.00 
  
 
Vital Signs & 
Temp.  
AE Check 
Check-in5 
No limit 
 
20:30 
-10.50 
  
 
  
  
 
200 
(water) 
Dinner6 
Day 1 
 
Period 1 
06:00 
-1.00 
1 
 
Vital Signs & 
Temp. 
AE Check 
i.v. catheter 
insertion 
2007 (water) 
No intake 
07:00   
0.00 
  
X 
  
  
 
No intake 
 
07:05 
0.08 
2 
 
 
 
 
07:10 
0.17 
3 
 
 
 
 
07:20 
0.33 
4 
 
 
 
 
07:30 
0.50 
5 
 
 
 
 
07:40 
0.67 
6 
 
 
 
 
07:50 
0.83 
7 
 
 
 
 
08:00 
1.00 
8 
 
 
 
 
Only water 
08:20 
1.33 
9 
 
 
 
 
08:30 
1.50 
10 
 
 
 
 
09:00 
2.00 
11 
 
Vital Signs 
AE Check 
 
09:30 
2.50 
12 
 
 
 
 
10:00 
3.00 
13 
 
 
 
 
11:00 
4.00 
 
14 
 
Vital Signs 
AE Check 
 
530 (water 
and soup) 
Lunch  
12:00 
5.00 
15 
 
 
 
 
Only water 
No intake 
13:00 
6.00 
16 
 
  
  
 
Only water 
No intake 
15:00 
8.00 
17 
 
 
 
 
200 
(water) 
Snack 
17:00 
10.00 
18 
 
 
 
Physical 
examination 
Only water 
No intake 
19:00 
12.00 
19 
 
Vital Signs& 
Temp. 
AE Check 
 
200 
(water) 
Dinner 
21:00 
14.00 
20 
 
 
 
 
Only water 
No intake 
23:00 
16.00 
21 
 
 
 
i.v. catheter 
removal 
Only water 
No intake 
Day 2 
07:00 
24.00 
 
 
Vital Signs & 
Temp. 
AE Check 
 
Only water 
No intake 
8:30 
 
 
 
 
 
 
Only water 
Breakfast 
                                                 
 
1 Absolute time is valid for subject No. 01. The activities in consecutive subjects follow in 2-minute intervals. 
2 Vital Signs – includes systolic and diastolic blood pressures, heart rate and respiratory rate measurement. 
3 Body temperature  
4 AE – Adverse Events. 
5 Drug screening from urine, urine pregnancy test (in females), alcohol breath test, cotinine test, body temperature, protocol 
restrictions compliance check 
6 Consumption of dinner must be finished 30 minutes after serving. 
7 The 200 mL of water has to be consumed completely. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 33 of 85 
Day 
Absolute 
Time1 
Relative 
Time 
Blood 
sample 
No. 
Drug 
Admin. 
Vital Signs2 
& Temp.3 
AE4 Check 
Others 
Fluids 
 (mL) 
Standard. 
Food 
Wash-
out 
13:00 
 
 
 
 
 
 
530 (water 
and soup) 
Lunch 
17:00 
 
 
 
 
 
 
Only water 
Snack 
20:30 
 
 
 
Temp. 
 
 
Only water 
Dinner 
Day 3 
Wash-
out 
07:00 
 
 
 
Temp. 
 
 
Only water 
No intake 
8:30 
 
 
 
 
 
 
Only water 
Breakfast 
13:00 
 
 
 
 
 
 
 530 
(water and 
soup) 
Lunch 
17:00 
 
 
 
 
 
 
Only water 
Snack 
19:00 
-12.00 
 
 
Vital Signs & 
Temp. 
AE Check 
 
Only water 
No intake 
20:30 
-10.50 
  
 
  
  
 
Only water 
Dinner6 
 
Day 4 
 
Period 2 
06:00 
-1.00 
1 
 
Vital Signs & 
Temp. 
AE Check 
i.v. catheter 
insertion 
2007 (water) 
 
 
 
 
 
 
 
 
 
No intake 
07:00 
0.00 
  
X 
  
  
 
No intake 
07:05 
0.08 
2 
 
 
 
 
07:10 
0.17 
3 
 
 
 
 
07:20 
0.33 
4 
 
 
 
 
07:30 
0.50 
5 
 
 
 
 
07:40 
0.67 
6 
 
 
 
 
07:50 
0.83 
7 
 
 
 
 
08:00 
1.00 
8 
 
 
 
 
Only water 
08:20 
1.33 
9 
 
 
 
 
08:30 
1.50 
10 
 
 
 
 
09:00 
2.00 
11 
 
Vital Signs 
AE Check 
 
09:30 
2.50 
12 
 
 
 
 
10:00 
3.00 
13 
 
 
 
 
11:00 
4.00 
 
14 
 
Vital Signs 
AE Check 
 
530 (water 
and soup) 
Lunch  
12:00 
5.00 
15 
 
 
 
 
Only water 
No intake 
13:00 
6.00 
16 
 
  
  
 
Only water 
No intake 
15:00 
8.00 
17 
 
 
 
 
200 
(water) 
Snack 
17:00 
10.00 
18 
 
 
 
Physical 
examination 
Only water 
No intake 
19:00 
12.00 
19 
 
Vital Signs & 
Temp. 
AE Check 
 
200 
(water) 
Dinner 
21:00 
14.00 
20 
 
 
 
 
Only water 
No intake 
23:00 
16.00 
21 
 
 
 
i.v. catheter 
removal 
Only water 
No intake 
 
Day 5 
Check-
out 
07:00 
24.00 
 
 
Vital Signs & 
Temp. 
AE Check 
Check-out 
 
 
 
 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 3 4  of 8 5  
4. 2  
S ci e ntifi c R ati o n al e f or St u d y D e si g n  
R ati o n ale f or Pri m a r y E n d p oi nts  
T he st u d y desi g n f oll o ws rec o m me n d ati o ns gi ve n b y t h e E M A i n t he a p plica ble G ui deli ne o n 
t he I n vesti gati o n of Bi oe q ui vale nce ( C P M P/ E W P/ Q W P/ 1 4 0 1/ 9 8 Re v. 1 / C orr * * ( 2 0 1 0)) a n d t he 
paraceta m ol s pecifi c bi oe q ui vale nce g ui deli nes ( E M A 2 0 1 7).  
F or esta blis hi n g bi oe q ui v ale nce C ma x  a n d t ma x a n d e xte nt of a bs or pti o n ( A U C 0 -tlast) of t he acti ve 
i n gre di e nt paraceta m ol, will be use d as pri mar y e n d p oi nts.  
R ati o n ale  f or St u d y Desi g n 
T he ra n d o mize d, si n gle d ose, t w o peri o d, t w o se q ue nce, i ntra -s u bject cr oss o ver st u d y desi g n is 
hi g hl y discri mi nati ve a n d he nce well acce pte d f or t he direct  c o m p aris o n of t he P K i n vi v o 
perf or ma n ce of t w o paraceta m ol i m me diate rel eas e pr o d ucts . 
F or t h e o verall o bje cti ves of t his P K -st u d y, t he o p e n-la bel st u d y d esi g n is c o nsi dere d acce pta ble 
a n d j ustifie d, beca use t he P K varia bles of t he st u d y are o bjecti vel y meas ure d bi o -a nal ytical 
o utc o mes t hat are u nli kel y t o be s u bj ect t o i n vesti gat or - o r s u bject-i n d uce d bias. H o we v er, t o 
facilitate o bje cti ve me as ure me nt of t he bi oa nal ytical o utc o mes, p ers o n nel perf or mi n g t he 
bi oa nal ytical a nal ysis will be bli n de d t o t he ra n d o mize d treat me nt.  
Carr y -o ver effects will be a v oi de d b y o bs er vati o n of a n a p pr o pr iate was h-o ut i nter val of at least 
7 2 h o urs bet w ee n treat m e nts  w hic h c o vers m ore t ha n 1 5  ti mes of t he a vera ge t1/ 2 val ue  of 4 
h o urs . T he st u d y c o n diti o ns a n d met h o d ol o gies will be c o ntr olle d a n d strictl y sta n d ar dize d t o 
kee p i nter - a n d i ntra-s u bj ect varia bilit y t o a mi ni m u m. 
B l o o d sa m pli n g will be d o ne at pre-d eter mi ne d ti mes f or 1 6 h o urs f oll o wi n g oral i nta k e of t he 
st u d y dr u gs. T he d urati o n of t he bl o o d sa m pli n g peri o d is base d o n t he a bs or pti o n a n d 
eli mi nati o n rates c haracteristics of b ot h c o m p o ne nts ( i.e. a vera ge t1/ 2-re p orte d) a n d was 
desi g ne d t o c o v er a peri o d of at least 4 -ti mes of t he a vera ge t1/ 2 val ues (t 1/ 2 f or paraceta m ol 1 -4  
h o urs).   
R ati o n ale f or St u d y P o p ul ati o n  
Healt h y a d ult is t he p o p ulati o n rec o m me n de d f or bi oe q ui vale nce st u dies.  
E M A 
P har mac o ki netic W or ki n g Part y [
] rec o m me n ds t hat, i n vi v o bi oe q ui vale nce is 
al m ost al wa ys esta blis he d i n healt h y s u bjects u nless t he dr u g carri es safet y c o ncer ns t hat ma ke  
t his u net hical. T his m o d el, i n vi v o healt h y s u bjects, is re gar de d a de q uate i n m ost i nsta nces t o 
detect si g nifi ca nt f or m ulati o n differe nces a n d t he res ults will all o w e xtra p olati o n t o p o p ulati o ns 
i n w hic h t he dr u g is a p pr o ve d (t he el derl y, patie nts wit h renal or li ver i m pair me nt etc.). T he 
sa me reas o ni n g a p plies als o t o c hil dre n. T his st u d y will be perf or me d i n healt h y a d ult s u bjects 
a ge d 1 8-4 5 years.  
4. 3  
J u stifi c ati o n f or D o s e  
T he sta n dar d si n gle d ose of paraceta m ol i n a d ults is 1 g of paraceta m ol [Gl o bal Data  S heet v 
7. 0 ]. B ot h st u d y treat me nts c o ntai n 2 4 m g/ ml paracet a m ol; t heref ore, a d ose of 4 2 ml ( 1 g 
paraceta m ol) will be a d mi nistere d  i n eac h p eri o d. 
4. 3. 1  
M e di c ati o n s a n d Tr e at m e nt  
N o c o nc o mita nt treat me nt is all o we d d uri n g t he e ntire peri o d of t he st u d y (f or e x ce pti o ns, see 
e x cl usi o n criteria  1 8 ). If c o nc o mita nt t hera p y is re q uire d f or me dical m a na ge me nt of A Es 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
C CI


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 35 of 85 
during the study, a decision for the subject’s continuation will be made by the investigator, 
based on the time the medication was administered and, on the pharmacology, and 
pharmacokinetics of the study drug and the concomitant medication. 
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. 
The end of this study is defined as the date of the last visit of the last subject in the study.  
5 
STUDY POPULATION 
5.1 
Type and Planned Number of Subjects 
Since the collection of detailed biopharmaceutic data in vulnerable children is difficult due to 
ethical considerations, this study plans to collect adult data with the assumption that the adult 
observations can be extrapolated to children. For the study healthy adult subjects aged 18-45 
years will be selected. 
Approximately 110 subjects will be screened to randomize approximately 37 healthy adult 
subjects to ensure at least 31 evaluable subjects complete the entire study. An enrolled subject 
will be the one who has agreed to participate in the clinical study following completion of the 
informed consent process 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. Subject provision of a 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. Subject is male or female 
3. Subject is 18 to 45 years of age inclusive, at the signing of the informed consent. 
4. A subject who is willing and able to comply with scheduled visits, treatment plan, laboratory 
tests, study restrictions and other study procedures. 
5. A subject in good general and mental health with, in the opinion of the investigator or 
medically qualified designee, as determined by medical evaluation, including medical 
history, full physical examination, including blood pressure and pulse rate measurement, 
12-lead ECG or clinical laboratory tests 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 3 6  of 8 5  
6.  A s u bject wit h a B o d y 
Mass I n de x ( B MI) of 1 8. 5  t o 3 0. 0 k g/ m 2; a n d a t otal b o d y 
wei g ht > 6 0  k g  
7.  Fe male s u bjects of c hil d beari n g p ote ntial a n d  at ris k f or pre g na n c y m ust a gree t o use a 
hi g hl y effecti ve m et h o d of c o ntrace pti o n t hr o u g h o ut t he st u d y a n d f or 7 da ys after t he last 
d ose of assi g ne d tr eat me nt.  Fe male s u bjects w h o are n ot of c hil d beari n g p ote ntial m ust 
meet re q uir e me nts i n 
. 
8.  S u bject wit h tw o c o nsec uti ve ne gati ve tests f or acti ve C O VI D -1 9 , se parate d b y > 2 4 h o urs. 
9.  Czec h citiz e ns hi p  
5. 3  
E x cl u si o n Crit eri a  
A n i n di vi d ual w h o meets a n y of t he f oll o wi n g e x cl usi o n criteria will n ot be i ncl u de d i n t he 
st u d y:  
1.  A s u bject w h o is a n e m pl o yee of t he i n vesti gati o nal site, eit her directl y i n v ol ve d i n t he 
c o n d uct of t he st u d y or a me m ber of t heir i m me diate fa mil y; or a n e m pl o yee of t he 
i n vesti gati o nal site ot her wise s u per vise d b y t he i n vesti gat or; or, a G S K C H  e m pl o yee 
directl y i n v ol ve d i n t he c o n d uct of t he st u d y or a me m ber of t heir i m me diate fa mil y.  
2.  A s u bject w h o has partici pate d i n ot her st u dies (i ncl u di n g n o n -me dici nal st u dies) i n v ol vi n g 
i n vesti gati o nal pr o d u ct(s) wit hi n 3 0  da ys b ef ore d osi n g.  
3.  A s u bject wit h , i n t he o pi ni o n of t he i n vesti gat or or me dicall y q ualifi e d  desi g nee,  a n ac ut e 
or c hr o nic me dical or ps yc hiatric c o n diti o n or la b orat or y a b n or m alit y t hat m a y i n crease t he 
ris k ass ociate d wit h st u d y p artici pati o n or i n vesti gati o nal pr o d uct a d mi nistrati o n or ma y 
i nterfere with t he i nter pretati o n of st u d y res ults a n d, i n t he j u d g me nt of t he i n vesti gat or or 
me dicall y q ualifie d d esi g nee, w o ul d ma ke t he s u bj ect i na p pr o priate f or e ntr y i nt o t his st u d y.  
4.  A s u bject w h o is pre g na nt as c o nfir me d b y a p ositi ve h C G la b orat or y t est or i nte n di n g t o 
bec o me pre g na nt o ver t he d urati o n of t he st u d y.  
5.  A s u bject w h o is breastfee di n g.  
6.  A s u bject wit h k n o w n or s us pecte d i nt olera nce or h y perse nsiti vit y t o t he st u d y m aterials ( or 
cl osel y rel ate d c o m p o u n ds) or a n y of t heir state d i n gre die nts.  T his i ncl u d es p araceta m ol a n d 
e x ci pie nts i n t he pr o d ucts e. g. s or bit ol, maltit ol gl ycer ol etc.  
7.  A s u bject u n willi n g or u na ble t o c o m pl y wit h Lif est yle C o nsi derati o ns  (Secti o n 5. 5  of 
pr ot oc ol) descri be d i n t his pr ot oc ol.  
8.  Dia g n osis of l o n g Q T s y n dr o me or Q Tc  > 4 5 0 msec f or mal es a n d > 4 7 0 msec f or fe males 
at scree ni n g.  
9.  A s u bject wit h e vi de nce or hist or y of cli nicall y si g nifica nt la b orat or y a b n or malit y, 
he mat ol o gic al, re nal, 
e n d ocri ne, 
p ul m o nar y, 
car di o vasc ul ar, 
he patic, 
ps yc hiatric, 
ne ur ol o gi c, or aller gic di sease wit hi n t he last 5 years t hat ma y i ncrease t he ris k ass ociate d 
wit h st u d y partici pati o n.   
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
C CI


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 37 of 85 
10. 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) or urea (≥ 8.9 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 one or more of the following lab value 
deviations are found: 1) AST/SGOT (≥ 1.2 ULN), ALT/SGPT (≥ 1.2 ULN), 2) GGT 
(≥ 1.2 ULN), ALP (≥ 1.2 ULN), 3) bilirubin (≥ 1.2 ULN) or CK (≥ 3 ULN); 
• Evidence of urinary obstruction or difficulty in voiding at screening. 
• History or clinical evidence at screening of pancreatic injury or pancreatitis 
11. A subject with history of regular 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 
12. 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) 
13. Positive results in any of the virology tests for HIV-Ab, HCV-Ab, HBsAg and HBc-Ab 
(IgG + IgM)  
14. 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. 
15. 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 
16. A subject who has previously been enrolled in this study. 
17. A subject who, in the opinion of the investigator or medically qualified designee, should not 
participate in the study 
18. Use of any medication (including over-the-counter medications, vitamins, herbal remedies, 
dietary supplements) within 2 weeks prior to  admission to the unit 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: 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 38 of 85 
a) systemic contraceptives and hormone replacement therapy, as long as female subject is 
on stable treatment for at least 3 months and continues treatment throughout the study; 
b) occasional use of ibuprofen 200 mg (up to 1200 mg daily) or equivalent analgesic 
19. 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 
20. Sitting blood pressure after a minimum of 5 minutes of rest is out of the range of 90-140 
mmHg for systolic BP and/or 60-90 mmHg for diastolic BP and/or heart rate out of the 
range of 50-100 bpm during the screening procedure. 
21. Body temperature is consistently out of the range of 35.4-37.3°C at screening, at check-in 
or during the study. 
22. Anemia, defined as level of hemoglobin in women below 120 g/L and in men below 130 
g/L at screening. 
23. Clinically relevant chronic or acute infectious illnesses or febrile infections within 2 weeks 
prior to screening till admission to the unit 
24. A subject with a positive urine drug screen, alcohol breath test at screening and on day of 
admission to the unit 
25. Smokers, defined as the use of tobacco products during the 3 months prior to screening till 
admission to the unit or a positive urine cotinine test at screening 
26. Performance of strenuous physical exercise (body building, high performance sports) from 
2 weeks prior to admission to the unit 
27. Donation or loss of at least 500 mL of blood within 90 days or any donation of plasma or 
platelets from 2 weeks prior to admission to the unit 
28. Getting a tattoo, body piercing or any cosmetic treatment involving skin penetration within 
90 days before the screening till admission to the unit, unless evaluated by Investigator as 
non-significant for inclusion in the study 
29. Subject with signs and symptoms suggestive of COVID-19 (i.e. fever, cough, etc.)1 from 2 
weeks prior to screening till admission to the unit 
30. Subject with known COVID-19 positive contacts in the past from 2 weeks prior to screening 
till admission to the unit 
31. Subjects who were hospitalized for COVID-19 related reasons 
                                                 
 
1 as defined by WHO or local guidance 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 39 of 85 
5.4 
Randomization Criteria 
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria. Subjects will be allocated to receive two test regimens in a specific order determined 
by a randomization schedule. 
5.5 
Lifestyle Considerations 
Subjects will be required to reside at the study site from admission on Day -1 until the morning 
of Day 5 after the end of Study visit procedures have been performed. Following lifestyle 
restrictions will apply to all study participants: 
• Meals intake during the study will also be standardized (only water will be allowed 
unrestricted at certain times). 
• Subjects will receive standardized food and beverages throughout the study. 
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 the collection of the pre-dose 
PK sample.  Water is permitted until 1 hour prior to investigational product 
administration. Water may be consumed without restriction beginning 1 hour after 
dosing. 
• Liquid intake during the study will also be standardized (only water will be allowed 
unrestricted at certain times). 
• Lunch will be provided approximately 4 hours after dosing. 
• An evening snack may be permitted approximately 8 hours after dosing. 
• Dinner will be provided approximately 12 hours after dosing. 
• 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 14 days 
prior to the first dose of investigational product until collection of the final 
pharmacokinetic blood sample. 
• While confined, the total daily nutritional composition should be approximately 
55% carbohydrate, 30% fat and 15% protein.  The daily caloric intake per subject 
should not exceed approximately 3200 kcal.  
5.5.2 
Alcohol, Caffeine and Tobacco 
• Subjects will abstain from alcohol for 72 hours prior to the start of dosing and continue 
abstaining from alcohol until completion of study.  Subjects may undergo an alcohol 
breath test at the discretion of the investigator. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 4 0  of 8 5  
•  S u bjects will a bstai n fr o m caffei n e -c o ntai ni n g pr o d ucts (i.e. tea, c offee, c h oc olate, 
c ola), c he wi n g g u ms, ot her x a nt hi ne or C O2 c o ntai ni n g f o o d a n d be vera ges  f or 2 4 h o urs 
pri or t o t he star t of d osi n g u ntil c o m pleti o n of  st u d y.  
•  S u bjects will a bstai n fr o m t he use of t o bacc o - or nic oti ne -c o ntai ni n g pr o d ucts i ncl u di n g 
nic oti ne patc hes a n d ot her deli ver y d e vices s uc h as electr o nic ci garettes or va p orizers) 
d uri n g c o nfi ne me nt at t h e cli nical site.  
5. 5. 3  
A cti vit y  
T o sta n dar dize gast ric e m pt yi n g, s u bjects will sit u pri g ht o n t he e d ge of t heir be ds f or 2 0 
mi n utes after d osi n g. T hereafter, t he y will be as ke d t o lie o n t heir ri g ht si des f or t he re mai n der 
of t he first h o ur p ost -a d mi nistrati o n. E x ce pt f or bla d der v oi di n g , bl o o d sa m pli n g a nd i n gesti o n 
of f o o d a n d be vera ges as i n dicate d, s u bjects will re mai n rec u m be nt u ntil 5 h o urs after 
a d mi nistrati o n of st u d y m e dicati o n, aft er w hic h n o restricti o ns c o ncer ni n g p ost ure or m o ve me nt 
will a p pl y. P ost ure c o ntr ol pr oce d ures will be d oc u me nte d  
5. 5. 4  
C o n tr a c e pti o n 
All fe male s u bjects w h o are of c hil d beari n g p ote ntial a n d are se x uall y acti ve a n d at ris k f or 
pre g na nc y m ust a gree t o use a hi g hl y effecti ve met h o d of c o ntrace pti o n c o nsiste ntl y a n d 
c orrectl y f or t he d urati o n of t he acti ve st u d y p eri o d a n d f or 7  d a ys after t he last d os e of 
i n vesti gati o nal pr o d u ct.  
A fe mal e s u bject will be c o nsi dere d of n o n -c hil d beari n g p ote ntial if t he y s atisf y at least o n e of 
t he f oll o wi n g criteria: 
1.  Ac hie ve d me n o pa us al stat us, defi ne d as f oll o ws: cessati o n of re g ular me nses f or  at least 
1 2 c o nsec uti ve m o nt hs wit h n o alter nati ve pat h ol o gical or p h ysi ol o gical ca use  
2.  Ha ve u n der g o ne a d oc u me nte d h ysterect o m y a n d/ or bilateral o o p h orect o m y  
3.  Ha ve me dicall y c o nfir me d o varia n fail ure  
T he i n vesti gat or or his or her desi g nee will disc uss wit h t he s u bject t he nee d t o use hi g hl y 
effecti ve c o ntrace pti o n c o nsiste ntl y a n d c orrectl y acc or di n g t o t he sc he d ule of acti vities a n d 
d oc u me nt s uc h c o n ve rs ati o n .  I n a d diti o n, t he i n vesti gat or or his or h er desi g nee will i nstr uct 
t he s u bject t o call i m me diatel y if t he selecte d c o ntrace pti o n met h o d is disc o nti n ue d or if 
pre g na nc y is k n o w n or s us pecte d i n t he s u bject or t he s u bject’s part n er.  
T he f oll o wi n g is t he all -i ncl usi ve list of t he hi g hl y effecti ve met h o ds f or a v oi di n g pre g n a nc y 
t hat meets t he G S K defi niti o n (i.e., ha ve a fail ure rate of less t ha n 1 % p er year w he n use d 
c o nsiste ntl y a n d c orrectl y a n d, w he n a p plica ble, i n acc or da nce wit h t he pr o d uct la bel).  
T he list d oes n ot a p pl y t o fe males of re pr o d ucti ve p ote ntial wit h sa me se x part ners or f or 
s u bjects w h o are a n d will c o nti n ue t o be a bsti ne nt fr o m pe nile -va gi nal i nterc o urse o n a l o n g 
ter m a n d persiste nt basis, w he n t his is t heir preferre d a n d us ual lifest yle. Peri o dic a bsti ne nce 
(e. g. cal e n dar, o v ulati o n, s y m pt ot her mal, p ost -o v ulati o n met h o ds) a n d wit h dra wal are n ot 
acce pta ble met h o ds of c o ntrace pti o n.  
1.  C o ntrace pti ve s u b der mal i m pla nt  
2.  I ntr a uteri ne d e vice or i ntra uteri ne s yste m 
3.  C o m bi ne d estr o ge n a n d pr o gest o ge n oral c o ntrace pti ve (
) 
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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 5 2 6 2   
 
