An 8 Week, Randomised, Examiner-blind, Controlled Clinical Study to Evaluate the Efficacy of a Stannous Fluoride Dentifrice in the Relief of Dentinal Hypersensitivity in a Chinese Population
Phase: NA
Conditions: Dentin Sensitivity
Sponsor: HALEON

GSK Consumer Healthcare 
Clinical Protocol 
Protocol Number: 216954 
CLINICAL PROTOCOL 
An 8 Week, Randomised, Examiner-blind, Controlled 
Clinical Study to Evaluate the Efficacy of a Stannous 
Fluoride Dentifrice in the Relief of Dentinal Hypersensitivity 
in a Chinese Population 
Protocol Number: 
216954 
Compound/Product Name: 
Stannous fluoride (SnF2) 
United States (US) Investigational 
New Drug (IND) Number: 
Not applicable 
European Clinical Trials Database 
(EudraCT) Number: 
Not applicable 
Other Regulatory Agency Identified 
Number: 
Not applicable 
Phase: 
Not applicable 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0
This document contains confidentiality statements that are not relevant for this 
publicly available version

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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  of 8 5  
 
 
S p o n s or I nf or m ati o n  
 
S p o n s or N a m e & L e g al 
R e gi st er e d A d dr e s s  
 
Gl a x o S mit h Kli n e C o n s u m er H e alt h c ar e 
( U K) Tr a di n g Li mit e d 
 
S p o n s or C o nt a ct D et ail s  
 
Gl a x o S mit h Kli n e C o n s u m er H e alt h c ar e 
( C hi n a) C o, Lt d 
 
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
P P D
P P D

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Document History 
 
Document 
Version Summary of Changes  
Original protocol 
1.0 
Not applicable  
Amended 
protocol 
2.0 
The following administrative changes have been 
made: 
1) clarifications in the administrative change letter 
dated 24 February 2021 have been added 
2) clarification in “Section 12.3.1 Primary Analysis(es)” 
for the calculation of the % difference between 
treatment was added 
 
Amendments incorporate all revisions to date, including amendments made at the request of 
country health authorities, institutional review boards/ethics committees (IRBs/ECs), etc. 
 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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 m e nt t o c o n d 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 nter n ati o nal C o nfere nce o n Har m o nisati 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 u ct. I a gree t o p ers o nall y 
c o n d uct or s u per vise t he descri be d st u d y.  
•  I a gree t o e ns ure 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 m e d a bo 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 ul ati o ns of t he 
c o u ntr y i n w hic h t he researc h is c o n d u cte d  a n d t he Declarati o n of Helsi n ki.  
 
I n v esti gat or Na me: 
I n v esti gat or Q ualificati o ns: 
 
I n v esti gat or Si g nat ure: 
Date of Si g nat ure/ A gree me nt:  
D D -M m m -Y Y Y Y  
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
P P D
P P D
P P D

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Table of contents 
List of tables ........................................................................................................................ 9 
1 
PROTOCOL SUMMARY ................................................................................................ 10 
1.1 
Synopsis ................................................................................................................. 10 
2 
INTRODUCTION ............................................................................................................. 16 
2.1 
Study Rationale and Background .......................................................................... 16 
2.2 
Benefit/Risk Assessment ....................................................................................... 17 
2.3 
Mechanism of Action/Indication ........................................................................... 17 
3 
STUDY OBJECTIVES AND ENDPOINTS .................................................................... 17 
4 
STUDY DESIGN .............................................................................................................. 19 
4.1 
Overall Design ....................................................................................................... 19 
4.2 
Scientific Rationale for Study Design ................................................................... 19 
4.3 
Justification for Dose and Regimen ....................................................................... 22 
4.4 
End of Study Definition ......................................................................................... 23 
5 
STUDY POPULATION .................................................................................................... 23 
5.1 
Type and Planned Number of Subjects ................................................................. 23 
5.2 
Inclusion Criteria ................................................................................................... 24 
5.3 
Exclusion Criteria .................................................................................................. 25 
5.4 
Randomisation Criteria and Stratification ............................................................. 27 
5.5 
Lifestyle Considerations ........................................................................................ 27 
5.5.1 
Oral Care Restrictions ........................................................................... 27 
5.5.2 
Meals and Dietary Restrictions ............................................................. 28 
5.5.3 
Alcohol .................................................................................................. 28 
5.5.4 
Contraception ........................................................................................ 28 
5.6 
Screen Failures ....................................................................................................... 28 
5.7 
Sponsor’s Qualified Medical Personnel ................................................................ 28 
5.8 
Rater/Clinical Assessor Qualifications .................................................................. 29 
6 
INVESTIGATIONAL/STUDY PRODUCTS ................................................................... 29 
6.1 
Investigational/Study Product Supplies ................................................................. 29 
6.1.1 
Dosage Form and Packaging ................................................................. 32 
6.1.2 
Preparation and Dispensing ................................................................... 32 
6.2 
Administration ....................................................................................................... 33 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

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Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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6.2.1 
Medication/Dosing Errors ..................................................................... 33 
6.2.2 
Overdose ............................................................................................... 34 
6.3 
Investigational/Study Product Storage .................................................................. 34 
6.4 
Investigational/Study Product Accountability ....................................................... 34 
6.4.1 
Destruction of Investigational/Study Product Supplies ........................ 35 
6.5 
Blinding and Allocation/Randomisation ............................................................... 35 
6.6 
Breaking the Blind ................................................................................................. 36 
6.7 
Compliance ............................................................................................................ 36 
6.8 
Concomitant Medication/Treatment(s) .................................................................. 37 
7 
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ......................................................................... 38 
7.1 
Subject Discontinuation/Withdrawal ..................................................................... 38 
7.2 
Lost to Follow up ................................................................................................... 38 
8 
STUDY PROCEDURES ................................................................................................... 39 
8.1 
Visit 1/ Screening .................................................................................................. 39 
8.1.1 
Informed Consent .................................................................................. 39 
8.1.2 
Review of Subjects Oral Care Products ................................................ 40 
8.1.3 
Review of Subjects Brushing Habits..................................................... 40 
8.1.4 
Demographics and Ethnicity ................................................................. 40 
8.1.5 
Medical History and Prior Medication/Treatment ................................ 40 
8.1.6 
Full Oral Soft Tissue (OST) and Oral Hard Tissue (OHT) 
Examinations ......................................................................................... 41 
8.1.7 
Eligible Teeth and Qualifying Sensitivity Assessments ....................... 41 
8.1.8 
Inclusion/Exclusion Criteria.................................................................. 41 
8.1.9 
Subject Eligibility.................................................................................. 41 
8.1.10 
Dispense Acclimatisation Products ....................................................... 42 
8.1.11 
Supervised Brushing with Acclimatisation Dentifrice .......................... 42 
8.1.12 
Adverse Events ...................................................................................... 42 
8.2 
Study Period........................................................................................................... 42 
8.2.1 
Visit 2 (Baseline/Day 1) ........................................................................ 42 
8.2.2 
Visit 3 (Day 29±3) and Visit 4 (Day 57±3) .......................................... 44 
8.3 
Study Conclusion ................................................................................................... 46 
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Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
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8.4 
Diary Review ......................................................................................................... 46 
8.5 
Brushing Compliance Check at 2 and 6 Weeks ..................................................... 47 
8.6 
Follow-up Visit"/ Phone Call"  .............................................................................. 47 
9 
STUDY ASSESSMENTS ................................................................................................. 47 
9.1 
Screening Assessments .......................................................................................... 47 
9.1.1 
Eligible Tooth Assessments .................................................................. 48 
9.1.2 
Qualifying Tactile Sensitivity ............................................................... 49 
9.1.3 
Qualifying Evaporative Air Sensitivity ................................................. 50 
9.1.4 
Selection of Test Teeth .......................................................................... 50 
9.2 
Dentine Hypersensitivity Assessments .................................................................. 50 
9.2.1 
Tactile Sensitivity Assessment (Yeaple Probe) .................................... 50 
9.2.2 
Evaporative Air Sensitivity Assessment ............................................... 51 
9.3 
Safety and Other Assessments ............................................................................... 52 
9.3.1 
Oral Hard Tissue (OHT) Examination .................................................. 52 
9.3.2 
Oral Soft Tissue (OST) Examination .................................................... 52 
9.3.3 
Pregnancy Testing ................................................................................. 53 
10 ADVERSE EVENT AND SERIOUS ADVERSE EVENTS ........................................... 53 
10.1 
Definition of an Adverse Event (AE) .................................................................... 53 
10.2 
Definition of a Serious Adverse Event (SAE) ....................................................... 54 
10.3 
Time Period and Frequency for Collecting AE and SAE Information .................. 55 
10.4 
Reporting Procedures ............................................................................................. 56 
10.4.1 
Reporting of an Adverse Event ............................................................. 57 
10.4.2 
Reporting of a Serious Adverse Event .................................................. 57 
10.5 
Evaluating Adverse Events .................................................................................... 58 
10.5.1 
Assessment of Intensity......................................................................... 58 
10.5.2 
Assessment of Causality ....................................................................... 59 
10.6 
Follow-up of AEs and SAEs .................................................................................. 59 
10.7 
Withdrawal Due to an Adverse Event ................................................................... 60 
10.8 
Regulatory Reporting Requirements for SAEs ...................................................... 60 
10.9 
Pregnancy .............................................................................................................. 61 
10.9.1 
Time Period for Collecting Pregnancy Information .............................. 61 
10.9.2 
Action to be Taken if Pregnancy Occurs .............................................. 61 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

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Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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11 DATA MANAGEMENT .................................................................................................. 61 
11.1 
Case Report Form .................................................................................................. 62 
11.2 
Data Handling ........................................................................................................ 62 
11.2.1 
Data Queries .......................................................................................... 63 
11.3 
Processing Patient Reported Outcomes ................................................................. 63 
12 STATISTICAL CONSIDERATIONS AND DATA ANALYSES .................................. 64 
12.1 
Sample Size Determination ................................................................................... 64 
12.2 
Populations for Analysis ........................................................................................ 64 
12.2.1 
Definition of Analysis Populations ....................................................... 64 
12.2.2 
Exclusion of Data from Analysis .......................................................... 64 
12.3 
Statistical Analyses ................................................................................................ 65 
12.3.1 
Primary Analysis(es) ............................................................................. 65 
12.3.2 
Secondary Analyses .............................................................................. 65 
12.3.3 
Exploratory Analyses ............................................................................ 66 
12.3.4 
Safety Analysis(es) ................................................................................ 67 
12.3.5 
Exclusion of Data from Analysis .......................................................... 67 
12.3.6 
Demographic and Baseline Characteristics ........................................... 67 
12.3.7 
Study Product Compliance and Use of Other Therapies ...................... 67 
12.3.8 
Handling of Dropouts and Missing Data .............................................. 68 
12.3.9 
Interim Analysis .................................................................................... 68 
13 STUDY GOVERNANCE CONSIDERATIONS .............................................................. 68 
13.1 
Quality Control ...................................................................................................... 68 
13.2 
Quality Assurance .................................................................................................. 69 
13.3 
Regulatory and Ethical Considerations ................................................................. 69 
13.3.1 
Institutional Review Board/ Ethics Committee ..................................... 69 
13.3.2 
Ethical Conduct of the Study ................................................................ 70 
13.3.3 
Subject Information and Consent .......................................................... 70 
13.3.4 
Subject Recruitment .............................................................................. 70 
13.3.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP ............................................................................................... 71 
13.4 
Posting of Information on Publicly Available Clinical Trial Registers ................. 71 
13.5 
Provision of Study Results to Investigators ........................................................... 71 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

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Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
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13.6 
Records Retention .................................................................................................. 72 
13.7 
Conditions for Terminating the Study ................................................................... 72 
14 REFERENCES .................................................................................................................. 74 
15 APPENDICIES .................................................................................................................. 78 
15.1 
ABBREVIATIONS ............................................................................................... 78 
15.2 
Dentine Hypersensitivity Experience Questionnaire (DHEQ) – Short-form ........ 80 
15.3 
Video Compliance Check-list ................................................................................ 85 
 
List of tables 
Table 1-1 
Schedule of Activities ........................................................................... 13 
Table 6-1 
Investigational Product Supplies ........................................................... 29 
Table 6-2 
Acclimatisation Product Supplies ......................................................... 30 
Table 6-3 
Sundry Items ......................................................................................... 31 
Table 15-1 
Abbreviations ........................................................................................ 78 
 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

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Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
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1 
PROTOCOL SUMMARY  
1.1 
Synopsis 
Short Title: 
A Randomised Controlled Clinical Study to Evaluate the Efficacy of a Dentifrice in the Relief 
of Dentinal Hypersensitivity in a Chinese Population. 
Background and Rationale: 
The Chinese Ministry of Health (MoH) guidelines (Ministry of Health China, 2010) stipulate 
that two clinical studies are required to support the efficacy of a functional toothpaste, with at 
least one of these studies (for each claimed benefit) to be conducted on a local Chinese 
population.  
To support long-term dentinal hypersensitivity (DH) relief claims of 0.454% stannous fluoride 
(SnF2) containing toothpastes in China, a clinical study is required to be conducted in a local 
Chinese population.  
Objectives and Endpoints: 
Objective(s) 
Endpoint(s) 
Primary 
To compare the clinical efficacy of a 
0.454% w/w SnF2 dentifrice for the relief of 
DH, as elicited by an evaporative air 
stimulus (with Schiff sensitivity score), 
against a negative control dentifrice, when 
used twice daily for 8 weeks. 
Change from Baseline in Schiff sensitivity 
score at 8 weeks. 
Secondary 
To compare the clinical efficacy of a 
0.454% w/w SnF2 dentifrice for the relief of 
DH, as elicited by a tactile stimulus (yeaple 
probe), against a negative control dentifrice, 
when used twice daily for 8 weeks. 
Change from Baseline in tactile threshold at 
4 and 8 weeks. 
To compare the clinical efficacy of a 
0.454% w/w SnF2 dentifrice for the relief of 
DH, as elicited by an evaporative air 
stimulus (with Schiff sensitivity score), 
Change from Baseline in Schiff sensitivity 
score at 4 weeks. 
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Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
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against a negative control dentifrice, when 
used twice daily for 4 weeks. 
To compare the clinical efficacy of a 
positive control dentifrice for the relief of 
DH, as elicited by an evaporative air 
stimulus (with Schiff sensitivity score) and a 
tactile stimulus (yeaple probe), against a 
negative control dentifrice, when used twice 
daily for 8 weeks. 
Change from Baseline in Schiff sensitivity 
score and tactile threshold at 4 and 8 weeks. 
Safety 
To evaluate the safety and oral tolerability 
of the test dentifrices when used twice daily 
for 8 weeks. 
Adverse Events 
Exploratory 
To characterise Oral Health Related Quality 
of Life (OHRQoL) as measured by the 
short-form of the Dentine Hypersensitivity 
Experience Questionnaire (DHEQ-15) 
after  8 weeks treatment with a 0.454% 
w/w SnF2 dentifrice compared to a negative 
control dentifrice. 
At 8 weeks, change from Baseline in:  
• responses to Questions 7-9, DHEQ 
Section 1  
• Total Score, Questions 1-15, DHEQ 
Section 2   
• Restrictions, Adaptation, Social 
Impact, Emotional Impact & 
Identity Domains  
 
To characterise OHRQoL as measured by 
the short-form of the DHEQ-15 after  8 
weeks treatment with a positive control 
dentifrice compared to a negative control 
dentifrice. 
At 8 weeks, change from Baseline in:  
• responses to Questions 7-9, DHEQ 
Section 1  
• Total Score, Questions 1-15, DHEQ 
Section 2   
• Restrictions, Adaptation, Social 
Impact, Emotional Impact & 
Identity Domains  
 
Study Design: 
This will be a single centre, randomised, controlled, examiner-blind, 3 treatment arm, parallel 
group design study, stratified by maximum baseline Schiff sensitivity score (of the 2 selected 
‘test teeth’), with a treatment period of 8 weeks, to investigate the clinical efficacy of a SnF2 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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 2  of 8 5  
 
de ntifrice i n t he re d u cti o n of D H  i n a C hi nes e p o p ulati o n. T he S n F 2 test de ntifrice will b e 
c o m pare d t o c o m mercialise d ne gati ve a n d p ositi ve c o ntr ol de ntifrices.  
St u d y Pr o d u ct s : 
 
* F oll o w i n g t o ot h br u s hi n g a n d/ or ri n si n g s u bj e ct s m a y al s o c o n d u ct a di s cr eti o n ar y t o n g u e cl e a n u si n g t h e pr o vi d e d 
t o ot h br u s h, b ut t hi s i s n ot a st u d y r e q uir e m e nt. 
T y p e a n d Pl a n n e d N u m b er of S u bj e ct s : 
A s ufficie nt n u m ber of s u bjects will be scree n e d t o ra n d o mise a p pro xi matel y 1 9 5  s u bjects t o 
e ns ure a p pr o xi matel y 1 8 0  s u bjects (a p pr o xi matel y 6 0 per treat me nt gr o u p) c o m plete t he st u d y, 
all o wi n g f or dr o p o uts.  
St ati sti c al A n al y si s S u m m ar y:  
T he pri mar y efficac y varia ble is t he c ha n ge fr o m baseli ne i n Sc hiff sc ore at 8 wee ks . T h e 
pri mar y c o m paris o n is bet wee n t he test pr o d u ct a n d t he ne gati ve  c o ntr ol.  
T he sec o n d ar y efficac y v aria ble s wit h c orres p o n di n g c o m p aris o ns are as f oll o ws:  
I n v e sti g ati o n al 
Pr o d u ct  
T e st Pr o d u ct  
R ef er e n c e Pr o d u ct 
( N e g ati v e C o ntr ol)  
R ef er e n c e Pr o d u ct 
(P o siti v e C o ntr ol)  
Pr o d u ct N a m e  
S e n s o d y n e S e n siti vit y & 
G u m ( C hr y s a nt h e m u m) ; 
C hi n e s e c o m m er ci ali s e d 
d e ntifri c e c o nt ai ni n g 
0. 4 5 4 % S n F 2 .  
 
