A Randomized, 8 Week Clinical Study to Evaluate the Efficacy of an Experimental Stannous Fluoride Dentifrice in the Relief of Dentinal Hypersensitivity
Phase: NA
Conditions: Dentin Sensitivity
Sponsor: GlaxoSmithKline

Stannous fluoride
Protocol Number 208153
Final1.0 Clinical Protocol
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CLINICAL PROTOCOL
A Randomized, 8 Week Clinical Study to Evaluate the 
Efficacy of an Experimental Stannous Fluoride Dentifrice in 
the Relief of Dentinal Hypersensitivity
Active Name:  
Stannous Fluoride (SnF2) 
United States (US) Investigational 
New Drug (IND) Number:
N/A
European Clinical Trials Database 
(EudraCT) Number:
N/A
Other Regulatory Agency Identified 
Number:
N/A
Protocol Number:
208153
Phase:
N/A
Sponsor information
Sponsor LegalRegistered Address
GlaxoSmithKline Research & Development 
Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Sponsor Contact Address
GlaxoSmithKline Consumer Healthcare(China) Co, 
Ltd
7F, The Headquarters building, No. 168 Tibet Road 
(M), Shanghai, China, 200001,
Tel: 
 
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Document History
Document
Version Date
Summary of Changes 
Original protocol
18-August-2017
Not applicable (N/A)
Amendments incorporate all revisions to date, including amendments made at the request of 
country health authorities, independent ethics committee (EC), etc. 
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT PAGE
I confirm agreement to conduct the study in compliance with the protocol and any 
amendments and according to the current ICH GCP guidelines.
I acknowledge that I am responsible for overall study conduct. I agree to personally 
conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the conduct of 
the study are informed about their obligations. Mechanisms are in place to ensure site staff 
receives all appropriate information throughout the study.
I agree to conduct this study in full conformance with the laws and regulations of the 
country in which the research is conducted and the Declaration of Helsinki.
Investigator Name:
ProfessorFeng Xiping
Investigator Qualifications:
DDS, MDS
Investigator Signature:
Date of Signature/ Agreement:
DD/MMM/YYYY
 
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Table of contents
Sponsor information........................................................................................................1
Document History...........................................................................................................2
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT PAGE..............................2
Table of contents.............................................................................................................3
List of tables...................................................................................................................7
SCHEDULE OF ACTIVITIES.......................................................................................8
1 INTRODUCTION........................................................................................................10
1.1
Mechanism of Action/Indication........................................................................10
1.2
Background and Rationale.................................................................................11
1.2.1
Justification on the Requirement to Conduct the Study.......................11
1.2.2
Study Design and Dose Rational........................................................11
2 STUDY OBJECTIVES AND ENDPOINTS.................................................................13
3 STUDY DESIGN AND SUBJECT POPULATION......................................................14
4 SUBJECT SELECTION...............................................................................................15
4.1
Inclusion Criteria...............................................................................................15
4.2
Exclusion Criteria..............................................................................................16
4.3
Randomization Criteria......................................................................................18
4.4
Lifestyle Guidelines...........................................................................................18
4.4.1
Dietary and Alcohol Restrictions........................................................18
4.4.2
Contraception....................................................................................19
4.5
Screen Failures..................................................................................................20
4.6
Sponsor’s Qualified Medical Personnel..............................................................20
5 STUDY TREATMENTS..............................................................................................21
5.1
Blinding and Allocation to Treatment/Randomization........................................21
5.2
Breaking the Blind.............................................................................................21
5.3
Subject Compliance...........................................................................................22
5.4
Investigational Product Supplies........................................................................22
5.4.1
Dosage Form and Packaging..............................................................23
5.4.2
Preparation and Dispensing................................................................23
5.5
Administration...................................................................................................23
5.5.1
Medication Errors..............................................................................24
5.6
Investigational Product Storage..........................................................................24
5.7
Investigational Product Accountability...............................................................25
 