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 6. 0  
Pa ge 4 1  of 8 5  
4.  I nje cta ble pr o gest o ge n (
) 
5.  C o ntrace pti ve va gi n al  ri n g (
) 
6.  Perc uta ne o us c o ntrace pti ve patc hes (
) 
7.   Bilateral t u bal li gati o n at least si x wee ks bef ore ta ki n g st u d y treat me nt 
8.   Male part n er steriliz ati o n wit h d oc u me ntati o n of az o os per mia pri or t o t he fe mal e 
s u bject's e ntr y i nt o t he st u d y, a n d t his male is t he s ole part ner f or t hat s u bject ( 
 
. T he d oc u me nt ati o n o n male sterilit y ca n c o me fr o m site pers o n nel re vie w of 
s u bject’s me dical rec or ds, me dical e x a mi nati o n a n d/ or se me n a nal ysis, or me dical 
hist or y i nter vie w pr o vi de d  b y her or her part n er.  
T hese all o w e d met h o ds of c o ntrace pti o n are o nl y effecti ve w he n us e d c o nsiste ntl y, c orrectl y 
a n d i n acc or da n ce wit h t he pr o d uct la bel. T he i n vesti gat or is res p o nsi ble f or e ns uri n g t hat 
s u bjects u n dersta n d h o w t o pr o perl y use t hese m et h o ds of c o ntrace pti o n. 
5. 6  
S cr e e n F ail ur e s  
Scree n fail ures are defi n e d as s u bjects w h o c o nse nt t o partici pate i n t he cli nical st u d y b ut are 
n ot s u bse q ue ntl y ra n d o mize d. T o e ns ure tra ns p are nt re p orti n g of s cree n fail ure s u bjects, a 
mi ni mal set of scree n fail ur e i nf or mati o n will i ncl u de de m o gra p h y, scree n fail ure d etails ( e. g.  
wit h dra wal of c o nse nt), eli gi bilit y criteria, a n y pr ot oc ol de viati o ns a n d a n y a d v erse e v e nts or 
i nci de nts as a p plica ble.  
I n di vi d uals w h o d o n ot meet t he criteria f or partici pati o n i n t his st u d y (scree n fail ure) will n ot 
be re -s cree ne d. 
5. 7  
S p o n s or’ s Q u alifi e d M e di c al P er s o n n el  
C o ntact i nf or mati o n f or t he s p o ns or's a p pr o priatel y q u alifie d me dical pers o n nel f or t he st u d y is 
d oc u me nte d i n t he  St u d y C o ntact List l ocate d i n t he i n vesti gat or st u d y m aster file hel d at t he 
st u d y site. 
T he c o ntact n u m ber is o nl y t o be use d b y i n vesti gati o nal staff see ki n g a d vice o n me dical/ de ntal 
q uesti o ns or pr o ble ms i n t he e v e nt t hat t he esta blis he d c o m m u nicati o n pat h wa ys bet w ee n t h e 
i n vesti gati o nal site a n d t he st u dy te a m are n ot a vaila ble.   
T he c o ntact n u m b er is n ot i nte n de d f or direct us e b y st u d y s u bjects.  T o facilitate access t o 
a p pr o priatel y q ualifie d me dical/ de ntal pers o n nel o n st u d y -rel ate d me dical/ de ntal q uesti o ns or 
pr o ble ms, s u bjects will be pr o vi de d wit h  a c o nt act n u m ber i n t he I C F . T he d oc u me nt  will 
pr o vi de, as a mi ni m u m, pr ot oc ol i de ntifiers, c o ntact i nf or mati o n f or t he i n vesti gati o nal site, a n d 
c o ntact details i n t he e ve nt t hat t he i n vesti gati o nal site ca n n ot be reac he d t o pr o vi de a d vice o n 
a me dical q uesti o n or pr o ble m i de ntifie d b y a healt hc are pr ofessi o nal ot her t ha n t he i n vesti gat or.  
5. 8  
R at er/ Cli ni c al A s s e s s or Q u alifi c ati o n s  
Assess me nt of me dical hist or y, a n d pri or me di cati o n/treat me nt, p h ysic al e x a mi nati o n, safet y 
e val uati o n a n d a d v erse e ve nts re p orti n g nee ds t o be perf or me d b y q ualifie d me d ical p h ysi cia n.   
6  
S T U D Y P R O D U C T S  
F or t he p ur p oses of t his st u d y, per I nter nati o nal C o nfere n ce o n Har m o nizati o n (I C H) g ui d eli nes, 
a n d G S K p olic y, st u d y i nter ve nti o n is defi ne d as an y i n vesti gati o nal i nter ve nti o n(s), mar kete d 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 42 of 85 
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.  
The selection of  Panadol B&I (reference product) will be based on assay content to ensure that 
this test product does not differ by more than 5% from that of the batch used as reference product 
according 
to 
the 
European 
Guideline 
on 
the 
investigation 
of 
bioequivalence 
(CPMP/EWP/QWP/1401/98 Rev. 1/Corr **(2010)). 
6.1 
Study Product Supplies 
The following study products will be manufactured according to Good Manufacturing Practice 
and will be supplied by the Clinical Supplies Department, GSKCH: 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 4 3  of 8 5  
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 
 
Test Pr o d uct  
Refere nce Pr o d uct  
Pr o d uct N a me  
Paracet a m ol  
S us pe nsi o n, 
Stra w berr y fla v or, c ol or -free 
( 2 4 m g/ ml paracet a m ol) 
Pa na d ol  B &I ( Mar kete d as 
Pa na d ol 
pr o 
děti 
ja h o da 
per orál ní 
s us pe nze), 
Stra w berr y fla v or, c ol or-free 
s us pe nsi o n 
( 2 4  
m g/ ml 
paraceta m ol)  
P ac k D esi g n  
Glass b ottle wit h a s yri n ge  
Glass b ottle wit h a s yri n ge  
Dis pe nsi n g Det ails  
T o be a d mi nistere d orall y via 
a s yri n ge  
T o be a d mi nistere d orall y via 
a s yri n ge  
Pr o d uct M aster 
F or m ul ati o n C o de ( M F C)  
 
Czec h 
Re p u blic 
mar kete d 
pr o d uct  
M A n u m ber: 
 
M a n uf act urer  
G S K C H,  N y o n , S witzerl a n d  
Far maclair  
( a 
C o ntract 
M a n ufact uri n g O r ga nizati o n 
u n der G S K C H ), Fra n ce  
M ar keti n g A ut h oriz ati o n 
h ol der  
G S K C H, Fi nla n d  
G S K, Czec h Re p u blic  
S o urce M ar ket  
N A  
Czec h Re p u blic  
D ose  
4 2 ml ( 1 g paraceta m ol)  
4 2 ml ( 1 g paraceta m ol)  
R o ute of A d mi nistr ati o n  
Oral  
Oral  
Us a ge I nstr ucti o ns  
V ol u me 
of 
4 2 ml t o 
be 
a d mi nistere d 
orall y 
vi a 
a 
s yri n ge 
V ol u me 
of 
4 2 ml t o 
be 
a d mi nistere d 
orall y 
vi a 
a 
s yri n ge 
Ret ur n Re q uire me nts  
All use d/ u n use d sa m ples t o be 
ret ur ne d 
All use d/ u n use d sa m ples t o be 
ret ur ne d 
Detail i nstr ucti o ns f or d osi n g will be descri be d i n d osa ge a n d a d mi nistrati o n i nstr ucti o ns.  
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 hec ks 
a n d s u bse q ue nt destr u cti o n w hic h will be pr o vi d e 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. 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 44 of 85 
Table 6-2 
Sundry Items 
Sundry Items to be supplied: 
Item 
Supplied By 
Pack Design 
Dispensing 
Details 
Return/Disposal Details 
Used Samples 
Unused Samples 
Pregnancy 
Test kits 
Site 
Commercial 
pack 
Use as per 
study 
schedule 
 
Disposal to be 
managed by the 
site  
Disposal to be 
managed by the 
site  
Alcohol 
breath 
analyzer 
Site 
Commercial 
pack 
Use as per 
study 
schedule 
Disposal to be 
managed by 
the site  
Disposal to be 
managed by the 
site 
Oral 
Dosing 
Syringes 
GSKCH 
Commercial 
pack 
Use as per 
study 
schedule 
Destroy at site 
using site 
disposal 
procedures 
Return as per 
instructions 
provided by 
GSKCH 
Dosing 
cups 
GSKCH 
Commercial 
pack 
Use as per 
study 
schedule 
Destroy at site 
using site 
disposal 
procedures 
Return as per 
instructions 
provided by 
GSKCH 
Detailed instructions for the return of study product/study supplies for the accountability checks 
and subsequent destruction which will be provided by GSKCH during the study in time for 
study close out visit. 
6.1.1 
Dosage Form and Packaging 
The test product and the reference products will be supplied to the clinical site as packaged 
bottles. Each bottle will have a clinical study label affixed. 
The content of the product labels will be in accordance with all applicable regulatory 
requirements and will be the responsibility of the GSKCH Global Clinical Supplies group. Each 
study label will contain, but not be limited to, protocol number, directions for use and storage 
requirements.  
Care should be taken with the supplied products and their labels so that they are maintained in 
good condition.  It is important that all labels remain intact and legible for the duration of the 
study. Subjects should be instructed to not remove or deface any part of the study label. 
All products supplied are for use only in this clinical study and should not be used for any other 
purpose.  
6.1.2 
Preparation and Dispensing  
Paracetamol and Panadol B& I suspensions will be prepared and/or dispensed by qualified site 
personnel according to the dosage and administration instruction.  
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 4 5  of 8 5  
S u bjects wil l be assi 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 a n a p pr o ve d G S K C H  ve n d or  (
), pri or t o t he start of t he st u d y, usi n g vali date d 
s oft ware. 
St u d y pr o d uct will be dis pe nse d b y q ualifie d site pers o n nel p er  t he d osage/a d mi nistrati o n 
i nstr ucti o ns. 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 urat el y.  
6. 2  
A d mi ni str ati o n  
A p h ysici a n or a n a p pr o priate me m ber of t he st u d y site pers o n nel, will a d mi nister st u d y 
f or m ulati o ns, a sec o n d s uita bl y q u alifie d pers o n will wit ness t his. T he a p pr o priate v ol u me of 
eac h st u d y treat me nt will be a d mi nistere d orall y vi a a si n gl e use s yri n ge. Detail i nstr ucti o ns f or 
d osi n g will be descri be d i n d osa ge a n d a d mi nistrati o n i nstr ucti o ns.  
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.  
6. 2. 1  
M e di c ati o n/ D o si n g Err or s  
Me dicati o n/ d osi n g err ors ma y res ult, i n t his st u d y, fr o m t he a d mi nistrati o n or c o ns u m pti o n of:  
•  t he wr o n g pr o d uct, 
•  b y t he wr o n g s u bject,  
•  at t he wr o n g ti me,  
•  or at t he wr o n g d os a ge.  
S uc h me dicati o n/ d osi n g err ors occ urri n g t o a st u d y s u bj ect are t o be ca pt ure d i n t h e C R F.  I n 
t he e ve nt of me di cati o n d osi n g err or, t he s p o ns or s h o ul d be n otifie d i m me di atel y a n d u n der 
n o circ u mst a nce s h o ul d t his e xcee d 2 4 h o urs.  
Me dicati o n/ d osi n g err ors are re p orta ble irres pecti ve of t he prese n ce of a n ass ociate d A E, 
i ncl u di n g: 
•  Me dicati o n/ d osi n g err ors i n v ol vi n g s u bject e x p os ure t o a n y of t he st u d y pr o d ucts;  
•  P ote ntial me dicati o n/ d osi n g err ors or uses o utsi de of w hat is f oresee n i n t he pr ot oc ol 
t hat d o or d o n ot i n v ol ve t he partici pati n g s u bject. 
If a me dicati o n/ d osi n g err or is acc o m p a nie d b y a n A E, as deter mine d b y t he i n vesti gat or, t h e 
me dicati o n/ d osi n g err or a n d, a n y ass ociate d a d verse e ve nt(s) are t o be ca pt ure d i n t he C R F A E 
f or m.  
6. 2. 2  
O v er d o s e  
A n o ver d ose is a deli berate or i na d verte nt a d mi nistrati o n of a pr o d uct at a n a m o u nt hi g her t ha n 
s pecifie d i n t he pr oto c ol. O ver d ose is n ot li kel y t o occ ur i n t his st u d y. Li mit e d q ua ntities of t he 
st u d y pr o d uct(s) will be s u p plie d, a n d cl osel y m o nit ore d b y t he site f or eac h s u bject.  
O ver d ose p er se is n ot a n A E. H o we v er, a n y cli nical se q uelae of a n o v er d ose s h o ul d be re p o rt e d 
as a n A E (a n d seri o us a d verse e ve nt ( S A E), if a p pr o priate). F or re p orti n g, f oll o w t he A E a n d 
S A E re p orti n g i nstr ucti o ns.  
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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 5 2 6 2   
 
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 6. 0  
Pa ge 4 6  of 8 5  
6. 3  
I n v e sti g ati o n al/ St u d y Pr o d u ct St or a g e  
T he i n vesti gat or or desi g nee m ust c o nfir m a p pr o priate te m perat ur e c o n diti o ns ha ve bee n 
mai ntai ne d d uri n g tra nsit f or all st u d y pr o d ucts recei ve d a n d a n y discre p a ncies are re p orte d a n d 
res ol ve d bef ore us e acc or di n g t o t he s u p plie d s hi p pi n g d oc u me nt ati o n. 
T he i n vesti gat or, or d esi g nee, will e ns ure t hat all st u d y pr o d ucts are st ore d i n a s ec ure d area 
wit h c o ntr olle d access u n der re q uire d st or a ge c o n diti o ns a n d i n acc or da n ce wit h a p plica ble 
re g ulat or y re q uire me nts, t he pr o d uct la bel, a n d t h e Cli nical St u d y S u p plies C hec klist.   
Site s yst e ms m ust be ca pa ble of meas uri n g a n d d oc u me nti n g (f or e x a m pl e, via a l o g), at a 
mi ni m u m, dail y mi ni m u m a n d ma xi m u m te m perat ur es f or all site st ora ge l ocati o ns (as 
a p plica ble, i ncl u di n g fr o ze n, refri gerate d, a n d/ or r o o m -te m perat ure pr o d ucts).  T his s h o ul d be 
ca pt ure d fr o m t he ti me of first pr o d uct recei pt t hr o u g h o ut  t he st u d y.  E ve n f or c o nti n u o us 
m o nit ori n g s yste ms, a l o g or site pr oce d ure t hat e ns ures acti ve dail y e val u ati o n f or e x c ursi o ns 
s h o ul d be a v aila ble.  T he o perati o n of t h e te m perat ure-m o nit ori n g de vice a n d st ora ge u nit (f or 
e x a m ple, refri gerat or), as a p pli ca ble, s h o ul d b e re g ularl y i ns pecte d t o e ns ure it is mai ntai ne d i n 
w or ki n g or der.  
A n y e x c ursi o ns fr o m t he pr o d uct -la bel st ora ge c o n diti o ns s h o ul d be re p orte d t o a p pr o priate sit e 
staff u p o n disc o ver y a n d c o m m u nicate d t o s p o ns or as s o o n as p ossi ble.  T he si te s h o ul d acti vel y 
p urs ue o pti o ns f or ret ur ni n g t he pr o d uct t o t he st ora ge c o n diti o ns as descri be d i n t he la beli n g, 
as s o o n as p ossi ble.  E x c ursi o ns fr o m t he st ora ge re q uir e me nts, i ncl u di n g a n y acti o ns ta ke n, 
m ust be d oc u me nte d as a pr ot oc ol de viati o n a n d re p orte d t o t he S p o ns or.   
O nce a n e x c ursi o n is i de ntifie d, t he affect e d pr o d uct ( or pr o d ucts) m ust be q uara nti ne d a n d n ot 
use d u ntil t he s p o ns or pr o vi des d oc u me ntati o n of per missi o n t o use. Use of a n y of t he affecte d 
pr o d uct(s) pri or t o s p o ns or a p pr o val w ill be c o nsi dere d a pr ot oc ol de viati o n.  
6. 4  
I n v e sti g ati o n al/ St u d y Pr o d u ct A c c o u nt a bilit y 
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.  
All st u d y dr u g recei v e d at t he site will be i n ve nt orie d a n d acc o u nte d f or t hr o u g h o ut t he st u d y 
a n d t he res ult rec or de d i n t he dr u g acc o u nta bilit y rec or ds acc or di n g t o
 
 a p pr o priat e S O P. 
All st u d y pr o d ucts m ust b e recei ve d b y a desi g n ate d pers o n at t he st u d y sites, ha n dle d a n d st or e d 
safel y a n d pr o perl y, a n d ke pt i n a sec ure d l ocati o n t o w hic h o nl y t he staff ha ve access. U p o n 
recei pt, all st u d y pr o d ucts s h o ul d be st or e d acc or di n g t o t he i nstr ucti o ns s p ecifie d o n t he pr o d uct 
la bels. St u d y pr o d ucts are t o be dis pe nse d o nl y t o s u bjects e nr olle d i n t he st u d y i n acc or da n ce 
wit h t he pr ot oc ol, b y a ut h orize d site staff.  
T he i n vesti gati ve site m ust mai ntai n a de q uate rec or ds d oc u me nti n g t he recei pt, use, l oss, or 
ot her dis p ositi o n of all t he pr o d uct s u p plies. All st u d y pr o d u cts will be acc o u nte d f or usi n g t he 
i n vesti gati o nal/st u d y pr o d uct acc o u nta bilit y f or m/rec or d. T he i n vesti gat or is res p o nsi ble f or 
st u d y pr o d uct acc o u nt a bilit y, rec o n ciliati o n, a n d rec or d mai nte n a nce.  
T he acc o u nt a bilit y rec or ds m ust be a vaila 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.  
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Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber : 2 1 5 2 6 2   
 