Cr e st C a vit y Pr ot e cti o n 
Fr e s h Li m e ( 1 1 5 0 p p m 
fl u ori d e a s N a F); 
C hi n e s e c o m m er ci ali s e d 
d ail y fl u ori d e d e ntifri c e . 
S e n s o d y n e R e p air a n d 
Pr ot e ct; C hi n e s e 
c o m m er ci ali s e d 
d e ntifri c e c o nt ai ni n g  
5. 0 % w/ w c al ci u m 
s o di u m p h o s p h o sili c at e.  
Pr o d u ct 
M a st er 
F or m ul ati o n 
C o d e ( M F C)  
C o m m er ci al Pr o d u ct  
 
C o m m er ci al Pr o d u ct  
C o m m er ci al Pr o d u ct  
 
U s a g e 
I n str u cti o n s 
A p pl y a f ull ri b b o n of 
t o ot h p a st e o n t h e h e a d of 
t h e t o ot h br u s h pr o vi d e d. 
B r u s h t e et h f or 1*-ti m e d 
mi n ut e , f oll o w e d b y 
br u s hi n g  of t h e q u alif yi n g 
s e n siti v e t e et h . F oll o wi n g 
br u s hi n g ri n s e o n c e wit h 
1 0 ml of w at er fr o m t h e 
ri n si n g c u p pr o vi d e d.  
A p pl y a f ull ri b b o n of 
t o ot h p a st e o n t h e h e a d 
of t h e t o ot h br u s h 
pr o vi d e d; br u s h t e et h f or 
1* -ti m e d mi n ut e. 
F oll o wi n g br u s hi n g ri n s e 
o n c e wit h 1 0 ml of w at er 
fr o m t h e ri n si n g c u p 
pr o vi d e d.  
A p pl y a f ull ri b b o n of 
t o ot h p a ste o n t h e h e a d 
of t h e t o ot h br u s h 
pr o vi d e d; br u s h t e et h f or 
1* -ti m e d mi n ut e. 
F oll o wi n g br u s hi n g ri n s e 
o n c e wit h 1 0 ml of w at er 
fr o m t h e ri n si n g c u p 
pr o vi d e d.  
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
C CI
C CI

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Clinical Protocol 
 
 
Protocol Number: 216954 
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• Change from baseline in tactile threshold at 4 and 8 weeks; “test product versus negative 
control” and “positive control versus negative control”.  
• Change from baseline in Schiff sensitivity score at 4 weeks; “test product versus 
negative control” and “positive control versus negative control”. 
• Change from baseline in Schiff sensitivity score 8 weeks; “positive control versus 
negative control”. 
The change from baseline in Schiff sensitivity score will be analysed using analysis of 
covariance (ANCOVA) with treatment as a factor and baseline Schiff sensitivity score as a 
covariate. Note that since the baseline Schiff sensitivity score will be included as a covariate, 
the baseline Schiff stratification value will not be included in the model. 
Tactile is analysed in the same way with the addition of a factor for baseline Schiff stratification. 
Table 1-1 
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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Procedure/ 
Assessment 
Screening 
ACCLIMATISATION PERIOD 14 TO 28 DAYS 
Study Period 
Visit 1 
 
Baseline 
Visit 2 
Day 1 (Up to 
28 days 
after Visit 1) 
Visit 3 
Day 
29±3 
Visit 4 
Day 57±3 
Informed consent 
X 
 
 
 
Review of Subjects Oral Care Products to 
Confirm They Don’t Contain any Anti-
sensitivity Ingredients 
X 
 
 
 
Review of Subjects Brushing Habits 
X 
 
 
 
Demographics, Ethnicity 
X 
 
 
 
Medical History and Prior 
Medication/Treatment 
X 
 
 
 
Concomitant Medications 
 
X 
X 
X 
Full OST Examination 
X 
X 
X 
X 
Full OHT Examination  
X 
 
 
X 
Eligible Teeth Assessments (Dentition 
Exclusions, EAR, MGI, Tooth Mobility) 
X 
 
 
 
Qualifying Tactile Assessment (Yeaple 
Probe)1 
X 
 
 
 
Qualifying Evaporative Air Sensitivity (Schiff 
Sensitivity Score)1 
X 
 
 
 
Identify Test Teeth 
X 
 
 
 
Inclusion/Exclusion Criteria 
X 
 
 
 
Subject Eligibility 
X 
 
 
 
Dispense Acclimatisation Dentifrice, 
Toothbrush, Rinsing Cups, Diary and Timer2 
X 
 
 
 
Supervised Brushing with Acclimatisation 
Dentifrice3 
X 
 
 
 
Subject Adherence and Continuance 
 
X 
X 
X 
Subject completion of DHEQ-15 
 
X 
 
X 
Tactile Assessment (Yeaple Probe)4 
 
X 
X 
X 
Evaporative Air Assessment (Schiff 
Sensitivity Score)5 
 
X 
X 
X 
Confirm Test Teeth6  
 
X 
 
 
Stratification and Randomisation  
 
X 
 
 
Dispense Randomised Dentifrice, 
Toothbrush, Rinsing Cups and Diary 
 
X 
 
 
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Abbreviations: OST = Oral Soft Tissue; OHT = Oral Hard Tissue; EAR = Erosion, Abrasion, Recession; MGI = Modified Gingival Index; ; SnF2 = 
stannous fluoride; DHEQ = Dentine Hypersensitivity Experience Questionnaire. 
 
Footnotes: 
1 Qualifying Schiff sensitivity and tactile threshold scores will be recorded in the case report form (CRF). Evaporative air assessment to follow tactile 
assessment; minimum 5 minutes time lapse between the two assessment types for tooth recovery. At Screening, maximum force for tactile = 20g. 
2 Subject is instructed to bring all supplies back to next visit. 
3 Study supplies to be returned to subject (for use at home) after supervised brushing. 
4 At Baseline, maximum force = 20g, at all subsequent visits maximum force = 80g. 
5 Evaporative air assessment to follow tactile assessment; minimum 5 minutes time lapse between the two assessment types for tooth recovery.  
6.Subject’s with ‘test teeth’ that don’t respond to tactile and/or Schiff at Baseline, may be required to have all eligible teeth identified at Screening re-
assessed to identify ‘test teeth’. A minimum of 5 minutes time lapse will be required between assessments. 
7 Subject is instructed to bring all supplies back to subsequent visits for compliance checks. Study supplies to be returned to subject after supervised 
brushing. Subject is re-dispensed a new toothbrush at Visit 3. 
8 Adverse Events (AEs) and therefore all Serious Adverse Events (SAEs) will be collected immediately after a subject provides consent to participate 
in the study by the completion of the informed consent form (ICF). 
 
Supervised Brushing with Allocated 
Dentifrice and Reminder of Product Usage 
Instructions7 
 
X 
X 
 
Subjects Bring Study Supplies and Diary to 
Site 
 
X 
X 
X 
Weight Check of Returned Study Dentifrice 
and Subject Brushing Video’s, and 
Compliance Discussion7 
 
X 
X 
X 
Adverse Events8 
X 
X 
X 
X 
Study Conclusion 
 
 
 
X 
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2 
INTRODUCTION 
Dentine hypersensitivity (DH) has been defined as ‘pain derived from exposed dentine in 
response to chemical, thermal, tactile, or osmotic stimuli which can’t be explained as arising 
from any other dental defect or disease’ (Addy, 1985; Canadian Advisory Board on Dentin 
Hypersensitivity, 2003). The primary aetiological factors associated with the onset of DH 
include gingival recession and/or enamel loss (e.g. through erosion or abrasion) that result in 
exposure of dentine with patent dentinal tubules (Orchardson, 2000). The hydrodynamic theory 
of DH hypothesises that a stimulus external to the tooth (e.g. a temperature/osmotic differential) 
causes transport of the fluid resident within dentinal tubules (Brännström, 1962). This fluid 
movement may stimulate nerve processes in the pulpal area of the dentine including irritation 
of odontoblasts, pulpal neurons, and even subodontonblastic blood vessels (Hall, 2000), 
resulting in the characteristic short, sharp pain of DH. 
Currently there are two approaches to the management of DH: either nerve depolarisation or 
dentinal tubule occlusion. Nerve depolarising agents, typically potassium salts, generally 
require a period of use (for example, 14 to 28 days) before their benefit is established. The 
delivery of potassium ions to the dentine-pulp junction (odontoblastic layer) via dentinal tubules 
is believed to result in depolarisation of the afferent nerve membrane thereby interrupt the pain 
response (Orchardson, 2000). The second approach uses tubule occluding agents which 
physically block the exposed end of the dentinal tubules, thus reducing dentinal fluid movement 
and pulpal irritation. Tubule occluding agents, like stannous salts, serve to seal or block the 
dentine tubules and thereby reduce the effect of external stimuli. Such agents are believed to 
function by precipitating insoluble materials onto the dentine surface and/or within the dentinal 
tubules to reduce dentinal fluid transport (Pashley, 1986).   
Stannous fluoride (SnF2) has been incorporated into oral hygiene products indicated for the 
reduction of DH since the 1960’s (Schiff, 2006). SnF2 provides relief from DH by the occlusion 
of the dentinal tubules through chemical precipitation of stannous oxides and hydroxides onto 
the surface of the dentine. Proctor and Gamble (P&G) and GlaxoSmithKline Consumer 
Healthcare (GSK CH) have marketed SnF2-containing dentifrices indicated for DH relief, with 
published evidence demonstrating longitudinal clinical efficacy (Ni, 2010; Parkinson, 2011; 
Makin, 2013).  
2.1 
Study Rationale and Background 
The Chinese Ministry of Health (MoH) guidelines (Ministry of Health China, 2010) stipulate 
that two clinical studies are required to support the efficacy of a functional toothpaste, with at 
least one of these studies (for each claimed benefit) to be conducted on a local Chinese 
population.  
To support DH efficacy claims GSK CH holds an extensive global clinical data package for 
0.454% SnF2 dentifrices (Creeth et al, 2019; Goyal et al, 2017; Parkinson et al, 2013; Parkinson 
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et al, 2015; Parkinson et al, 2016;). To support long-term dentine hypersensitivity claims in 
China, two further DH clinical studies have been conducted.  
The first DH study (GSK CH Clinical Study 205794, 2017) met the primary objective (Schiff 
sensitivity score, at both 4 and 8 weeks), but did not meet the secondary objective (tactile 
threshold). A further clinical study was conducted (Tao, 2020), which demonstrated 
significantly reduced dentine hypersensitivity from baseline for the SnF2 dentifrice, however, 
there was no between treatment differences when compared to a negative and positive control. 
To support long-term DH relief claims of 0.454% SnF2 containing toothpastes in China, a 
clinical study is required to be conducted in the local Chinese population.  
2.2 
Benefit/Risk Assessment  
Complete information for the acclimatization and  study products may be found on the product 
labels.  
 
2.3 
Mechanism of Action/Indication 
SnF2 is a dentine tubule occluding agent that is being investigated in subjects with DH. Such 
agents have been shown to function by precipitating insoluble materials onto the dentine surface 
and/or within the dentinal tubules to reduce dentinal fluid transport (Parkinson 2011; Parkinson 
2013). 
3 
STUDY OBJECTIVES AND ENDPOINTS 
Objective(s) 
Endpoint(s) 
Primary 
To compare the clinical efficacy of a 
0.454% w/w SnF2 dentifrice for the relief of 
DH, as elicited by an evaporative air 
stimulus (with Schiff sensitivity score), 
against a negative control dentifrice, when 
used twice daily for 8 weeks. 
Change from Baseline in Schiff sensitivity 
score at 8 weeks. 
Secondary 
To compare the clinical efficacy of a 
0.454% w/w SnF2 dentifrice for the relief of 
DH, as elicited by a tactile stimulus (yeaple 
probe), against a negative control dentifrice, 
when used twice daily for 8 weeks. 
Change from Baseline in tactile threshold at 
4 and 8 weeks. 
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To compare the clinical efficacy of a 
0.454% w/w SnF2 dentifrice for the relief of 
DH, as elicited by an evaporative air 
stimulus (with Schiff sensitivity score), 
against a negative control dentifrice, when 
used twice daily for 4 weeks. 
Change from Baseline in Schiff sensitivity 
score at 4 weeks. 
To compare the clinical efficacy of a 
positive control dentifrice for the relief of 
DH, as elicited by an evaporative air 
stimulus (with Schiff sensitivity score) and a 
tactile stimulus (yeaple probe), against a 
negative control dentifrice, when used twice 
daily for 8 weeks. 
Change from Baseline in Schiff sensitivity 
score and tactile threshold at 4 and 8 weeks. 
Safety 
To evaluate the safety and oral tolerability 
of the test dentifrices when used twice daily 
for 8 weeks. 
Adverse Events 
Exploratory 
To characterise Oral Health Related Quality 
of Life (OHRQoL) as measured by the 
short-form of the Dentine Hypersensitivity 
Experience Questionnaire (DHEQ-15) 
after  8 weeks treatment with a 0.454% 
w/w SnF2 dentifrice compared to a negative 
control dentifrice. 
At 8 weeks, change from Baseline in:  
• responses to Questions 7-9, DHEQ 
Section 1  
• Total Score, Questions 1-15, DHEQ 
Section 2   
• Restrictions, Adaptation, Social 
Impact, Emotional Impact & 
Identity Domains  
 
To characterise OHRQoL as measured by 
the short-form of the DHEQ-15 after  8 
weeks treatment with a positive control 
dentifrice compared to a negative control 
dentifrice. 
At 8 weeks, change from Baseline in:  
• responses to Questions 7-9, DHEQ 
Section 1  
• Total Score, Questions 1-15, DHEQ 
Section 2   
• Restrictions, Adaptation, Social 
Impact, Emotional Impact & 
Identity Domains  
 