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5.7.1
Destruction of Investigational Product Supplies.................................25
5.8
Concomitant Treatment(s).................................................................................26
6 STUDY PROCEDURES...............................................................................................26
6.1
Screening -Visit 1 (FSFV)................................................................................26
6.2
Study Period......................................................................................................27
6.2.1
Day 1; Baseline-Visit 2....................................................................27
6.2.2
Day 29 (±3 days) -Visit 3..................................................................28
6.2.3
Day 57 (±3 days) -Visit 4..................................................................29
6.3
Follow-up Phone Call........................................................................................30
6.4
Subject Withdrawal............................................................................................30
7 ASSESSMENTS...........................................................................................................31
7.1
Screening...........................................................................................................31
7.1.1
Informed Consent..............................................................................31
7.1.2
Eligible Tooth Assessments...............................................................31
7.2
Efficacy.............................................................................................................34
7.2.1
Tactile Sensitivity Assessment (Yeaple probe)...................................34
7.2.2
Evaporative Air Sensitivity Assessment.............................................35
7.3
Safety................................................................................................................36
7.3.1
Oral Soft Tissue (OST) Examination..................................................36
7.3.2
Full Oral Hard Tissue (OHT) Examination.........................................37
7.3.3
Urine Pregnancy Test.........................................................................37
8 ADVERSE EVENT AND OTHER EVENTS OF SPECIALINTEREST 
REPORTING................................................................................................................37
8.1
Definitions of Adverse Events and Serious Adverse Events...............................37
8.1.1
Adverse Event...................................................................................37
8.1.2
Serious Adverse Event.......................................................................38
8.2
Reporting Period................................................................................................40
8.2.1
Adverse Event...................................................................................40
8.2.2
Serious Adverse Event.......................................................................40
8.3
Reporting Procedures.........................................................................................40
8.3.1
Adverse Event...................................................................................41
8.3.2
Serious Adverse Event.......................................................................41
8.3.3
Sponsor’s Reporting Requirements to Regulatory Authorities and 
Ethics Committees.............................................................................42
 
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8.4
Evaluating Adverse Events and Serious Adverse Events....................................42
8.4.1
Severity Assessment..........................................................................42
8.4.2
Causality Assessment.........................................................................43
8.5
Withdrawal Due to an Adverse Event and Serious Adverse Events....................43
8.6
Pregnancy..........................................................................................................44
8.6.1
Time Period for Collecting Pregnancy Information............................44
8.6.2
Action to be Taken if Pregnancy Occurs............................................44
8.7
Follow-up of Adverse Events and Serious Adverse Events.................................44
9 DATA MANAGEMENT..............................................................................................45
9.1
Source Documents/ Data....................................................................................45
9.2
Case Report Form..............................................................................................45
9.3
Data Handling....................................................................................................46
9.3.1
Queries..............................................................................................46
9.4
Processing Patient Reported Outcomes..............................................................46
10 STATISTICAL CONSIDERATIONS AND DATA ANALYSES.................................47
10.1 Sample Size Determination................................................................................47
10.2 Statistical Methods and Analytical Plan.............................................................47
10.2.1
Demographic and Baseline Characteristics.........................................47
10.2.2
Primary Analysis...............................................................................47
10.2.3
Secondary Analyses...........................................................................48
10.2.4
Exploratory Analyses.........................................................................48
10.2.5
Safety Analyses.................................................................................49
10.2.6
Definition of Analysis Populations.....................................................49
10.2.7
Exclusion of Data from Analysis........................................................50
10.2.8
Handling of Dropouts and Missing Data............................................50
10.2.9
Interim Analysis................................................................................50
10.2.10 Other Analyses..................................................................................50
11 STUDY GOVERNANCE CONSIDERATIONS...........................................................50
11.1 Quality Control..................................................................................................50
11.2 Quality Assurance..............................................................................................51
11.3 Regulatory and Ethical Considerations...............................................................52
11.3.1
Ethics Committee...............................................................................52
11.3.2
Ethical Conduct of the Study..............................................................52
11.3.3
Subject Information and Consent.......................................................52
 