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 6. 0  
Pa ge 4 7  of 8 5  
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 he Pri nci p al I n vesti gat or or a n a p pr o p riate desi g n ee, a n d a 
re pres e 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 nta 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 us e d) f or t his cli nical st u d y 
(i ncl u di n g e m pt y c o ntai n ers), will be ret ur n e d f or destr ucti o n t o t he G S K C H  Cli nical S u p plies  
or a p pr o priate G S K a p pr o ve d ve n d or . Use d s u n dr y it e ms will be destr o ye d at t he site, per Ta ble 
6 -2 , a n d s h o ul d n ot be ret ur ne d.  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 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 os e 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  
R a n d o miz ati o n  
S u bjects w h o si g n t h e i nf or me d c o nse nt f or m (I C F), meet eli gi bilit y criteria, a n d c h ec k i nt o t he 
st u d y cli nic o n Da y -1 will be ra n d o ml y assi g n e d t o 1 of t h e 2 tr eat m e nt se q ue n ces: ( 1) 
Test/ Refere n ce; a n d ( 2) Refere n ce/ T est.  
A ra n d o mizati o n list  will be ge nerate d b y a n  
 ra n d o mizati o n statisticia n*, w h o is  
i n de pe n de nt fr o m t he st u d y te a m, pri or t o t he start of st u d y f or i m ple me nt ati o n at st u d y site. 
Ra n d o mizati o n m ust be f oll o we d e x actl y as ge nerate d, a n d eli gi ble s u bjects will be assi g ne d 
seq ue ntiall y (i.e., base d o n Scree ni n g or der) .   
T he res p o nsi bilit y of t his statisticia n is li mite d t o ge nerati o n a n d mai nte na nce of ra n d o mizati o n 
relate d materials. 
T he r a n d o mizati o n list will be sa ve d i n a sec ure access-restri cte d f ol der o n  
 n et w or k 
d ri ve. O nl y t he ra n d o mi zati o n statisticia n a n d a n ot her se ni or re vie wer (a n ot her i n de pe n de nt 
statisticia n) will ha ve access t o t his f ol der. O nl y aft er data base l oc k a n d  recei pt of t he u n bli n di n g 
re q uest f or t he st u d y (t o b e si g n e d b y G S K a n d 
, will  t he ra n d o mizati o n statisticia n will 
releas e t he ra n d o mizati o n files f or use b y st u d y tea m i n ge n erati o n of T L Fs.  
G S K C H  Cli nical S u p plies will be pr o vi de d wit h ra n d o mizati o n sc he d ule pri or t o st u d y 
i nitiati o n t o all o w t he p ac ka gi n g of st u d y pr o d ucts i n di vi d uall y f or eac h s u bject a n d t heir 
verificati o n. St u d y pr o d ucts  will be i n di vi d uall y pac ke d a n d la belle d f or eac h s u bject a n d peri o d 
acc or di n g t o t he Ra n d o miz ati o n Sc he d ule b y res p o nsi ble pers o ns dele gat e d b y G S K C H .  
Ret ur ne d st u d y pr o d ucts s h o ul d n ot  be re -dis pe nse d t o a n y s u bject.  
Bli n di n g  
St u d y will be  o pe n la bel , b ut la b orat or y a nal ysis will be bli n de d . A nal ysts of bi oa nal ytical 
la b orat or y will ha ve n o access t o ra n d o mizati o n sc he d ule, a n d, sa m ples will be se nt t o a nal yti cal 
la b orat or y wit h bli n de d c o de t o e ns ure t hat staff at a nal ytical la b are n ot a ware of treat me nt 
stat us of t he s u bjects. Als o, st u d y pers o n nel w h o  will be  i n v ol ve d i n data a n al ysis are t o re m ai n 
bli n de d t o treat me nt c o des  u ntil t he data base l oc k . 
6. 6  
Br e a ki n g t h e Bli n d  
N ot a p plica ble  gi ve n t he o pe n la bel st u d y d esi g n.  
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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6.7 
Compliance 
Study products will be administered under the supervision of investigator site personnel. The 
designated dosing personnel must check the mouth to ensure that the suspension has been 
swallowed. A record of the administration of study treatments (time and date of preparation of 
study drug, study drug ingestion start and stop time and date, including dates for intervention 
delays) will be kept using the Dosing Accountability Log and the CRF, any comments on the 
performance of this procedure should be recorded on the CRF. Any violation of compliance 
will require evaluation by the investigator and sponsor to determine if the subject will continue 
in the study. 
6.8 
Concomitant Medication/Treatment(s) 
Any medications, treatments or vaccine (including over-the-counter or prescription medicines, 
dietary supplements, 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 30 days prior to signing the informed consent form and 
before first dose of study product will be documented as a prior medication/treatment.  
Medications/treatments taken after first dose of study product will be documented as 
concomitant medication/treatments. 
Subjects will abstain from all concomitant treatments, except for contraceptives and those used 
for the treatment of adverse events.  
6.9 
Rescue Medication  
Not applicable as study subjects are healthy and thus there is no disease condition symptoms to 
be controlled. 
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 for safety, behavioral reasons, 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: 
At subject’s discretion   
• Withdrawal of informed consent 
• Subject lost to follow-up  
At investigator’s discretion 
• Protocol violation that may impact the subject’s safety 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 4 9  of 8 5  
•  If t h e s u bject is n o l o n ger a ble t o partici pate f or ot h er cli nicall y rele va nt me dical reas o ns 
(e. g. diffic ult bl o o d dra wi n g, s ur ger y, a d v er se e ve nt)  
•  S eri o us a d verse e ve nt  
•  P re g n a nc y 
•  E mesis s h ortl y/i m me diat el y bef ore a d mi nistrati o n of i n vesti gati o nal pr o d uct (assesse d 
o n case b y case b asis)  
•  E mesis  wit hi n 1 0 3 mi n utes 1 p ost d osi n g  
•  Diarr hea  wit hi n 1 0 h o urs p ost d osi n g  
•  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 v esti gat or 
•  B o d y te m perat ure c o nsiste ntl y < 3 5. 4 a n d/ or ≥ 3 7. 3° C  (t hree c o nsec uti ve meas ure me nts 
assesse d at least 1 5  mi n utes  a part in a si n gle da y ) 
•  If t he s u bject re q uires tr eat me nt wit h a n y me dicati o n w hic h is k n o w n or s us pecte d t hat 
it ca n i nterfere wit h t he st u d y dr u gs p har mac o ki netics or a nal ytical  met h o d ol o g y  
•  T here is e vi de nce t hat t he s u bject fails t o c o m pl y wit h t he st u d y pr ot oc ol directi ves ( n o n -
atte n da nce at st u d y ass ess me nts, n o n -c o m plia nce wit h t he tr eat me nt sc he d ule, n o n -
a d here n ce t o dietar y r ules or ot her restri cti o ns w hic h ma y i nfl ue n ce o n p har mac o ki netic 
st u d y res ults). Disc o nti n uati o n of t he s u bject de pe n ds o n I n vesti gat or’s j u d ge m e nt a n d 
decisi o n  
•  A n y ot her c o n diti o n occ urs w hic h i n t he o pi ni o n of t he I n vesti gat or n o l o n ger j ustifies 
or per mits a safe partici p ati o n of t he s u bject.  
If a s u bj ect is disc o nti 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 h e ass ociate d date m ust be d oc u me nt e d i n t he rele va nt 
secti o n(s) of t he C R F. S u bjects w h o wit h dra w or are wit h dra w n fr o m t he st u d y after d osi n g will 
n ot be re place d. S u bjects wit h dra w n f or safet y reas o ns or f oll o wi n g a v o miti n g e pis o de will be 
as ke d t o re mai n at t he cli nic u ntil t he I n vesti gat or(s) a grees t hat t he s u bject is fi ne a n d ca n be 
disc har ge d. As s o o n as s u bject wit h dra wal is c o nfir me d, bl o o d sa m pli n g will be st o p pe d.  
I n t he e ve nt of a pre m at ure wit h dra wal aft er d osi n g, t he s u bject will be re q ueste d t o c o m plete a 
safet y ass ess me nt at t he ti me of disc o nti n uati o n ( or as s o o n as p ossi ble after t he ti me of 
disc o nti n uati o n)  
 
7. 2  
L o st t o F oll o w u p  
A s u bject will be c o nsi dere d l ost t o f oll o w u p if he or s he re p eate dl y fails t o ret ur n f or sc h e d ule d 
visits a n d is u na ble t o be c o ntacte d b y t he st u d y sit e. Bef ore a s u bject is dee me d l ost t o f oll o w 
u p, t he i n vesti gat or or d esi g nee m ust ma ke e ver y eff ort t o re gai n c o ntact wit h t he s u bject. T hese 
c o ntact atte m pts s h o ul d be d oc u me nte d. If c o ntact is ma de wit h t he s u bject, t he i n vesti gat or 
s h o ul d i n q uire a b o ut t he reas o n f or wit h dr a wal, re q uest t hat t he s u bject ret ur n f or a fi nal visit 
a n d f oll o w-u p wit h t he s u bject re gar di n g a n y  u nres ol ve d a d verse e v e nts ( A Es).  
                                                 
 
1 T his e q uals t wice t he refere nc e’s tma x ; o bser ve d i n G S K st u d y A 2 2 1 0 3 7 8 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 50 of 85 
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. 
8 
STUDY PROCEDURES 
This section lists the procedures to be completed at each planned study visit.  An overview of 
study activities is provided in Table 4-1 and Table 4-2. 
Adherence to the study design requirements, including all procedures are essential and required 
for study conduct.  
The site may contact subjects prior to study visit as part of pre-screening activities and follow 
up of AEs as detailed in Section 8.4: Follow up Visits Further details will be included in the 
Informed Consent Form (ICF). Subjects will be invited for antigen test at least 16 hours before 
check-in. Subjects will be then confined from at least 12 hours before dosing until after the 
second 24-hour post-dose blood collection. There will be a washout of at least 72 hours between 
drug administration.  
Participation of each subject in this study should last approximately 1 month (from the time of 
ICF signature to the end of the clinical part of the study). 
8.1 
Screening 
Screening procedures will be conducted by the Investigator, or suitably qualified designee. 
Subjects will be screened within 15 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. Two copies of the ICF will be signed and dated by the subject, the subject will retain 
one copy and the other will be kept at site. 
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 GSKCH. 
The investigator, or designee, should sign and date each copy of 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. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 51 of 85 
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 
8.1.2 
Demographics 
The following demographic information will be recorded in the CRF: year of birth, gender 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 
Medical History 
The Investigator, or medically qualified designee, will take a medical history from each subject. 
Details of relevant medical and surgical history (in the last 1 year), including allergies or drug 
sensitivity, will be documented in the CRF. 
8.1.4 
Prior Medication/Treatment 
Prior medications/treatments, including prescription and non-prescription drugs, dietary 
supplements and herbal remedies, taken in the last 30 days prior to signing the informed consent 
form, will be documented in the CRF. 
8.1.5 
Physical Examination 
Physical examination will be performed, and findings will be documented in the CRF. 
8.1.6 
Height and Weight 
Height and weight measurements will be recorded in the CRF. 
8.1.7 
Vital Signs  
Vital signs will be assessed, and readings will be documented in the CRF. 
8.1.8 
Body Temperature 
Body temperature will be checked, and readings will be documented in the CRF. 
8.1.9 
Screening Procedures  
Nasopharyngeal swab sample will be collected for COVID19 test once for screening. The 
second test will be done on the day of check-in (Day -1). Date and time of sample collection 
and test results (positive or negative) will be documented in the CRF. 
12-lead ECG assessment will be performed, and findings; normal or abnormal (with details), 
and clinical significance will be documented in the CRF. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 52 of 85 
Blood sample will be collected for blood pregnancy test, Biochemistry, Hematology and 
coagulation. Date and time of sample collection will be documented in the CRF. 
Blood sample will be collected for Virology. Date and time of sample collection will be 
documented in the CRF. 
Urine sample will be collected for analysis. Date and time of sample collection will be 
documented in the CRF. 
Urine sample will be collected for illicit drug screen. Date and time of sample collection and 
test’s outcome (positive or negative) for each drug will be documented in the CRF. 
Urine sample will be collected to perform cotinine test. Date and time of sample collection and 
test’s outcome (positive or negative) will be documented in the CRF. 
Alcohol screen with breath analysis will be performed. Date and time of sample collection and 
test’s outcome (positive or negative) will be documented in the CRF. 
8.1.10 
Inclusion/Exclusion Criteria 
Inclusion and exclusion criteria information, as specified in Section 5, will be documented in 
the CRF. 
8.1.11 
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 in the Informed Consent Form 
and 
information 
for 
volunteers, 
Lifestyle 
Guidelines 
and 
any 
Concomitant 
Medication/Treatment(s) requirements of the protocol. 
8.2 
Study Period 
8.2.1 
Day -1   
During check-in, the subject receives an unremovable bracelet with Study number, Subject 
Number and Period Number. Subjects must wear the bracelet until the last blood collection in 
the second Study Period. 
Randomization of subjects to either of test or control arms will be performed 
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF. 
Body temperature will be checked, and readings will be documented in the CRF. 
Nasopharyngeal swab sample will be collected for COVID19 antigen test. Date and time of 
sample collection and test results (positive or negative) will be documented in the CRF. 
Urine Pregnancy test will be done with female subjects. Date and time of test and test’s outcome 
(positive or negative) will be documented in the CRF. 
Urine sample will be collected for illicit drug screen. Date and time of sample collection and 
test’s outcome (positive or negative) for each drug will be documented in the CRF. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 53 of 85 
Urine sample will be collected to perform cotinine test. Date and time of sample collection and 
test’s outcome (positive or negative) will be documented in the CRF. 
Alcohol screen with breath analysis will be performed. Date and time of sample collection and 
test’s outcome (positive or negative) 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. 
The admission procedure must be completed before dinner is served. The dinner should be 
consumed within 30 minutes after being served in order to keep the fasting period for at least 
10 hours prior to dosing. 
Thirty-seven (37) subjects and two (2) over-night standby subjects will be confined. The 
standby subjects follow all Day -1 and Day 1 study procedures until the first study product 
administration. Catheter insertion and pre-dose blood sample are not applicable for standby 
subjects if not necessary.  
8.2.2 
Day 1  
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF.  
Physical examination will be performed, and findings will be documented in the CRF. 
Vital signs will be assessed, and readings will be documented in the CRF. 
Body temperature will be checked, and finding is to be documented in the CRF 
Continued eligibility criteria will be checked. If a subject is not found eligible for further 
continuation in the study, reason should be documented in the CRF.  
Standby subjects can replace a subject who are not randomized on Day 1, otherwise he/she is 
discharged. 
Study product (test and control) will be administered as per the study groups to which subjects 
are randomized for period 1. A record of the administration of study treatments (intervention 
start and stop dates, including dates for intervention delays and/or dose reductions) will be kept 
using the Dosing Accountability Log and the CRF, any comments on the performance of this 
procedure should be recorded on the CRF. 
Blood sample collection for PK parameters will be done as per the schedule outlined in the 
Table 4-2. Actual times of PK-blood sampling will be recorded in 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 
Day 2 
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF.  
Vital signs will be assessed, and readings will be documented in the CRF. 
Body temperature will be checked, and finding is to be documented in the CRF. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 54 of 85 
Continued eligibility criteria will be checked. If a subject is not found eligible for further 
continuation in the study, reason should be documented in the CRF. 
Blood sample collection for PK parameters will be done as per the schedule outlined in the 
Table 4-2. Actual times of PK-blood sampling will be recorded in CRF. 
Spontaneous reporting of AEs 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. 
8.2.4 
Washout 
There will be a 72-hour washout scheduled between each dose administered. 
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF. 
Vital signs will be assessed, and readings will be documented in the CRF. 
Body temperature will be checked, and finding is to be documented in the CRF. 
Urine Pregnancy test will be done. Date and time of test along with test’s outcome (positive or 
negative) will be documented in the CRF. 
Continued eligibility criteria will be checked. If a subject is not found eligible for further 
continuation in the study, reason should be documented in the CRF.  
Spontaneous reporting of AEs 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. 
The dinner should be consumed within 30 minutes after being served in order to keep the fasting 
period for at least 10 hours prior to dosing. 
8.2.5 
Day 4 
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF.  
Physical examination will be performed, and findings will be documented in the CRF. 
Vital signs will be assessed, and readings will be documented in the CRF. 
Body temperature will be checked, and reading will be documented in the CRF. 
Continued eligibility criteria will be checked. If a subject is not found eligible for further 
continuation in the study, reason should be documented in the CRF.  
Study product (test and control) will be administered as per the study groups to which subjects 
are randomized in period 2 of study i.e. post crossover. A record of the administration of study 
treatments (intervention start and stop dates, including dates for intervention delays and/or dose 
reductions) will be kept using the Dosing Accountability Log and the CRF, any comments on 
the performance of this procedure should be recorded on the CRF. 
Blood sample collection for PK parameters will be done as per the schedule outlined in the 
Table 4-2. Actual times of PK-blood sampling will be recorded in CRF. 
Spontaneous reporting of AEs 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. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 55 of 85 
8.2.6 
Day 5 
Continued eligibility criteria will be checked. If a subject is not found eligible for further 
continuation in the study, reason should be documented in the CRF.  Blood sample collection 
for PK parameters will be done as per the schedule outlined in the Table 4-2. Actual times of 
PK-blood sampling will be recorded in CRF. 
Spontaneous reporting of AEs 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 
End of Study /Day 5 
The exit examination procedure will be done before check-out from the clinic in case of subjects 
withdrawn from the study, within 72 hours after withdrawal, if possible. 
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF. 
Physical examination will be performed, and findings will be documented in the CRF. 
Vital signs will be assessed, and readings will be documented in the CRF. 
Body temperature will be checked, and reading will be documented in the CRF. 
Nasopharyngeal swab sample will be collected for COVID19 antigen test. Date and time of 
sample collection and test results (positive or negative) will be documented in the CRF. 
Continued eligibility criteria will be checked. If a subject is not found eligible for further 
continuation in the study, reason should be documented in the CRF.   
Blood sample will be collected for Biochemistry, Hematology and coagulation. Date and time 
of sample collection will be documented in the CRF. 
Urine sample will be collected for analysis. Date and time of sample collection will be 
documented in the CRF. 
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. 
If a subject has any clinically significant, study-related abnormalities or AEs at the end of the 
study, the GSKCH 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.  
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 5 6  of 8 5  
I n t hes e cas es, t he i n vesti gat or m ust ta ke all ste ps necessar y t o e ns ure t h e safet y a n d well-bei n g 
of t he s u bje ct.  W he n a pr ot oc ol -re q uir e d assess me nt ca n n ot be p erf or me d, t he i n vesti gat or ( or 
desi g nee) will d oc u me nt t he reas o n f or t he misse d assess me nt as a pr ot oc ol de viati o n a n d a n y 
c orrecti ve a n d pre v e ntati ve acti o ns t hat he or s he has ta ke n t o e ns ure t hat re q u ire d pr ocesses are 
a d here d t o as s o o n as p ossi ble.  T he S p o ns or m ust be i nf or me d of a n y misse d assess me nts i n a 
ti mel y ma n ner. 
9. 1  
S cr e e ni n g A s s e s s m e nt s  
Scree ni n g ass ess me nts will be perf or me d b y a p pr o priatel y trai n e d staff/ cli nical e x a mi ners at 
t he ti mes, a n d i n t he or der, defi ne d i n t he Secti o n 8: St u d y Pr oce d ures  of t his pr ot oc ol  
9. 2  
Effi c a c y A s s e s s m e nt s  
N ot a p plica ble . 
9. 3  
S af et y a n d Ot h er A s s e s s m e nt  
O ver t he c o urse of t he st u d y, s u bjects will be m o nit ore d b y 
 
cli nical staff. Ot her Healt h -relate d e ve nts/A d verse e ve nts will be c ollecte d b y 
. A n y res ult o utsi de n or mal ra n ges will be e val u ate d b y I n v esti gat or. T he 
assess me nts ma y be re peate d f or safet y reas o ns if a b n or mal res ults are o bs er ve d at t he i nitial 
rea di n g. 
At scre e ni n g p has e, Safet y M o nit ori n g i ncl u des c ollecti o n a n d assess m e nt of me di cal a n d 
me dicati o n hist ories, p h ysical e x a mi nati o n i ncl u di n g b o d y hei g ht a n d wei g ht , 1 2-lea d E C G, 
vital si g ns, b o d y t e m perat ure, hae m at ol o g y, cli nical c h e mistr y , s er u m F S H if a p plica ble, 
c oa g ulati o n, uri nal ysis a n d pre g na nc y t est.  
D uri n g c o nfi ne me nt p has e, Safet y M o nit ori n g i ncl u des c ollecti o n a n d assess me nt of vital si g ns. 
At Cli nical U nit, t he s u bjects will be weari n g wireless pa ger f or acti vati o n of t he e mer ge nc y 
alar m s yste m.  O ne p h ysicia n a n d o ne n urse will be prese nt at Cli nical U nit d uri n g w h ol e 
c o nfi ne me nt p has e as a mi ni m u m.  
T he f oll o wi n g safet y assess me nts will be perf or me d b y a p pr o priatel y trai ne d staff/cli nical 
e x a mi ners, at t he ti mes a n d i n t he or der defi ne d i n t he Secti o n 8 : St u d y Pr oce d ures.   
9. 3. 1  
L a b or at or y T e st s  
T he f oll o wi n g la b orat or y tests/a nal ytical meas ures will be perf or me d b y a p pr o priatel y tr ai ne d 
staff/cli nical e x a mi ners, at t he ti mes a n d i n t he or der defi ne d i n t h e Secti o n 8 : St u d y Pr oce d ures. 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
P P D
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 57 of 85 
Table 9-1 
Laboratory Tests 
Hematology 
Chemistry 
Urinalysis 
Other 
Hemoglobin 
Hematocrit  
RBC count  
MCV 
MCH 
MCHC 
Platelet count  
WBC count 
Neutrophils 
(Absolute count) 
Eosinophils 
(Absolute count) 
Monocytes 
(Absolute count) 
Basophils 
(Absolute count) 
Lymphocytes 
(Absolute count)  
PT/INR 
Urea  
Creatinine 
Glucose (fasting)  
Calcium  
Magnesium  
Sodium  
Potassium  
Chloride 
AST  
ALT 
Direct Bilirubin 
Indirect Bilirubin 
Total Bilirubin 
Alkaline phosphatase 
Uric acid 
Albumin 
Total protein 
Creatine kinase 
GGT 
Cholesterol 
Serum FSHa 
pH 
Glucose  
Protein  
Blood   
Ketones  
Nitrites 
Urobilinogen 
Urine Bilirubin 
Specific gravity 
Hemoglobin 
Microscopy (RBC, 
WBC, squamous 
epithelial cells, 
transitional epithelial 
cells and casts) 
Urine drug screenb 
Urine cotinine screen 
Serum pregnancy 
testc 
 
Definitions:  RBC= Red blood cell; MCV= Mean corpuscular volume; MCH= Mean corpuscular 
hemoglobin; MCHC= Mean corpuscular hemoglobin concentration; ; WBC= White blood cells; ; HIV= 
Human immunodeficiency virus; AST= transaminase; ALT= alanine transaminase; PT/INR= 
prothrombin time/ international normalized ratio; GGT= Gamma-glutamyl transpeptidase. 
a FSH done at Screening Period only in females who have been amenorrhoeic for 1 year. 
b Minimum requirement for drug testing includes cocaine, THC, morphine, benzodiazepines, 
amphetamines, barbiturates, tricyclic antidepressants, methamphetamine, methadone and ecstasy; to 
be done at screening and Day - 1  
c Female subjects of childbearing potential will be tested for serum human chorionic gonadotropin (hCG) 
as applicable-see section 9.3.2  
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 
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.  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 at baseline and at 
all times post-dosing must be retained and stored for the duration of the study. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 5 8  of 8 5  
All H u ma n Bi ol o gi cal Sa m ples ( H B S)  will be  refri gerate d ( or ke pt c ol d i n a c o oler wit h a fr oze n 
ice pac k) u ntil tra ns p orte d t o t he l a b orat or y f or a n al ysis. T h e c o oler will be sec urel y seal e d wit h 
ta pe a n d se nt t o t he La b orat or y, prefera bl y o n t he sa me da y as c ollecti o n.  
All H B S  t o be st or e d till it is pr o perl y dis p ose d of at t he e n d of its rete nti o n p eri o d ( i.e. till st u d y 
re p ort is iss ued), or  usef ul life ( i.e. till e x pir y of sta bilit y), or u p o n recei pt of a re q u est t o destr o y 
t he H B S  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 1 year fr o m last 
partici pa nt last visit.  
9. 3. 2  
Pr e g n a n c y T e sti n g  
F or fe male s u bjects of c hil d beari n g p ote ntial, a bl o o d pre g na n c y test, will be perf or me d d uri n g 
scree ni n g. Uri ne pre g n a n c y test will be perf or me d o n Da y -1  a n d  Da y 3 . Fe male wit h a p ositi ve 
uri ne pre g n a nc y test s h o ul d n ot be d ose d u ntil a ser u m ß -h C G is ne gati ve .  
A sa m ple of uri ne will b e c ollect e d i nt o a u ni versal c o nt ai ner a n d a pre g n a nc y t est  will b e  
perf or me d usi n g  uri nar y pre g na nc y  kit.  
T he i n vesti gat or a n d site pers o n nel will re mi n d s u bjects at eac h visit t o i nf or m site pers o n nel if 
t heir me nstr ual c ycle has c ha n ge d or if t he y ha v e a n y ot her reas o n t o s us pect t he y ma y b e 
pre g na nt ( e. g. ha d u n pr ot ecte d i nterc o urse si nc e t h e last visit).  
A ne gati ve pre g n a nc y res ult is re q uire d bef ore t he s u bject ma y recei ve t he i n vesti gati o nal 
pr o d uct.  Pre g na n c y tests will als o be d o ne w he ne ver o ne me nstr ual c ycle is misse d d uri n g t he 
acti ve st u d y p eri o d ( or w he n p ote ntial pre g na n c y is ot her wise s us pecte d). Pre g na nc y t ests ma y 
als o be re p eate d as per re q uest of I R Bs/ E Cs or if re q uire d b y l ocal re g ulati o ns.  
I n t h e cas e of a p ositi ve c o nfir me d pre g na n cy, t h e s u bject 
will b e 
wit h dra w n fr o m 
a d mi nistrati o n of i n vesti gati o nal pr o d u ct a n d fr o m t he st u d y.  
9. 3. 3  
P h y si c al E x a mi n ati o n  
P h ysical e x a mi nati o ns ma y b e c o n d u cte d b y a p h ysicia n, trai ne d p h ysicia n's assista nt, or n urse 
practiti o ner as acce pta bl e acc or di n g t o l ocal re g ulati o n.  A f ull p h ysical e x a mi nati o n will 
i ncl u de hea d, ears, e yes, n ose, m o ut h, s ki n, heart a n d l u n g e x a mi nati o ns, l y m p h n o des, 
gastr oi ntesti nal, m usc ul os keletal, vasc ular a n d ne ur ol o gical s yste ms.   
Partici pa nts wit h  fi n di n gs o utsi de t he n or mal ra n ge, o bser ve d d uri n g s cree ni n g , s h o ul d b e 
e x cl u de d fr o m t he  st u d y base d o n i n vesti gat or’ s discreti o n. A n y u nt o war d fi n di n gs i de ntifie d 
o n p h ysic al e x a ms c o n d u cte d aft er t he a d mi nistrati o n of t he first d ose of i n v esti gati o nal pr o d uct 
will be ca pt ure d as a n A E , if t h ose fi n di n gs me et t he defi niti o n of a n A E . 
9. 3. 4  
H ei g ht , W ei g ht a n d B MI  
Hei g ht will be meas ur e d usi n g a p orta ble sta di o -meter, wit h t he s u bject sta n di n g bare -f o ot, t o 
t he nearest 0. 1 c m. A n a v era ge of 3 meas ure me nts will be rec or de d . 
Wei g ht will be m eas ur e d i n sta n dar d cl ot hi n g o n st a n dar dize d wei g hi n g scal e t o t he nearest 0. 1 
k g. S u bjects m ust re m o ve s h oes, b ul k y la yers of cl ot hi n g, a n d jac k ets s o t hat o nl y li g ht cl ot hi n g 
re mai ns.  T he y m ust als o re m o ve t he c o nte nts of t heir p oc kets a n d re mai n still d uri n g 
meas ure me nt of wei g ht.  
B MI will be calc ulate d acc or di n g t o  
 S O P  
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
P P D