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This study will be considered successful if there is a statistically significant difference in the 
primary efficacy variable, change from baseline in Schiff sensitivity score and a between 
treatment difference in favour of the SnF2 dentifrice compared to the negative control, after 8 
weeks of treatment. The size of the effect is important to meet Chinese MoH guidelines, a 15% 
difference between the SnF2 dentifrice and the negative control must be observed.  
4 
STUDY DESIGN  
4.1 
Overall Design 
This will be a single centre, randomised, controlled, examiner-blind, 3 treatment arm, parallel 
group design study, stratified by maximum baseline Schiff sensitivity score (of the 2 selected 
‘test teeth’), with a treatment period of 8 weeks, to investigate the clinical efficacy of a SnF2 
dentifrice in the reduction of DH in a Chinese population. The SnF2 test dentifrice will be 
compared to commercialised negative and positive control dentifrices. 
In line with published recommendations (Holland, 1997) and the requirement of Chinese 
Ministry of Health guidelines (Ministry of Health (China), 2010) for the testing of functional 
dentifrices (desensitising), two independent stimulus-based efficacy measures will be employed 
(tactile and evaporative air sensitivity) to evaluate the DH efficacy of the test dentifrice. A 
tactile stimulus will be administered using a constant pressure probe (yeaple Probe (Polson, 
1980)). An evaporative (air) stimulus will be administered using a dental air syringe. Response 
to this stimulus will be evaluated using the Schiff sensitivity scale (Schiff, 1994). DH 
assessments will be conducted at Baseline, 4 and 8 weeks. 
Subjects will also be requested to complete a short-form version of the Dentine Hypersensitivity 
Experience Questionnaire (DHEQ-15) at the Baseline and Week 8 Visits. 
A sufficient number of subjects will be screened to randomise approximately 195 subjects to 
ensure approximately 180 subjects (approximately 60 per treatment group) complete the study. 
4.2 
Scientific Rationale for Study Design 
A randomised, examiner-blind, parallel group design is a recognised approach for providing 
evidence of the clinical efficacy of a product in the reduction of DH (Holland, 1997). In order 
to establish longitudinal performance, with the opportunity for benefit to be observed, an eight 
week treatment period will be used (Murray, 1994; Irwin, 1997; Ministry of Health (China), 
2010). 
The proposed examiners will be dentally qualified and trained in the clinical assessments of DH, 
using both the air syringe (Schiff sensitivity scale) and yeaple probe (Tactile threshold). To 
minimise assessment variability, where feasible the same examiner will be responsible for a 
given clinical assessment from Screening until the end of the study. To manage logistics at the 
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clinical study site, additional dentally qualified examiners who may have not trained in the 
clinical assessments of DH will be permitted to conduct oral hard tissue (OHT)/oral soft tissue 
(OST) assessments and those screening procedures that do not use the air syringe (Schiff 
sensitivity scale) and yeaple probe (Tactile threshold). 
Subjects will be asked to bring their regular oral care products to the Screening visit, and 
following signature of the informed consent form (ICF), their products will be checked to ensure 
that they do not contain any ingredients that are known to impart a DH benefit. This will provide 
confidence that subjects currently using any oral care products for the treatment of anti-
sensitivity are not enrolled into the study. Following this product check, subjects will then be 
asked to demonstrate their daily oral care regimen using their own products in the manner that 
they normally would at home. A member of the study site staff will observe subjects, and 
anyone who rinses with water during the first minute of toothbrushing will be excluded from 
undergoing any further screening procedures. Subjects who rinse after brushing will not be 
excluded.  
Subjects will be asked to attend the study site for the Baseline visit and then every 4 weeks for 
the duration of the study. At each visit subjects will be requested to conduct a supervised 
brushing and reminded of the product usage instructions. Subjects will also be sent daily 
reminders on WeChat to brush with their allocated study product as directed and adhere to study 
lifestyle restrictions.  
To monitor subject adherence to the product usage instructions, subjects will be asked to record 
2 brushing occasions per week using their smartphone video. Every 2 weeks a designated 
member of the clinical study team will review these videos and confirm compliance with 
product usage instructions in the case report form (CRF). These video’s will not be considered 
to be source data. Subjects confirmed as non-compliant (Eg. subjects who don’t correctly follow 
the product use instructions) will be reminded about the product usage instructions and 
documented as a protocol deviation. A check-list will be provided to the clinical study site so 
that they correctly understand what is considered to be compliant with the product usage 
instructions. 
In line with published recommendations (Holland, 1997) and the requirement of Chinese 
Ministry of Health guidelines (Ministry of Health (China), 2010) for the testing of functional 
dentifrices (desensitising), two independent stimulus-based efficacy measures will be employed 
(tactile and evaporative air sensitivity) to evaluate the DH efficacy of the experimental 
dentifrice. A tactile stimulus will be administered using a constant pressure probe (yeaple probe 
(Polson, 1980)). An evaporative (air) stimulus will be administered using a dental air syringe. 
Response to this stimulus will be evaluated using the Schiff sensitivity scale (Schiff, 1994). In 
accordance with the MoH guidelines, the mean values of each index should decrease during the 
clinical trial, and have statistical significance compared with the control group. When one of 
the mean values of the indices decreases by 15% or more than 15%, then the trial group can be 
considered to have DH efficacy (Ministry of Health China, 2010). 
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A qualifying response to a tactile stimulus followed by a qualifying air blast on all teeth 
qualifying for tactile will be included in this study. At Screening and Baseline subjects will 
have a minimum of two teeth with a tactile score of ≤20g and Schiff sensitivity score of ≥2. To 
ensure consistent responders are entered into the study, the 2 ‘test teeth’ must be selected from 
those teeth eligible for both Schiff and tactile at Screening, and confirmed at Baseline. 
Orchardson & Collins tested 516 sensitive teeth and found that while around half were sensitive 
to both evaporative air and tactile stimuli, 33% were sensitive only to an evaporative air 
stimulus and 16% were sensitive only to a tactile probe (Orchardson, 1987). Given that 
individual teeth may react differently to different stimuli it would be pragmatic to say the same 
for people. Therefore, some people may respond well to evaporative air sensitivity at Screening, 
but perhaps not to the same degree for tactile at Baseline, hence both tactile and evaporative air 
stimuli have been included at the Screening visit. This will help ensure that consistent 
responders to both stimuli are entered into the study.  
At all visits following Screening, the 2 selected ‘test teeth’ will be assessed using each of the 
clinical efficacy assessments. The selection of 2 ‘test teeth’ to evaluate changes in DH is 
common practice in sensitivity studies (Docimo, 2009). The subjects will be stratified at the 
Baseline visit according to their maximum Schiff sensitivity score of the 2 selected ‘test teeth’ 
to enable the treatment groups to be balanced in terms of the subject’s sensitivity severity. 
Subjects will also be requested to complete the short-form version of the DHEQ-15 at the 
Baseline and Week 8 Visits. Measuring a change from Baseline in DHEQ end-points will 
provide a richer understanding of the impact of using a 0.454% SnF2 dentifrice on subject 
perceived Oral Health Related Quality of Life (OHRQoL) parameters related to DH. The DHEQ 
has been previously validated in a Chinese population and demonstrated that individuals with 
greater severity of DH suffered from poorer OHRQoL (He, 2015; He 2015*).  
According to ICH guidelines, for a study to be classed as truly double blind, not only does the 
examiner (and any appropriate member of staff who may be involved in the dispensing of 
products, analysis of data etc.) need to be blinded to the treatment the subject receives, but the 
products under test must be identical (color, flavor, appearance, packaging). Given it is almost 
impossible to ensure identical appearance, taste and packaging for the dentifrices evaluated in 
oral care studies, the level of blindness for this study is described as ‘examiner blind’ only. 
Clinical trials evaluating clinical end points relating to pain can be prone to ‘placebo effects’ 
(Addy, 1985; West, 1997). Such effects are frequently observed in dentine hypersensitivity 
studies. A study conducted to evaluate the natural history of the dentine hypersensitivity 
condition highlighted the existence of a ‘no treatment’ effect characterised by an improvement 
in sensitivity simply as a function of clinical study participation (Leight, 2008). To help 
minimise the potential impact of such ‘placebo’ and ‘no treatment’ effects, an acclimatisation 
period of 2-4 weeks will be included in this study from Screening, ahead of the Baseline 
assessments and randomisation. During this period subjects will be provided with a toothbrush 
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and a marketed, standard fluoride dentifrice to use in place of their regular oral hygiene 
products. Crest Cavity Protection has been selected as it is a daily use regular fluoride dentifrice 
that is currently sold in China. Use of the acclimatisation dentifrice will also help provide a 
standardised oral hygiene regimen prior to the Baseline visit. Subjects will brush twice daily, 
in line with recommended oral hygiene practice, and typical Chinese consumer habit, during 
this period. 
In line with Chinese Ministry of Health guidelines (Ministry of Health (China), 2010) for the 
testing of functional dentifrices (desensitising), a standard fluoride dentifrice with no specific 
anti-sensitivity, anti-gingivitis and anti-plaque activity will be included as the negative control. 
Crest Cavity Protection has been selected as it has been evaluated not to have any DH clinical 
efficacy (GSK CH clinical study RH02294). 
A 5.0% w/w calcium sodium phosphosilicate containing positive control dentifrice (Chinese 
marketed Sensodyne Repair and Protect) with proven long-term DH efficacy in China (GSK 
CH clinical studies: RH01422 and RH01748), in clinical studies that satisfied the MoH 
requirements, will be included in this study as a benchmark of performance in the Chinese 
population. 
In this study the MGI inclusion criteria has been set at ≤1 for the area adjacent to the 2 ‘test 
teeth’. In previous DH studies, MGI for the area adjacent to the 2 ‘test teeth’ has been set at 0. 
This has been modified due to a request from the Investigator, as it is understood from general 
dental practise in China that a MGI score of 0 is atypical, and MGI ≥1 is more prevalent in a 
Chinese population. A score of 1 represents relatively subtle localised mild inflammation, and 
this would not be expected to impact on DH efficacy measures.  
4.3 
Justification for Dose and Regimen 
The dosage regimen of twice daily (morning and evening) brushing with a full ribbon of 
dentifrice on the supplied toothbrush for 1-timed minute will be the same for all subjects, and 
has been selected based on the minimum amount of time required to achieve DH efficacy in 
previously conducted clinical studies containing a SnF2 dentifrice (Parkinson, 2011; Makin, 
2013). Additional focused brushing of the identified ‘test teeth’ has been included for the Test 
dentifrice to ensure that the ‘test teeth’ are being treated, and to standardise treatment and 
facilitate monitoring of compliance. These instructions for use are aligned with the current 
product usage instructions in the USA, as determined by the US FDA Monograph for OTC Oral 
Health Care Drug Products; “Apply at least a 1-inch strip of the product onto a soft bristle 
toothbrush. Brush teeth thoroughly for at least 1 minute twice a day (morning and evening) or 
as recommended by a dentist or doctor. Make sure to brush all sensitive areas of the teeth” 
(FDA, 1991). Focused brushing of the sensitive teeth is not required for the Negative control as 
it is not marketed as an anti-sensitivity dentifrice, and therefore the usage instructions reflect 
those of a standard daily fluoride dentifrice, and do not require the sensitive areas of the teeth 
to be brushed. The usage instructions of the positive control dentifrice containing 5% w/w 
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calcium sodium phosphosilicate are aligned with the usage instructions that were used in GSK 
CH clinical studies where long-term DH efficacy was demonstrated in China (GSK CH clinical 
studies: RH01422 and RH01748). 
Discretionary tongue cleaning with the supplied toothbrush has also been included in this study, 
as this is typical oral hygiene practise in China. Subjects will be asked not to rinse with water 
during toothbrushing. It is understood that the dentifrice needs to be present in the oral cavity 
for a minimum of 1-minute to provide DH efficacy. Therefore, it can be hypothesised that if 
subjects rinse excessively with water during toothbrushing that the active ingredient responsible 
for providing DH relief may be expectorated and not adhere to the surface of the tooth and block 
the patent tubules. During a recent consumer study (GSK CH data on file) that observed Chinese 
consumers following their daily oral care regimen at home it was noted to be common practice 
for subjects to rinse with excessive water following toothbrushing, therefore subjects will be 
allowed to rinse with water following toothbrushing. In this same consumer study, the volume 
of water that subjects rinsed with was quite variable, therefore, to standardise subject rinsing, 
subjects will be provided with a rinsing cup with a 10 ml dosing line and will be allowed to 
rinse once with 10 ml of water following each brushing occasion. 
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 scheduled procedure, for the last subject, 
shown in the Schedule of Activities 
5 
STUDY POPULATION 
5.1 
Type and Planned Number of Subjects 
To meet MoH guidelines (Ministry of Health China, 2010), subjects will be located in China. 
Subjects will be male or female, with good general health and oral health, with a minimum of 
20 natural teeth and with self-reported history of DH. 
The age range over which an individual can experience DH is wide (from early teens to 70s) 
(Fischer et al, 1992), with peak incidence known to occur between the ages of 20-40 years 
(Flynn et al, 1985). The fall in prevalence observed in later decades reflects age related changes 
in the dentine and pulp of the tooth which act to reduce dentine permeability and the tooth’s 
response to the external triggers of DH (Pashley, 2008; Seltzer and Bender, 1975). Given that 
the dental pain experienced by older members of the population is less likely to be diagnosed 
as DH (Rees, 2000), the age range of 18-70 selected for this study targets individuals suffering 
from tooth sensitivity which is most likely due to DH. This will facilitate recruitment and 
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minimise inconvenience to older participants who may be more likely to be excluded at 
Screening. 
Diversity in clinical trials is increasingly important and should be representative of the 
population being studied. To promote clinical diversity a balanced female:male ratio (heavy 
bias towards female participants to date) should be considered. Whilst there is no known 
evidence demonstrating that gender may influence DH, a 2009 National DH Survey conducted 
in rural China showed that a greater proportion of those diagnosed with DH were female 
(35.8%), in comparison to a lower proportion that were male (23.4%) (Liang, 2017). Therefore, 
an approximate female:male ratio of 3:2 should be attempted to be recruited.  
A sufficient number of subjects will be screened to randomise approximately 195 subjects to 
ensure approximately 180 subjects (approximately 60 per treatment group) complete the study, 
allowing for dropouts. 
An enrolled subject is one who has agreed to participate in the clinical study following 
completion of the informed consent process directly or via their legally authorised 
representative 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 of the following inclusion criteria to be eligible for enrollment 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 who, at the time of screening, is between the ages of 18 to 70 
years, inclusive. 
3. A subject who is willing and able to comply with scheduled visits, treatment plan, and 
other study procedures. 
4. A subject in good general and mental health with, in the opinion of the investigator or 
medically qualified designee, no clinically significant or relevant abnormalities in medical 
history or upon oral examination, or condition, that would impact the subject’s safety, 
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wellbeing or the outcome of the study, if they were to participate in the study, or affect the 
individual’s ability to understand and follow study procedures and requirements. 
5. Subject must own a smartphone with the WeChat application installed. 
6. A subject who presents the following oral and dental inclusions will apply at Screening 
(Visit 1): 
a) Self-reported history of dentinal hypersensitivity lasting more than six months but 
not more than 10 years. 
b) Good general oral health, with a minimum of 20 natural teeth. 
c) Minimum of 2 accessible non-adjacent teeth (incisors, canines, pre-molars), 
preferably in different quadrants, that meet all of the following criteria: 
i. Signs of facial/cervical gingival recession and/or signs of erosion or abrasion 
(EAR). 
ii. Tooth with MGI score ≤1 adjacent to the test area (exposed dentine) only 
(Lobene, 1986) and a clinical mobility of ≤1. 
iii. Tooth with signs of sensitivity measured by a qualifying tactile stimulus (yeaple 
≤20g) and qualifying evaporative air assessment (Schiff sensitivity score 2). 
The following dental inclusions will apply at Baseline (Visit 2): 
d) Minimum of two, non-adjacent accessible teeth (incisors, canines, pre-molars), with 
signs of sensitivity, measured by response to a qualifying tactile stimulus (yeaple 
≤20g) and evaporative air assessment (Schiff sensitivity score ≥2). The 2 selected 
‘test teeth’ must have also qualified at Screening for this criteria. 
Note: The Investigator will select 2 ‘test teeth’ from those which meet both the tactile threshold 
and Schiff sensitivity score criteria, in addition to meeting all other criteria. Test teeth should 
not be adjacent to each other and preferably in different quadrants.   
5.3 
Exclusion Criteria 
An individual who meets any of the following exclusion criteria will not be eligible for 
enrollment into the study: 
1. A subject who is an employee of the investigational site, either directly involved in the 
conduct of the study or a member of their immediate family; or an employee of the 
investigational site otherwise supervised by the investigator; or, a GSK CH employee 
directly involved in the conduct of the study or a member of their immediate family. 
2. A subject who has participated in other studies (including non-medicinal studies) 
involving investigational product(s) within 30 days prior to study entry and/or during 
study participation. 
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3. A subject who has participated in another tooth desensitising treatment study within 8 weeks 
of the Screening visit. 
4. A subject with, in the opinion of the investigator or medically qualified designee, has an 
acute or chronic medical or psychiatric condition or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator or medically qualified designee, would make the subject 
inappropriate for entry into this study. 
5. A subject who is pregnant or intending to become pregnant over the duration of the study. 
This will be confirmed verbally at Screening. 
6. A subject who is breastfeeding. 
7. A subject with known or suspected intolerance or hypersensitivity to the study materials 
(or closely related compounds) or any of their stated ingredients.  
8. A subject who rinses with water during the first minute of toothbrushing at the Screening 
visit. 
9. A subject unwilling or unable to comply with product usage instructions or Lifestyle 
Considerations that will be described in the protocol.  
10. A subject with history of regular alcohol and/or substance abuse. 
11. A subject who has received treatment with another investigational product within 30 days 
of the first dose of investigational product  
12. A subject who has had dental prophylaxis within 4 weeks of Screening, or who requires 
antibiotic prophylaxis for dental procedures. 
13. A subject with a tongue or lip piercing. 
14. A subject with advanced periodontal disease, treatment of periodontal disease (including 
surgery) within 12 months of Screening, scaling or root planning within 3 months of 
Screening. 
15. A subject who has had teeth bleaching within 8 weeks of Screening. 
16. A subject who has used an over-the-counter (OTC) desensitising product (Eg. dentifrice) 
and/or professional desensitising treatment within 8 weeks of Screening. Subjects will be 
required to bring their current oral care products to the site in order to verify the absence 
of known anti-sensitivity ingredients. 
17. A subject with exposed tooth dentine but with deep, defective or facial restorations, teeth 
used as abutments for fixed or removable partial dentures, teeth with full crowns or 
veneers, orthodontic bands or cracked enamel.  
18. A subject with sensitive teeth with contributing aetiologies other than erosion, abrasion or 
recession of exposed dentine Eg. current or recent dental caries, or reported treatment of 
decay within 12 months of Screening.  
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19. A subject who has taken daily doses of medication/treatments or traditional herbal 
ingredients/treatments which, in the opinion of the investigator, could interfere with the 
perception of pain. Examples of such medications include analgesics, anticonvulsants, 
antihistamines that cause marked or moderate sedation, sedatives, tranquilisers, anti-
depressants, mood-altering and anti-inflammatory drugs. Examples of herbal 
ingredients/treatments include clove oil, olive oil, or other treatments that are directly 
applied to the oral cavity for the treatment of oral health conditions. 
20. A subject who is taking antibiotics and/or has taken antibiotics within 2 weeks of 
Screening and/or Baseline. 
21. A subject who has taken daily dose of a medication which, in the opinion of the 
investigator, is causing xerostomia. 
22. Any subject who, in the judgment of the investigator, should not participate in the study. 
 
5.4 
Randomisation Criteria and Stratification 
Subjects will be randomised into the study provided they have satisfied all subject selection 
criteria.  
Subjects will be stratified according to their maximum baseline Schiff sensitivity score of the 
two selected teeth (sensitivity score of 2 or 3). Randomisation numbers will be assigned in each 
stratum in ascending numerical order as each subject is determined to be fully eligible. The 
stratification factor will give rise to two strata. 
• Stratum 1: Maximum Schiff=2. These are subjects with maximum baseline Schiff 
sensitivity score of 2 for the 2selected ‘test teeth. 
• Stratum 2: Maximum Schiff=3. These are subjects with the maximum baseline Schiff 
sensitivity score of 3 for the 2 selected test teeth. 
5.5 
Lifestyle Considerations 
5.5.1 
Oral Care Restrictions 
Eligible subjects will be asked to stop using their regular oral care products, and will only be 
allowed to use the oral care products provided from Screening for the duration of the study. Use 
of dental floss will be for the removal of impacted food only.  
Subjects will not be permitted to chew gum.  
Prior to study visit days (Visits 2 to 4) subjects will be asked to refrain from all oral hygiene 
procedures for at least 8 hours prior to their appointment in order to standardise oral hygiene 
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practices. Subjects will be sent a WeChat reminder the day before their appointment reminding 
them of this. 
5.5.2 
Meals and Dietary Restrictions 
A subject must not eat or drink (except water) for at least 2 hours before Visits 2 to 4. Small 
sips of room-temperature water will be permitted to take medications and relieve a dry mouth 
within 1 hour before their visit. 
5.5.3 
Alcohol 
Subjects will be requested to refrain from excessive alcohol consumption for 24 hours before 
each visit. If, in the opinion of the Investigator, the subject has consumed an excessive amount 
of alcohol they will be withdrawn from the study. 
5.5.4 
Contraception 
No drug is being utilised in this clinical study, the study products are commercialised 
toothpastes in China, and are regulated as General Goods. Therefore, pregnancy testing and 
contraceptive requirements are not deemed necessary for this study. 
5.6 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not subsequently randomised. To ensure transparent reporting of screen failure subjects, a 
minimal set of screen failure information will include demography, screen failure details (e.g. 
withdrawal of consent), eligibility criteria, any protocol deviations and any adverse events or 
incidents as applicable.  
Individuals who do not meet the criteria for participation in this study (screen failure) may not 
be re-screened. 
5.7 
Sponsor’s Qualified Medical Personnel 
Contact information for the sponsor's appropriately qualified dental personnel for the study is 
documented in the Study Contact List located in the investigator study master file held at the 
study site. 
The contact number is only to be used by investigational staff seeking advice on medical/ dental 
questions or problems in the event that the established communication pathways between the 
investigational site and the study team are not available.   
The contact number is not intended for direct use by study subjects. To facilitate access to 
appropriately qualified medical/dental personnel on study-related medical/dental questions or 
problems, subjects will be provided with a contact card.  The contact card will provide, as a 
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minimum, protocol identifiers, the subject’s study identification number, contact information 
for the investigational site, and contact details in the event that the investigational site cannot 
be reached to provide advice on a medical question or problem identified by a healthcare 
professional other than the investigator.   
5.8 
Rater/Clinical Assessor Qualifications  
The clinical examiner(s) responsible for Schiff and tactile assessments will be dentally qualified 
and trained in the clinical assessments of DH, using both the air syringe (Schiff sensitivity scale) 
and yeaple probe (Tactile threshold). To minimise assessment variability, where possible the 
same examiner will be responsible for a given clinical assessment from Screening until the end 
of the study. 
To manage logistics at the clinical study site, additional dentally qualified examiners who have 
not trained in the clinical assessments of DH will be permitted to conduct OHT/OST 
assessments and those screening procedures that do not use the air syringe (Schiff sensitivity 
scale) and yeaple probe (Tactile threshold). 
6 
INVESTIGATIONAL/STUDY PRODUCTS 
For the purposes of this study, per International Conference on Harmonization (ICH) guidelines, 
and GSK policy, study intervention is defined as any investigational intervention(s), marketed 
product(s), placebo, or medical device(s) intended to be administered to a study participant 
according to the study protocol. 
6.1 
Investigational/Study Product Supplies 
The following investigational/study products will be supplied by the Clinical Supplies 
Department, GSK CH or designated vendor: 
Table 6-1 
Investigational Product Supplies 
Investigational 
Product 
Test Product 
Reference Product 
(Negative Control)  
Reference Product 
(Positive Control)  
Product Name 
Sensodyne 
Sensitivity & Gum 
(Chrysanthemum); 
Chinese 
commercialised 
toothpaste containing 
0.454% SnF2 
 
Crest Cavity 
Protection Fresh 
Lime (1150ppm 
fluoride as NaF); 
Chinese 
commercialised daily 
fluoride dentifrice 
Sensodyne Repair 
and Protect; Chinese 
commercialised 
dentifrice containing 
5.0% w/w calcium 
sodium 
phosphosilicate 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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 0  of 8 5  
 