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11.3.4
Subject Recruitment...........................................................................53
11.3.5
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP...........................................................................................53
11.4 Posting of Information on Publicly Available Clinical Trial Registers................53
11.5 Provision of Study Results to Investigators........................................................53
11.6 Records Retention..............................................................................................54
11.7 Conditions for Terminating the Study................................................................55
11.8 Definition of Study End/ End of Study...............................................................55
12 REFERENCES.............................................................................................................55
13 APPENDIX..................................................................................................................57
13.1 Appendix I –Instructions...................................................................................57
13.2 Appendix II -Abbreviations..............................................................................58
 
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List of tables
Table 1-1
Schedule of Activities..........................................................................8
Table 2-1
Study objectives and endpoints..........................................................13
Table 13-1
Abbreviations....................................................................................58
 
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SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  
The investigator may schedule visits (unplanned visits) in addition to those listed on the 
schedule of activities, in order to conduct evaluations or assessments required to protect the 
well-being of the subject.
Table 1-1
Schedule of Activities
Procedure/Assessment
Screening
Acclimatization period 2-6weeks
Study Period
End of 
Treatment
Visit1
Visit 2
Day 1
Baseline
Visit 3
Day 29±3
Visit 4
Day 57±3
Informed consent
X
Demographics, Ethnicity
X
Medical History,Current Medications
X
Concomitant Medications
X
X
X
Review of Subjects Current Oral Care Products to Confirm 
They Don’t Contain any Anti-sensitivity Ingredients
X
Urine Pregnancy Test in Female Subjects of Childbearing 
Potential
X
OST Examination
X
X 
X
X
OHT Examination 
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
Inclusion/Exclusion Criteria
X
X2
Subject Eligibility
X
X
Dispense Acclimatization Dentifrice, Toothbrush, Diary and 
Timer3
X
Supervised Brushing with Acclimatization Dentifrice4
X
Return Acclimatization Dentifrice, Toothbrush, Diary
X
Subject Adherenceand Continuance
X 
X
X
Tactile Assessment (Yeaple Probe)5
X
X
X
Evaporative Air Assessment (Schiff Sensitivity Score)6
X
X
X
Identify Two Test Teeth
X
Stratification and Randomization 
X
Dispense Randomized Dentifrice, Toothbrush, Diary and Timer7
X
X
Supervised Brushing with Allocated Dentifrice4
X 
X
Subjects Return Study Suppliesto Site
X
X
 
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Procedure/Assessment
Screening
Acclimatization 
period 2-6
weeks
Study Period
End of 
Treatment
Visit1
Visit 2
Day 1
Baseline
Visit 3
Day 29±3
Visit 4
Day 57±3
Visual Compliance Check of Returned Study Dentifrice and 
Review of Subject Diary
X 
X
X
Adverse Events8
X
X 
X
X
Study Conclusion
X
Abbreviations: OST = Oral Soft Tissue; OHT = Oral Hard Tissue; EAR = Erosion, Abrasion, Recession; MGI = Modified Gingival 
Index.
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. AtScreening, 
maximum force for tactile = 20g.
2. Inclusion criteria 6dand exclusion criteria 13b.
3. Subject is instructed to bring all supplies back to next visit.
4. Study supplies to be returned to subject(for use at home)after supervised brushing.
5. AtBaseline, maximum force = 20g., at all subsequent visits maximum force = 80g.
6. Evaporative air assessment to follow tactile assessment; minimum 5 minutes time lapse between the two assessment types for tooth 
recovery. 
7. Subject is instructed to bring all supplies backto subsequent visits for compliance checks.Study supplies to be returned to subject after 
supervised brushing.At the Week 4 visit subjects will be re-dispensed with a new diary and new tubes of their allocated dentifrice prior 
to conducting their supervised brushing.
8. Any serious adverse event assessed as related to study participation that occurs subsequent to the signing of informed consent and 
any adverse event that occurs subsequent to the first dose of the acclimatization dentifrice will be recorded.
 