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 59 of 85 
9.3.5 
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. 
Supine blood pressure will be measured with the subject’s arm supported at the level of the 
heart and recorded to the nearest mm Hg after a minimum 5 minutes of rest.  The same arm 
(preferably the dominant arm) will be used throughout the study.  The same properly sized and 
calibrated blood pressure cuff will be used to measure blood pressure each time. The use of an 
automated device for measuring BP and pulse rate is acceptable, although, when done manually, 
pulse rate will be measured in the brachial/radial artery for at least 30 seconds.   In case of 
coincidence of one or more clinical procedures, and unless deemed by the Investigator 
necessary otherwise, the order of procedures is: Blood Sampling > Vital Signs Reading > AE 
Checks > water intake and/or food intake. 
Systolic and diastolic blood pressures (BP, mmHg) and heart rate (HR, bpm) will be monitored 
during screening procedure, check in, prior to dosing (-1.00) and 2.00, 4.00 and 12.00 and 24.00 
hours after dosing, every day during the subjects’ stay in clinical unit and at exit examination. 
Additional measurements will be performed for medical reasons if necessary. 
Pre-dose vital signs (-1.00 hour) will be measured with allowance up to +50 minutes from the 
scheduled time but must be measured before intravenous catheter insertion. After the drug 
administration, the vital signs will be measured after blood samples drawing with allowance up 
to +15 minutes from the scheduled time. 
The Investigator should be notified immediately, if BP (systolic/diastolic) is outside the range 
of 90-140/60-90 mmHg or HR out of range 50-100 bpm during check-in on day -1, prior to 
dosing (-1.00 hour) and 2.00, 4.00, 12.00 and 24.00 hours after dosing in each period. The 
Investigator should assess clinical significance of each deviation from above described range 
of BP or HR. 
9.3.6 
Respiratory Rate 
Respiratory rate will be measured as a part of vital signs, along with blood pressure and heart 
rate assessment. It will be measured after approximately 5 minutes rest in supine 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 during the 
5 minutes of rest and before blood pressure measurement. 
9.3.7 
Body Temperature 
Body temperature will be measured during screening procedures, check in, in the morning and 
in the evening during the subjects’ stay at the clinical unit, and at exit examination and 
additionally based on Investigator’s judgement. 
Abnormal values ranges are < 35.4 and/or ≥ 37.3°C. 
9.3.8 
COVID-19 Test 
Nasopharyngeal swab will be collected to test for COVID-19 using RT PCR or antigen test, at 
times specified in the Section 8: Study procedures. Two consecutive negative tests for active 
COVID-19 separated by > 24 hours are required for inclusion in the study. The second test will 
be done on the day of check-in (Day -1). 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 6 0  of 8 5  
F or dete cti o n of C O VI D -1 9, test/s are t o be perf or me d as f oll o ws: 
•  At scree ni n g visit  - R T P C R test is t o be d o ne.  
•  At c hec k -i n a n d earl y disc o nti n uati o n or e n d of st u d y - A nti ge n test is t o be d o ne.  
•  At a n y ti me d uri n g resi de ntial peri o d i n st u d y, w he n s u bject re p ort s y m pt o ms s u g gesti ve 
of C O VI D -1 9, s u bject will b e is olate d i n t he u nit a n d a nti ge n t est will be d o ne.   
•  If a nti ge n t est res ult is ne gati ve, R T P C R test will be c o n d uct e d, a n d s u bject will be 
is olate d i n t he u nit.  If t h e R T P C R test res ult is n e gati ve, d ecisi o n o n f urt h er st u d y 
partici pati o n will be as p er i n vesti gat or’s discreti o n b ase d o n s u bject’s me dical 
c o n diti o n. If R T P C R test res ult is p ositi ve, s u bject will be wit h dra w n fr o m t he st u d y 
as per pr ot oc ol S ecti o n 7. 1 : S u bject Disc o nti n uati o n/ Wit h dra wal  a n d disc har ge d f or 
f urt her ma n a ge me nt of t h e disease.  
•  If a nti ge n test res ult is p ositi ve, R T P C R test will be c o n d ucte d a n d wit h o ut waiti n g 
f or test res ults, s u bject will be wit h dra w n fr o m t he st u d y as per pr ot oc ol S ecti o n 7. 1 : 
S u bject Disc o nti n uati o n/ Wit h dra wal  a n d disc har ge d f or f urt her ma na ge me nt of t he 
disease.  
C O VI D -1 9 hist or y s h o ul d be c o m plete d f or eac h p ote ntial partici pa nt ma xi mall y 4 d a ys b ef ore 
t he partici pa nt e nters t he ce ntre. 
T he staff a n d t he st u d y partici pa nts will a d here t o S U K L´s lat est rec o m me n dati o n a n d t o 
 meas ures t o e ns ure t he safet y of t he st u d y partici pa nts d uri n g 
t he C O VI D-1 9 pa n d e mic (e. g. weari n g mas ks, e ns uri n g s ocial dista nci n g a n d i ncreasi n g t he 
disi nfecti o n sc he d ule , as well as c hec ki n g t h e b o d y te m perat ur e). 
9. 3. 9  
El e ctr o c ar di o gr a m  
A sta n dar d 1 2 lea d E C G will be perf or me d f or scree ni n g p ur p oses o nl y. I nter pretati o n of t h e 
traci n g m ust be ma de b y a q ualifie d p h ysici a n a n d d oc u me nte d o n t he E C G secti o n of t he e C R F. 
A si n gle E C G traci n g will be la bele d wit h t he st u d y n u m ber, s u bject i ni tials, s u bject n u m ber, 
date, a n d ke pt i n t he s o urce d oc u me nts at t he st u d y site. Cli nicall y si g nifi ca nt a b n or malities will 
be rec or de d o n t he rele v a nt me dical hist or y/ C urre nt me dical c o n diti o ns e C R F pa ge.  
T he Fri d ericia  Q T C c orrecti o n f or m ula  will be us e d . 
S u bjects s h o ul d be i n a q uiet e n vir o n me nt a n d n ot s pea k d uri n g t he resti n g peri o d or 
meas ure me nt.  Ge n erall y, E C Gs s h o ul d n ot be c ollecte d wit hi n 3  h o urs after f o o d or be v era ge 
c o ns u m pti o n.   
9. 3. 1 0  
Vir ol o g y  
Vir us ser ol o g y will be p erf or me d at ti mes s p ecifie d i n t he Secti o n 8 : St u d y Pr oce d ures f or H Bs 
A g, a nti -H Bc (I g G + I g M), a nti -H C V A b, HI V 1 a n d HI V 2 a nti b o dies. Ser ol o g y will be 
perf or me d b y usi n g t he s a me sa m ple dra w n f or c h e mistr y; t heref ore, n o a d diti o nal bl o o d nee ds 
t o be dra w n f or ser ol o g y. I n case of a p ositi ve fi n di n g i n vir us ser ol o g y scree n, t he s u bject m ust 
be e x cl u de d fr o m trial partici pati o n.  
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
P P D


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9.3.11 
Urine illicit drug screen 
Urine will be collected at times specified in the Section 8: Study Procedures. 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). 
9.3.12 
Urine cotinine level  
Urine cotinine level will be measured at times specified in the Section 8: Study Procedures. In 
case of positive urine cotinine test, the subject must be excluded from trial participation. 
9.3.13 
Alcohol test 
An alcohol breath tests will be conducted at times specified in the Section 8: Study Procedures. 
In case of a positive finding in the alcohol breath test, the subject must be discontinued from 
the trial.  
9.4 
Standard Meals 
During confinement in Study Periods all subjects will be provided with standard meals at 
scheduled times (see Table 1-2). The composition of the standard meals follows the restrictions 
mentioned in Section 5.5: Lifestyle Considerations and will be identical for all study periods. 
An example of the standardized meal composition is shown in Table 9-1 Example Standard 
Meal Composition. 
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Table 9-2  
Example Standard Meal Composition 
Day -1 
Dinner  
Wholegrain roll 2pcs, Butter 10g, Ham salami 100g, Banana, water 
200ml 
Day 1 and Day 4 
Lunch  
Chicken broth with meat and noodles (330ml), Potato dumplings 
stuffed with smoked meat, with cabbage, Water 200ml  
Snack  
Croissant, banana, water 200ml 
Dinner  
Wholemeal roll 3pcs, Lučina 120g, Apple, Water 200ml 
Day 2 
Breakfast Roll 2pcs, Butter 10g, Jam 20g, Water 200ml 
Lunch 
Pea soup scrubs (330ml + 10g), Gypsy pork ribs with rice (100g meat, 
200g sauce, 200g rice), Water 200ml 
Snack  
Croissant, banana, water 200ml 
Dinner 
Bread 2pl., Butter 10g, Ham 100g, Tomato 100g, Water 200ml 
Day 3 
Breakfast Roll 2pcs, Butter 10g, Jam 20g, Water 200ml 
Lunch 
Beef soup with meat and rice (330ml), Beef goulash with dumplings 
(100g meat + 200ml sauce + 160g dumplings), Water 200ml 
Snack  
Corny BIG cranberry, Apple1pc, Water 200ml 
Dinner 
Goulash soup (330ml), Roll 2pcs, Water 200ml 
9.5 
 Pharmacokinetics (PK) 
9.5.1 
Plasma for Analysis of Paracetamol 
In morning of dosing days of both study periods a dead-volume intravenous catheter will be 
inserted into a forearm vein (starting at 06:00 o’clock) by skilled nurses under Investigator’s 
supervision. Catheter insertion is not applicable for stand-by subjects if not necessary. Blood 
samples will be obtained by the catheter for the first 16 hours post-dose. The blood samples 
may be collected by direct venipuncture in case that subject refuses the insertion of the catheter 
or if the catheter is blocked and/or needs replacement. 
During all study periods, blood samples (2mL in each sampling) for pharmacokinetic analysis 
will be collected into appropriately labeled tubes at times specified in the Section 8: Study 
Procedures. 
Total number of blood collections in each study period will be 21. Blood samples will be taken 
at Pre-dose (1 hour before dosing) , and 5, 10, 20, 30, 40, 50, 60, 80, 90, 120, 150, 180 minutes, 
4, 5, 6, 8, 10, 12, 14, 16 hours post-doses.  
Actual times of PK-blood sampling will be recorded immediately after each blood sampling. 
The actual sample times may change but the number of samples will remain the same.  All 
efforts will be made to obtain the pharmacokinetic samples at the exact nominal time relative 
to dosing.  Sampling time deviations ≥ 2 minutes will be repotted during the first 6 hours after 
drug administration. Sampling time deviations ≥  15 minutes will be reported for all remaining 
sampling intervals. During each sampling, venous blood samples (2 ml) will be withdrawn by 
a suitable trained member of the study staff, either from an indwelling cannula or venipuncture 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 6 3  of 8 5  
sit uate d i n a f orear m v ei n. I n or der t o a v oi d cl otti n g, t he cat h eter will be ri nse d wit h 
a p pr o xi matel y 2 m L of a he pari nize d sali ne s ol uti o n ( 5 0 0 I U he pari n i n 1 0 0 m L 0. 9 % w/ v Na Cl 
s ol uti o n) after eac h bl o o d sa m ple c ollecti o n. Pri or t o eac h bl o o d sa m ple c ollecti o n fr o m t he 
cat heter, t he c o nte nt of t he cat heter, i.e. he pari n l oc k s ol uti o n a n d a p pr o xi matel y 2 m L of bl o o d 
will be as pirate d a n d dis car de d . F urt her det ails re gar di n g t he c ollecti o n, pr ocessi n g, st ora ge a n d 
s hi p pi n g of t he bl o o d sa m ples s h o ul d be descri be d i n t he Sa m ple Ha n dli n g M a n ual.  
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 pli a nce wit h a p plica bl e 
 sta n dar d o perati n g pr oce d ures. 
Bi oa nal ytic  of p araceta m ol i n plas ma sa m ples will be perf or m e d b y a s pecific a n d hi g hl y 
se nsiti ve L C-M S/ M S met h o d ol o g y i n a la b orat or y wit h G L P certificati o n.  T he a nal yses of 
pla s ma sa m ples will f oll o w t he pri nci ples of G L P [O E C D Pri nci ples  of G L P ] a n d G C P [I C H 
T o pic E 6 ] w he n e ver a p plica ble  Met h o d vali dati o n will ha ve t o b e c o n d ucte d i n f ull c o m plia nce 
wit h t he res pecti ve g ui d a nce d oc u me nt: ( E M A G ui deli ne o n Bi oa nal ytical Met h o d V ali dati o n 
E M E A/ C H M P/ E W P/ 1 9 2 2 1 7/ 2 0 0 9 Re v. 1 C orr. 2 * *) . T he tar gete d L L O Q of t he met h o d is 0. 2 5  
µ g / m L. Refere nce a n d i nter nal sta n d ar ds will be s u p plie d b y 
. T h e 
P K sa m ples m ust be pr ocesse d a n d s hi p pe d as i n dicate d t o m ai 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 orte d t o t he s p o ns or.  O n a cas e -b y -case b asis, t he s p o ns or ma y ma k e a deter 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 mise d.  A n y s a 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 oc ol de viati o n.  
9. 5. 2  
S a m pl e H a n dli n g  
Bi oa nal ytical La b orat or y  of 
 will iss ue Sa m ple Ha n dli n g Ma n ual 
wit h i nstr ucti o ns f or pr ocessi n g of sa m ples.  
O ver t he c o urse of st or a ge, t he te m p erat ur e will be c o nsta ntl y m o nit ore d a n d rec or de d i n 
acc or da nce wit h 
 S O P. T u be la bels c o ntai n t he i nf or mati o n o n 
S u bject N u m ber, Peri o d N u m ber ( A = peri o d 1, B = peri o d 2 ). Sa m ple N u m ber a n d  
 
St u d y N u m ber.  
E x a m ple: 1 1 A 1 6/ 8 1 1  mea ns 1 6 t h sa m ple of t he first Peri o d of s u bject N o. 1 1, 
 
 
9. 6  
Bl o o d V ol u m e   
T he t otal bl o o d sa m pli n g v ol u me f or eac h s u bject i n t his st u d y is H 1 8 7  m L. T he ta ble bel o w 
reflects a p pr o xi mate sa m ple v ol u mes nee de d f or eac h meas ure d e n d p oi nt.  T he act ual c ollecti o n 
ti mes of bl o o d sa m pli n g ma y c ha n ge, b ut t he t otal bl o o d v ol u me c ollecte d will n ot i ncrease.  
A d diti o nal bl o o d  sa m ples ma y be t a ke n f or s afet y ass ess me nts at t h e discreti o n of t he 
i n vesti gat or or G S K C H . 
T a bl e 9 -2  
Bl o o d V ol u m e  
S a m pl e 
T y p e  
S a m pl e 
V ol u m e ( m L)  
N u m b er of S a m pli n g Ti m e s  
T ot al V ol u m e 
( m L) 
S cr e e ni n g  St u d y 
P eri o d 1  
St u d y 
P eri o d 2  
E n d of 
St u d y 
vi sit  
S af et y 
L a b s  
1 1. 5  
1  
0  
0  
1  
2 3  
P K  
2  
0  
2 1  
2 1  
0  
8 4  
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
P P D
P P D
P P D
P P D
P P D
P P D


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Sample 
Type 
Sample 
Volume (mL) 
Number of Sampling Times 
Total Volume 
(mL) 
Screening 
Study 
Period 1 
Study 
Period 2 
End of 
Study 
visit  
Catheter 
purge 
2 
0 
20 
20 
0 
80 
TOTAL 
 
 
  
 
 
187 
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 product, whether or not considered 
related to the study product, including any washout product. 
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 
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 
medical and scientific judgment of the investigator (i.e., not related to normal/ expected 
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.  
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• 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  
▪ 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 
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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. 
10.3 
Time Period and Frequency for Collecting AE and SAE 
Information 
The Adverse event reporting period begins when the subject first signs informed consent and 
continues until 7 days following last administration of the study product (or last procedure. All 
AEs should be recorded in the CRF in a timely manner. Serious AEs MUST be recorded and 
reported to the Sponsor or designee in the eSAE CRF page immediately (within a maximum of 
24 hours). The investigator will submit any updated SAE data to GSK within 24 hours of it 
being informed. 
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. 
Details recorded by the subject on a diary or similar document that meet the definition of an AE 
must also be discussed with the subjects and transcribed in the AE section of the CRF.  
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 eSAE Form. 
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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 GSKCH in lieu of completion of the AE CRF page/eSAE 
form. 
There may be instances when copies of medical records for certain cases are requested by 
GSKCH.  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 GSKCH. 
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 be then 
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 eSAE 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 electronic 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 eSAE form should be 
completed, as fully as possible.  
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. 
The following are desirable and are of particular relevance for investigator and GSKCH 
assessment of the eSAE report: 
• Date of onset of AE  
• Date AE stopped, if relevant 
• Study product start date 
• Study product end date if relevant 
• Action taken in relation to the study product 
• Outcome if known 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 6 8  of 8 5  
T he eS A E f or m, c o m plet e d as f ull y as p ossi ble, m ust be se nt t o C R O i m me di atel y a n d u n der 
n o circ u mst a nce s h o ul d t his e xcee d 2 4 h o urs of a ware ness.  
S A E C o nt act I nf or m ati o n:  
, 
 
C R O will t he n e mail t he eS A E f or m t o t he Cas e 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 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 le ar n of t he e ve nt. T he G S K C H  St u d y M a na ger will be res p o nsi ble f or 
f or war di n g t h e eS 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 olerat e d b y t he 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 ve 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 ve nt t hat pr e ve nts n or mal e ver y da 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.  
F or eac h A E (seri o us a n d n o n -seri o us), t he i n vesti gat or ( or me di call y q ualifie d desi g n ee) m ust  
pr o vi de a n assess me nt of ca usalit y o n t he A E C R F pa ge a n d t he eS A E f or m (s u bject t o t he 
classificati o n of t he A E). T he i n vesti gat or will als o d oc u me nt i n t he me dical n otes t hat he/s he 
has re v ie we d t he A E a n d assesse d ca usalit y, w here a p plica ble.  
A “reas o na ble p ossi bilit y” of a rel ati o ns hi p c o n ve ys t hat t here are facts, e vi de nce, a n d/ or 
ar g u me nts t o s u g gest a ca usal rel ati o ns hi p, rat her t ha n a relati o ns hi p ca n n ot be r ule d o ut. 
Ge nerall y, t he f acts (e vi d e nce) or ar g u m e nts t o s u g gest a ca us al relati o ns hi p s h o ul d be pr o vi de d.  
T he i n vesti gat or will use cli nical j u d g me nt t o deter mi ne t he relati o ns hi p a n d will als o c o ns ult 
t he I n vesti gat or Br oc h ure (I B), S afet y State me nt a n d/ or Pr o d uct I nf or mati o n, of t he pr o d ucts, 
i n t he deter mi nati o n of his/ her assess me nt.  Alter nati ve ca us es, s uc h as u n derl yi n g dis ease(s), 
c o nc o mita nt t hera p y, ot her ris k fact ors, a n d t he te m p oral relati o ns hi p of t h e e ve nt t o t he st u d y 
pr o d uct will be c o nsi dere d a n d i n vesti gat e d.  
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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 5 2 6 2   
 
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 6. 0  
Pa ge 6 9  of 8 5  
F o r eac h A E/ S A E, t h e i n vesti gat or m ust d oc u me nt i n t he me di cal n otes t hat he/s he has re vie we d 
t he A E/ S A E a n d has pr o vi de d a n assess me nt of ca usalit y. 
T he i n vesti gat or’s assess me nt of ca usalit y m ust be pr o vi d e d f or all A Es (seri o us a n d n o n -
seri o us); t he i n vesti gat or m ust rec or d t he ca usal relati o ns hi p i n t he C R F, as a p pr o pri ate, a n d 
re p ort s uc h a n assess me nt i n acc or da n ce wit h t he S A E re p orti n g re q uir e me nts if a p plica ble. 
T here ma y b e sit uati o ns w he n a n S A E has o cc urre d, a n d t he i n vesti gat or h as mi ni mal 
i nf or mati o n t o i ncl u de i n t he i nitial re p ort t o G S K.  H o w e ver, it is ver y i m p ort a nt t h at t he 
i n vesti g at or al w a ys m a ke a n assess me nt of c a us alit y f or e ver y e ve nt pri or t o t he i niti al 
tr a ns missi o n of t he eS A E d at a t o G S K C H . T he i n vesti gat or ma y c ha n ge his/ her o pi ni o n of 
ca usalit y i n li g ht of f oll o w -u p i nf or mati o n a n d s e n d a n eS A E f oll o w -u p re p ort wit h t he u p d ate d 
ca usalit y assess me nt.   
1 0. 6  
F oll o w -u p of A E s a n d S A E s  
After t he i nitial A E/ S A E re p ort, t he i n vesti gat or is re q uire d t o  pr oacti vel y f oll o w u p wit h eac h 
s u bject a n d pr o vi de f urt h er i nf or mati o n o n t he s u bject’s c o n diti o n. 
All A Es (seri o us a n d n o n -seri o us) will be 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 plai ne d, or u ntil t he s u bject is l ost t o f oll o w -u p.   
T he i n vesti gat or is o bli gate d t o perf or m or arra n ge f or t he c o n d uct of s u p ple me ntal 
meas ure me nts a n d/ or e val uati o ns as ma y be i n dicate d or as re q ueste d b y G S K C H  t o el uci date 
as f ull y as p ossi ble t he nat ure a n d/ or ca usalit y of  t he A E. T his ma y i ncl u de a d diti o nal la b orat or y 
tests or i n vesti gati o ns, hist o pat h ol o gical e x a mi nati o ns, or c o ns ultati o n wit h ot her healt h care 
pr ofessi o nals.  
Ne w or u p date d i nf or mati o n will be rec or de d o n t he A E C R F pa ge a n d o n t he eS A E f or m 
(s u bject t o the classificati o n of t he A E).  
T he i n vesti gat or will s u b mit a n y u p date d eS 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 see k A Es i n f or mer s u bjects.  H o we v er, if t he 
i n vesti gat or le ar ns of a S A E, incl 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 
( wit hi n 
2 4 
h o urs) 
n otif y 
C R O  
 C R O will t he n e mail t o G S K C H  b y e maili n g t he i nf or mati o n t o 
t he G S K C H  Cli nical O perati o ns Safet y Re p orti n g e mail b o x
). 
T he G S K C H  St u d y Ma n a ger or desi g n ee will be res p o nsi ble f or f or war di n g t h e i nf or m ati o n t o 
t he Case Ma n a 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 gr o u p mail b o x at 
G S K 
 