* F oll o wi n g t o ot h br u s hi n g a n d/ or ri n si n g s u bj e ct s m a y al s o c o n d u ct a di s cr eti o n ar y t o n g u e cl e a n u si n g 
t h e pr o vi d e d t o ot h br u s h, b ut t hi s i s n ot a st u d y r e q uir e m e nt. 
T a bl e 6 -2  
A c cli m ati s ati o n Pr o d u ct S u p pli e s  
 
 
A c cli m ati s ati o n Pr o d u ct  
Pr o d u ct N a m e  
Cr e st C a vit y Pr ot e cti o n Fr e s h 
Li m e; C hi n e s e c o m m er ci ali s e d 
d ail y fl u ori d e d e ntifri c e 
( 1 1 5 0 p p m fl u ori d e a s N a F) 
P a c k D e si g n  
C art o n of 2 o v er -wr a p p e d t u b e s  
P a c k D e si g n  
C art o n of 4 o v er -
wr a p p e d t u b e s  
C art o n of 4 o v er -
wr a p p e d t u b e s  
C art o n of 4 o v er -
wr a p p e d t u b e s  
Di s p e n si n g 
D et ail s  
O n e c art o n –  
b a s eli n e vi sit  
O n e c art o n –  
b a s eli n e vi sit  
O n e c art o n –  
b a s eli n e vi sit  
Pr o d u ct M a st er 
F or m ul ati o n 
C o d e ( M F C)  
C o m m er ci al Pr o d u ct  
 
C o m m er ci al Pr o d u ct  
C o m m er ci al Pr o d u ct  
 
U s a g e 
I n str u cti o n s 
A p pl y a f ull ri b b o n of 
t o ot h p a st e o n t h e 
h e a d of t h e 
t o ot h br u s h pr o vi d e d. 
Br u s h t e et h f or 1* -
ti m e d mi n ut e, 
f oll o w e d b y br u s hi n g 
of t h e q u alif yi n g 
s e n siti v e t e et h . 
F oll o wi n g br u s hi n g 
ri n s e o n c e wit h 1 0 ml 
of w at er fr o m t h e 
ri n si n g c u p pr o vi d e d. 
A p pl y a f ull ri b b o n of 
t o ot h p a st e o n t h e 
h e a d of t h e 
t o ot h br u s h pr o vi d e d; 
br u s h t e et h  f or 1*-
ti m e d mi n ut e. 
F oll o wi n g br u s hi n g 
ri n s e o n c e wit h 1 0 ml 
of w at er fr o m t h e 
ri n si n g c u p pr o vi d e d. 
A p pl y a f ull ri b b o n of 
t o ot h p a st e o n t h e 
h e a d of t h e 
t o ot h br u s h pr o vi d e d; 
br u s h t e et h f or 1* -
ti m e d mi n ut e. 
F oll o wi n g br u s hi n g 
ri n s e o n c e wit h 1 0 ml 
of w a t er fr o m t h e 
ri n si n g c u p pr o vi d e d. 
R o ut e of 
A d mi ni str ati o n  
Or al t o pi c al  
Or al t o pi c al  
Or al t o pi c al  
R et ur n 
R e q uir e m e nt s  
All u s e d/ u n u s e d 
s a m pl e s t o b e 
r et ur n e d 
All u s e d/ u n u s e d 
s a m pl e s t o b e 
r et ur n e d 
All u s e d/ u n u s e d 
s a m pl e s t o b e 
r et ur n e d 
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
C CI
C CI

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Dispensing 
Details 
One carton – Screening visit 
Product MFC 
Commercial Product 
Usage 
Instructions 
Apply a full ribbon of toothpaste 
on the head of the toothbrush 
provided; brush teeth for 1*-
timed minute. Following 
brushing rinse once with 10 ml 
of water from the rinsing cup 
provided. 
Route of 
Administration 
Oral topical 
Return 
Requirements 
All used/unused samples to be 
returned 
*Following toothbrushing and/or rinsing subjects may also conduct a discretionary tongue clean using 
the provided toothbrush, but this is not a study requirement. 
Table 6-3 
Sundry Items 
 
Item 
Supplied 
By 
Pack Design 
Dispensing 
Details 
Return/Disposal Details 
Used Samples 
Unused 
Samples 
Lion Thin 
Bristle Chinese 
commercialised 
Toothbrush  
GSK CH or 
designated 
vendor 
Individual 
commercial 
pack – 3 per 
subject 
1 at screening for 
use with 
acclimatisation 
product 
1 at baseline for 
use with 
investigational 
product 
1 at Visit 3. 
Destroy at site 
using site 
disposal 
procedures 
 
Return 
Countdown 
Timer 
GSK CH or 
designated 
vendor 
Individual 
commercial 
pack – 1 per 
subject 
Screening visit 
Subject to keep 
or destroyed at 
site using site 
disposal 
procedures 
Return 
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Rinsing cups 
GSK CH or 
designated 
vendor 
N/A 
Screening visit and 
baseline 
Subject to keep 
or destroyed at 
site using site 
disposal 
procedures 
 
Return 
Plastic bags 
GSK CH or 
designated 
vendor 
N/A 
Screening visit and 
baseline 
Subject to keep 
or destroyed at 
site using site 
disposal 
procedures 
 