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1
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, 1987].  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 depolarizationor 
dentinal tubule occlusion. Nerve depolarising agents, typically potassium salts, generally 
require a period of use (for example, 14 to 28 days) before theirbenefit is established.The 
delivery of potassium ions to the dentine-pulp junction (odontoblastic layer) viadentinal 
tubules is believed to result in depolarisation of the afferent nerve membrane thereby blocking 
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 (SnF
2) 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. More recently Proctor and Gamble (P&G) and 
GSKCH have marketed SnF2-containing dentifrices indicated for DH relief, with published 
evidence demonstratinglongitudinalclinical efficacy [Ni, 2011; Parkinson, 2011; Makin, 
2013].In this study the efficacy of an experimental formulation containing 0.454% w/w SnF
2
will be compared to a negative control dentifriceand aChinesemarketed positive control 
dentifrice (Crest 7-Effects Strengthen Dental Enamel) for the relief of DH pain.
1.1
Mechanism of Action/Indication
Stannous fluoride is adentine tubule occluding agent that is being investigated in subjects 
with DH. 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].
 
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1.2
Background and Rationale
1.2.1
Justification on the Requirement to Conduct the Study
A similarly designed randomized, examiner-blind, two treatment arm parallel group DH study 
was previously conducted in a Chinese population [GSKCH Study 205794]. The results of 
this study demonstrated a statistically significant reduction in DH for Schiff sensitivity score 
for the experimental product containing SnF2compared to a regular fluoride dentifrice, but 
failed to demonstrate a statistically significant greater reduction in tactile threshold. Given 
that a number of successful 8 week DH studies have been conducted on SnF2containing 
dentifrices by GSKCH and competitors,there is a need to repeat this study in a Chinese 
population to demonstrate statistically significant improvements in both sensitivity measures 
that meet the Chinese Ministry of Health guidelines [Ministry of Health (China), 2010].
1.2.2
Study Design and Dose Rational 
A randomized, examiner-blind, parallel group design is a recognized approach for providing 
evidence of the clinical effectiveness 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].
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 (desensitizing), 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]. 
One of the eligibility criteria at Screening in earlier DH studies was subject response to
evaporative air sensitivity. In this study a qualifying response to a tactile stimulus will be 
included followed by a qualifying air blast on all teeth qualifying for tactile. 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 two test 
teeth selected at Baseline must be selected from those teeth eligible for both Schiff and tactile 
at Screening.
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]. Giventhat 
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 why both tactile 
 
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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, but will also enable more 
data to be gathered to understand the disparate response between the different stimuli that has 
been seen in previous studies. 
Post-randomization, the two selected test teeth will be assessed using each of the clinical 
efficacy assessments. The selection of two ‘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 to enable the treatment groups to be 
balanced in terms of the subject’s sensitivity severity.
The dosage regimen of twice daily treatment (morning and evening) brushing will be the same 
for all subjects, and has been selectedbased on widely recommended oral hygiene practice, 
and typical consumer habit.
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 as to the treatment the subject receives, but 
the products under test must be identical in every way (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 studyparticipation [Leight, 2008]. To help 
minimise the potential impact of such ‘placebo’ and ‘no treatment’ effects, an acclimatization 
period of 2-6weeks will be included in this study from Screening, ahead of the Baseline 
assessments and randomization. During this period subjects will be provided with a 
toothbrush and a marketed, standard fluoride dentifrice to use in place of their regular oral 
hygiene products. Use of the acclimatization 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 consumer habit, during this period.
The proposed examiners will be clinically qualified and will have been trained and have 
experience in the clinicalassessments of DH, using both the Schiff sensitivity scale and a 
Yeaple probe.Tominimize assessment variability,the same examiner will be responsible for 
a givenclinical assessment from the Screening visit to the end of the study.
Complete information for this compound may be found in the single reference safety 
document (SRSD), which for this study is theSafety Statement.
 