T he i n vesti gat or will s u b mit a n y u p date d eS A E data 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. 
At a n y ti me d uri n g resi d e ntial peri o d i n st u d y, w he n s u bject re p ort s y m pt o ms s u g gesti ve of 
C O VI D -1 9, s u bject will be is olate d i n t he u nit a n d a nti ge n t est will be d o ne.   
•  If a nti ge n t est res ult is n e gati ve, R T P C R test will be c o n d ucte d, a n d s u bject will be 
is olate d i n t he u nit.  If t he R T P C R test res ult is ne gati ve, decisi o n o n f urt her st u d y 
partici pati o n will be as p er i n vesti gat or’s discreti o n basis s u bject’s me dical c o n diti o n. 
If R T P C R test res ult is p ositi ve, s u bject will be wit h dra w n fr o m t he st u d y as per 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
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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 5 2 6 2   
 
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 6. 0  
Pa ge 7 0  of 8 5  
pr ot oc ol S ecti o n 7. 1 : S u bject Disc o nti n uati o n/ Wit h dra wal  a n d disc har ge d f or f urt her 
ma na ge me nt of t he dis ease.  
•  If a nti ge n test res ult is p ositi ve, R T P C R test will be c o n d ucte d a n d wit h o u t waiti n g f or 
test res ults, s u bject will b e wit h dra w n fr o m t he st u d y as per pr ot oc ol S ecti o n 7. 1 : S u bject 
Disc o nti n uati o n/ Wit h dra wal  a n d disc har ge d f or f urt her ma na ge me nt of t he disease.  
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 d isti 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 otif icati 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 l e 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 gulat 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) accor 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 safet 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 I n vesti gat or’s Br oc h ure i n t he i n vesti gat or st u d y master file, a n d will n otif y t h e 
I R B/I E C, if a p pr o priate acc or di n g t o l ocal r e q uire me nts. 
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 nse nt u ntil 7 da ys after t he 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 rec or d pre g n a nc y i nf or m ati o n o n t he a p pr o priate f or m sca n a n d e -mail it 
t o C R O 
) wit hi n 2 4 h o urs of lear ni n g of t h e s u bject bec o mi n g 
pre g na nt . C R O will t he n e mail t o t he G S K C H  Cli nical O perati o ns Safet y Re p orti n g e m ail b o x 
) wit hi n 2 4 h o urs of lear ni n g of t he s u bject bec o mi n g 
pre g na nt. T he G S K C H  St u d y M a na ger or d esi g nee 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 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 
). Ori gi nal pre g na nc y i nf or mati o n f or ms will 
be retai ne d i n t he i n v esti gat or st u d y master file.  
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
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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 5 2 6 2   
 
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 6. 0  
Pa ge 7 1  of 8 5  
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 h e i n vesti gat or t o t he G S K C H  Cli nical 
O perati o ns Safet y Re p orti n g e mail b o x a n d t he G S K C H  St u d y Ma na ger or desi g n ee will 
f or war d t his i nf or mati o n 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 gr o u p mail b o x at G S K  
). 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 
ter mi nati o n of t he pre g n a nc y will be re p ort e 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 will be wit h dra w n fr o m t he st u d y.  
T he i n vesti gat or w ill c ollect pre g n a nc y i nf or mati o n o n a n y s u bject w h o bec o mes pre g na nt 
w hile partici p ati n g i n t he st u d y after a d mi nistrati o n of t he i n vesti gati o nal pr o d uct. T he 
i n vesti gat or will rec or d pre g na nc y i nf or mati o n o n t he a p pr o priate f or m a n d s u b mit it t o C R O 
wit h i n 2 4 h o urs of lear ni n g of t he s u bject bec o mi n g pre g n a nt. T he s u bject will be f oll o we d t o 
deter mi ne t he o utc 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 nate (i ncl u di n g c o nc o mita nt me dicati o ns ta ke n b y t he m ot her d uri n g t he pre g na n c y) 
will be f or war de d t o C R O. Ge n erall y, f oll o w -u p will be n o l o n ger t h a n 6 t o 8 w ee 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.  
C R O will sca n a n d e mail t he pre g n a nc y f or m 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 C H  
 wit h c o p y t o t h e a p pr o priate G S K C H  St u d y Ma n a ger. Ori gi nal pre g n a nc y 
i nf or mati o n f or ms will be retai ne d i n t he i n v esti gat or st u d y master file. 
1 1  
D A T A M A N A G E M E N T  
F or t his st u d y, s u bject data will be e ntere d i nt o a n electr o nic C R F (e C R F), usi n g a v ali date d 
s yste m. Dat a relati n g t o S A Es, pre g na nc y a n d i nci de nts will als o be c ollecte d o n pa per f or ms . 
T he i n vesti gat or is res p o nsi ble f or verif yi n g t hat data e ntries are acc urate a n d c orrect b y 
p h ysicall y or electr o ni call y si g ni n g t he C R F.  
T he s o urce d o c u me nts (e. g. h os pital rec or ds, cli nical a n d office c harts, la b orat or y n otes, 
me m ora n da, s u bject diari es, q uesti o n naires, e val uati o n c hec klists, p har mac y dis pe ns i n g rec or ds, 
rec or de d d ata fr o m a ut o mate d i nstr u me nts, micr ofic hes, p h ot o gra p hic n e gati ves, micr ofil m or 
ma g n etic me dia, x -ra ys, s u bject files a n d rec or ds ke pt at t he p har mac y, at t he la b orat or y a n d at 
t he me dic o-te c h nical de p art me nts i n v ol ve d i n t he cli nical st u d y) w hic h c o ntai n t he s o urce of 
data rec or de d i n t he C R F s h o ul d be s pecifie d.  T he C R F  ca n be use d as a s o urce d oc u me nt at 
t he discreti o n of data m a na ge me nt. 
Eac h s u bject will be assi g ne d a n d i de ntifie d b y a u ni q ue S u bject N u m ber. A n y refere n ce ma de  
t o a n i n di vi d ual s u bject wit hi n t he st u d y m ust be d o ne usi n g t heir u ni q ue Scree ni n g S u bject 
N u m ber.  
T he cli nical data will be c ollecte d o n pa per s o urce d oc u me nts or i n ot her s uita ble wa y ( S u bjects 
Car ds, see Secti o n 1 1. 5  a n d/ or S o urce Dat a F or ms, see Sect i o n 1 1. 6 ) i n li ne wit h t he res pecti ve 
S O Ps b y 
 a n d s u bse q ue ntl y tra nscri be d, w here necessar y, o nt o 
t he C R Fs b y t he cli nical researc h st aff of t he Cli nical Site. T he s o urce data/ d oc u me nts will be 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
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P P D
P P D


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 5 2 6 2   
 
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 6. 0  
Pa ge 7 2  of 8 5  
retai ne d b y t he Cli nical Site i n line wit h re q uire me nts liste d i n Secti o n 8 of  t he I C H c o ns oli date d 
g ui deli ne o n ( G C P) R 2  [I C H G C P E 6 R 2 ]. 
1 1. 1  
C a s e R e p ort F or m  
A C R F is a pri nte d, o ptical, or electr o ni c d oc u me nt desi g ne d t o rec or d t he pr ot oc ol re q uire d 
i nf or mati o n t o be re p ort e d t o t he s p o ns or o n eac h trial s u bject.  
F or eac h s u bject w h o h as gi ve n i nf or me d c o nse nt/asse nt t he C R F m ust b e c o m plete d a n d si g ne d 
b y t he Pri nci pal I n v esti gat or ( or a ut h orize d desi g nee) t o certif y t hat t he data are c o m plete a n d 
c orrect.  T he i n v esti gat or m ust mai ntai n acc urate d oc u me ntati o n (s o urce dat a) t hat s u p p orts t he 
i nf or mati o n e ntere d i n t h e C R F. 
Ma na ge me nt of cli nical data will be perf or me d i n acc or da nce wit h T hir d Part y B D M Ve n d or 
a p plica ble sta n d ar ds a n d data cle a ni n g pr oce d ures wit h o versi g ht b y G S K C H t o e ns ure i nte grit y 
of t he data, f or e x a m ple, t o re m o ve err ors a n d i nc o nsiste ncies i n t he data.  
T o pr otect t he pri vac y of s u bjects, n o Pers o nal I nf or mati o n (i ncl u di n g t h e s u bject's na me or 
i nitials or f ull birt h date) is t o be rec or de d i n t he C R F or as part of t he quer y te xt.  
All C R F pa ges s h o ul d be c o m plete d d uri n g a s u bject assess me nt w he n t he C R F h as b ee n 
desi g nat e d as t he s o urce.  Data t hat is s o urce d else w here s h o ul d be e ntere d i nt o t he C R F i n a n 
a gree d u p o n ti mefra me b et wee n t he I n vesti gat or a n d S p o ns or.   
G S K C H  will o btai n a n d retai n all C R Fs a n d ass ociate d st u d y data as a p plica ble at t he 
c o m pleti o n of t he st u d y.  
1 1. 2  
D at a H a n dli n g  
D oc u me ntati o n of all d ata ma na ge me nt acti vities s h o ul d all o w ste p -b y -ste p retr os p ecti ve 
assess me nt of data q u alit y a n d st u d y p erf or m a nc e.  
A n y c h a n ges or c orrecti o ns t o data will be perf or me d i n t he Electr o nic Data Ca pt ure ( E D C) 
S yste m, a n d it will i ncl u d e rati o nale f or c ha n ges. T he E D C s yste m has a n a u dit trail, w hic h will 
pr o vi de a c o m plete rec or d of t he c ha n ges a n d c orrecti o ns e n d orse d  b y t he I n vesti gat or.  
A d verse e v e nts will be c o de d usi n g Me di cal Di cti o nar y f or Re g ulat or y Acti vities ( Me d D R A) 
a n d a n y c o n c o mita nt me dicati o ns ter ms (if a p plica ble) usi n g a n i nter nal v ali date d me dicati o n 
dicti o nar y,  
   
1 1. 2. 1  
D at a Q u eri e s  
Pr o gra m me d e dit c hec ks will be ge n erat e d a ut o maticall y, as t he d ata are bei n g e nt ere d i nt o t he 
s yste m. Re p orts a n d listi n gs o n t he C R F data will als o be r u n, i n a d diti o n t o t he q ueries alrea d y 
pr o gra m me d a n d ge n erate d b y t he s yste m, t o raise ma n ual q ueries as nee d e d f or s ite 
clarificati o n or c orrecti o n. T he Cli nical Dicti o nar y De vel o p me nt a n d Ma n a ge me nt Gr o u p will 
raise q u eries as n ee d e d o n safet y data t o c o de t he ter ms ( A Es a n d Dr u gs or c o nc o mita nt 
me dicati o n) a p pr o priatel y.  
T he st u d y m o nit or will p erf or m o n g oi n g re vi e w of t he C R Fs i n acc or da n ce wit h t he m o nit ori n g 
pla n, t o c o nfir m t hat data e ntere d i nt o t he C R F b y a ut h orize d site pers o n nel are acc urate, 
c o m plete, a n d verifi a ble fr o m s o urce d oc u m e nts; t hat t he safet y a n d ri g hts of partici pa nts are 
bei n g pr otecte d; a n d t ha t t he st u d y is bei n g c o n d u ct e d i n acc or da nce wit h t he c urre ntl y a p pr o ve d 
pr ot oc ol a n d a n y ot her st u d y a gree me nts, I C H G C P, a n d all a p plica ble re g ulat or y re q uir e me nts.  
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
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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 5 2 6 2   
 
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 6. 0  
Pa ge 7 3  of 8 5  
A n y q u eries will be ge nerate d i n t he E D C S yste m t o t he I n vesti gat or or desi g nee, e na bli n g  t he 
err ors t o be a d dress e d i n parallel wit h Data Ma n a ge m e nt re vie w. T h e st u d y m o nit or ca n als o 
r u n re p orts a n d listi n gs o n t he C R Fs, t o raise ma n ual q ueries as nee d e d f or site clarificati o n or 
c orrecti o n.  
1 1. 3  
Pr o c e s si n g P ati e nt R e p ort e d O ut c o m e s  
N ot a p plica bl e.  
1 1. 4  
E xt er n al D at a  
E xter nal Data are s u bject data o btai ne d e xter nall y t o t he C R F. T hese data are ge n erate d fr o m 
la b orat or y i nstr u me nts, c o m p uters or ot her s o urces a n d t he n tra nscri be d i nt o a file a n d f or mat 
a gree d u p o n b y G S K C H  t o i de ntif y t he s u bject a n d ti me p oi nt refere nce d i n t he C R F a n d/ or 
pr ot oc ol.  
A n a gree d q ualit y c o ntr ol pr ocess will 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 1. 5  
S u bj e ct C ar d s  
S u bject Car ds are pers o n al me dical rec or ds. A n i n di vi d ual S u bject Car d f or eac h s u bject is ke pt 
at Cli nical U nit of 
. S u bject Car d c o ul d c o ntai n st u d y s pecific 
i nf or mati o n o n scree ni n g e x a mi nati o ns. Als o, t he y c o ntai n ot her i n di vi d ual rec or ds o n 
pr oce d ures/i n vesti gati o ns re q uire d b y I n vesti gat or o n a d h oc basis f or me dical reas o ns, u nless 
rec or de d i n S u bject D ata F or ms. T he rec or ds are s orte d o ut st u d y-b y -st u d y wit hi n t he S u bject 
Car d. S u bject Car ds are ke pt at Cli nical U nit of 
. 
1 1. 6  
S u bj e ct D at a F or m s  
S u bject Data F or ms ( S D Fs) are c o m plete d d uri n g t he st u d y a n d t he y are s o urce d oc u m e nts. 
T hese d oc u me nts are c o m m o n f or all st u d y s u bjects. C o m plete d S D Fs are ke pt at 
 
. a n d c o pies of t hese d oc ume nts ( wit h bli n de d s u bjects’ pers o nal data) will 
be pr o vi de d t o t he S p o ns or i n t he Cli nical Re p ort.  
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 p pr o xi matel y 1 1 0  s u bjects will be scree ne d t o ra n d o mize a p pr o xi matel y 3 7 healt h y a d ult 
s u bjects t o e ns ure at least 3 1 e val ua ble s u bjects c o m plete t he e ntire st u d y, ass u mi n g a 1 5 % 
dr o p o ut a n d n o n -e val ua bl e rate. 
 
 
 
 
 
 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
P P D
P P D
P P D
C CI


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 5 2 6 2   
 
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 6. 0  
Pa ge 7 4  of 8 5  
 
 
 
 
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 mi ze d s u bjects w h o c o m plete t he t w o peri o ds 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 . S u bjects wit h baseli ne * 
paraceta m ol 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 x cl u de d fr o m 
P K p o p ulati o n . 
If si g nifica nt n u m ber  of s u bjects/ peri o ds are e x cl u de d fr o m P K p o p ulati o n d ue t o baseli ne * 
paraceta m ol c o n ce ntrati o n > 5 % of t he i n di vi d ual C ma x , a se nsiti vit y a n al ysis will be c o n d ucte d 
i ncl u di n g all s u bjects e v e n t h ose wit h t he affecte d data.  
* Baseli ne is defi ne d  as t h e last a vaila ble val ue bef ore d osi n g.  
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 nal ysis pla n ( R A P), w hic h will be writte n f oll o wi n g fi nalizati o n of t he pr ot oc ol 
a n d pri or t o st u d y a n al ysis  a n d fi nalize d pri or t o data base l oc k . 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 he 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 k e y 
sec o n dar y e n d p oi nts. T he R A P creati o n a n d statistical a nal ysis will be perf or me d b y 
. 
1 2. 3. 1  
Pri m ar y A n al y si s( e s)  
T he pri m ar y p h ar m a c o ki netics A n al ysis V ari a bles:  
• A U C0 -tlast -area u n der t he plas ma c o nce ntr ati o n -ti me c ur ve fr o m zer o t o t he last meas ura ble 
sa m pli n g ti me p oi nt, t, c o m p ute d usi n g t he li near tra pez oi dal r ule. 
• C ma x -ma xi m u m plas ma c o nce ntr ati o n  
• tma x -ti me t o ma xi m u m plas ma c o nce ntrati o n 
P K para meters will be deri ve d usi n g act ual sa m pli n g ti mes aft er data base l o c k a n d u n bli n di n g.   
Criteri a f or assessi n g bi oe q ui v ale nce:  
T he bi oe q ui vale n ce b et wee n a ne w paraceta m ol  oral s us pe nsi o n (T est) a n d t he mar ket e d 
paraceta m ol oral s us pe nsi o n (Pa na d ol B &I ) (R efere nce)  i n faste d stat e will be assesse d :  
•  If t he 9 0 % CI s f or t he rati o of t he mea ns of t he pri mar y p har mac o ki netic para meters, 
A U C 0 -tlast a n d C ma x  of t he paraceta m ol pr ofiles lie c o m pletel y wit hi n t he ra n ge 0. 8 -1. 2 5.  
•  If t here is n o differe nce b et wee n t he t w o tr eat me nts i n ter ms of tma x .  
T he n ull a n d alter n ati ve h y p ot heses t o be teste d i n t he pri m ar y a n al yses are:  
A U C 0 -tlast a n d C ma x  
H 0: T he ( ge o metric) mea n A U C 0 - tlast (li ke wise Cma x ) of a ne w paraceta m ol oral s us pe nsi o n ( Test) 
is less t ha n 8 0. 0 % or greater t ha n 1 2 5. 0 % of t hat of Pa na d ol B & I ( Refere nce). 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
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C CI


GSK Consumer Healthcare 
 
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Protocol Number: 215262  
 
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May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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H1: The (geometric) mean AUC0- tlast (likewise Cmax) of a new paracetamol oral suspension 
(Test) is between 80.0% and 125.0% of that of Panadol B&I (Reference). 
tmax 
H0: There is no difference between a new paracetamol oral suspension (Test) and Panadol B&I 
(Reference). 
H1: There is a difference between a new paracetamol oral suspension (Test) and Panadol B&I 
(Reference). 
An Analysis of Variance (ANOVA) model will be fit to the log-transformed PK parameters 
(AUC0- tlast and Cmax), as the dependent variable, and treatment, period, sequence and subject 
nested within sequence as fixed effects. For each pairwise comparison, only the data from the 
two, corresponding treatments will be included in the model. The presence of a statistically 
significant sequence effect will be noted, and its implications will be discussed. Least squares 
estimates of treatment effects will be calculated and a 90% CI for the treatment difference will 
be computed. The treatment difference and its CI will be exponentiated to obtain the ratio of 
the geometric least square means between the test and reference and its CI. Bioequivalence will 
be determined if the 90% CI for the treatment geometric least square mean ratio lies completely 
within the range 0.80 – 1.25.  
tmax will be analyzed nonparametrically using Wilcoxon signed-rank test. Median of differences 
between treatments will be presented with 90% CI for the median difference based on a method 
by Hodges and Lehman based on the PK population. 
Individual plasma concentrations of paracetamol will be summarized descriptively by treatment 
and each time point for the PK population and will be listed for the safety population.  Mean 
plasma concentration vs. nominal time profiles by treatment will be graphed for the PK 
population. Individual plasma concentration vs. actual time profiles by treatment and individual 
plasma concentrations vs. actual time profiles by subject will be graphed for the safety 
population. All concentration-time profiles will be shown on both original and semi-logarithmic 
scales. 
All PK parameters will be summarized for each treatment by descriptive statistics (for tmax 
and %AUCex, N, arithmetic mean, standard deviation, first and third quartiles, median, 
minimum, and maximum; for the rest of PK parameters, N, arithmetic mean, standard deviation, 
geometric mean, coefficient of variation of geometric mean, median, minimum, and maximum) 
for the PK population.  
A listing containing individual statistics for each PK parameter will be provided for the safety 
population.  
12.3.2 
Secondary Analysis(es) 
The secondary pharmacokinetics Analysis Variables: 
• AUC0-inf-area under the plasma concentration time curve from zero and extrapolated to infinity 
time. 
• %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.  
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 76 of 85 
AUC0-inf will be analyzed using the same ANOVA model method as for AUC0-tlast and Cmax. 
%AUCex and λz will be summarized for each treatment using descriptive statistics same as for 
the primary PK parameters.  
12.3.3 
Safety Analysis(es) 
Safety variables will be summarized for the safety population. 
Adverse Event: 
Treatment Emergent adverse events (TEAEs), i.e. AEs that are emergent or that worsen after 
the first study product (test or reference) administration, 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 similarly. All treatment-emergent 
AEs will also be tabulated by severity. Any other information collected (e.g. action taken, 
duration, outcome) will be listed. Each AE will be attributed to the treatment taken most 
recently before the onset of the AE. Adverse events due to COVID-19 will be listed and 
tabulated separately. 
Vital signs: 
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. 
Physical examination: 
Physical Examination data will be listed with abnormal values flagged. 
Laboratory tests: 
Safety Laboratory data will be listed with abnormal values flagged. 
Note: Laboratory data at the screening is considered source and will not be listed unless 
otherwise noted. 
Criteria for assessing safety: 
Vital signs, clinical safety laboratory tests and monitoring of adverse events will be used to 
assess the safety and tolerability of the study products. 
12.3.4 
Exclusion of Data from Analysis  
Subjects who deviate from the protocol will be identified and excluded from analyses as agreed 
by the biostatistician and clinical scientist or designee. *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. 
* Exclusion of subjects with baseline > 5% of the Cmax will be determined after database lock 
and unblinding. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 77 of 85 
12.3.5 
Demographic and Baseline Characteristics 
The Safety population will be used for demographic and baseline characteristics. Descriptive 
statistics (number of subjects, mean, standard deviation, median, minimum and maximum for 
continuous variables, and frequency and percentage for categorical variables) will be provided 
for demographic, and baseline characteristics. Medical history will be listed. 
12.3.6 
Study Drug/Product Compliance and Use of Other Therapies 
12.3.6.1  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. Cases of partial 
exposure, including subjects vomiting of the treatment within 103 minutes post dosing, and 
subjects with baseline > 5% of the Cmax will also be summarized. Other medications and other 
concomitant non-drug therapies will be listed for the safety population. 
12.3.6.2  Prior and Concomitant Medications 
Prior medications, concomitant medications, and other concomitant non-drug therapies will be 
listed for the safety population. 
12.3.6.3 Other Therapy/Rescue Medication (if applicable) 
Not applicable 
12.3.7 
Handling of Dropouts and Missing Data  
Subjects who withdraw from the study early will be included in the study analysis up to the 
point of withdrawal. Subjects who withdraw will not be replaced. No data will be imputed in 
the case of dropouts or missing data.  Missing plasma concentrations values or those below the 
lower limit of quantification (BLOQ) will be indicated in the data listings.  
12.3.8 
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 GSKCH procedures, GSKCH 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 GSKCH 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. 
GSKCH 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. 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 78 of 85 
• 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 
GSKCH. 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, GSKCH 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 
findings/relevant issues and to implement any corrective and/or preventative actions to address 
any findings/issues identified. 
The investigator(s) will notify GSKCH or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with GSKCH 
or its agents to prepare the study site for the inspection and will allow GSKCH or its agent, 
whenever feasible, to be present during the inspection. The investigator will promptly apply 
copies of the inspection finding to GSKCH or its agent. Before response submission to the 
regulatory authority, the investigator will provide GSKCH 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 GSKCH 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 GSKCH 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), 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 79 of 85 
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. 
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 GSKCH and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by GSKCH in order to de-identify study subjects.   
Note that 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, GSKCH 
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.  Both investigator 
and subject 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.   
GSKCH 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 GSKCH 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 
GSKCH-sponsored human subject research studies.  
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 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 80 of 85 
information that might influence the evaluation of the benefits and risks of the investigational 
product, GSKCH should be informed immediately.  
In addition, the investigator will inform GSKCH 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 GSKCH 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 GSKCH site or other mutually-agreeable location. 
GSKCH 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 GSKCH 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 GSKCH audit or regulatory inspection) and must be available for review in 
conjunction with assessment of the facility, supporting systems, and relevant site staff. 
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 GSKCH, 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, 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