Return 
Detailed instructions for the return of study product/study supplies for the accountability checks 
and subsequent destruction which will be provided by GSK CH during the study in time for 
study close out visit. 
6.1.1 
Dosage Form and Packaging 
The test product, negative and positive controls, acclimatisation product and toothbrush will be 
sourced from China. 
All dentifrices in this study will be presented to the clinical study site in tubes that have been 
overwrapped in white vinyl to obscure any branding on the commercial packs with a study label 
affixed. The contents of the label will be in accordance with all applicable regulatory 
requirements and will be the responsibility of the Global Clinical Supplies Department, GSK 
CH. Each subject will receive a sufficient number of tubes to cover usage during the treatment 
phase.  
All sundry items will be supplied in their commercial packaging for dispensing by study staff 
as required.  
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  
Study products will be prepared and/or dispensed by qualified unblinded site personnel 
according to the dosage and administration instruction. To help mitigate against unblinding the 
same personnel responsible for preparing and/or dispensing will also be responsible for 
reviewing subject’s brushing video’s.  
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Subjects will be assigned to products in accordance with the randomisation schedule generated 
by an approved GSK CH vendor, prior to the start of the study, using validated software. 
Study product will be dispensed by qualified unblinded site personnel. These staff members 
will not be involved in any safety, efficacy assessments or other aspects of the study that could 
be influenced by the knowledge of product a subject has been assigned to use. An additional 
member of site staff should ensure the dispensing procedures are completed accurately. The 
investigational products will be dispensed in blinded fashion to the subject.  
A record of product dispensing to each subject will be maintained in the dispensing log; 
completion of the dispensing procedure will be recorded in the case report form (CRF). 
6.2 
Administration 
A record of the administration of the study products will be kept using a dispensing log and will 
be recorded in the CRF. 
Subjects will be instructed to brush with their assigned dentifrice according to the product use 
instructions provided to the subject. Subjects will receive a brushing instruction/diary sheet. 
This will outline the brushing instructions and will be used to record each brushing occasion 
during the treatment period. Subjects will also be asked to note any missed brushings, and to 
use the diary to record any changes in medications, or new medications, or to diet. To ensure 
that subjects understand the dose of dentifrice to be used, staff will demonstrate what is meant 
by a ‘full ribbon’ (i.e. covering the length of the toothbrush head) and provide detailed oral 
hygiene instruction during the supervised toothbrushing in agreement with the study schedule 
and product usage instructions. 
6.2.1 
Medication/Dosing Errors 
Dosing errors may result, in this study, from the administration or consumption of:  
• the wrong product, 
• by the wrong subject,  
Such dosing errors occurring to a study subject are to be captured in the CRF.  In the event of 
medication dosing error, the sponsor should be notified immediately and under no 
circumstance should this exceed 24 hours. 
Medication/dosing errors are reportable irrespective of the presence of an associated AE, 
including: 
• Medication/dosing errors involving subject exposure to any of the study products; 
• Potential medication/dosing errors or uses outside of what is foreseen in the protocol 
that do or do not involve the participating subject. 
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If a medication/dosing error is accompanied by an AE, as determined by the investigator, the 
medication/dosing error and, any associated adverse event(s) are to be captured in the CRF AE 
form.  
6.2.2 
Overdose 
An overdose is a deliberate or inadvertent administration of a product at an amount higher than 
specified in the protocol. Overdose is not likely to occur in this study. 
6.3 
Investigational/Study Product Storage  
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study products received and any discrepancies are reported and 
resolved before use according to the supplied shipping documentation. 
The investigator, or designee, will ensure that all study products are stored in a secured area 
with controlled access under required storage conditions and in accordance with applicable 
regulatory requirements and the product label.   
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily (dispensing, assessment and work days) minimum and maximum temperatures 
for all site storage locations (as applicable, including frozen, refrigerated, and/or room-
temperature products).  This should be captured from the time of first product receipt throughout 
the study.  Even for continuous monitoring systems, a log or site procedure that ensures active 
daily evaluation for excursions should be available.  The operation of the temperature-
monitoring device and storage unit (for example, refrigerator), as applicable, should be 
regularly inspected to ensure it is maintained in working order.  
Any excursions from the product-label storage conditions should be reported to appropriate site 
staff upon discovery and communicated to sponsor as soon as possible.  The site should actively 
pursue options for returning the product to the storage conditions as described in the labeling, 
as soon as possible. Excursions from the storage requirements, including any actions taken, 
must be documented as a protocol deviation and reported to the Sponsor.   
Once an excursion is identified, the affected product (or products) must be quarantined and not 
used until the sponsor provides documentation of permission to use. Use of any of the affected 
product(s) prior to sponsor approval will be considered a protocol deviation.  
Site staff will instruct subjects on the proper storage requirements for all take-home products.  
6.4 
Investigational/Study Product Accountability 
All products supplied are for use only in this clinical study and should not be used for any other 
purpose. 
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All study products must be received by a designated person at the study sites, handled and stored 
safely and properly, and kept in a secured location to which only the staff have access. Upon 
receipt, all study products should be stored according to the instructions specified on the product 
labels. Study products are to be dispensed only to subjects enrolled in the study in accordance 
with the protocol, by authorised site staff. 
The investigative site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of all the product supplies. All study products will be accounted for using the 
investigational/study product accountability form/record. The investigator is responsible for 
study product accountability, reconciliation, and record maintenance.  
Subjects will return used and unused tubes of the acclimatisation dentifrice to the investigator 
site at their Baseline visit (Visit 2). Subjects will return used and unused tubes of their assigned 
study dentifrice to the investigator site at their visits to the clinical study site as per the Schedule 
of Activities, with all study products returned at the end of the study (for most subjects this will 
be Visit 4). Study product return will be documented using the investigational/study product 
accountability form/record.  
The accountability records must be available for inspection by the study monitor during the 
study. Monitoring of product accountability will be performed by the monitor during site visits 
and at the completion of the study.  
6.4.1 
Destruction of Investigational/Study Product Supplies  
At the end of the study, the Principal Investigator (PI) or an appropriate designee, and a 
representative of GSK CH (study monitor) will inventory all used and unused study products 
and sundry items. The investigational/study product accountability record for returned study 
products will then be completed. All study product (used and unused) for this clinical study, 
will be returned for destruction to the GSK CH Clinical Supplies Department or designated 
vendor using the return instructions provided. Detailed instructions for the return of study 
product/study supplies (including empty tubes) for the accountability checks and subsequent 
destruction will be provided by GSK CH during the study in time for study close out visit. 
6.5 
Blinding and Allocation/Randomisation 
All subjects will be centrally randomised to one of the study arms using an Interactive Response 
Technology (IRT). Before the study is initiated, training, login information and directions for 
the IRT will be provided to the clinical study site. Study products will be dispensed according 
to the instruction received through the IRT at the appropriate study visits. 
Returned study products should not be re-dispensed to any subject. 
This study is described as examiner-blind (the subjects, investigator and clinical examiner(s) 
will be blinded to product received). The study statistician, other employees of the Sponsor 
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(including the Clinical Research Scientist (CRS)) and vendors acting on behalf of the sponsor, 
who may influence study outcomes will also be blinded to product allocation. 
To ensure the examiner remains blinded throughout the study, staff involved in the preparation 
and dispensing of study products will work in a separate area. The examiner is not permitted in 
any area where study product is stored, dispensed, or in use. Examiners must also not have any 
visibility, or access to subject brushing video’s. The same personnel responsible for preparing 
and/or dispensing will also be responsible for reviewing subject’s brushing video’s, and the 
study examiners will not be permitted in the area where these video’s are viewed. 
Subjects will be instructed not to remove study products from the opaque bags provided outside 
of the dispensing room, while at the study site. They will also be instructed not to discuss the 
use of their study products with any of the study examiners. Dispensing staff will not be 
involved in any efficacy/safety assessment procedures during the study.   
6.6 
Breaking the Blind 
At the initiation of the study, the study site will be instructed on the method for breaking the 
blind in case of emergency. The method will be an electronic process. 
The electronic system will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding of a 
subject’s product assignment is warranted. Subject safety must always be the first consideration 
in making such a determination. If the investigator decides that unblinding is warranted, the 
investigator should make every effort to contact the sponsor prior to unblinding a subject’s 
product assignment unless this could delay emergency treatment of the subject. 
If a subject’s product assignment is unblinded, the sponsor must be notified within 24 hours 
after breaking the blind. The date and reason that the blind was broken must be recorded in the 
source documentation and case report form, as applicable. 
Any AE associated with breaking the blind must be recorded and reported as specified in this 
protocol. The study site may also be required be required to inform the IRB/EC if the blind is 
broken.  
6.7 
Compliance 
Throughout the duration of the study subjects will be sent daily reminders on WeChat to brush 
with their allocated dentifrice as per the usage instructions, and to adhere to study lifestyle 
restrictions.  
To monitor subject adherence to the usage instructions subjects will also be asked to record 2 
brushing occasions per week using their smartphone video. At each visit to the clinical study 
site a designated member of the clinical study team will check these videos from the previous 
2 weeks and confirm compliance with the product usage instructions. After 2 and 6 weeks of 
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using their allocated study product, subjects will be requested to send their brushing video’s 
from the previous 2 weeks (2 per week) to the study site using WeChat. A member of the clinical 
study site staff will confirm compliance with the product usage instructions, as per protocol To 
assist the clinical study staff to determine which subjects are non-compliant with the brushing 
instructions a check-list has been provided (Appendix 15.3). Subjects confirmed as non-
compliant (Eg. Subjects that have a “no” response to any of the check-list items)) will be 
reminded about the study product use instructions. Non-compliance will be recorded as a 
protocol deviation, and subjects who are repeatedly non-compliant, defined as ≥5 brushing 
occasions that were not conducted according to the product usage instructions may be 
withdrawn from the study. Missed video recordings will be considered as non-compliance and 
recorded as a protocol deviation. 
Subjects will also be requested to bring their study products to each clinical study site visit, 
where a member of the clinical study team will weigh the returned dentifrice. If treatment use 
is deemed to be outside of the pre-defined acceptable range, subjects will be re-educated on the 
correct dosage amount. Where the amount of dentifrice used is outside of the pre-defined 
allowable range, a protocol deviation will be recorded in the CRF and subjects will be re-
educated on the correct dose. In this study the pre-defined range will be calculated as the 
expected weight of dentifrice used for the treatment window (Section 12.3.7.1). The amount of 
dentifrice used during each treatment period will be recorded in a source document and later 
transcribed to the CRF. 
At the same visit subjects will be asked to conduct a supervised and timed brushing according 
to the product usage instructions. Confirmation of supervised brushing per protocol will be 
captured in the CRF. Any deviations from the product usage instructions will be captured as a 
protocol deviation in the CRF, and subjects will be reminded of the correct directions for use.  
A paper diary will also be supplied to promote compliance and to capture details of daily 
product use throughout the study period. Subjects may also record additional information such 
as AEs or medications used. Any additional details relevant to efficacy or safety should be 
reviewed by the investigator (or suitably qualified designee) with the subjects and transcribed 
to the CRF as appropriate. 
The number of any missed or additional applications or doses will be captured as protocol 
deviations and transcribed from the diary to the CRF. Subjects will be re-instructed in the 
correct usage requirements and diary completion as needed. 
6.8 
Concomitant Medication/Treatment(s) 
Any medications, treatments or vaccine (including over-the-counter or prescription medicines, 
vitamins, and/or herbal supplements) taken during the study, from signing the informed consent, 
must be recorded in the CRF with indication, reason for use, unit dose, daily dose, and start and 
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stop dates of administration. All subjects will be questioned about medications/treatments at 
each site visit. 
Medication/treatments taken within 30 days of signing the informed consent form will be 
documented as a prior medication/treatment. Medications/treatments taken after signing the 
informed consent form will be documented as concomitant medication/treatments. 
7 
DISCONTINUATION OF STUDY INTERVENTION AND 
SUBJECT DISCONTINUATION/WITHDRAWAL 
7.1 
Subject Discontinuation/Withdrawal  
A subject may withdraw from the study at any time at his or her own request or may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral 
reasons, or the inability of the subject to comply with the protocol-required schedule of study 
visits or procedures.   
The following circumstances require discontinuation of study product and/or premature subject 
withdrawal: 
• Protocol violation that may impact the subject’s safety 
• Withdrawal of informed consent 
• Subject lost to follow-up  
• Unblinding of the subject  
• Pregnancy 
If a subject is discontinued or prematurely withdraws from the study, the reason(s) for 
discontinuation or withdrawal and the associated date must be documented in the relevant 
section(s) of the CRF.  
7.2 
Lost to Follow up 
If a subject fails to return to the site for a required study visit the site must attempt to contact 
the subject and reschedule the missed visit as soon as possible and counsel the subject on the 
importance of maintaining the assigned visit schedule and ascertain whether the subject wishes 
to and/or should continue in the study. 
A subject will be considered lost to follow up if he or she repeatedly fails to return for scheduled 
visits and is unable to be contacted by the study site. Before a subject is deemed lost to follow 
up, the investigator or designee must make every effort to regain contact with the subject (where 
possible, 3 telephone calls and, if necessary, a certified letter to the subject’s last known mailing 
address or local equivalent methods). These contact attempts should be documented. If contact 
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is made with the subject, the investigator should inquire about the reason for withdrawal, request 
that the subject return all products that they had been dispensed and if appropriate request that 
the subject return for a final visit and follow-up with the subject regarding any unresolved 
adverse events (AEs). 
Final safety assessments may be carried out when the subject returns to the study site, at the 
investigator’s discretion, which could include an examination of the oral soft tissue and/or oral 
hard tissue. 
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. The timing of each 
procedure is listed in the Schedule of Activities section. 
Adherence to the study design requirements, including all procedures are essential and required 
for study conduct. 
8.1 
Visit 1/ Screening  
Subjects will be screened within 28 days prior to administration of the investigational product 
to confirm that they meet the subject selection criteria for the study. 
The following procedures and assessments will be completed, and where practically feasible 
they should be completed in the order listed below: 
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 GSK CH. 
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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 ICF will be captured as this is the point at which all AEs will 
be captured from. The date and time of consent will be captured in the CRF. 
If, during a subject’s participation in the study, any new information becomes available that 
may affect the subject’s willingness to participate in the study, each ongoing subject should 
receive a copy of this new information and be re-consented into the study. Each subject should 
be provided with a copy of the signed and dated amended consent form. The date of re-consent 
will be recorded on the CRF. 
After signing the ICF, subjects will undergo the screening assessments to confirm that they 
meet all the inclusion criteria and none of the exclusion criteria. If the subject is confirmed 
eligible by the investigator (or designee) to participate in the study, the subject is considered 
enrolled in the study. 
8.1.2 
Review of Subjects Oral Care Products 
Subjects will be requested to bring their current oral care products from home and a member of 
the clinical study site staff will verify that they don’t contain any ingredients known to impart 
an anti-sensitivity benefit, or make any anti-sensitivity treatment claims on the product 
packaging. This product check will be documented in the CRF. 
8.1.3 
Review of Subjects Brushing Habits 
Subjects who have not been using an anti-sensitivity oral care product will then be asked to 
demonstrate their daily oral care regimen using their own products in the manner that they 
normally would at home. A member of the study site staff will observe subjects, and anyone 
who rinses with water during toothbrushing will be excluded from undergoing any further 
screening procedures.  
8.1.4 
Demographics and Ethnicity 
The following demographic information will be recorded in the CRF: year of birth, gender and 
race. Ethnicity will also be recorded in the CRF. 
8.1.5 
Medical History and Prior Medication/Treatment 
Details of relevant medical and surgical history (within the last year), including allergies or drug 
sensitivity, will be documented in the CRF. 
Prior medications/treatments, including prescription and non-prescription drugs, dietary 
supplements and herbal remedies, taken in the last 30 days and prior to signing the informed 
consent form, will be documented in the CRF. 
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8.1.6 
Full Oral Soft Tissue (OST) and Oral Hard Tissue (OHT) Examinations 
Full OST and OHT assessments as described in Study Assessments will then be conducted by 
an appropriately trained clinical examiner(s) and recorded in the CRF. 
8.1.7 
Eligible Teeth and Qualifying Sensitivity Assessments 
Eligible teeth and qualifying sensitivity assessments to be conducted: 
• Eligible teeth assessments (dentition exclusions, Erosion, Abrasion, Recession (EAR), 
modified gingival index (MGI), tooth mobility). 
• Qualifying evaporative air sensitivity. 
• Qualifying tactile threshold. 
Data for eligible teeth assessments, tactile stimuli (yeaple probe) and evaporative air stimuli 
(Schiff sensitivity score) may be recorded on a source document and later transcribed into the 
CRF, or directly entered into the CRF. This will be done by the designated scribe.  
Eligible teeth and qualifying sensitivity assessments as described in Study Assessments will be 
conducted by an appropriately trained clinical examiner(s).. Assessments may be recorded on 
a source document and later transcribed into the CRF, or directly entered into the CRF. This 
will be done by the designated scribe. 
8.1.7.1 
Selection of Test Teeth 
The 2 ‘test teeth’ with be identified in the CRF. 
8.1.8 
Inclusion/Exclusion Criteria 
Inclusion and exclusion criteria information will be documented in the CRF. Pregnancy status 
will be confirmed verbally by the subject. 
8.1.9 
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 study. This 
will be documented in the CRF. 
To prepare for study participation, subjects will be instructed in the Lifestyle Guidelines and 
any Concomitant Medication/Treatment(s) requirements of the protocol. 
• Adverse Events (AEs) will be documented from the time that informed consent is taken. 
Assess symptoms by spontaneous reporting of AEs and by asking the subjects to 
respond to a non-leading question such as “How do you feel?” 
• To prepare for study participation, subjects will be reminded of the requirements of the 
use of the Lifestyle Guidelines and Concomitant Treatment(s) sections of the protocol. 
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Subjects will be asked to show a member of the clinical study site staff their mobile phone to 
confirm that they have the WeChat application installed.  
Adherence to the study design requirements, including all procedures are essential and required 
for study conduct. 
8.1.10 
Dispense Acclimatisation Products 
The acclimatisation dentifrice, toothbrush, rinsing cups, diary and timer will be dispensed to 
each subject.  
8.1.11 
Supervised Brushing with Acclimatisation Dentifrice 
Subjects will be instructed to perform a supervised and timed brushing according to the product 
usage instructions as detailed in Table 6-2. Confirmation of supervised brushing per protocol 
will be captured in the CRF and an entry recorded on the subject diary card. 
Subjects will be reminded to bring their study products to their next clinical study site visit 
8.1.12 
Adverse Events 
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 
Study Period 
8.2.1 
Visit 2 (Baseline/Day 1) 
The following procedures and assessments will take place on Visit 2 (Baseline/Day1) following 
subject Screening at Visit 1, and where practically feasible they should be completed in the 
order listed below: 
8.2.1.1 
Concomitant Medications. 
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF.  
8.2.1.2 
Full OST Examination 
Full OST examination as described in Study Assessments will be conducted by the 
appropriately trained clinical examiner(s) and recorded in the CRF. 
8.2.1.3 
Subject Adherence and Continuance 
Subject adherence to the Lifestyle Guidelines and Study Schedule will be documented in the 
CRF. 
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8.2.1.4 
Subject Completion of DHEQ 
Subjects will complete a paper copy of the short-form version of the validated DHEQ at the 
clinical study site. Subject responses will be later transcribed into the CRF. 
8.2.1.5 
Tactile Sensitivity Assessment. 
The tactile sensitivity assessments as described in Study Assessments will be conducted by an 
appropriately trained clinical examiner. Where possible, the same clinical examiner will be 
responsible for all tactile assessments conducted at all assessment visits. Assessments may be 
recorded on a source document and later transcribed into the CRF, or directly entered into the 
CRF. This will be done by the designated scribe. 
8.2.1.6 
Evaporative Air Sensitivity Assessment (Schiff Sensitivity Score)  
The evaporative air sensitivity assessments as described in Study Assessments will be 
conducted by an appropriately trained clinical examiner. Where possible, the same clinical 
examiner will be responsible for all Schiff sensitivity assessments conducted at all assessment 
visits. Assessments may be recorded on a source document and later transcribed into the CRF, 
or directly entered into the CRF. This will be done by the designated scribe. 
8.2.1.7 
Confirm Test Teeth 
If any of the ‘test teeth’ identified at Screening do not respond to either tactile and/or Schiff, all 
eligible teeth that qualified at Screening may be re-assessed for tactile and Schiff, and the new 
2 ‘test teeth’ will be identified in the CRF. Subjects will be informed of the sensitive teeth that 
have been identified  
8.2.1.8 
Stratification and Randomisation 
Subjects will be stratified to one of two strata as described in Section 5.4. 
Subject stratum will be entered directly into the CRF. Each subject will be assigned a 
randomisation number from their designated stratum in ascending numerical order, and as each 
subject is determined to be fully eligible.  
8.2.1.9 
Dispense Randomised Dentifrice and Study Products 
Each subject will be assigned their randomised dentifrice, study toothbrush, diary card and 
rinsing cups. The randomised dentifrice code will be entered directly into the CRF. 
8.2.1.10 Supervised Brushing with Study Dentifrice 
Subjects will be asked to conduct a supervised and timed brushing according to the study 
product usage instructions, as detailed in Table 6-1. Confirmation of supervised brushing per 
protocol will be captured in the CRF and an entry recorded on the subject diary card. Any 
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deviations from the product usage instructions will be captured as a protocol deviation, and 
subjects will be reminded of the correct directions for use. 
Subjects will be reminded to bring their study products to their next clinical study site visit.  
8.2.1.11 Compliance Check on Returned Dentifrice and Brushing 
A member of the clinical study site staff will weigh the returned dentifrice, and if treatment use 
is deemed to be outside of the expected range, as detailed under Compliance, subjects will be 
re-educated on the correct dosage amount. 
Subjects will then show their brushing video’s from the acclimatisation period (2 per week) to 
a member of the clinical study site staff and confirmation of compliance with the product usage 
instructions, as per protocol, will be captured in the CRF. Any deviations from the product 
usage instructions or missed video brushings will be captured as a protocol deviation and 
subjects will be re-educated on the correct directions for use. To assist the clinical study staff 
to determine which subjects are non-compliant with the product usage instructions a check-list 
has been provided (Appendix 15.3). 
8.2.1.12 Adverse Events 
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. 
At the end of the visit subjects should be reminded to note any untoward medical occurrence, 
use of any new medications or new treatments in their diary or report to study site between 
visits, and to inform the site at their next visit as required  
8.2.2 
Visit 3 (Day 29±3) and Visit 4 (Day 57±3) 
The following procedures and assessments will take place on Visit 3 (Day 29±3) and Visit 4 
(Day 57±3), and where practically feasible they should be completed in the order listed below: 
8.2.2.1 
Concomitant Medications. 
Changes in concomitant medication or non-drug treatments/procedures will be documented in 
the CRF.  
8.2.2.2 
Full OST Examination 
Full OST examination as described in Study Assessments will then be conducted by the 
appropriately trained clinical examiner(s) and recorded in the CRF. 
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8.2.2.3 
Full OHT Examination 
Full OHT examination as described in Study Assessments will then be conducted by the 
appropriately trained clinical examiner(s) and recorded in the CRF. Note: this is only 
applicable at Visit 4, and should not be completed at Visit 3. 
8.2.2.4 
Subject Adherence and Continuance 
Subject adherence to the Lifestyle Guidelines and Study Schedule will be documented in the 
CRF. 
8.2.2.5 
Subject Completion of DHEQ 
Subjects will complete a paper copy of the short-form version of the validated DHEQ at the 
clinical study site at Visit 4. Subject responses will be later transcribed into the CRF. 
Note: this is only applicable at Visit 4, and should not be completed at Visit 3. 
8.2.2.6 
Tactile Sensitivity Assessment. 
The tactile sensitivity assessments as described in Study Assessments will be conducted by the 
appropriately trained clinical examiner. Where, possible the same clinical examiner will be 
responsible for all tactile assessments conducted at all assessment visits. Assessments may be 
recorded on a source document and later transcribed into the CRF, or directly entered into the 
CRF. This will be completed by the designated scribe. 
8.2.2.7 
Evaporative Air Sensitivity Assessment (Schiff Sensitivity Score).  
The evaporative air sensitivity assessments as described in Study Assessments will be 
conducted by the appropriately trained clinical examiner. Where possible, the same clinical 
examiner will be responsible for all Schiff sensitivity assessments conducted at all assessment 
visits. Assessments may be recorded on a source document and later transcribed into the CRF, 
or directly entered into the CRF. This will be completed by the designated scribe. 
8.2.2.8 
Supervised Brushing with Randomised Dentifrice 
At Visit 3 subjects will be instructed to perform a supervised and timed brushing according to 
the product usage instructions, as detailed in Table 6-1. Confirmation of supervised brushing 
per protocol will be captured in the CRF and an entry recorded on the subject diary card. Any 
deviations from the product usage instructions will be captured as a protocol deviation, and 
subjects will be reminded of the correct directions for use. 
Subjects will be re-dispensed a new toothbrush at Visit 3 and reminded to bring their study 
products to their next clinical study site visit.  
Note: this is only applicable at Visit 3, and is not required at Visit 4. 
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8.2.2.9 
Compliance Check on Dentifrice and Brushing 
A member of the clinical study site staff will weigh the returned dentifrice, and if treatment use 
is deemed to be outside of the expected range, as detailed under Compliance, subjects will be 
re-educated on the correct dosage amount. 
Subjects will then show their brushing video’s from the previous 2 weeks (2 per week) to a 
member of the clinical study site staff and confirmation of compliance with the product usage 
instructions, as per protocol, will be captured in the CRF. Any deviations from the product 
usage instructions or missed video brushings will be captured as a protocol deviation and 
subjects will be re-educated on the correct directions for use. To assist the clinical study staff 
to determine which subjects are non-compliant with the product usage instructions a check-list 
has been provided (Appendix 15.3). 
8.2.2.10 Adverse Events 
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. 
At the end of Visit 3 subjects should be reminded to note any untoward medical occurrence, 
use of any new medications or new treatments in their diary (if used) or report to study site 
between visits, and to inform the site at their next visit as required.  
8.3 
Study Conclusion 
The Study Conclusion page of the CRF will be completed for all subjects whether they 
completed all study procedures, or if they were discontinued from the study early. If the subject 
discontinued early, at any point during the study, the primary reason for withdrawal should be 
recorded on the Study Conclusion page. Unless subjects were discontinued early the Study 
Conclusion page of CRF will be completed at Visit 4. 
If a subject has any clinically significant, study-related abnormalities or AEs at the end of the 
study, the GSK CH medical monitor (or designated representative) should be notified and, the 
subject may be asked to return for a follow-up visit to ensure any issue is resolved or deemed 
not clinically significant.  
At the end of Visit 4 subjects should be reminded to inform the site if they experience any 
untoward medical occurrence in the next 5 days (i.e. for 5 days after their last dose of study 
treatment). 
8.4 
Diary Review 
The diary should be reviewed at every visit by the investigator, or suitably qualified designee, 
and the subject. Any subject comment captured in the diary which is considered an adverse 
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event will be assessed and reported as per the defined procedure in this protocol. Adverse event 
reporting procedures are summarised in Adverse Event and Serious Adverse Events.  
Any additional comments relating to medications/treatments provided in the diary will be 
reviewed by the investigator or medically qualified designee with the subject and entered into 
the CRF as appropriate.  
Additional and missed product applications will be considered deviations from the protocol and 
will be recorded as a protocol deviation in the CRF. 
8.5 
Brushing Compliance Check at 2 and 6 Weeks 
After 2 and 6 weeks of using their allocated study product, subjects will be requested to send 
their brushing video’s from the previous 2 weeks (2 per week) to the study site using WeChat. 
A member of the clinical study site staff will confirm compliance with the product usage 
instructions, as per protocol. This will be captured in the CRF, and any deviations from the 
product usage instructions or missed video brushings will be captured as a protocol deviation 
and subjects will be re-educated on the product usage instructions. To assist the clinical study 
staff to determine which subjects are non-compliant with the product usage instructions a check-
list has been provided (Appendix 15.3). 
8.6 
Follow-up Visit"/ Phone Call"  
The study site may contact a subject to follow up an AE post-study completion/withdrawal and, 
in some circumstances, request they return to the site for additional follow-up visits (final safety 
assessments). If needed, additional examinations may be carried out at such visits. 
9 
STUDY ASSESSMENTS 
Every effort should be made to ensure that protocol-required tests and procedures are completed 
as described. However, it is anticipated that from time to time there may be circumstances, 
outside the control of the investigator that may make it unfeasible to complete an assessment.  
In these cases, the investigator must take all steps necessary to ensure the safety and well-being 
of the subject. When a protocol-required assessment cannot be performed, the investigator (or 
designee) will document the reason for the missed assessment as a protocol deviation and any 
corrective and preventative actions that he or she has taken to ensure that required processes are 
adhered to as soon as possible. The Sponsor must be informed of any missed assessments in a 
timely manner. 
9.1 
Screening Assessments 
Screening assessments will be performed by appropriately trained clinical examiner(s) at the 
times, and in the order, defined in the Study Procedures section of this protocol.  
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9.1.1 
Eligible Tooth Assessments 
Eligible tooth assessments will include an OHT examination to evaluate dentition exclusions; 
erosion, abrasion and/or gingival recession; modified gingival index; tooth mobility and 
qualifying evaporative air and tactile threshold assessments. Assessments will be carried against 
the inclusion/exclusion criteria and recorded in the CRF. 
9.1.1.1 
Erosion, Abrasion and Recession (EAR) assessment 
The presence of cervical erosion, abrasion and/or gingival recession (EAR) (Addy, 2000) will 
be determined on the facial surfaces of individual teeth. Teeth exhibiting EAR will be assessed 
to ensure they do not meet any of the general dentition exclusion criteria and the specific 
dentition exclusion criteria for eligible teeth. 
9.1.1.2 
Modified Gingival Index (MGI) Assessment 
The MGI is a non-invasive visual evaluation of gingival health, scored on a scale of 0-4 (Lobene, 
1986). MGI will only be assessed for the facial gingiva adjacent to the test area (exposed 
dentine); MGI ≤1 is required for eligible teeth. 
Score 
Description 
0 
Absence of inflammation 
1 
Mild inflammation; slight change in colour, little change in colour; little 
change in texture of any portion of the marginal or papillary gingival unit. 
2 
Mild inflammation; criteria as above but involving the entire marginal or 
papillar gingival unit. 
3 
Moderate inflammation; glazing, redness, edema, and/or hypertrophy of the 
marginal or papillary gingival unit. 
4 
Severe inflammation; marked redness, edema and/or hypertrophy of the 
marginal or papillary gingival unit, spontaneous bleeding, congestion, or 
ulceration. 
9.1.1.3 
Tooth Mobility Assessment 
Clinical mobility will be classified in the following way (based on a modification to the Miller 
Index) (Laster, 1975); clinical mobility ≤1 is required for eligible teeth. 
Degree 0 
No movement or mobility of the crown of the tooth < 0.2mm in a 
horizontal direction. 
Degree 1 
Mobility of the crown of the tooth 0.2 - 1mm in a horizontal direction 
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Degree 2 
Mobility of the crown of the tooth exceeding 1mm in a horizontal 
direction 
Degree 3 
Mobility of the crown of the tooth in a vertical direction as well. 
9.1.2 
Qualifying Tactile Sensitivity 
Qualifying tactile sensitivity assessments will be conducted at Screening (Visit 1) by an 
appropriately trained examiner who is dentally qualified and trained in the clinical assessments 
of DH. The tactile sensitivity of incisor, canine and pre-molar teeth as detailed in Figure 9-1 
exhibiting none of the dentition exclusions, and meeting the EAR, MGI and clinical mobility 
criteria, will be assessed using a constant pressure probe (yeaple probe (Polson, 1980).  
 
Figure 9-1 
Dental Nomenclature. (Dempsey, 2001) 
The probe tip will be placed perpendicular to the facial surface of the tooth and drawn slowly 
across the exposed dentine to ensure application of the stimulus across the potentially ‘sensitive’ 
area.  
After each application, subjects will be asked to indicate whether the sensation caused pain or 
discomfort. Only “yes” and “no” are acceptable answers. The examiner will tell the subject that 
they should indicate “yes” only if they feel PAIN or DISCOMFORT each time the probe is 
applied to their tooth. The subject may respond “yes” if they feel pressure, so it is important to 
remind them, as much as necessary, that they will feel pressure but to only respond “yes” if they 
feel pain or discomfort. If the subject fails to give a definite answer, the examiner should re-
prompt them to provide a “yes” or “no” response. If they continue to be reluctant, their 
uncertainty should be indicated on the score sheet and the next stimulus should be at the next 
step in the upward direction. The examiner will generally make the force setting adjustments 
(may be carried out by an assistant/scribe) and the scribe will record the micro-amperage force 
setting and subject’s responses. If unsure of the reliability of the subject’s response, the 
examiner may opt to re-probe at the same force setting. This can be indicated to the assistant by 
a non-verbal signal (i.e. a hand gesture). The gram setting, which elicits the two consecutive 
“yes” responses, will be recorded as the tactile threshold. At Screening (Visit 1), the upper force 
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setting is 20g. In order for a tooth to qualify at Screening, it must have a tactile threshold ≤20g. 
If no pain response is found, the tactile threshold will be recorded as >20 g and the tooth will 
be disqualified from further testing. 
9.1.3 
Qualifying Evaporative Air Sensitivity 
Qualifying evaporative air sensitivity assessments will be conducted at Screening (Visit 1) by 
an appropriately trained examiner who is dentally qualified and trained in the clinical 
assessments of DH. Qualifying evaporative air sensitivity will be assessed on the facial surfaces 
of incisor, canine and pre-molar teeth as detailed in Figure 9-1, exhibiting none of the dentition 
exclusions, and meeting the EAR, MGI, clinical mobility and tactile threshold (≤20g) criteria, 
a minimum of 5 minutes after the tactile assessments have been completed.  
The assessment will be made by directing a one second application of air from a standard dental 
syringe held perpendicular to the tooth surface, approximately 1-2 mm coronal to the gingival 
margin, and from a distance of approximately 1 cm. The dental examiner will take appropriate 
measures to isolate the tooth surface to prevent stimulation of adjacent teeth or surrounding soft 
tissue. 
9.1.4 
Selection of Test Teeth  
From the teeth that meet the tactile threshold (yeaple ≤20g) and Schiff sensitivity score criteria 
(Schiff ≥2) the 2 ‘test teeth’ will be selected. Teeth must be non-adjacent and preferably in 
different quadrants. 
9.2 
Dentine Hypersensitivity Assessments 
The following assessments will be performed by examiners who are dentally qualified and have 
been trained in the clinical assessments of DH, using both the air syringe (Schiff sensitivity 
scale) and yeaple probe (tactile threshold). Assessments will be conducted at the times and in 
the order defined in the Study Procedures section of this protocol. Where possible, the same 
examiner will be responsible for a given dentin hypersensitivity assessment (Schiff and/or 
Tactile) from Screening and for the remaining duration of the study. 
If in the opinion of the dental examiner a subject is between defined grades/scores, a 
conservative approach should be used to provide the final score. The same approach should be 
applied throughout the study to ensure consistency in the grading of the scores at all timepoints.  
9.2.1 
Tactile Sensitivity Assessment (Yeaple Probe)  
The dental examiner may assess the tactile sensitivity of all clinically eligible teeth that qualify 
on EAR, MGI and tooth mobility criteria, without any of the dentition exclusions, and meet the 
qualifying tactile threshold and Schiff sensitivity score criteria at screening. The stimulus will 
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be administered as described in Section 9.1.2. Where possible the same examiner will assess 
the tactile sensitivity of the same teeth determined to be clinically eligible teeth at Screening 
At Baseline (Visit 2) the 2 ‘test teeth’ identified at Screening will be tested first; the upper test 
limit is 20g. If no pain response is found, the threshold will be recorded as >20g and the tooth 
will be disqualified from further tactile testing. If any of the test teeth identified at Screening 
do not respond to tactile, all eligible teeth that qualified at Screening may be re-assessed for 
tactile threshold and Schiff sensitivity until 2 new ‘test teeth’ are qualified. Before the teeth are 
re-assessed subjects must wait a minimum of 5 minutes recovery time. 
At Visits 3 and 4 the tactile assessments will be conducted as described on the 2 selected ‘test 
teeth’ only, the upper force setting will be 80g. If no sensitivity is found, the threshold will be 
recorded as >80g. 
The response will be evaluated as described in Section 9.1.2. The gram setting, which elicits 
the two consecutive “yes” responses, will be recorded as the tactile threshold.  
9.2.2 
Evaporative Air Sensitivity Assessment  
After 5 minutes recovery time following completion of the tactile assessments the evaporative 
air sensitivity assessments will be completed. Where possible the same examiner will assess the 
evaporative air sensitivity of the same teeth determined to be clinically eligible teeth at 
Screening. This assessment will be conducted by directing a maximum one second application 
of air from a dental air syringe to the exposed dentine surface, as described in Section 9.1.3.  
Subject response to this stimulus will be evaluated using the Schiff sensitivity scale (Schiff, 
1994). This is an examiner based index, scored immediately following administration of the 
evaporative air stimulus. This scale focuses on a combination of specific, observable, physical, 
behavioural and verbal responses from the subject as a result of the stimulation of exposed 
dentine, rather than solely an oral request from the subject to discontinue stimulation and may 
facilitate discrimination. The examiner will indicate the subject’s response to the evaporative 
air stimulus, after the stimulation of each individual tooth, using the Schiff sensitivity scale as 
follows: 
 
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Score 
Description 
0 
Subject does not respond to air stimulation 
1 
Subject responds to air stimulus but does not request discontinuation of 
stimulus 
2 
Subject responds to air stimulus and requests discontinuation or moves from 
stimulus 
3 
Subject responds to stimulus, considers stimulus to be painful, and requests 
discontinuation of the stimulus 
If any of the test teeth identified at Screening do not respond to the stimulus, all eligible teeth 
that qualified at Screening may be re-assessed for tactile threshold and Schiff sensitivity until 2 
new ‘test teeth’ are qualified. Before the teeth are re-assessed subjects must wait a minimum of 
5 minutes recovery time. 
9.3 
Safety and Other Assessments 
The following safety assessments will be performed by an appropriately trained clinical 
examiner,  at the times and in the order defined in the Study Procedures section of this protocol.   
9.3.1 
Oral Hard Tissue (OHT) Examination 
Subjects with evidence of gross intra-oral neglect or the need for extensive dental therapy will 
be excluded. The OHT examination will assess for enamel irregularities, tooth fracture, 
grossly carious lesions/gross decay, defective/faulty restorations (all direct & indirect 
restorations including fixed/removal prostheses), non-carious tooth surface loss (abrasion, 
attrition, abfraction and erosion), any other hard tissue irregularity (e.g. 
hypo/hypermineralisation, decalcification) and tooth staining. Observations will be listed as 
“Absent” or “Present” and conditions noted as present will be described. Examination 
findings will be described and documented in the CRF. Any observation that changes from 
“Absent” to “Present” from the screening assessment must be recorded as an AE. 
9.3.2 
Oral Soft Tissue (OST) Examination 
An OST examination will be conducted for each subject at every visit prior to any clinical 
assessments. The examination will be accomplished by direct observation and palpation with 
retraction aids as appropriate. The examiner will include examination of the labial mucosa 
(including lips), buccal mucosa, and mucogingival folds, gingival mucosa, hard palate, soft 
palate, tonsilar area, pharyngeal area, tongue, sublingual area, submandibular area and salivary 
glands. The results of the examination will be recorded in the CRF as either normal or abnormal 
with details of any abnormalities. Any observation that changes from “Absent” to “Present” 
from the screening assessment must be recorded as an AE. 
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9.3.3 
Pregnancy Testing 
This clinical study is investigating products classified as general goods in China. For GSK CH 
studies in which no drug is utilised a pregnancy test is not required.  
Subjects will need to provide verbal confirmation of negative pregnancy status and this must 
be documented as part of the exclusion criteria. 
10 
ADVERSE EVENT AND SERIOUS ADVERSE EVENTS 
The investigator and any qualified designees are responsible for detecting, documenting, and 
reporting events that meet the definition of an AE or SAE and remain responsible for following 
up AEs that are serious, considered related to the study product or the study, or that caused the 
subject to discontinue the study product or study 
10.1 
Definition of an Adverse Event (AE) 
An AE is any untoward medical occurrence in a clinical study subject, temporally associated 
with the use of a study product including any washout or lead-in product (or medical device), 
whether or not considered related to the study product, including any washout or lead-in product 
(or medical device). 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a study product including any washout or lead-in product (or medical device). 
Events Meeting the AE Definition:   
• Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g. ECG, radiological scans, vital sign measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (i.e., not related to progression of 
underlying disease). 
• Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition. 
• New conditions detected or diagnosed after study product administration even though 
it may have been present before the start of the study. 
• Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
product or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae. 
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• "Lack of efficacy" or "failure of expected pharmacological action" per se will not be 
reported as an AE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of 
efficacy will be reported as AE if they fulfill the definition of an AE.  
Events NOT meeting the AE definition:  
• Any clinically significant abnormal laboratory findings (if applicable) or other abnormal 
safety assessments which are associated with the underlying disease, unless judged by 
the investigator to be more severe than expected for the subject’s condition.  
• The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the subject’s 
condition.  
• Medical or surgical procedure (e.g. endoscopy, appendectomy) is not the AE. The 
condition that leads to the procedure is an AE (e.g. appendicitis). 
• Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen.  
10.2 
Definition of a Serious Adverse Event (SAE) 
A Serious Adverse Event (SAE) is a particular category of an adverse event where the adverse 
outcome is serious. If an event is not an AE per definition above, then it cannot be an SAE even 
if serious conditions are met (e.g. hospitalisation 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 hospitalisation or prolongation of existing hospitalisation  
▪ In general, hospitalisation 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 
hospitalisation are AEs. If a complication prolongs hospitalisation or fulfills any 
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other serious criteria, the event is serious. When in doubt as to whether 
“hospitalisation” occurred, or was necessary, the AE should be considered serious. 
▪ Hospitalisation 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 hospitalisation but 
may jeopardise the subject or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious. 
▪ Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalisation, 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 
All AEs, and therefore all SAEs will be collected immediately after a subject provides consent 
to participate in the study by the completion (signature) of the ICF and until 5 days following 
last administration of the study product (or last procedure).  
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.  
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All SAEs will be recorded and reported to the sponsor or designee immediately and under no 
circumstance should this exceed 24 hours. The investigator will submit any updated SAE data 
to the sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek AEs or SAEs after the conclusion of the study 
participation. However, if the investigator learns of any SAE, including a death, at any time 
after a subject has been discharged from the study, and he/she considers the event to be 
reasonably related to the study product or study participation, the investigator must promptly 
notify the sponsor. 
10.4 
Reporting Procedures 
The investigator and any designees are responsible for detecting, documenting and reporting 
events that meet the definition of an AE and remain responsible for following up on AEs that 
are serious, considered related to the study product(s), participation in the study, or a study 
procedure, or that caused the subject to discontinue the study product or study.  
Spontaneous reporting of adverse events and those elicited by asking subjects to respond to 
non-leading such as “How do you feel” will be assessed and any AE’s recorded in the CRF and 
reported appropriately. 
The investigator (or medically qualified designee) is to report all directly observed AEs and all 
AEs spontaneously reported by the study subject. In addition, each study subject will be 
questioned about AEs. 
Each AE is to be assessed to determine if it meets the criteria for a SAE.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate. 
When an AE occurs, it is the responsibility of the investigator (or medically qualified designee) 
to review all documentation (e.g. hospital progress notes, laboratory, and diagnostics reports) 
related to the event. 
The investigator or site staff will then record all relevant information regarding an AE in the 
CRF and all details relating to an SAE in the paper SAE Form provided. 
It is not acceptable for the investigator (or medically qualified designee) to send photocopies 
of the subject’s medical records to GSK CH in lieu of completion of the AE CRF page/SAE 
form. 
There may be instances when copies of medical records for certain cases are requested by GSK 
CH.  In this instance, all subject identifiers, except for the subject number, will be redacted on 
the copies of the medical records prior to submission to GSK CH. 
The investigator (or medically qualified designee) will attempt to establish a diagnosis of the 
event based on signs, symptoms, and/or other clinical information.  The diagnosis will be the 
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documented as the AE/SAE where known and not the individual signs/symptoms. (e.g. upper 
respiratory tract infection, seasonal allergy, etc. instead of runny nose). 
AEs elicited by the investigator (or medically qualified designee) in a standard manner at the 
study visits should also be recorded in the AE section of the CRF and/or using the SAE form 
(subject to the classification of the AE). Care will be taken not to introduce bias when 
questioning a subject about any changes in their health. Open-ended and non-leading verbal 
questioning should be used. 
10.4.1 
Reporting of an Adverse Event 
All AEs will be reported on the AE page of the CRF by the investigator or site staff.  It should 
be noted that the form for collection of SAE information is not the same as the AE CRF.  Where 
the same data are collected, the AE CRF page and the SAE form must be completed in a 
consistent manner.  For example, the same AE term should be used on both.  AEs should be 
reported using concise medical terminology on the CRF as well as on the form for collection of 
SAE information. 
10.4.2 
Reporting of a Serious Adverse Event 
In addition to recording the details of each AE on the AE CRF page, an SAE form should be 
completed, as fully as possible. Hard copies of the ‘paper’ SAE form will be provided in the 
investigator study master file. Original SAE forms will be retained in the investigator study 
master file. 
It is essential to enter the following information:  
• Protocol and subject identifiers 
• Subject demography 
• Description of events, with diagnosis if available 
• Investigator opinion of relationship to study product (or study procedure, if appropriate) 
• Criterion for seriousness. 
The following are desirable and are of particular relevance for investigator and GSK CH 
assessment of the SAE report: 
• Date of onset of AE  
• Date AE stopped, if relevant 
• Study product start date 
• Study product end date if relevant 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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  
 
•  Acti o n  ta ke n i n relati o n t o t he st u d y pr o d u ct 
•  O utc o me if k n o w n  
T he S A E f or m, c o m plete d as f ull y as p ossi ble, m ust be sca n n e d a n d e -maile d 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 wit h t he st u d y n u m ber a n d s u bject n u m ber i n 
t he s u bject li ne of t he e m ail 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  after st u d y site pers o n nel lear n of t he e ve nt. T he i n vesti gat or will s u b mit a n y u p dat e d 
S A E data t o t he s p o ns or, 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 it bei n g a vaila bl e. T he G S K C H St u d y M a na ger s h o ul d als o be n otifie d of t h e sit uati o n 
b y tele p h o n e or e m ail.  
E m ail Seri o us A d verse E ve nts t o:  
 
T he G S K C H St u d y Ma n a ger or d esi g n ee will be res p o nsi ble f or f or war di n g t he S A E f or m t o 
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 mail b o x 
 
T he i nitial re p ort wil l be f oll o we d u p wit h m ore i nf or mati o n as rele va nt, or as re q ueste d b y t h e 
G S K C H st u d y ma na ger.  
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 utilise 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 vent 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.  
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
P P D
P P D

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10.5.2 
Assessment of Causality 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.  
For each AE (serious and non-serious), the investigator (or medically qualified designee) must 
provide an assessment of causality on the AE CRF page and the SAE form (subject to the 
classification of the AE). The investigator will also document in the medical notes that he/she 
has reviewed the AE and assessed causality, where applicable.  
A “reasonable possibility” of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
Generally, the facts (evidence) or arguments to suggest a causal relationship should be provided. 
The investigator will use clinical judgment to determine the relationship and will also consult 
the Product Information, for marketed products, in the determination of his/her assessment.  
Alternative causes, such as underlying disease(s), concomitant therapy, other risk factors, and 
the temporal relationship of the event to the study product will be considered and investigated. 
For each AE/SAE, the investigator must document in the medical notes that he/she has reviewed 
the AE/SAE and has provided an assessment of causality. 
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious); the investigator must record the causal relationship in the CRF, as appropriate, and 
report such an assessment in accordance with the SAE reporting requirements if applicable. 
There may be situations when an SAE has occurred, and the investigator has minimal 
information to include in the initial report to GSK. However, it is very important that the 
investigator always make an assessment of causality for every event prior to the initial 
transmission of the SAE data to GSK CH. The investigator may change his/her opinion of 
causality in light of follow-up information and send an SAE follow-up report with the updated 
causality assessment.  
10.6 
Follow-up of AEs and SAEs  
After the initial AE/SAE report, the investigator is required to proactively follow up with each 
subject and provide further information on the subject’s condition. 
All AEs (serious and non-serious) will be followed until resolution, until the condition stabilises, 
until the event is otherwise explained, or until the subject is lost to follow-up.   
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as may be indicated or as requested by GSK CH to elucidate 
as fully as possible the nature and/or causality of the AE. This may include additional laboratory 
tests or investigations, histopathological examinations, or consultation with other health care 
professionals. 
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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  
 
Ne w or u p d ate d i nf or m ati 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 S A E f or m (s u bject 
t o t he classificati o n of t h e A E). 
T h e i n vesti gat or will s u b mit a n y u p date d S A E d ata t o G S K C H wit hi n 2 4 h o urs of recei pt of 
t he i nf or mati o n. 
I n v esti gat ors are n ot o bli ge d t o acti vel y 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, i ncl u di n g d eat h, at a n y ti me after a s u bject h as bee n dis c har ge d 
fr o m t he st u d y, a n d c o nsi ders t he e ve nt reas o n a bl y rel ate d t o t he st u d y pr o d uct or st u d y 
partici pati o n, t he i n vesti gat or will pr o m ptl y n otif y G S K C H b y e maili n g t he i nf or mati o n t o t he 
G S K C H Cli nical O p erati 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 na ger or desi g nee will be res p o nsi ble f or f or war di n g t he i nf or mati 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 dat e d S A E dat a t o G S K C H wit hi n t he desi g nat e d re p orti n g 
ti me fra mes. 
1 0. 7  
Wit h dr a w al D u e t o a n A d v er s e E v e nt  
Wit h dra wal d ue t o A Es s h o ul d be disti n g uis he d fr o m wit h dra wal d ue t o ot her ca us es, acc or di n g 
t o t he defi niti o n of a n A E n ote d earlier, a n d rec or de d o n t he a p pr o priate A E C R F pa ge.  
W he n a s u bject wit h dra ws beca use of a n S A E, t he S A E m ust be re p orte d i n acc or da n ce wit h 
t he re p orti n g re q uire me nts defi ne d. 
1 0. 8  
R e g ul at or y R e p orti n g R e q uir e m e nt s f or S A E s  
G S K C H has a le gal res p o nsi bilit y t o n otif y, as a p pr o priate, t he l ocal re g ul at or y a ut h orit y a n d 
ot her re g ulat or y a ut h orities a b o ut t he safet y of a pr o d uct u n der cli nical i n vesti gati o n.  Pr o m pt 
n otificati o n of S A Es b y t he i n vesti gat or t o G S K C H is esse ntial s o t hat le gal o bli gati o ns a n d 
et hical res p o nsi bilities t o war ds t he safet y of s u bjects are met.  
G S K C H will c o m pl y wit h c o u ntr y s p ecific re g ulat or y r e q uire m e nts relati n g t o safet y re p orti n g 
t o t he re g ulat or y a ut h orit y, I R B/ E C a n d i n vesti gat ors. 
i n vesti gat or safet y re p orts m ust be pre pare d f or s us pecte d u n e x pecte d seri o us a d verse reacti o ns 
( S U S A R) acc or di n g t o l ocal re g ulat or y re q uire m e nts a n d s p o ns or polic 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. 
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
P P D
P P D