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 5 2 6 2   
 
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 6. 0  
Pa ge 8 1  of 8 5  
na mes a n d a d dresses.  D o c u m e nts n ot f or s u b missi o n t o G S K C H , e. g. s u bjects’ writte n c o nse nt 
f or ms, s h o ul d be mai ntai ne d b y t h e i n vesti gat or i n strict c o nfi de nce. 
Rec or ds a n d d o c u me nts, i ncl u di n g si g ne d I C F, pertai ni n g t o t he c o n d uct of t his st u d y m ust be 
retai ne d b y t he i n vesti gat or as per t he si g ne d c o ntr act ual a gree me nt, fr o m t he iss ue of t he fi nal 
Cli nical St u d y Re p ort ( C S R) or e q ui vale nt s u m mar y, u nless l ocal re g ulati o ns or i nstit uti o nal 
p olicies re q uir e a l o n ger rete nti o n peri o d. T he mi ni m u m rete nti o n ti me will meet t he strictes t 
sta n dar d a p plica bl e t o t hat site f or t he st u d y, as dictate d b y a n y i nstit uti o nal re q uire me nts or 
l ocal la ws or re g ulati o ns, G S K C H  sta n dar ds/ pr oce d ures, a n d/ or i nstit uti o nal re q uire me nts.   
N o st u d y d o c u me nt s h o ul d be destr o ye d wit h o ut a pri or writte n a gr ee me nt bet wee n G S K C H  
a n d t he i n vesti gat or. T h e i n vesti gat or m ust n otif y G S K C H  of a n y c h a n ges i n t he arc hi val 
arra n ge me nts, i ncl u di n g, b ut n ot li mite d t o, arc hi val at a n off -site facilit y or tra nsfer of 
o w ners hi p of t he rec or ds i n t he e ve nt t he i n vesti gat or  is n o l o n ger ass ociate d wit h t he site. 
1 3. 7  
C o n diti o n s f or T er mi n ati n g t h e St u d y  
Pre mat ure ter mi nati o n of t his st u d y ma y o cc ur beca use of a re g ulat or y a ut h orit y decisi o n, 
c ha n ge i n o pi ni o n of t he I R B/ E C, or st u d y pr o d uct safet y pr o ble ms, or at t he discreti o n of 
G S K C H .  I n a d diti o n, G S K C H  retai ns t he ri g ht t o disc o nti n ue de vel o p me nt of paracet a m ol 
f or m ulati o n t o be use d as test pr o d uct at a n y ti me.   
If a st u d y is pre m at urel y t er mi nate d, G S K C H  will pr o m ptl y n otif y t he i n vesti gat or.  After 
n otificati o n, t he i n ve sti gat or m ust pr o m ptl y c o ntact all partici pati n g s u bjects a n d s h o ul d ass ur e 
a p pr o priate t hera p y/ f oll o w -u p f or t he s u bjects.  As directe d b y G S K C H , all st u d y m aterials 
m ust be c ollecte d a n d all C R F’s c o m plete d t o t he greatest e xte nt p ossi ble. W here re q uir e d b y 
t he a p plica ble re g ulat or y re q uire me nts, G S K C H  s h o ul d i nf or m t he re g ulat or y a ut h orit y(ies) a n d 
t he i n vesti gat or s h o ul d pr o m ptl y i nf or m t he I R B/ E C a n d pr o vi de t he I R B/ E C a detaile d writte n 
e x pla nati o n of t he ter mi nati o n or s us pe nsi o n.  
If t h e I R B/ E C termi nates or s us pe n ds its a p pr o val/fa v ora ble o pi ni o n of a trial, t he i n vesti gat or 
s h o ul d pr o m ptl y n otif y t h e G S K C H  a n d pr o vi de G S K C H  wit h a det aile d writte n e x pla nati o n of 
t he ter mi nati o n or s us pe nsi o n. 
U p o n c o m pleti o n or pre mat ure disc o nti n uati o n of t he st u d y, t he G S K C H  m o nit or will c o n d uct 
site cl os ure acti vities wit h t he i n vesti gat or or site staff, as a p pr o priate, i n acc or da nce wit h 
a p plica ble re g ulati o ns i ncl u di n g G C P, a n d G S K C H  Sta n dar d O perati n g Pr o ce d ures.  
1 4  
F a ciliti e s  
T he st u d y will be perf or me d b y 
 
 
. Q UI N T A -A N A L Y TI C A s.r. o. acts i n t his st u d y as Cli nical Site, 
Bi oa nal ytical La b orat or y a n d C R O.  
, M. D., P h D., is t he Pr i nci pal I n v esti gat or.  
Cli nical la b orat or y tests ( hae m at ol o g y, c oa g ul ati o n, viral ser ol o g y, cli nical c he mistr y, 
uri nal ysis, pre g n a nc y test) will be carrie d  o ut b y t h e Cli nical Safet y la b orat or y Aes k u La b k. s., 
 
T he P C R testi n g f or C O VI D -1 9, will be carrie d o ut b y s y nla b czec h s.r. o., 
 
 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
P P D
P P D
P P D
P P D
P P D


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 5 2 6 2   
 
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 6. 0  
Pa ge 8 2  of 8 5  
1 5  
C o m p et e nt A ut h orit y a n d Et hi c s C o m mitt e e  
Fi nal St u d y Pr ot oc ol, I nf or me d C o nse nt F or m a n d I nf or mati o n f or S u bjects  a n d ot her rele va nt 
d oc u me nts will be re vi e w e d b y C o m pete nt A ut h orit y –  State I nstit ute f or Dr u g C o ntr ol ( S Ú K L), 
 a n d als o b y Et hics C o m mittee ( E C) of I K E M 
a n d T N, 
 bef ore st u d y i nitiati o n. T he St u d y will 
n ot be gi n u ntil S Ú K L a n d E C fa v ora ble writte n a p pr o vals f or t he a b o v e -me nti o ne d st u d y 
d oc u me nts a n d/ or t heir s u bsta ntial a me n d me nts i n li ne wit h  I C H G C P ( R 2) [ 6] ha ve bee n 
o btai ne d.  
If a n y c ha n ges i ntr o d uce d t o t he pr ot oc ol or ne w i nf or mati o n relati n g t o t he s cie ntific d oc u me nts 
i n s u p p ort of t he trial are s u bsta ntial, i.e.: 
•  t he safet y or p h ysic al or me ntal i nte grit y of t he s u bjects 
•  t he scie ntific val ue of t he trial  
•  t he c o n d uct or ma n a ge m e nt of t he trial 
•  t he q ualit y or s afet y of a n y st u d y pr o d ucts use d i n t he trial  
T h ose c ha n ges are t he s u bject of a n A me n d me nt t o t he Cli nical St u d y a n d S Ú K L a n d E C m ust 
re vie w t he A m e n d me nt a n d a p pr o ve it bef ore st ud y i nitiati o n or c o nti n uati o n.  
If t he c h a n ges i n St u d y Pr ot oc ol i n v ol ve o nl y l o gistical or a d mi nistrati ve as pects of t he st u d y 
(e. g. c ha n ge of m o nit or(s), tele p h o ne n u m ber(s)), writte n a p pr o vals are necessar y fr o m S p o ns or, 
b ut n ot fr o m t he E C a n d t he S Ú K L bef ore t heir i m ple me ntati o n.  
D oc u me ntati o n of S Ú K L a n d E C a p pr o vals m ust be recei ve d b y t he S p o ns or as s o o n as 
a vaila ble bef ore t he st u d y c o m me nce me nt. T he m e dicati o n ca n be releas e d b y t he S p o ns or o nce 
sca n ne d c o pi es of b ot h E C a n d S Ú K L a p pr o vals are recei ve d b y t h e S p o ns or. 
1 6  
I n s ur a n c e 
T he S p o ns or will c o ntract a cli nical st u d y i ns ur a nce p olic y i n c o m plia nce wit h all a p plica ble 
la ws, r ules, a n d re g ulati o ns. S u bjects will be i ns ure d a gai nst p ossi ble har mf ul c o nse q ue nces of 
t he cli nical st u d y. S p o ns or will i nde m nif y a n y s u bject i ncl u de d i n t he cli nical st u d y f or a n y 
da ma ge t o t he h ealt h if t he da ma ge is eit her ass o ciate d wit h t he st u d y dr u g itself or wit h t he 
cli nical st u d y.  
 s hall i n de m nif y a n y s u bject f or a n y clai m of c o ncer ni n g a n y 
da ma ge t o t he healt h of t he s u bject ot her t ha n da ma ge relate d t o t he st u d y dr u g itself or t o t he 
cli nical st u d y f or e x a m ple mal practice.  
1 7  
R E F E R E N C E S  
Brass E P, Re y n ol ds K M, B ur n ha m RI a n d Gree n J L ( 2 0 1 8) M e dicati o n Err ors Wit h Pe diatric 
Li q ui d Aceta mi n o p he n After Sta n dar dizati o n of C o nce ntrati o n a n d Pac ka gi n g I m pr o v e me nts, 
A C A D E MI C P E DI A T RI C S, 1 8, p. 5 6 3 – 5 6 8. E va ns S R. Cli nical trial str uct ures.  J E x p Str o ke 
Tra nsl Me d. 2 0 1 0; 3( 1): 8 -1 8. d oi: 1 0. 6 0 3 0/ 1 9 3 9 -0 6 7 x -3. 1 . 8 
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
P P D
P P D
P P D


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 5 2 6 2   
 
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 6. 0  
Pa ge 8 3  of 8 5  
E M A ( 2 0 1 7) C H M P Paracet a m ol oral use i m me diate r eleas e f or m ulati o ns pr o d uct s pecific 
bi oe q ui vale nce g ui d a nce E M A/ C H M P/ 3 5 6 8 7 7/ 2 0 1 7  
E M A Bi oe q ui vale n ce g ui deli nes ( 2 0 1 0). E ur o pea n 
Me dici nes 
A ge n c y. C o m mittee f or 
Me dici nal Pr o d ucts f or H u ma n Use ( C H M P), G ui deli ne o n t he I n vesti gati o n of Bi oe q ui vale nce. 
C P M P / E W P/ Q W P/ 1 4 0 1/ 9 8 Re v. 1/ C orr * * 
E M A Bi oe q ui vale n ce g ui deli nes ( 2 0 0 1). E ur o pea n 
Me dici nes 
A ge n c y. C o m mittee f or 
Me dici nal Pr o d ucts f or H u ma n Use ( C H M P), 
N ote  f or g ui da nce  o n t he  i n vesti gati o n of 
bi oa vai la bilit y a n d bi oe q u i vale nce. C P M P/ E W P/ Q W P/ 1 4 0 1/ 9 8 
E M A Bi oe q ui val e nce f or Paraceta m ol f or oral use g ui deli nes ( 2 0 1 7). E ur o pea n M e dici nes 
A ge nc y. C o m mittee f or Me dici nal Pr o d ucts f or H u ma n Use ( C H M P), P araceta m ol oral us e 
i m me diate  
release  
f or m ulati o ns  
pr o d uct-s pecific  
bi oe q ui vale nce  
g ui da nce 
E M A/ C H M P/ 3 5 6 8 7 7/ 2 0 1 7  
E M A P K W P. E ur o pea n Me dici nes A ge n c y. P har mac o ki netic W or ki n g P art y ( P K W P), Cli nical 
p har mac ol o g y 
a n d 
p h ar mac o ki netics: 
q u esti o ns 
a n d 
a ns wers. 
R es o urce 
[i nter net] 
htt ps:// w w w.e ma.e ur o pa. e u/e n/ h u ma n -re g ulat or y/r esearc h de v el o p me nt/scie ntific 
g ui deli nes/cli nical -p h ar m ac ol o g y -p har mac o ki netics/cli nical p har mac ol o g y -p har mac o ki netics -
q uesti o ns -a ns wers # 5. -bi oe q ui vale nce -i n-s pecial p o p ulati o ns-secti o n. ( Accesse d 1 4 
Oct o ber 
2 0 2 0).  
E M A ‘ C H M P P har mac o ki netics W or ki n g Part y ( P K W P). Q uesti o ns & A ns wers:  P ositi o ns o n 
s pecific q u esti o ns a d dresse d t o t he P har mac o ki netics 
W or ki n g Part y’ ( E M A/ 6 1 8 6 0 4/ 2 0 8 8 
Re v. 1 3).  
 
 
I C H T o pi c E 6 ( R 2) G ui d eli ne f or G o o d Cli nical Practice, N o v 2 0 1 6. 
O E C D Pri nci ples of G o o d La b orat or y Practice (as re vise d i n 1 9 9 7), E N V/ M C/ C H E M( 9 8) 1 7, 
O E C D, Paris, 1 9 9 8. ( N o. 1 i n O E C D Seri es o n G o o d La b orat or y Practice a n d C o m plia nce 
M o nit ori n g)  
Gl o bal Data S heet, Paraceta m ol v 7. 0.  G S K C H I nt er nal D oc u m e nts. U n p u blis he d.  
W orl d Me dical Ass ociati o n Declarati o n of Helsi n ki, 6 4t h Ge neral Ass e m bl y, F ortaleza 2 0 1 3.  
1 8  
A P P E N DI CI E S  
1 8. 1  
A B B R E VI A TI O N S  
T he f oll o wi n g is a list of a b bre viati o ns use d i n t he pr ot oc ol.  
T a bl e 1 8 -1  
A b br e vi ati o n s  
A b br e vi ati o n  
T er m  
λ z 
T h e t er mi n al eli mi n ati o n r at e c o n st a nt  
% A U C
e x   
P er c e nt a g e of A U C 0 -i nf o bt ai n e d b y e xtr a p ol ati o n  
A E  
a d v er s e e v e nt  
A L T  
al a ni n e tr a n s a mi n a s e 
A N O V A  
a n al y si s of v ari a n c e  
A S T  
a s p art at e tr a n s a mi n a s e  
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
C CI


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 84 of 85 
Abbreviation 
Term 
AUC 
area under the curve 
AUC24 
area under the concentration-time curve from time 0 to 24 hours 
AUC0-10 
area under the plasma concentration time curve from zero to 10 hours 
AUC0-inf 
area under the concentration-time curve from time 0 to infinity 
AUC0-tlast 
area under the concentration-time curve from time 0 to the time of the last 
quantifiable concentration 
BA 
bioavailability 
BDR 
blinded data review 
BE 
bioequivalence 
BMI 
body mass index 
BP 
blood pressure 
BPM 
beats per minute 
BUN 
blood urea nitrogen 
CDS 
core data sheet 
CI 
confidence interval 
CLr 
renal clearance 
Cmax 
peak or maximum observed concentration 
CRF 
case report form 
CSA 
clinical study agreement 
CTA 
clinical trial application 
EC 
ethics committee 
ECG 
electrocardiogram 
eCRF 
Electronic Case Report Form 
EDTA 
edetic acid (ethylenediaminetetraacetic acid) 
EudraCT 
European Clinical Trials Database 
FDA 
Food and Drug Administration (United States) 
FDAAA 
Food and Drug Administration Amendments Act (United States) 
FRP 
Females of Reproduction Potential 
FSH 
follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transferase 
HBS 
Human Biological Samples 
hCG 
human chorionic gonadotropin 
HIV 
human immunodeficiency virus 
IB 
investigator’s brochure 
ICH 
International Conference on Harmonization 
ID 
identification 
EC 
Ethics Committee 
IND 
investigational new drug  
INR 
international normalized ratio 
IRB 
institutional review board 
IRC 
internal review committee 
IUD 
intrauterine device 
IUS 
Intrauterine system 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 215262  
 
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 v6.0 
Page 85 of 85 
Abbreviation 
Term 
K2EDTA 
dipotassium ethylene diamine tetra acetic acid 
LDL-C 
low density lipoprotein-cholesterol 
LFT 
liver function test 
LSLV 
last subject last visit  
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MedDRA 
medical Dictionary for Regulatory Activities 
N/A 
not applicable 
PD 
pharmacodynamics 
PG  
pharmacogenomics 
PI 
principal investigator 
PI 
Personal information 
PK 
pharmacokinetics 
PR 
pulse rate 
PT 
prothrombin time 
QC 
quality control 
QTc 
corrected QT 
RBC 
red blood cell 
SAE 
serious adverse event 
SCr 
serum creatinine 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SmPC  
summary of product characteristics 
SOP 
standard operating procedure 
SRSD 
single reference study document 
SS 
safety statement 
T1/2 
terminal half-life 
THC 
tetrahydrocannabinol 
tmax 
time to reach maximum concentration 
US 
United States 
USPI 
United States package insert 
WBC 
white blood cell 
 
215262 | Protocol Amendment  03 Dec 2021 | TMF-212417 | 3.0


Si g nat ure Pa ge f or  2 1 5 2 6 2 T M F- 2 1 2 4 1 7 v 3. 0
Si g nat ure Pa ge f or T M F- 2 1 2 4 1 7 v 3. 0
Reas o n f or si g ni n g: A p pr o ve d
Na me: 
R ole: A
Date of si g nat ure: 
G M T + 0 0 0 0
Reas o n f or si g ni n g: A p pr o ve d
Na me: 
R ole: A
Date of si g nat ure: 
G M T + 0 0 0 0
Reas o n f or si g ni n g: A p pr o ve d
Na me: 
R ole: A
Date of si g nat ure:
G M T + 0 0 0 0
2 1 5 2 6 2 | Pr ot oc ol A me n d me nt  0 3 Dec 2 0 2 1 | T M F- 2 1 2 4 1 7 | 3. 0
P P D
P P D
P P D
P P D
P P D
P P D

SAP_001.pdf: 
Paracetamol 24mg/mL Strawberry oral suspension 
215262 
Property of GSK Consumer Healthcare 
Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of GSK 
SOP-208559 Statistical Reporting and Analysis plan template v4.0 
Page 1 of 20 
STATISTICAL REPORTING AND ANALYSIS PLAN 
A RANDOMIZED, OPEN LABEL, SINGLE CENTER, SINGLE DOSE, 
TWO PERIOD, TWO SEQUENCE, CROSSOVER BIOEQUIVALENCE 
STUDY OF PARACETAMOL IN A NEW PEDIATRIC PARACETAMOL 
ORAL SUSPENSION COMPARED TO A MARKETED PARACETAMOL 
ORAL SUSPENSION (PANADOL BABY & INFANT) IN HEALTHY 
ADULT SUBJECTS 
Protocol Number: 215262 
Phase: 
1 
This document contains confidentiality statements that are not relevant for this publicly
available version


Paracetamol 24mg/mL Strawberry oral suspension  
215262 
 
 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
SOP-208559 Statistical Reporting and Analysis plan template v4.0 
Page 2 of 20 
 
Document History 
 
Document 
Version Date 
Summary of Changes (New analysis or 
Change in planned analysis) 
Original Analysis Plan 
21-Oct-2021 
Not applicable (N/A) 
 
Amendments incorporate all revisions to date.  
 
 
 


Paracetamol 24mg/mL Strawberry oral suspension  
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GlaxoSmithKline Consumer Healthcare Confidential 
SOP-208559 Statistical Reporting and Analysis plan template v4.0 
Page 3 of 20 
 
Table of contents 
Document History ........................................................................................................... 2 
Table of contents ............................................................................................................. 3 
1 
Summary of Key Protocol Information ............................................................................ 5 
1.1 
Study Design ....................................................................................................... 5 
1.2 
Study Objectives .................................................................................................. 5 
1.3 
Treatments ........................................................................................................... 6 
1.4 
Sample Size Calculation ...................................................................................... 6 
2 
Planned Analyses ............................................................................................................ 7 
2.1 
Interim Analysis .................................................................................................. 7 
2.2 
Final Analyses ..................................................................................................... 7 
3 
Considerations for data analyses and Data Handling Conventions ................................... 7 
3.1 
Baseline Definition .............................................................................................. 7 
3.2 
Subgroups/Stratifications ..................................................................................... 8 
3.3 
Pooling by center ................................................................................................. 8 
3.4 
Timepoints and Visit Windows ............................................................................ 8 
4 
Data Analysis .................................................................................................................. 8 
4.1 
Populations for Analysis ...................................................................................... 8 
4.1.1 
Subject Disposition and Eligibility for Analysis Populations ................ 9 
4.1.2 
Protocol Deviations .............................................................................. 9 
4.1.3 
Analysis Populations .......................................................................... 10 
4.2 
Subject Demographics and Other Baseline Characteristics ................................. 10 
4.2.1 
Demographic Characteristics ............................................................. 11 
4.2.2 
Other Baseline Characteristics ........................................................... 11 
4.2.3 
Medical History ................................................................................. 11 
4.3 
Treatments (Study Products, Other Concomitant Therapies, Compliance) .......... 11 
4.3.1 
Study Product Compliance and Exposure ........................................... 11 
4.3.2 
Prior and Concomitant Medication ..................................................... 12 
4.4 
Analysis of Pharmacokinetics ............................................................................ 12 
4.4.1 
Primary Pharmacokinetic Endpoint .................................................... 12 
4.4.2 
Handling of Missing Values/Censoring/Discontinuations ................... 15 


Paracetamol 24mg/mL Strawberry oral suspension  
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GlaxoSmithKline Consumer Healthcare Confidential 
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4.5 
Analysis of Secondary Objectives ...................................................................... 16 
4.5.1 
Pharmacokinetics (Secondary) ........................................................... 16 
4.6 
Analysis of Safety .............................................................................................. 18 
4.6.1 
Adverse Events and Serious Adverse Events ...................................... 18 
4.6.2 
Laboratory Tests ................................................................................ 19 
4.6.3 
Vital Signs ......................................................................................... 19 
4.6.4 
Findings on Physical Examination ..................................................... 19 
5 
Changes to the Protocol Defined Statistical Analysis Plan ............................................. 19 
Attachment 1: List of Data Displays ..................................................................................... 20 
 


Paracetamol 24mg/mL Strawberry oral suspension  
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GlaxoSmithKline Consumer Healthcare Confidential 
SOP-208559 Statistical Reporting and Analysis plan template v4.0 
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The purpose of this Statistical Reporting and Analysis Plan is to describe the planned analyses 
and outputs to be included in the Clinical Study Report for Protocol 215262. 
1 
Summary of Key Protocol Information 
1.1 
Study Design 
This is a 2-arm, single center, single dose, open-label, randomized, two-sequence, two-
period crossover, bioequivalence study in healthy adult subjects. 
Subjects will be screened for eligibility within 15 days prior to dosing. Subjects will receive 
each of the two study treatments in fasted state during a 6-day (5-overnight stay) residential 
period at the study site. Subjects will receiveeach treatment in a randomized order with a 
washout period of at least 72 hours between doses. During each treatment period, subjects will 
provide a pre-dose blood sample 1 hour before dosing and 20 post-dose blood samples at 5, 10, 
20, 30, 40, 50, 60, 80, 90, 120, 150, 180 minutes, 4, 5, 6, 8, 10, 12, 14, 16 hours, for bioanalytical 
analyses of paracetamol. 
 