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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 1  of 8 5  
 
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 e s 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 a n d u ntil 5 da ys after l ast 
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 he 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 t he 
G S K 
C H 
Cli nical 
O perati o ns 
Safet y 
R e p orti n g e mail 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 Ma na ger or d esi g n ee will be res p o nsi ble f or f or war di n g t he pre g n a nc y f or m t o 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 mail b o x 
. Ori gi nal pre g na n c y i nf or mati o n f or ms will be retai ne d i n t he 
i n vesti gat or st u d y master file.  
T he s u bject will be f oll o we d t o deter mi ne t he o ut c o me of t he pre g n a nc y. I nf or mati o n o n t he 
stat us of t he m ot her a n d i nfa nt / ne o n ate (i ncl u di n g c o nc o mita nt me di cati o ns ta ke n b y t h e 
m ot her d uri n g t he pre g n a nc y) will be f or war de d b y t he i n vesti gat or t o t he G S K C H Cli nical 
O perati o ns Safet y R e p orti n g e mail b o x a n d t he G S K C H St u d y Ma n a ger or desi g nee 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.  
1 1  
D A T A M A N A G E M E N T  
As use d i n t his pr ot oc ol, t he ter m C R F is u n derst o o d t o refer t o eit her a pa per f or m or a n 
electr o nic d ata rec or d or b ot h, de pe n di n g o n t h e d ata c ollecti o n met h o d.  
F or t his st u d y, s u bject d ata will be e ntere d i nt o a n electr o nic C R F, usi n g a vali date d s yst e m. 
Data rel ati n g t o S A Es, pr e g n a 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.  
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
P P D
P P D
P P D

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
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 
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The source documents (e.g. hospital records, clinical and office charts, laboratory notes, 
memoranda, subject diaries, questionnaires, evaluation checklists, pharmacy dispensing records, 
recorded data from automated instruments, microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, subject files and records kept at the pharmacy, at the laboratory and at 
the medico-technical departments involved in the clinical study) which contain the source of 
data recorded in the CRF should be specified.  The CRF and diary can be used as a source 
document at the discretion of data management. 
Each subject will be assigned and identified by a unique Screening Subject Number. Any 
reference made to an individual subject within the study must be done using their unique 
Screening Subject Number. 
11.1 
Case Report Form 
A CRF is a printed, optical, or electronic document designed to record the protocol required 
information to be reported to the sponsor on each trial subject. 
For each subject who has given informed consent/assent the CRF must be completed and signed 
by the Principal Investigator (or authorised designee) to certify that the data are complete and 
correct.  The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. 
Management of clinical data will be performed in accordance with Third Party Biostatistics and 
Data Management (BDM) Vendor applicable standards and data cleaning procedures with 
oversight by GSK CH to ensure integrity of the data, for example, to remove errors and 
inconsistencies in the data.  
To protect the privacy of subjects, no Personal Information (PI) (including the subject's name 
or initials or full birth date) is to be recorded in the CRF or as part of the query text. 
All CRF pages should be completed during a subject assessment when the CRF has been 
designated as the source.  Data that is sourced elsewhere should be entered into the CRF in an 
agreed upon timeframe between the Investigator and Sponsor.   
GSK CH will obtain and retain all CRFs and associated study data as applicable at the 
completion of the study.  
11.2 
Data Handling 
Documentation of all data management activities should allow step-by-step retrospective 
assessment of data quality and study performance.  
Any changes or corrections to data will be performed in the Electronic Data Capture (EDC) 
System, and it will include rationale for changes. The EDC system has an audit trail, which will 
provide a complete record of the changes and corrections endorsed by the Investigator. 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
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 
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Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA) 
and any concomitant medications terms (if applicable) using an internal validated medication 
dictionary, GSKDrug.   
11.2.1 
Data Queries 
Programmed edit checks will be generated automatically, as the data are being entered into the 
system. Reports and listings on the CRF data will also be run, in addition to the queries already 
programmed and generated by the system, to raise manual queries as needed for site 
clarification or correction. The Clinical Dictionary Development and Management Group will 
raise queries as needed on safety data to code the terms (AEs and Drugs or concomitant 
medication) appropriately.  
The study monitor will perform ongoing review the of the CRFs in accordance with the 
monitoring plan, to confirm that data entered into the CRF by authorised site personnel are 
accurate, complete, and verifiable from source documents; that the safety and rights of 
participants are being protected; and that the study is being conducted in accordance with the 
currently approved protocol and any other study agreements, ICH GCP, and all applicable 
regulatory requirements. 
Any queries will be generated in the EDC System to the Investigator or designee, enabling the 
errors to be addressed in parallel with Data Management review. The study monitor can also 
run reports and listings on the CRFs, to raise manual queries as needed for site clarification or 
correction. 
11.3 
Processing Patient Reported Outcomes 
Paper based patient reported outcome (PRO) data will be collected from a questionnaire 
(DHEQ), or other specified document, etc. and entered into the data management system 
(DMS).   
Electronic Patient reported outcome (ePRO) data may be collected using electronic devices and 
transferred electronically to GSK CH or Third-party DM vendor. 
All PRO source data should be reviewed by the study staff and the study monitor to ensure 
accurate transcription of data and that any potential AEs or concomitant medications reported 
on these documents are discussed with the subject and transcribed accurately to the CRF and/or 
DMS.  PROs that are classed as source data will be retained by the investigator and true/certified 
copies may be sent to a designated vendor or GSK CH as required. 
To protect the privacy of subjects, no Personal Information (PI) (including the subject's name 
or initials or birth date) is to be recorded on any PRO/ePRO that will be forwarded to GSK CH 
or Third-Party Vendor. 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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 4  of 8 5  
 
1 2  
S T A TI S TI C A L C O N SI D E R A TI O N S A N D  D A T A A N A L Y S E S  
1 2. 1  
S a m pl e Si z e D et er mi n ati o n  
A s ufficie nt n u m ber of s u bjects will be scree n e d t o ra n d o mise a p pr o xi matel y 1 9 5 s u bjects t o 
e ns ure a p pr o xi matel y 1 8 0 s u bjects (a p pr o xi matel y 6 0 p er gr o u p) c o m plete t he st u d y, all o wi n g 
f or dr o p o uts. 
C ha n ge fr o m basel i ne i n Sc hiff se nsiti vit y s c ore will be use d e val uate treat me nt effects a n d is 
t he pri mar y o utc o me varia ble. Wit h 6 0 e val ua ble s u bjects per gr o u p, t he st u d y has 9 0 % p o wer 
t o detect a mea n differe n ce of 0. 3 (sta n d ar d de viati o n (s d) = 0. 5 0 1) i n c ha n ge fr o m ba seli ne i n 
Sc hiff se nsiti vit y s c ore after 8 wee ks of treat me nt. T he differe nce of 0. 3 re prese nts r o u g hl y a 
1 5 % differe nce bet wee n treat me nt gr o u ps. T he esti mate of s d was o btai ne d fr o m G S K C H 
st u dies 
. T he s a m ple siz e is base d o n carr yi n g o ut a 2 -t aile d 
2 sa m ple t -test at a 5 % si g nifica nce l e vel. 
1 2. 2  
P o p ul ati o n s f or A n al y si s  
1 2. 2. 1  
D efi niti o n of A n al y si s P o p ul ati o n s  
All assess me nts of safet y will be b ase d o n t he S afet y p o p ulati o n. T he Safet y p o p ulati o n will 
c o m prise all ra n d o mise d s u bjects w h o recei ve at least o ne d os e of st u d y pr o d uct. T his 
p o p ulati o n will be base d o n t he pr o d uct t he s u bject act uall y recei ve d.  
T he pri mar y p o p ulati o n f or efficac y assess me nt will be t he m o difie d i nte nt -t o-treat ( m-I T T) 
p o p ulati o n, defi ne d as all s u bjects w h o are ra n d o mise d, recei ve d at least o ne d ose of t h e st u d y 
treat me nts a n d pr o vi de d at least o ne p ost-b aseli ne assess me nt of efficac y. All m -I T T p o p ulati o n 
s u m maries a n d a nal ys es will be prese nte d acc or di n g t o t he treat me nt ra n d o mise d.  
T he per pr ot oc ol ( P P) p o p ulati o n is defi ne d as all s u bjects i n t he m -I T T p o p ulati o n w h o ha ve 
at least o ne assess me nt of effic ac y c o nsi dere d u n affect e d b y pr ot oc ol vi olati o ns.  
1 2. 2. 2  
E x cl u si o n of D at a fr o m A n al y si s  
E x cl usi o n of a n y data fr o m t he a nal yses will be deter mi ne d d uri n g a Bl i n de d Data Re vie w 
( B D R) Meeti n g pri or t o data base l oc k. A n y reas o ns f or e x cl usi o n fr o m a n a nal ysis p o p ulati o n 
will be liste d, if a p plica ble . 
A P P a nal ysis will be perf or me d o nl y o n t he pri mar y varia ble ( Sc hiff sc ore) if t here is m ore 
t ha n 1 0 % differe nce i n t he n u m ber of s u bjects bet wee n t he P P a n d m-I T T p o p ulati o ns. A 
decisi o n o n w het her a P P a nal ysis will be p erf or me d will be ma de pri or t o st u d y u n bli n di n g 
(rele ase of t he ra n d o misati o n c o des). 
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
C CI

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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12.3 
Statistical Analyses 
Additional details of the proposed statistical analysis will be documented in the statistical 
reporting and analysis plan (RAP), which will be written following finalisation of the protocol 
and prior to database lock. This section is a summary of the planned statistical analyses of the 
most important endpoints including primary and key secondary endpoints. 
12.3.1 
Primary Analysis(es)  
The primary efficacy variable is the change from baseline in Schiff score at 8 weeks. The 
primary comparison is between the test product and the negative control. As there is only a 
single primary objective no adjustment for multiple comparisons is required. 
The Schiff sensitivity score is derived as the average score of the 2 test teeth. The change from 
baseline is derived from the individual teeth first before calculating the average change of the 
2 test teeth. 
A summary of the Schiff sensitivity score and change from baseline will be provided by 
treatment group and time. 
The change from baseline in Schiff sensitivity score will be analysed using analysis of 
covariance (ANCOVA) with treatment as a factor and baseline Schiff sensitivity score as a 
covariate. Note that since the baseline Schiff sensitivity score will be included as a covariate, 
the baseline Schiff stratification value will not be included in the model. 
The assumption of normality and homogeneity of variance in the ANCOVA model will be 
investigated. In case of violation of these assumptions a suitable transformation or a non-
parametric method eg the van Elteren test, adjusting for the maximum baseline Schiff 
Sensitivity scores will be performed and results will be compared with the ANCOVA results. 
If the inferences from the two analyses are similar then both sets of results will be reported and 
emphasis will be made on the ANCOVA results. In case of discrepancies between p-values of 
ANCOVA and non-parametric method, inferences will be drawn on the nonparametric 
anlayses. Ultimately inferences will be drawn on the size of difference rather than just the p-
value and it is hoped to see a difference of >15% between treatment groups.  This difference is 
based on the adjusted Test and Control means for the change from baseline: 100 x [Adjusted 
Mean Difference / Adjusted Mean of Negative Control] . This percentage difference will be 
reported and tabulated along with the change from baseline results. 
12.3.2 
Secondary Analyses 
The secondary efficacy variables with corresponding comparisons are as follows: 
• Change from baseline in tactile threshold at 4 and 8 weeks; “test product versus negative 
control” and “positive control versus negative control”.  
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Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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• Change from baseline in Schiff sensitivity score at 4 weeks; “test product versus 
negative control” and “positive control versus negative control”. 
• Change from baseline in Schiff sensitivity score 8 weeks; “positive control versus 
negative control”.  
Tactile score including the change is derived in the same manner as for the Schiff score. 
A summary of the secondary variables and change from baseline will be provided by treatment 
group and time. 
Change from baseline in Schiff will be analysed as per the primary variable. Change from 
baseline in Tactile variables will be analysed using ANCOVA with treatment as a factor and 
baseline Schiff sensitivity score as a covariate.  
The assumption of normality and homogeneity of variance in ANCOVA model will be assessed 
as described for the primary efficacy analysis. 
12.3.3 
Exploratory Analyses 
The exploratory efficacy variables are change from baseline in QOL (Total and each domain 
scores) at 8 weeks “test product versus negative control” and “positive control versus negative 
control” 
The following QOL domain scores derived from the DHEQ questionnaire will be investigated: 
• Total (Section 2, Q1-15) 
• Restrictions (Section 2, Q1-3) 
• Adaptation (Section 2, Q4-6) 
• Social Impact (Section 2, Q7-9) 
• Emotional Impact (Section 2, Q10-12) 
• Identity (Section 2, Q13-15). 
A summary of the exploratory variables and change from baseline will be provided by treatment 
group and time. This includes the individual questions from Section 1 (Q1-9). 
Change from baseline in QOL variables (Section 1 (Q7-Q9) and Section 2 domain scores) will 
be analysed using ANCOVA with treatment baseline Schiff stratification as factors and baseline 
score of relevant variable included as a covariate. 
The assumption of normality and homogeneity of variance in ANCOVA model will be assessed 
as described for the primary efficacy analysis. 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
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 
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12.3.4 
Safety Analysis(es) 
Safety variables will focus on: 
• Exposure 
• AEs 
• OST findings 
All AEs will be coded using the latest version of MedDRA. AEs will be categorised as oral and 
non-oral by the primary investigator. Treatment-emergent adverse events (Oral AEs as well as 
all AEs) will be associated with the most recent treatment received. The number of AEs and 
number of subjects with AEs will be listed and tabulated by treatment. The results of OST 
findings will be tabulated. 
Exposure to study product is covered under study product compliance and the number of 
brushings in Section 12.3.7.1. 
12.3.5 
Exclusion of Data from Analysis  
Exclusion of any data from the analyses will be determined during a Blind Data Review 
(BDR) Meeting prior to database lock. Any reasons for exclusion from an analysis population 
will be listed, if applicable.  
12.3.6 
Demographic and Baseline Characteristics 
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. Demographic and baseline 
characteristics will be summarised by treatment group and study site for the Safety and mITT 
populations and the PP population if a PP analysis is performed. 
12.3.7 
Study Product Compliance and Use of Other Therapies 
12.3.7.1 Study Product Compliance 
This will be assessed by: 
• Number of brushings 
• Study dentifrice weight 
The number of brushings and corresponding compliance rate will be summarised by treatment 
group between treatment visits and across the whole duration. 
Number of brushings compliance will be calculated as :- 
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Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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100 × (number of actual brushings)/(number of expected brushings) 
Number of expected brushings = 2 × number of days between Visitn and Visitn-1 
For the study dentifrice weight, the study dentifrice will be weighed at each visit. the pre-
defined range will be calculated as the expected weight of toothpaste used for the treatment 
window. E.g. (2g x 28 days ) ± 40%, therefore, in a 4 week treatment period the expected 
amount of toothpaste used would be ≥33.6g and ≤78.4g. The amount of dentifrice used during 
each treatment period will be recorded in a source document and later transcribed to the CRF. 
12.3.7.2 Prior and Concomitant Medications 
Prior medications, concomitant medications and significant non-drug therapies taken during the 
study will be listed for the Safety population. 
12.3.8 
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. 
12.3.9 
Interim Analysis  
No interim analysis is planned for this study. 
13 
STUDY GOVERNANCE CONSIDERATIONS 
13.1 
Quality Control  
In accordance with applicable regulations including GCP, and GSK CH procedures, GSK CH 
or designee (i.e. third-party vendor) monitors will contact the site prior to the start of the study 
to review with the site staff the protocol, study requirements, and their responsibilities to satisfy 
regulatory, ethical, and GSK CH requirements. 
When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the CRF will serve as the source 
document. 
GSK CH or designee will monitor the study and site activity to verify that the: 
• Data are authentic, accurate, and complete. 
• Safety and rights of subjects are being protected. 
• Study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements. 
216954 | Protocol  04 Feb 2022 | TMF-194033 | 2.0

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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The extent and nature of monitoring will be described in a written monitoring plan on file at 
GSK CH. The investigator (or designee) agrees to allow the monitor direct access to all relevant 
documents and agrees to co-operate with the monitor to ensure that any problems detected in 
the course of these monitoring visits are resolved. 
13.2 
Quality Assurance 
To ensure compliance with GCP and all applicable regulatory requirements, GSK CH may 
conduct a quality assurance assessment and/or audit of the site records, and the regulatory 
agencies may conduct a regulatory inspection at any time during or after completion of the 
study.  
In the event of an assessment, audit or inspection, the investigator (and institution) must agree 
to grant the advisor(s), auditor(s) and inspector(s) direct access to all relevant documents and 
to allocate their time and the time of their staff to discuss the conduct of the study, any 
findings/relevant issues and to implement any corrective and/or preventative actions to address 
any findings/issues identified. 
The investigator(s) will notify GSK CH or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with GSK CH 
or its agents to prepare the study site for the inspection and will allow GSK CH or its agent, 
whenever feasible, to be present during the inspection. The investigator will promptly apply 
copies of the inspection finding to GSK CH or its agent. Before response submission to the 
regulatory authority, the investigator will provide GSK CH or its agents with an opportunity to 
review and comment on responses to any such findings.  
The sponsor will be available to help investigators prepare for an inspection. 
13.3 
Regulatory and Ethical Considerations 
13.3.1 
Institutional Review Board/ Ethics Committee  
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent document, investigator brochure/safety statement 
(including any updates) and other relevant documents, e.g. recruitment advertisements, if 
applicable, from the IRB/EC.  All correspondence with the IRB/EC should be retained in the 
investigator file. Copies of IRB/EC approvals should be forwarded to GSK CH prior to the 
initiation of the study, and also when subsequent amendments to the protocol are made. 
The only circumstance in which an amendment may be initiated prior to IRB/EC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In that 
event, the investigator must notify the IRB/EC and GSK CH in writing immediately after the 
implementation. 
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Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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13.3.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol and legal and regulatory 
requirements, as well as the general principles set forth in the International Ethical Guidelines 
for Biomedical Research Involving Human Subjects (Council for International Organizations 
of Medical Sciences 2002), International Ethical Guidelines for Health-Related Research 
Involving Humans (Council for International Organizations of Medical Sciences, 2016), 
guidelines for GCP (ICH 1996 and revision 2), and the Declaration of Helsinki (World Medical 
Association 2013).  
In addition, the study will be conducted in accordance with the protocol, the ICH guideline on 
GCP, and applicable local regulatory requirements and laws. 
13.3.3 
Subject Information and Consent 
All parties will ensure protection of subject personal data and will not include subject names or 
other identifiable data in any reports, publications, or other disclosures, except where required 
by laws.  
When study data are compiled for transfer to GSK CH and other authorised parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by GSK CH in order to de-identify study subjects. 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, GSK CH 
will maintain high standards of confidentiality and protection of subjects’ personal data 
consistent with applicable privacy laws. 
The informed consent document must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws. 
The informed consent document 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.  
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.   
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Clinical Protocol 
 
 
Protocol Number: 216954 
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 71 of 85 
 
GSK CH will have an opportunity to review and approve the content of any study recruitment 
materials directed to potential study subjects before such materials are used.  
13.3.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP  
Within GSK CH a serious breach is defined as a breach likely to affect to a significant degree 
the safety and rights of a subject or the reliability and robustness of the data generated in GSK 
CH-sponsored human subject research studies.  
In the event of any prohibition or restriction imposed (i.e., clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product, GSK CH should be informed immediately.  
In addition, the investigator will inform GSK CH immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of any 
serious breaches of this protocol or of ICH GCP that the investigator becomes aware of. 
13.4 
Posting of Information on Publicly Available Clinical Trial 
Registers 
Study information from this protocol will be posted on publicly available clinical trial registers 
before enrollment of subjects begins in accordance with applicable GSK CH processes. 
GSK intends to make anonymised subject-level data from this trial available to external 
researchers for scientific analyses or to conduct further research that can help advance medical 
science or improve patient care. This helps ensure the data provided by trial participants are 
used to maximum effect in the creation of knowledge and understanding. 
13.5 
Provision of Study Results to Investigators 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the opportunity 
to review the complete study results at a GSK CH site or other mutually-agreeable location. 
GSK CH will also provide the investigator with the full summary of the study results.  The 
investigator is encouraged to share the summary results with the study subjects, as appropriate. 
The procedures and timing for public disclosure of the results summary and for development of 
a manuscript for publication will be in accordance with GSK CH Policy. 
A manuscript will be progressed for publication in the scientific literature if the results provide 
important scientific or medical knowledge. 
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Clinical Protocol 
 
 
Protocol Number: 216954 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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13.6 
Records Retention 
Following closure of the study, the investigator must maintain all site study records (except for 
those required by local regulations to be maintained elsewhere), in a safe and secure location.   
The records (study/ site master file) must be maintained to allow easy and timely retrieval, when 
needed (e.g. for a GSK CH audit or regulatory inspection) and must be available for review in 
conjunction with assessment of the facility, supporting systems, and relevant site staff. 
Where permitted by local laws/regulations or institutional policy, some or all of these records 
can be maintained in a format other than hard copy (e.g. microfiche, scanned, electronic); 
however, caution needs to be exercised before such action is taken.  
The investigator must ensure that all reproductions are legible and are a true and accurate copy 
of the original and meet accessibility and retrieval standards, including re-generating a hard 
copy, if required.  Furthermore, the investigator must ensure there is an acceptable back-up of 
these reproductions and that an acceptable quality control process exists for making these 
reproductions. 
The investigator must assure that the subject’s anonymity will be maintained.  On CRFs or other 
documents submitted to GSK CH, subjects should not be identified by their names or initials, 
but by an identification code. The investigator should keep a separate log of subjects’ codes, 
names and addresses.  Documents not for submission to GSK CH, e.g. subjects’ written consent 
forms, should be maintained by the investigator in strict confidence. 
Records and documents, including signed ICF, pertaining to the conduct of this study must be 
retained by the investigator as per the signed contractual agreement, from the issue of the final 
Clinical Study Report (CSR) or equivalent summary, unless local regulations or institutional 
policies require a longer retention period. The minimum retention time will meet the strictest 
standard applicable to that site for the study, as dictated by any institutional requirements or 
local laws or regulations, GSK CH standards/procedures, and/or institutional requirements.   
No study document should be destroyed without a prior written agreement between GSK CH 
and the investigator. The investigator must notify GSK CH of any changes in the archival 
arrangements, including, but not limited to, archival at an off-site facility or transfer of 
ownership of the records in the event the investigator is no longer associated with the site. 
13.7 
Conditions for Terminating the Study  
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or study product safety problems, or at the discretion of GSK 
CH.  
If a study is prematurely terminated, GSK CH will promptly notify the investigator. After 
notification, the investigator must promptly contact all participating subjects and should assure 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
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 
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appropriate therapy/ follow-up for the subjects. As directed by GSK CH, all study materials 
must be collected and all CRF’s completed to the greatest extent possible. Where required by 
the applicable regulatory requirements, GSK CH should inform the regulatory authority(ies) 
and the investigator should promptly inform the IRB/EC and provide the IRB/EC a detailed 
written explanation of the termination or suspension.  
If the IRB/EC terminates or suspends its approval/favorable opinion of a trial, the investigator 
should promptly notify the GSK CH and provide GSK CH with a detailed written explanation 
of the termination or suspension. 
Upon completion or premature discontinuation of the study, the GSK CH monitor will conduct 
site closure activities with the investigator or site staff, as appropriate, in accordance with 
applicable regulations including GCP, and GSK CH Standard Operating Procedures. 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
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 74 of 85 
 
 
14 
REFERENCES 
Addy M. Dentine hypersensitivity: Definition, prevalence, distribution and aetiology. Tooth 
wear and sensitivity. 2000:239-48. 
Addy M., Mostafa P., Absi E., Adams D., Cervical dentin hypersensitivity. Etiology and 
management with particular reference to dentifrice. In Proceedings of Symposium on 
Hypersensitive Dentin. Origin and Management; Rowe, N., Ed.; University of Michigan, Ann 
Arbor, MI, 1985; pp 147–167. 
Brännström M., A hydrodynamic mechanism in the transmission of pain producing stimuli 
through dentin. In Sensory Mechanisms in Dentin; Anderson, D., Ed.; Oxford: Pergamon Press, 
1962; pp 73–79. 
Canadian Advisory Board on Dentin Hypersensitivity, Consensus-based recommendations for 
the diagnosis and management of dentin hypersensitivity. J. Can. Dent. Assoc. 2003, 69, 221–
226. 
Creeth, J., Maclure, R., Seong, J., Gomez‐Pereira, P., Budhawant, C., Sufi, F., Holt, J., 
Chapman, N. and West, N., 2019. Three randomized studies of dentine hypersensitivity 
reduction after short‐term SnF2 toothpaste use. Journal of clinical periodontology, 46(11), 
pp.1105-1115. 
Dempsey Pa, Townsend G. Genetic and environmental contributions to variation in human 
tooth size. Heredity. 2001;86(6):685. 
Docimo R., Montesani L., Maturo P., Costacurta M., Bartolino M., Zhang Y. P., DeVizio W., 
Delgado E., Cummins D., Dibart S., et al., Comparing the efficacy in reducing dentin 
hypersensitivity of a new toothpaste containing 8.0% arginine, calcium carbonate, and 1450 
ppm fluoride to a benchmark commercial desensitizing toothpaste containing 2% potassium ion: 
An eight-week clinical study . J. Clin. Dent. 2009, 20, 137–143. 
Fischer C., Fischer R. G., Wennberg A., Prevalence and distribution of cervical dentine 
hypersensitivity in a population in Rio de Janeiro, Brazil. J. Dent. 1992, 20, 272–276. 
Flynn J., Galloway R., Orchardson R., The incidence of “hypersensitive” teeth in the West of 
Scotland. J. Dent. 1985, 13, 230–236. 
Gallagher, et al. 2009. The effect of brushing time and dentifrice on dental plaque removal in 
vivo. American Dental Hygienists' Association, 83(3), 111-116. 
Goyal C, Sufi F, Qaqish J, et al. Two-week efficacy of an occluding dentifrice on dentinal 
hypersensitivity. J Dent Res. 2017;96(Spec. Iss. A). 
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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 5  of 8 5  
 
Graf H., Galasse R., M or bi dit y, pre vale nce a n d i ntra oral distri b uti o n of h y p erse nsiti ve teet h. J. 
De nt. Res.  1 9 7 7 , 5 6 , A 1 6 2. 
Hall R., E m ber y G., S hellis R., Bi ol o gical a n d str u ct ural feat ures of e na mel a n d de nti n: c urre nt 
c o nce pts rele va nt t o er osi o n a n d de nti n h y perse nsiti vit y. I n T o ot h We ar a n d Se nsitivity ; A d d y, 
M., E m ber y, G., E d gar, W., Orc har ds o n, R., E ds.; Marti n D u nitz Lt d, L o n d o n, 2 0 0 0; p p 3 – 1 9.  
* He, S. L. a n d 
Wa n g, J. H., 2 0 1 5. De vel o p me nt of t he C hi nese v ersi o n of t he de nti ne 
h y perse nsiti vit y e x perie nce q uesti o n naire. I n 
De nti ne 
H y perse nsiti vit y ( p p. 1 6 5 -1 7 5). 
Aca de mic Press.  
He, S. L. a n d Wa n g, J. H., 2 0 1 5. Relia bilit y a n d vali dit y of t he C hi nese versi o n of t he s h ort f or m 
of t he 
De nti ne 
H y perse nsiti vit y E x perie nce 
Q uesti o n naire ( D H E Q -1 5).  Q ualit y of Lif e 
Researc h,  2 4( 6), p p. 1 4 6 5 -1 4 6 9.  
H olla n d G. R., Nar hi M. N., A d d y M., Ga n gar osa L., Orc har ds o n R., G ui deli nes f or t he desi g n 
a n d c o n d u ct of cli nical trials o n de nti ne h y p erse nsiti vit y. J. Cli n. Peri o d o nt ol.  1 9 9 7 , 2 4 , 8 0 8–
8 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. 
Ir wi n C. R., Mc C us ker P., Pre vale nce of de nti ne h y p erse nsiti vit y in a ge n eral de ntal p o p ulati o n. 
J. Ir. De nt. Ass oc.  1 9 9 7 , 4 3 , 7– 9.  
Last er L., La u d e n bac h K. 
W., St oller N. H., A n e val u ati o n of cli nical t o ot h m o bilit y 
meas ure me nts. J. Peri o d o nt ol.  1 9 7 5 , 4 6 , 6 0 3– 6 0 7.  
Lei g ht R., B o w m a n J., Barl o w A., De nti nal H y perse nsiti vi t y: E vi de nce f or a “ N o Treat me nt” 
Effect. J. De nt. R es.  2 0 0 8 , 8 7 , A bstract N o 3 4 9 8. 
Lia n g X, Wei Z, H u D , et al. Pre vale nce of d e nti n h y perse nsiti vit y a m o n g t he resi d e nts of xi’a n 
cit y, c hi n a. Acta O d o nt ol o gic a Sca n di na vica. 2 0 1 7; 7 5( 6): 3 8 7 -9 3.  
L o be n e R. R. , Weat herf or d T., R oss N. M., La m m R. A., Me na ker L., A m o difie d gi n gi v al 
i n de x f or use i n cli nical trials. Cli n. Prev. De nt.  1 9 8 6 , 8 , 3– 6.  
Ma ki n S. A., Sta n n o us fl u ori de de ntifrices. A m. J. De nt.  2 0 1 3 , 2 6 S pec N o , 3 A –  9 A.  
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
C CI
C CI

GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
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 
 
Ministry of Health, China. Efficacy evaluation of toothpaste - Part 4：Guidelines for efficacy 
evaluation on dentin hypersensitivity. Health Industrial Standard of the People's Republic of 
China. WS/T 326.4-2010. 
Murray L., Roberts A., The prevalence of self-reported hypersensitive teeth. Arch. Oral Biol. 
1994. 
Ni, L.X., He, T., Chang, A. and Sun, L., 2010. The desensitizing efficacy of a novel stannous-
containing sodium fluoride dentifrice: An 8-week randomized and controlled clinical trial. 
American Journal of Dentistry, 23, p.17B. 
Orchardson R., Collins W., Clinical features of hypersensitive teeth. Br. Dent. J. 1987, 162, 
253–256. 
Orchardson R., Gillam D.G., The efficacy of potassium salts as agents for treating dentin 
hypersensitivity. J. Orofac. Pain, 2000, 14, 9-19. 
Parkinson CR and R Willson. A comparative in vitro study investigating the occlusion and 
mineralization properties of commercial dentifrices in a four day dentine disc model. J. Clin. 
Dent. Spec Issue, 22(3) 2011.  
Parkinson C, Hughes N, Jeffery P, et al. The efficacy of an experimental dentifrice containing 
0.454% w/w stannous fluoride in providing relief from the pain of dentin hypersensitivity: An 
8-week clinical study. American journal of dentistry. 2013;26:25A-31A. 
Parkinson CR, Jeffery P, Milleman JL, et al. Confirmation of efficacy in providing relief from 
the pain of dentin hypersensitivity of an anhydrous dentifrice containing 0.454% with or 
without stannous fluoride in an 8-week randomized clinical trial. American journal of dentistry. 
2015;28(4):190-6. 
Parkinson CR, Hughes N, Hall C, et al. Three randomized clinical trials to assess the short-term 
efficacy of anhydrous 0.454% w/w stannous fluoride dentifrices for the relief of dentin 
hypersensitivity. American journal of dentistry. 2016;29(1):25-32. 
Pashley D. H., Dentin permeability, dentin sensitivity, and treatment through tubule occlusion, 
J Endodont. 1986, 12, 465-474. 
Pashley D., Tay F., Haywood V., Collins M., Drisko C., Consensus-based recommendations 
for the diagnosis and management of dentin hypersensitivity. Compend Cont Edu Dent 2008, 
29, 1–35. 
Polson A, Caton J, Yeaple R, et al. Histological determination of probe tip penetration into 
gingival sulcus of humans using an electronic pressure‐sensitive probe. Journal of Clinical 
Periodontology. 1980;7(6):479-88. 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
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 
 
Parkinson C, Hughes N, Targett D, Ferrier A, Jones S B, Seong J, Davies M, Macdonald E L, 
West N. Dentine tubule occlusion of an experimental anti-sensitivity toothpaste in-situ. IADR 
2013. 
Rees J. S., The prevalence of dentine hypersensitivity in general dental practice in the UK. J. 
Clin. Periodontol. 2000, 27, 860–865. 
Schiff T, Dotson M, Cohen S, et al. Efficacy of a dentifrice containing potassium nitrate, soluble 
pyrophosphate, pvm/ma copolymer, and sodium fluoride on dentinal hypersensitivity: A 
twelve-week clinical study. The Journal of clinical dentistry. 1994;5:87-92. 
Schiff T., He T., Sagel L., Baker R., Efficacy and safety of a novel stabilized stannous 
fluoride and sodium hexametaphosphate dentifrice for dentinal hypersensitivity. J. Contemp. 
Dent. Pract. 2006, 7, 1–8. 
Seltzer S., Bender I., The Dental Pulp: Biologic Considerations in Dental Procedures; JP 
Lippincott, 1975. 
Tao, D., Ling, M.R., Feng, X.P., Gallob, J., Souverain, A., Yang, W. and Alavi, A., 2020. 
Efficacy of an anhydrous stannous fluoride toothpaste for relief of dentine hypersensitivity: a 
randomised clinical study. Journal of Clinical Periodontology.  
West N. X., Addy M., Jackson R. J., Ridge D. B., Dentine hypersensitivity and the placebo 
response. A comparison of the effect of strontium acetate, potassium nitrate and fluoride 
toothpastes. J. Clin. Periodontol. 1997, 24, 209–215. 
World Medical Association Declaration of Helsinki, 64th General Assembly, Fortaleza 2013. 
 
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GSK Consumer Healthcare 
 
Clinical Protocol 
 
 
Protocol Number: 216954 
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 
 
 
15 
APPENDICIES 
15.1 
ABBREVIATIONS 
The following is a list of abbreviations that may be used in the protocol. 
Table 15-1 
Abbreviations 
Abbreviation 
Term 
AE 
Adverse event 
ANCOVA 
Analysis of covariance 
BDM 
Biostatistics and Data Management 
BDR 
Blinded data review 
CRF 
Case report form 
CRS 
Clinical Research Scientist 
DH 
Dentin Hypersensitivity 
DHEQ 
Dentin Hypersensitivity Experience Questionnaire 
DMS 
Document Management System 
EAR 
Erosion, Abrasion, Recession 
EDC 
Electronic data capture 
EC 
Ethics committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GSK CH 
GlaxoSmithKline Consumer Healthcare 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
ITT 
Intent-to-treat 
OHT 
Oral hard tissue 
OHRQoL 
Oral Health Related Quality of Life 
OST 
Oral soft tissue 
OTC 
Over-the-counter 
MFC 
Manufacturing formulation code 
MGI 
Modified gingival index 
MOH 
Ministry of Health 
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May not be used, divulged, published or otherwise disclosed without the consent of GSKCH 
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Abbreviation 
Term 
NaF 
Sodium fluoride 
N/A 
Not applicable 
PI 
Principal Investigator 
PI 
Personal information 
PP 
Per protocol 
PRO 
Patient Reported Outcome 
QOL 
Quality of Life 
RAP 
Reporting and analysis plan 
SAE 
Serious adverse event 
SD 
Standard deviation 
SnF2 
Stannous fluoride 
SRSD 
Single reference safety document 
SS 
Safety statement 
SUSAR 
Suspected unexpected serious adverse reaction 
UK 
United Kingdom 
US 
United States 
USA 
United States of America 
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G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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 0  of 8 5  
 
 
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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  
 
 
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
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  
 
T h e f oll o wi n g q u e sti o n s ar e a b o ut y o ur s e n siti v e t e et h, a n d t h e i m p a ct it h a s o n y o ur e v er y d a y lif e. 
 
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
 
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  
S E C TI O N T W O  
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
 
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 4  of 8 5  
 
 
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
C CI

G S K C o ns u mer Healt hcare  
 
Cli nical Pr ot oc ol  
 
 
Pr ot oc ol N u m ber: 2 1 6 9 5 4  
 
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 5  of 8 5  
 
 
 
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
C CI

Si g nat ure Pa ge f or  2 1 6 9 5 4 T M F- 1 9 4 0 3 3 v 2. 0
Si g nat ure Pa ge f or T M F- 1 9 4 0 3 3 v 2. 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: 
2 1 6 9 5 4 | Pr ot oc ol  0 4 Fe b 2 0 2 2 | T M F- 1 9 4 0 3 3 | 2. 0
P P D
P P D