Figure 1-1 Study design 
 
Screening 
Period 1 
Washouta 
Period 2 
End of study 
visit 
Day -15 to -2 
Day -1 to 2 
Day 1b-3 
Day 4-5 
Day 5 
a: Washout period of at least 72 hours between the doses 
b: Begins post administration of first dose 
1.2 
Study Objectives 
 
Objectives 
Endpoints 
Primary Objective
Primary Endpoint
 
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 
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O bje ctiv e s 
E n d p oi nt s 
Se c o n d ar y O bje ctiv e s 
Se c o n d ar y E n d p oi nt s 
 
Ass ess th e p h ar mac okin etic ( P K) pr ofile of 
th e n e w a n d th e mark ete d p ar ac eta mol or al 
s us p e nsio n 
 
A U C 0-inf ( T h e ar e a u n d er th e plas ma c o nc e ntr atio n 
v ers us ti me c urv e c alc ulate d fr o m ti me 0 to infinity 
A U C 0-inf = A U C0-tlast + Clastλ z w h er e Clast is th e last 
me as ur a ble c o nc e ntr atio n a n d λ z is th e ter min al 
eli min atio n r ate c o nsta nt) 
 
% A U C ex ( P erc e nta g e of A U C 0-inf o btain e d by 
extr a p olatio n, c alc ulate d as ( 1 － [ A U C0-tlast 
/ A U C0-i nf]) × 1 0 0) 
 
λ z ( T h e ter min al eli min atio n r ate c o nsta nt 
c o mp ute d as th e slo p e of th e r e gr essio n lin e of ln 
(c o nc e ntr atio n) vs ti me. T h e r e gr essio n s h o uld 
g e n er ally inv olv e at le ast 3 c o ns ec utiv e 
me as ur a ble c o nc e ntr atio ns th at d ecr e as e ov er 
ti me) 
S afety 
 
 
Ass ess th e s afety pr ofile of b oth pr o d ucts 
 
A Es, vital sig ns a n d clinic al s afety la b or atory test 
r es ults 
1. 3   
Tr e at m e nt s 
Si n gle oral d ose of  T est Pr o d uct ( ne w paracet a m ol oral s us pe nsi o n) or  Refere nce Pr o d uct 
( Pa na d ol B & I) will be a d mi nist ere d t o all s u bjects i n eac h st u d y peri o d. 
 
Test Pr o d uct  
Refere nce P r o d uct  
Pr o d uct 
Ne w 
paracet a m ol 
oral 
s us pe nsi o n 
( 2 4 m g/ ml paracet a m ol) 
Pa na d ol B &I 
( 2 4 mg/ ml paracet a m ol) 
D ose 
4 2 m L  ( 1 g paracet a m ol) 
4 2 m L  ( 1 g paracet a m ol) 
R o ut e of a d mi nistrati o n 
Oral 
Oral 
Mar keti n g  
A ut h orizati o n 
H ol der  & S o urce mar ket 
G S K C H, Fi nla n d 
G S K C H, Czec h Re p u blic ( C Z) 
1. 4   
S a m pl e Si z e C al c ul ati o n 
A p pr o xi mat el y 1 1 0 s u bjects will be scree ne d t o ra n d o mize a p pr o xi mat el y 3 7 he alt h y a d ult 
s u bje cts t o e ns ure at least 3 1 e val ua ble s u bjects c o m plet e t he e ntire st u d y, ass u mi n g a 1 5 % 
dr o p o ut a n d n o n- e val ua ble rat e. 
 
C CI


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2  
P l a n n e d A n al y s e s 
2. 1   
I nt eri m A n al y si s 
N o i nt eri m a nal ysis is pla n ne d. 
2. 2  
Fi n al A n al y s e s 
T he fi nal pla n ne d a nal ys es will be perf or me d aft er t he c o m pleti o n of t he f oll o wi n g se q ue ntial 
st e ps: 
1.  All s u bjects ha ve eit her c o m plet e d or disc o nti n ue d t he st u d y as defi ne d i n t he pr ot o c ol 
2.  All re q uire d dat a bas e clea ni n g acti vities i ncl u di n g a n y e xt er nal dat a rec o nciliati o n ha ve 
bee n c o m plet e d a n d dat a base has bee n l o c ke d. 
3.  T he r a n d o mizati o n c o des ha ve bee n distri b ut e d. 
3  
C o n si d er ati o n s f or d at a a n al y s e s a n d D at a H a n dli n g 
C o n v e nti o n s 
3. 1  
B a s eli n e D efi niti o n  
F or safet y a nal ys es: 
 S u bject le vel baseli ne is defi ne d as t he lat est assess me nt wit h a n o n- missi n g val ue bef ore 
t he first d osi n g.  
F or P K a nal yses: 
 S u bject le vel baseli ne is defi ne d as t he lat est assess me nt wit h a n o n- missi n g val ue bef ore 
d osi n g i n e ac h peri o d .  
C CI


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U nless ot her wise st at e d, if baseli ne dat a is missi n g n o i m p ut ati o n  will be perf or me d a n d will be 
set t o missi n g. 
3. 2  
S u b gr o u p s/ Str atifi c ati o n s  
N ot a p plica ble.  
3. 3  
P o ol i n g b y c e nt er 
T his will be a si n gle ce nt er st u d y.  
3. 4   
Ti m e p oi nt s a n d Vi sit Wi n d o w s 
Ref er t o Secti o n 4. 4. 1. 3 f or ha n dli n g of P K s a m ples t hat are o utsi d e t he of pr ot o c ol-s pecifie d 
c ollecti o n wi n d o w. 
4  
D at a A n al y si s 
Deri vati o n of t he P K para met ers f or paracet a m ol i n plas ma  will be t he res p o nsi bilit y of t he 
cli nical p har ma c o ki neticist at  
. T he P K a n d safet y s u m maries, fi g ures, a n d dat a listi n gs, 
as well as t he st atistical a nal ysis of t he P K varia bles, will be t he res p o nsi bilit y of t he st u d y 
bi ost atisticia n at 
. N o n - c o m part me nt al P K para met er calc ulati o ns will be perf or me d 
usi n g P h o e ni x ® 
Wi n N o nli n ® 8. 3 or hi g her ( Cert ara, L. P. Pri ncet o n, Ne w Jerse y). T he 
st atistical a nal ysis s oft ware use d will be S A S ® versi o n 9. 4 (i n a WI N D O W S e n vir o n me nt usi n g 
S A S E nt er pris e G ui de) .  
Pri or t o dat a base cl os ure, a Bli n d Dat a Re vie w M eeti n g ( B D R M) will be c o n d uct e d i n w hic h 
vari o us as pects of t he trial will be disc usse d a n d a gree d.  
 Bi ost atistics will ge nerat e 
listi n g o ut p uts wit h n o treat me nt i nf or mati o n f or i ncl usi o n/ e xcl usi o n, pr ot o c ol de viati o ns, 
a d vers e e ve nts, dr u g c o m plia nce, me dical hist or y, a n d c o nc o mit a nt me dicati o ns t o s u p p ort t he 
B D R M. 
O ne as pect t hat will be c o nsi dere d pri or t o or d uri n g B D R M is t he ass ess me nt of t he n u m ber of 
s u bje cts w h o ha ve disc o nti n ue d or bee n disc o nti n ue d fr o m t he st u d y d ue t o pa n de mic relat e d 
e ve nts (e. g. C O VI D- 1 9) a n d t he p ot e ntial nee d of a se nsiti vit y a nal ysis. A n y maj or c ha n ges t o 
pl a n ne d a nal yses will n ee d a n  a me n d me nt t o t he Re p orti n g a n d A nal ysis Pla n ( RA P ).  
E xce pt as descri be d bel o w, all listi n gs will be pr o d uce d f or all ra n d o mize d s u bjects.  
4. 1  
P o p ul ati o n s f or A n al y si s 
T a bles descri be d i n t his se cti o n will be pr o d uce d f or all ra n d o miz e d s u bjects. S u bject 
dis p ositi o n will i ncl u de all scree ne d s u bje cts (
). All scree n fail ure s u bje ct dat a will 
be l ist e d. 
C CI
P P D
P P D
P P D


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4. 1. 1 
S u bj e ct Di s p o siti o n a n d Eli gi bilit y f or A n al y si s P o p ul ati o n s 
S u bjec t dis p ositi o n f or all s cree ne d s u bjects will be s u m marize d as t he n u m ber of s u bjects 
scree ne d, n u m ber of s u bjects passe d scree ni n g, n u m ber of s u bjects faile d s cree ni n g wit h reas o n, 
n u m ber of s u bje cts ra n d o mize d, n u m ber a n d perce nt a ge of s u bjects w h o recei ve d a n y st u d y 
me dicati o n, c o m plet e d t he st u d y, a n d w h o disc o nti n ue d wit h t he reas o n f or dis c o nti n u ati o n b y 
se q ue nce a n d o verall (
). S u bject dis p ositi o n i ncl u di n g t he s u bject st at us 
( c o mplet e d, 
Yes/ N o), 
critical 
de m o gra p hic 
dat a 
(a ge, 
se x, 
race), 
dat e 
of 
c o m pleti o n/ disc o nti n uati o n a n d t he s pecific reas o n f or disc o nti n uati o n, will be list e d i n Listi n g 
1 6. 2. 1. 1 .  
4. 1. 2 
Pr ot o c ol D e vi ati o n s 
Pr ot o c ol de viati o ns will be c ollect e d a n d st ore d i n  
 Cli nic al Trial Ma na ge me nt S yst e m 
( C T M S). All de viati o ns c ollect e d i n C T M S will be pr o vi de d b y t he  
 cli nical st u d y 
ma na ger as a Micr os oft E xcel file a n d rea d i nt o S D T M t o ge nerat e t he dat a listi n g.  
T he pr ot o c ol de viati o n ma na g e me nt pla n ( P D M P) lists t he p ot e ntial pr ot o c ol de viati o ns a n d 
ass o ciat e d se verit y b y c at e g or y f or t he st u d y. Pri or t o dat a base l o c k, all pr ot o c ol de viati o ns will 
be classifie d as critical, maj or or mi n or. 
I m p ort a nt (critical a n d maj or) pr ot o c ol de viati o ns (i ncl u di n g de viati o ns relat e d t o st u d y 
i ncl usi o n/e xcl usi o n crit eria, c o n d uct of t he trial, patie nt ma na ge me nt or patie nt assess me nt) will 
be s u m marise d a n d list e d. T he n u m ber a n d perce nt a ge of s u bje cts wit h a n y critical or maj or 
pr ot o c ol de viati o n will be prese nt e d (
). Critical a n d maj or pr ot o c ol de viati o ns will 
be list e d i n Listi n g 1 6. 2. 2. 1 . Mi n or pr ot o c ol de viati o ns will be list e d si milarl y (
). 
Pr ot o c ol de viati o ns will be trac ke d b y t he st u d y t ea m t hr o u g h o ut t he c o n d uct of t he st u d y. Dat a 
will be re vie we d pri or t o cl os ure of t he dat a bas e t o e ns ure all de viati o ns are c a pt ure d a n d 
cat e g oris e d a p pr o priat el y.  
C ha n ges t o t he pr o ce d ures or e ve nts w hic h ma y i m pact t he q ualit y of t he P K dat a will als o be 
descri be d wit hi n t he cli nical st u d y re p ort b o d y t e xt. T hese c ha n ges or e ve nts will i ncl u de a n y 
circ u mst a nces t hat will alt er t he e val uati o n of t he P K. T he y ma y p ot e ntiall y affect as little as a 
si n gle c o nce ntrati o n rec or d or a n e ntire pr ofile (c o nce ntrati o n-ti me pr ofile a n d/ or pri mar y P K 
para met ers) . E xa m ples affecti n g a si n gle c o nce ntrati o n rec or d i ncl u de, b ut ma y n ot be li mit e d 
t o, a si n gle s a m ple misse d or c ollect e d o utsi de t he pr ot o c ol-s pecifie d wi n d o w at n o n-critical 
ti mes. T hes e pr ot o c ol de viati o ns ma y n ot i m pact t he q ualit y of t he P K dat a.  E xa m ples affecti n g 
a n e ntire pr ofile i ncl u d e, b ut ma y n ot be li mit e d t o, v o miti n g f oll o wi n g oral d osi n g o cc urri n g 
wit hi n 1 0 3 mi n ut es p ost- d ose, c o nc o mit a nt a d mi nistrati o n of me dicati o ns wit h t he p ot e ntial t o 
i m pact P K, a n d/ or i nacc urat e d osi n g o n t he da y of P K sa m pli n g. A s u bject ma y n ot ha ve Cma x  
or t ma x  c orrectl y e val uat e d if 2 or m ore sa m ples are misse d ar o u n d t he me dia n tma x . A s u bject 
ma y n ot ha ve A U C 0-tlast c orrectl y e val uat e d if 1 or m ore sa m ples are misse d i n t he desce n di n g 
C CI
C CI
C CI
P P D
P P D


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p hase of t he c ur ve f oll o wi n g t he last q ua ntifia ble c o nce ntrati o n. If pr ot o c ol de viati o ns or e ve nts 
i m pacti n g e ntire pr ofiles o cc ur i n a n y treat me nt peri o d, s u bjects will be e xcl u d e d fr o m t he P K 
a nal ysis p o p ulati o n a n d P K dat a c ollect e d d uri n g b ot h treat me nt peri o ds will be e xcl u d e d fr o m 
st atistical a nal yses.  
S u bjects wit h baseli ne paracet a m ol 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 p o p ulati o n. If > 1 0 % of s u bjects are e xcl u de d fr o m t he P K 
p o p ulati o n d ue t o baseli ne paracet a m ol c o nce ntrati o n > 5 % of t he i n di vi d ual C ma x , a se nsiti vit y 
a nal ysis will be c o n d uct e d i ncl u di n g all s u bjects, e ve n t h ose wit h t he affe ct e d dat a.  
4. 1. 3 
A n al y si s P o p ul ati o n s 
T hree a nal ysis p o p ulati o ns are defi ne d.  
P o p ulati o n 
D efi niti o n / Crit eria 
A n aly s e s Ev al u at e d 
All Su bj ects 
 C o m prise of all s u bj ects w h o si gn e d th e 
i nform e d c o nse nt to p artici p ate i n th e stu dy. 
 
 Dis p ositi o n 
 St u dy Po p ul ati o n 
 
Safety 
 C o m prise of all r a n d o miz e d s ubj ects w ho 
r eceiv e at l e ast o n e stu dy m e dic ati o n. 
 T his p o p ul ati o n will b e b as ed o n th e tr e at m e nt 
th e s u bj ect actu ally r ec eiv e d. 
 D e m o gr ap hy 
 Sa fety 
Ph ar m ac oki n etic  
 Su bj ects i n th e ‘ Safety’ p o p ul ati o n w h o  
c o m pl ete th e t w o p eri o ds a n d wh o h ave n o 
m aj or pr otoc ol d evi ati o ns co nc er ni n g P K. 
 P K  
N O T E S :  
 
Pl e as e ref er t o Att ach m e nt 1: List of D at a Displ ays w hich d et ails t he p o p ul ati o n t o b e use d f or e ach displ ay b ei n g 
g e n erat e d. 
 
T he n u m bers of s u bje cts i ncl u de d i n eac h of t he a nal ysis p o p ulati o ns, a n d t he n u m ber e xcl u d e d 
fr o m eac h p o p ulati o n br o ke n d o w n b y t he reas o n f or e xcl usi o n will be prese nt e d (
). 
S u bjec ts e xcl u de d fr o m a n y of t he a nal ysis p o p ulati o ns will be list e d i n Listi n g 1 6. 2. 3. 1 , wit h 
t he reas o n f or e xcl usi o n. A n y dat a e xcl u de d fr o m P K p o p ulati o n will be list e d i n Listi n g 
1 6. 2. 3. 2 . 
4. 2   
S u bj e ct D e mo gr a p hi c s a n d O t h er B a s eli n e Ch ar a ct eri sti c s  
De m o gra p hic a n d baseli ne c haract eristics s u m maries 
will be pr o d uce d f or t he Safet y 
p o p ulati o n. 
C CI


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4.2.1 Demographic Characteristics 
Categorical demographic variables include sex, race, ethnicity and method of contraception. 
These variables will be summarized by the number and percentage of subjects with each 
relevant characteristic by treatment sequence and for all subjects overall. Body Mass Index 
(BMI) will be calculated as weight (kg)/[height (m)]2. Age, weight, height and BMI will be 
summarized by the mean, standard deviation (SD), median, minimum and maximum values in 
each treatment sequence and overall. All demographic information will be tabulated in Table 
14.1.4.1 for safety population, Table 14.1.4.2 for pharmacokinetic population and listed in 
Listing 16.2.4.1 for all subjects screened. 
4.2.2 Other Baseline Characteristics 
Informed consent details will be listed in Listing 16.2.4.2. Study eligibility will be listed in 
Listing 16.2.4.3. Results from virology and pregnancy test (in females) will be presented in 
Listing 16.2.4.5 and Listing 16.2.4.6, respectively. Listing of drug and alcohol screen (urine 
illicit drug screen, urine cotinine, alcohol screen) will be provided in Listings 16.2.4.7 – 
16.2.4.9. 
4.2.3 Medical History 
Medical diagnoses/surgeries within the past 1 year will be listed in Listing 16.2.4.4, with start 
date and end date or ongoing at the start of study medication. Medical conditions will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA) version 24.0.  
4.3 
Treatments (Study Products, Other Concomitant Therapies, 
Compliance) 
Exposure to study products and other medications will be summarized on the Safety Population.  
4.3.1 Study Product Compliance and Exposure 
Study product exposure to the treatment will be summarized as follows by treatment (Table 
14.2.1.1): 
 number (%) of subjects exposed to each treatment 
 number (%) of subjects fully compliant to dosing requirements (without any deviation) 
 number (%) of subjects with deviations from dosing requirements: 
o partial exposure  
 number (%) of subjects vomiting within 103 minutes post-dose 
 number (%) of subjects with baseline > 5% of the Cmax post-dose 


Par a cet a m ol 2 4 m g/ m L Str a w berr y or al s us pe nsi o n  
2 1 5 2 6 2 
 
 
 
 
 
Gla x o S mit h Kli n e C o ns u mer Healt h car e C o nfi de ntial 
S O P - 2 0 8 5 5 9 Statistical Re p orti n g a n d A nal ysis pla n te m plate v 4. 0 
Pa ge 1 2  of 2 0  
 
St u d y pr o d uct a d mi nistrati o n will be list e d i n Listi n g 1 6. 2. 5. 1 . St u d y pr o d ucts will be 
a d minist ere d u n der t he s u per visi o n of i n vesti gat or sit e pers o n nel a n d he nce c o m plia nce is n ot 
calc ulat e d.  
4. 3. 2 
Pri or a n d C o n c o mit a nt M e di c ati o n 
Pri o r a n d c o nc o mit a nt me dic ati o ns will be c o de d usi n g G S K W H O Dr u g Dicti o nar y ( Versi o n 
3. 0 ). 
All pri or a n d c o nc o mit a nt me dicati o ns will be list e d. Me dic ati o n/treat me nts t a ke n wit hi n 3 0 
da ys pri or t o si g ni n g t he i nf or me d c o nse nt f or m a n d st o p pe d bef ore first d ose of st u d y pr o d uct 
a d mi nistrati o n will be d o c u me nt e d as a pri or me dicati o n/treat me nt. Me dicati o ns/treat me nts 
t a ke n 
aft er 
first 
d ose 
of 
st u d y 
pr o d uct 
will 
be 
d o c u me nt e d 
as 
c o nc o mit a nt 
me dicati o n/treat me nts. Pri or me dicati o ns a n d c o nc o mit a nt me dic ati o ns will be list e d b y s u bje ct, 
wit h preferre d t er m, i n dicati o n, d ose, d ose f or m, fre q ue nc y, r o ut e, st art dat e a n d e n d dat e 
(
). C o nc o mit a nt me dicati o ns ( o n g oi n g at Da y 1 or st art e d o n or aft er Da y 1) will 
be list e d si milarl y (
). C o nc o mit a nt me dicati o ns will be s u m marize d (
 
) f or t he safet y p o p ulati o n. 
4. 4   
A n al y si s of P h ar m a c o ki n eti c s  
4. 4. 1 
Pri m ar y P h ar m a c o ki n eti c E n d p oi nt 
4. 4. 1. 1 
Pri m ar y P h ar m a c o ki n eti c E n d p oi nt D efi niti o n 
P har mac o ki netic bl o o d sa m ples will be t a ke n at pre- d ose ( 1 h o ur bef ore d osi n g), a n d 5, 1 0, 2 0, 
3 0, 4 0, 5 0, 6 0, 8 0, 9 0, 1 2 0, 1 5 0, a n d 1 8 0 mi n ut es a n d 4, 5, 6, 8, 1 0, 1 2, 1 4, a n d 1 6 h o urs 
p ost- d ose i n Peri o d 1 a n d Peri o d 2.  
Plas ma c o nce ntrati o ns of paracet a m ol will be det er mi ne d usi n g a s pecific a n d hi g hl y se nsiti v e 
li q ui d c hr o mat o gra p h y-t a n de m mass s pectr o metr y ( L C- M S/ M S) met h o d ol o g y i n a la b orat or y 
wit h G o o d La b Practices ( G L P) certificati o n. T he t ar get e d l o wer li mit of q ua ntit ati o n ( L L O Q) 
f or paracet a m ol is 0. 2 5 µ g/ m L.  
T he pri mar y o bjecti ve will be e val uat e d bas e d o n t he f oll o wi n g c o m paris o n:  
T he ne w paracet a m ol oral s us pe nsi o n ( T est) vers us t he mar ket e d paracet a m ol oral s us p e nsi o n 
Pa na d ol B &I ( Refere nce), i n t er ms of A U C 0-tlast, Cma x , a n d tma x .  
T he pri mar y st atistical a nal ys es will be d o ne usi n g t he P K p o p ulati o n. T he s afet y p o p ulati o n 
will be use d f or t he i n di vi d ual plas ma c o nce ntrati o n listi n g  a n d fi g ures. T he P K p o p ulati o n will 
be us e d f or mea n c o nce ntrati o n-ti me fi g ures.  
C CI
C CI
C CI


Paracetamol 24mg/mL Strawberry oral suspension  
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SOP-208559 Statistical Reporting and Analysis plan template v4.0 
Page 13 of 20 
 
4.4.1.2 
Calculation of Primary Pharmacokinetic Parameters 
The appropriate noncompartmental PK parameters will be calculated from the plasma 
paracetamol concentration-time data using Phoenix® WinNonlin® Version 8.3. Actual sample 
times will be used in the calculations of PK parameters. The calculation of the actual time for 
paracetamol will be in respect to the start of dose administration time of oral suspension on 
Day 1 (Period 1) or Day 4 (Period 2). All primary PK parameters included in the protocol are 
listed in Table 4-1 below and are defined as appropriate for study design.  
 
 
#"#!$&(!"( &!&-&!(&'(# ) (
Pharmacokinetic parameters will not be calculated for profiles with less than 3 consecutive 
post-dose time points with quantifiable concentrations. Profiles with insufficient data to 
calculate PK parameters will be included in the concentration listings only and excluded from 
the statistical analysis (summary and inferential statistics).  
4.4.1.3 
Statistical Hypothesis, Model, and Method of Analysis 
Pharmacokinetic Population will be used for testing the statistical hypothesis. The PK 
parameters that will be used in the primary analyses are AUC0-tlast, Cmax, and tmax. 
Parameter  
Label to be Used in 
the Text, Tables, and 
Figures  
Definition  
Method of 
Determination  
AUC0-tlast 
AUC(0-tlast) 
Area under the plasma 
concentration 
versus 
time curve from time 
zero 
to 
the 
last 
measurable 
sampling 
time point, tlast  
Calculated 
using 
the 
Linear Trapezoidal with 
Linear 
Interpolation 
Method  
Cmax  
Cmax  
The 
maximum 
observed 
plasma 
paracetamol post-dose 
concentration  
Taken 
directly 
from 
bioanalytical data  
tmax  
tmax  
The 
time 
of 
the 
maximum 
observed 
plasma 
paracetamol 
post-dose 
concentration  
Taken 
directly 
from 
bioanalytical data  


Par a cet a m ol 2 4 m g/ m L Str a w berr y or al s us pe nsi o n  
2 1 5 2 6 2 
 
 
 
 
 
Gla x o S mit h Kli n e C o ns u mer Healt h car e C o nfi de ntial 
S O P - 2 0 8 5 5 9 Statistical Re p orti n g a n d A nal ysis pla n te m plate v 4. 0 
Pa ge 1 4  of 2 0  
 
T he n ull a n d alt er nat e h y p ot heses t o be t est e d i n t he pri mar y a nal yses are: 
A U C 0-tlast a n d C ma x 
H 0: T he ( ge o metric) me a n A U C 0- tlast (li ke wise Cma x ) of  a ne w paracet a m ol oral s us pe nsi o n ( T est) 
is less t ha n 8 0. 0 % or great er t ha n 1 2 5. 0 % of  t hat of Pa na d ol B &I ( Refere nce). 
H 1: T he ( ge o metric) mea n A U C 0-tlast (li ke wise Cm a x ) of  a ne w paracet a m ol oral s us pe nsi o n 
( T est) is bet wee n 8 0. 0 % a n d 1 2 5. 0 % of t hat of Pa na d ol B &I ( Refere nce). 
tma x 
H 0: T here is n o  differe nc e bet wee n a ne w paracet a m ol oral s us p e nsi o n ( T est) a n d Pa na d ol B &I 
( Refere nce). 
H 1: T here is a differe nce bet wee n a ne w paracet a m ol oral s us p e nsi o n ( T est) a n d Pa na d ol B &I 
( Refere nce). 
A n  A nal ysis of  Varia nce ( A N O V A) m o del will be  fit t o t he l o g-tr a nsf or me d P K  para met ers 
( A U C0-tlast a n d C ma x ), as t he de pe n de nt varia ble, a n d treat me nt, peri o d, se q ue nce, a n d s u bject 
nest e d wit hi n se q ue nce as fi xe d effects (
). F or eac h pair wise c o m paris o n, o nl y 
t he dat a fr o m t he t w o, c orres p o n di n g tr eat me nts will be  i ncl u de d i n t he m o del. T he prese nc e 
of  a st atisticall y si g nifica nt se q ue nce effect will be  n ot e d, a n d its i m plicati o ns will be 
disc usse d. Least s q uares 
esti mat e of tr eat me nt effects will be calc ulat e d a n d a 9 0 % 
c o nfi d e nc e i nt er v al ( CI ) f or t he treat me nt differ e nce will 
be  c o m p ut e d. T he tr eat me nt 
differe nce a n d its 9 0 % CI  will be e x p o ne ntiat e d t o o bt ai n t he rati o of  t he ge o metric least 
s q uare mea ns bet wee n t he t est a n d refere nce a n d its CI. Bi o e q ui vale nce will be  det er mi ne d if 
t he 9 0 % CI  f or t he treat me nt ge o metric least s q uare mea n rati o lies c o m plet el y 
wit hi n t he 
ra n ge 0. 8 0 t o 1. 2 5. 
tma x will be  a nal yze d n o n p ara metricall y usi n g Wilc o x o n si g ne d-ra n k t est (
 
). 
Me di a n of  differe nces bet wee n treat me nts will be prese nt e d wit h 9 0 % CI  f or t he me dia n 
differe nce base d o n  a met h o d b y H o d ges a n d Le h ma n base d o n  t he P K p o p ulati o n. 
I n di vi d ual plas ma c o nce ntrati o ns of paraceta m ol will be list e d (
 
) f or t he safet y p o p ulati o n a n d s u m marize d descri pti vel y b y treat me nt at eac h 
ti me p oi nt f or t he P K p o p ulati o n ( n u m ber of o bser vati o ns [ n], arit h metic mea n, S D, C V %, 
me dia n, 
mi ni m u m, a n d 
ma xi m u m) (
 
). Sa m ples t hat are o utsi de t he 
pr ot o c ol-s pecifie d c ollecti o n 
wi n d o w ( +/- 2 
mi n ut es d uri n g first 6 h o urs aft er dr u g 
a d mi nistrati o n, +/- 1 5 mi n ut es f or all re mai ni n g s a m pli n g i nt er vals) will n ot be i ncl u de d i n t he 
descri pti ve st atistics. Mea n plas ma c o nce ntrati o n vers us n o mi nal ti me pr ofiles b y treat me nt 
will be gra p he d f or t he P K p o p ulati o n (
). I n di vi d ual plas ma c o nce ntrati o n vers us 
act ual ti me pr ofiles b y treat me nt will be gra p he d f or t he safet y p o p ulati o n (
). 
C CI
C CI
C CI
C CI
C CI
C CI


Par a cet a m ol 2 4 m g/ m L Str a w berr y or al s us pe nsi o n  
2 1 5 2 6 2 
 
 
 
 
 
Gla x o S mit h Kli n e C o ns u mer Healt h car e C o nfi de ntial 
S O P - 2 0 8 5 5 9 Statistical Re p orti n g a n d A nal ysis pla n te m plate v 4. 0 
Pa ge 1 5  of 2 0  
 
All c o nce ntrati o n-ti me pr ofiles (e xce pt t ma x ) will be s h o w n o n b ot h li near a n d se mi-l o garit h mic 
scales.  
All P K para met ers 
will be s u m marize d f or eac h treat me nt b y descri pti ve st atistics. 
F or  
t ma x :  
n,  
me dia n,  
mi ni m u m,  
a n d  
ma xi m u m. 
F or A U C 0-tlast a n d Cma x : n, arit h metic mea n, S D, C V %, ge o metric mea n, ge o metric C V %, 
me dia n, mi ni m u m, a n d ma xi m u m) f or t he P K p o p ulati o n (
). C o m parati ve pl ots 
of i n di vi d ual paracet a m ol plas ma Cma x  a n d A U C0-tlast val ues vers us treat me nt will be pr o vi de d 
(
). A listi n g c o nt ai ni n g i n di vi d ual P K para met er val ues will be 
pr o vi de d (
).  
P har mac o ki netic para met ers will be re p ort e d t o 3 si g nifica nt fi g ures f or i n di vi d ual para met ers, 
wit h t he e xce pti o n of t ma x , w hic h will be prese nt e d t o 2 deci mal places. T he le vel of precisi o n 
f or eac h c o nce ntr ati o n a n d P K para met er st atistic will be prese nt e d as f oll o ws:  
 Mi ni m u m/ ma xi m u m i n sa me precisi o n as bi o a nal ytical dat a or para met er o ut p ut,  
 Ge o metric 
mea n/arit h metic 
mea n/ me dia n i n 1 
m ore le vel of precisi o n t ha n 
mi ni m u m/ ma xi m u m,  
 S D i n 1 m ore le vel of precisi o n t ha n ge o metric me a n/arit h metic mea n/ me dia n,  
 n will be prese nt e d as a n i nt e ger, a n d  
 Ge o metric C V %/ C V % will be prese nt e d t o t he nearest te nt h.  
4. 4. 2  
H a n dli n g of Mi s si n g V al u e s/ C e n s ori n g/ Di s c o nti n u ati o n s 
S u bjects w h o de viat e fr o m t he pr ot o c ol , as well as i n di vi d ual P K sa m ples wit h pr ot o c ol 
de viati o ns i m pa cti n g P K, will be i de ntifie d a n d e xcl u de d fr o m t he P K a nal ys es as a gree d b y t he 
bi ost atisticia n, p har mac o ki neticist, a n d me dical dir ect or or desi g nee. F or t he pri mar y a nal ysis 
of P K para met ers, s u bjects wit h baseli ne c o nce ntrati o ns great er t ha n 5 % C ma x  will be e xcl u de d 
fr o m t he P K p o p ulati o n.  
F or c o nce ntrati o n listi n gs: 
 Bel o w l o wer li mit of q ua ntit ati o n ( B L O Q) val ues will be list e d as “ N ot det ect a ble” ( N D)  
F or t he c o m p ut ati o n of descri pti ve st atistics a n d mea n c o nce ntrati o n-ti me pl ots:: 
 B L O Q val ues will be treat e d as zer o. 
F or P K para met er calc ulati o ns a n d i n di vi d ual c o nc e ntrati o n-ti me pl ots :  
 B L O Q val u es prece di n g q ua ntifia ble sa m ples i n t he i nitial p orti o n of t he pr ofile will be 
assi g ne d a val u e of zer o,  
C CI
C CI
C CI


Paracetamol 24mg/mL Strawberry oral suspension  
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 BLOQ values that occur between quantifiable data points, especially prior to Cmax, will 
be evaluated to determine if an assigned concentration of zero makes sense, or if 
exclusion of the BLOQ is warranted,  
 Following Cmax, BLOQ values embedded between 2 quantifiable data points will be 
treated as missing,  
 BLOQ values at the end of the collection interval (after the last quantifiable 
concentration) will be set to missing.  If consecutive BLOQ concentrations are followed 
by quantifiable concentrations in the terminal portion of the concentration curve, these 
quantifiable values will be excluded from the PK parameter calculation by setting them 
to missing, unless otherwise warranted by the concentration-time profile.   
Missing concentration or parameter values will not be imputed.  
4.5 
Analysis of Secondary Objectives 
4.5.1 
Pharmacokinetics (Secondary) 
4.5.1.1 
Secondary Pharmacokinetic Endpoint Definition 
The secondary statistical analyses will be done using the PK population.  
4.5.1.2 
Calculation of Secondary Pharmacokinetic Parameters  
The appropriate noncompartmental PK parameters will be calculated from the plasma 
paracetamol concentration-time data using Phoenix® WinNonlin® Version 8.3. Actual sample 
times will be used in the calculations of PK parameters. The calculation of the actual time for 
paracetamol will be in respect to the start of dose administration time of oral suspension on 
Day 1 (Period 1) or Day 4 (Period 2). All secondary PK parameters included in the protocol are 
listed in Table 4-2 below and are defined as appropriate for study design.  
 
 
	#"#!$&(!"( #"&-&!(&'(# ) (
Parameter  
Label to be Used in 
the Text, Tables, 
and Figures  
Definition  
Method of 
Determination  
AUC0-inf 
AUC(0-inf) 
Area 
under 
the 
plasma concentration 
versus time curve 
calculated from time 
zero to infinity  
AUC0-inf = AUC0-tlast + 
(Clast/λz) where Clast is the 
last 
measurable 
concentration and λz is the 


Par a cet a m ol 2 4 m g/ m L Str a w berr y or al s us pe nsi o n  
2 1 5 2 6 2 
 
 
 
 
 
Gla x o S mit h Kli n e C o ns u mer Healt h car e C o nfi de ntial 
S O P - 2 0 8 5 5 9 Statistical Re p orti n g a n d A nal ysis pla n te m plate v 4. 0 
Pa ge 1 7  of 2 0  
 
 
T he λ z will be det er mi ne d usi n g li ne ar re gressi o n c o m p ose d of at least 3 dat a p oi nts. T he λ z will 
n ot be assi g ne d if 1) t he t er mi nal eli mi nati o n p hase is n ot a p pare nt or  2) if tma x  is 1 of t he 3 last 
dat a p oi nts. I n cases w here t he λ z is n ot assi g ne d, t he val ues of λ z, A U C0-i nf, a n d % A U Ce x are 
n ot calc ula ble a n d will n ot be re p ort e d. T he λ z will be c o nsi dere d u nrelia ble 1) if t he a dj ust e d 
re gressi o n c o efficie nt val ue is less t ha n 0. 8 0 or 2) if % A U C e x is great er t ha n 2 0 %. I n cases 
w here t he λ z is c o nsi dere d u nrelia ble, t he val ues of λz, A U C0-i nf, % A U Ce x, a n d t1/ 2 will be 
i ncl u de d i n t he listi n g o nl y a n d e xcl u d e d fr o m t he s u m mar y st atistics 
A d diti o nal P K para met ers ma y be calc ulat e d or st atistical a nal ys es perf or me d, as a p pr o priat e.  
4. 5. 1. 3 
St ati sti c al H y p ot h e si s, M o d el, a n d M et h o d of A n al y si s 
A U C 0-i nf will be a nal yz e d a n d prese nt e d usi n g t he s a me A N O V A m o del met h o d as f or A U C0-tlast  
a n d C ma x  (
) b ut will n ot be a part of B E det er mi nati o n. 
All s ec o n dar y P K para met ers will be s u m marize d f or eac h tr eat me nt b y descri pti ve st atistics 
( n, arit h metic mea n, S D, C V %, ge o metric mea n, ge o metric C V %, me dia n, mi ni m u m, a n d 
ma xi m u m) f or t he P K p o p ulati o n. A listi n g c o nt ai ni n g i n di vi d ual P K para met er val ues will be 
pr o vi de d.  
t er mi nal eli mi nati o n rat e 
c o nst a nt 
% A U C
e x 
% A U Ce x 
Perce nt a ge  
of 
A U C 0- i nf o bt ai ne d b y 
e xtra p olati o n 
% A U C
e x  
=  
(1 
–  
[ A U C0-tlast/ A U C0-i nf]) * 1 0 0 
λ z 
λz  
T he  
t er mi nal 
eli minati o n  
rat e 
c o nst a nt 
C o m p ut e d as t he sl o pe of 
t he re gressi o n li ne 
of 
l n(c o nce ntrati o n) vs 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 me as ura ble 
c o nce ntrati o ns (i ncl u di n g 
t he  
last  
q ua ntifia ble 
c o nce ntrati o n)  
t hat 
decrease 
m o n ot o nicall y 
o ver ti me.  
t1/ 2 
t 1/ 2 
A p pare nt eli mi nati o n 
half- life 
t1/ 2 =  l n( 2)/ λz 
C CI


Par a cet a m ol 2 4 m g/ m L Str a w berr y or al s us pe nsi o n  
2 1 5 2 6 2 
 
 
 
 
 
Gla x o S mit h Kli n e C o ns u mer Healt h car e C o nfi de ntial 
S O P - 2 0 8 5 5 9 Statistical Re p orti n g a n d A nal ysis pla n te m plate v 4. 0 
Pa ge 1 8  of 2 0  
 
P har mac o ki netic para met ers will be re p ort e d t o 3 si g nifica nt f i g ures f or i n di vi d ual para met ers. 
T he le vel of precisi o n f or eac h P K para met er st atistic will be prese nt e d as f oll o ws:  
 Mi ni m u m/ ma xi m u m i n sa me precisi o n as bi o a nal ytical dat a or para met er o ut p ut,  
 Ge o metric 
mea n/arit h metic 
mea n/ me dia n i n 1 
m ore le vel of precisi o n t ha n 
mi ni m u m/ ma xi m u m,  
 S D i n 1 m ore le vel of precisi o n t ha n ge o metric me a n/arit h metic mea n/ me dia n,  
 n will be prese nt e d as a n i nt e ger, a n d  
 Ge o metric C V %/ C V % will be prese nt e d t o t he nearest te nt h.  
4. 6   
A n al y si s of S af et y 
F or t he re p orti n g of descri pti ve st atistics of t he s afet y varia bles ( e. g. vit al si g ns), t he mea n, 
me dia n, st a n dar d de viati o n, a n d c o nfi d e nce i nt er vals will be prese nt e d t o o ne di git m ore 
precisi o n t ha n t he s o urce dat a. T he mi ni m u m a n d ma xi m u m will be prese nt e d t o t he sa me 
precisi o n as t he s o urce dat a. 
4. 6. 1  
A d v er s e E v e nt s a n d S eri o u s A d v er s e E v e nt s 
Treat me nt E mer ge nt a d verse e ve nts ( T E A Es) are A Es t hat are e mer ge nt or t hat w orse n aft er 
t he first st u d y pr o d uct (t est of refere nce) a d mi nistrati o n. All T E A Es will be s u m marize d b y 
pri mar y s yst e m or ga n class a n d preferre d t er m.  
Treat me nt e mer ge nt a d verse e ve nts will be s u m marize d wit h a n o ver vie w (
) a n d 
t he n b y t he n u m ber a n d perce nt a ge of s u bjects ha vi n g a n y T E A E, a T E A E i n eac h S yst e m 
Or ga n Class, a n d eac h i n di vi d ual T E A E ( preferre d t er m) (
). Treat me nt-e mer ge nt 
A Es  s us pect e d of a relati o ns hi p t o st u d y me dicati o n will be pres e nt e d i n a si milar ma n ner (
 
). All T E A Es will als o be t a b ulat e d b y se verit y (
) a n d b y relat e d ness a n d 
se verit y (
). 
A d dit i o nall y, all T E A Es will be list e d 
 
E ac h  A E will be attri b ut e d t o t he treat me nt t a ke n m ost rece ntl y bef ore t he o nset of t he A E. 
 
A d vers e e ve nts d ue t o C O VI D- 1 9 will be list e d a n d t a b ulat e d se parat el y (
 a n d 
).  
A d ve rs e e ve nts wit h fat al o ut c o me will be list e d b y treat me nt. (
). N o n-fat al 
seri o us a d verse e ve nts a n d a d verse e ve nts ca usi n g st u d y treat me nt disc o nti n uati o n will be list e d 
(
).  
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI
C CI


Par a cet a m ol 2 4 m g/ m L Str a w berr y or al s us pe nsi o n  
2 1 5 2 6 2 
 
 
 
 
 
Gla x o S mit h Kli n e C o ns u mer Healt h car e C o nfi de ntial 
S O P - 2 0 8 5 5 9 Statistical Re p orti n g a n d A nal ysis pla n te m plate v 4. 0 
Pa ge 1 9  of 2 0  
 
4. 6. 2  
L a b or at or y T e st s 
List i n g of all la b orat or y t est res ults ( bi o c he mistr y, he mat ol o g y, c o a g ulati o n, uri nal ysis) will be 
pr o vi de d i n 
 –  
. wit h a b n or mal val ues fla g ge d f or t he safet y p o p ulati o n. 
Res u lts fr o m C O VI D- 1 9 t est will be pr o vi de d i n 
 a n d 
. 
4. 6. 3 
Vit al Si g n s 
 
Vit al si g ns (s yst olic a n d diast olic bl o o d press ure, p uls e rat e, res pirati o n a n d b o d y t e m p erat ure ) 
will be s u m marize d f or t he safet y p o p ulati o n wit h descri pti ve st atistics ( mea n, S D , me dia n, 
mi ni m u m a n d ma xi m u m) f or t he o bser ve d a n d c ha n ge fr o m baseli ne val ues b y ti me p oi nt 
). Vit al si g ns at eac h assess me nt, i ncl u di n g b o d y wei g ht, 
will als o be list e d (
). 
4. 6. 4 
Fi n di n g s o n P h y si c al E x a mi n ati o n 
Fi n di n gs fr o m p h ysical e xa mi nati o n will be list e d (
). A n y a b n or mal fi n di n gs 
j u d ge d t o be cli nicall y si g nifica nt w hic h o cc urre d aft er si g ni n g t he i nf or me d c o nse nt f or m will 
be rec or de d as a n A E. A n y p h ysical e xa mi nati o n fi n di n gs d o c u me nt e d as A Es will be i ncl u de d 
i n t he s u m mar y of A Es. 
4. 6. 5  
Ot h er S af et y V ari a bl e s 
Dat a f or E C G (
) will be list e d o nl y. 
5  
C h a n g e s t o t h e Pr ot o c ol D efi n e d St ati sti c al A n al y si s Pl a n 
 
T here were n o c ha n ges or de viati o ns t o t he ori gi nall y pla n ne d st atistic al a nal ysis s pecifie d i n 
t he pr ot o c ol a me n d me nt 3 Versi o n 4. 0 ( Dat e d: 0 5/A U G/ 2 0 2 1).  
 
 
 
C CI
C CI
C CI
C CI
P P D
P P D
P P D
P P D


Par a cet a m ol 2 4 m g/ m L Str a w berr y or al s us pe nsi o n  
2 1 5 2 6 2 
 
 
 
 
 
Gla x o S mit h Kli n e C o ns u mer Healt h car e C o nfi de ntial 
S O P - 2 0 8 5 5 9 Statistical Re p orti n g a n d A nal ysis pla n te m plate v 4. 0 
Pa ge 2 0  of 2 0  
 
Att a c h m e nt 1: Li st of D at a Di s pl a y s 
 
 
C CI


St atistic al A n al ysis Pl a n - Re p orti n g a n d A n al ysis Pl a n - S A P or P K- P D Secti o ns 
T here of - 2 2- Oct- 2 0 2 1
Electr o nic Si g n at ure M a nifest ati o n 
T his pa ge is a ma nifestati o n of t he electr o nic si g nat ure(s) use d i n c o m plia nce wit h t he or ga nizati o n's 
electr o nic si g nat ure p olicies a n d pr oce d ures.
P a ge 2 1 - O bject 1 0 0 0 5 5 1 A 0 0 0 0 0 0 0 0 4 E 9 F 1 4 6 2
Si g ner F ull 
N a me
Me a ni n g of Si g n at ure
D ate a n d Ti me
D oc u me nt A p pr o val (I certif y t hat I ha ve t he e d ucati o n, trai ni n g 
a n d e x perie nce t o perf or m t his tas k)
D oc u me nt A p pr o val (I certif y t hat I ha ve t he e d ucati o n, trai ni n g 
a n d e x perie nce t o perf or m t his tas k)
D oc u me nt A p pr o val (I certif y t hat I ha ve t he e d ucati o n, trai ni n g 
a n d e x perie nce t o perf or m t his tas k)
D oc u me nt A p pr o val (I certif y t hat I ha ve t he e d ucati o n, trai ni n g 
a n d e x perie nce t o perf or m t his tas k)
D oc u me nt A p pr o val (I certif y t hat I ha ve t he e d ucati o n, trai ni n g 
a n d e x perie nce t o perf or m t his tas k)
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