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2
STUDY OBJECTIVES AND ENDPOINTS
Table 2-1
Study objectives and endpoints
Objectives
Endpoints
Efficacy
Primary
To compare the clinical efficacy of an 
experimental 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 an 
experimental 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 8 weeks.
Exploratory
To compare the clinical efficacy of an 
experimental 0.454% w/w 
SnF2 
dentifrice for the relief of DH, as elicited 
by an evaporative air stimulus (with 
Schiff sensitivity score), against a 
positive control dentifrice, when used 
twice daily for 4 and 8 weeks.
Change from Baseline in Schiff 
sensitivity score at 4 and 8 weeks.
To compare the clinical efficacy of an 
experimental 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 comparethe clinical efficacy of an 
experimental 0.454% 
w/w 
SnF2
dentifrice for the relief of DH, as elicited 
by a tactile stimulus (yeaple probe), 
against a negative control dentifrice, 
Change from Baseline in tactile 
thresholdat 4 weeks.
 
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Protocol Number 208153
Final 1.0 Clinical Protocol
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Page 14of 60
when used twice daily for 4 weeks.
To compare the clinical efficacy of an 
experimental
0.454% 
w/w 
SnF2
dentifrice for the relief of DH, as elicited 
by a tactile stimulus (yeaple probe), 
against a positive control dentifrice, 
when used twice daily for4 and 8 weeks.
Change from Baseline in tactile 
threshold at 4 and 8 weeks.
To compare the clinical efficacy of a
positive control dentifrice for the relief of 
DH, as elicited by a tactile stimulus 
(yeaple probe), against a negative control 
dentifrice, when used twice daily for 4 
and 8 weeks.
Change from Baseline in tactile 
threshold at 4 and 8 weeks.
To compare the clinical efficacy of a 
positive control dentifrice for the relief of 
DH, as elicited by anevaporative air 
stimulus (with Schiff sensitivity score)
against a negative control dentifrice, 
when used twice daily for 4 and 8 weeks.
Change from Baseline in Schiff 
sensitivity score 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
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,after 8 weeks of 
treatment. The difference should be viewed as clinically relevant in addition to being 
statistically significant
3
STUDY DESIGN AND SUBJECT POPULATION
This will be a single centre, randomized, controlled, examiner-blind, 3 treatment arm, parallel 
group design study, stratified by maximum baseline Schiff sensitivity score (of the two 
selected test teeth), with a treatment period of 8 weeks, to investigate the clinical effectiveness 
of an experimental SnF2dentifrice in the reduction of DH.DH will be assessed at Baseline, 
and after 4 and 8 weeks treatment.
The study will be conducted in healthy subjects with pre-existing self-reported and clinically 
diagnosed tooth sensitivity at Screening, in a Chinese population.A sufficient number of 
subjects will be screened to randomize approximately 180 subjects toensure 165 subjects 
complete the study.
 
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Stannous fluoride
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Final 1.0 Clinical Protocol
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Page 15of 60
The age range over which an individual can experience DH is wide (from early teens to 70s) 
[Fischer, 1992], with peak incidence known to occur between the ages of 20-40 years [Graf, 
1977; Flynn, 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 [Seltzer, 1975; Pashley, 2008].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 18-70selected for this study targets individuals suffering 
from tooth sensitivity which is most likely due to DH. This will facilitate recruitment and 
minimise inconvenience to older participants who may be more likely to be rejected at 
Screening.
An acclimatization period of 2-6weekswill be included in this study, given that 2weeks is 
understood to be an expected amount of time to minimize the potential for carry over effects 
from prior use of anti-sensitivity products.
In line with Chinese Ministry of Health guidelines [Ministry of Health (China), 2010]for the 
testing of functional dentifrices (desensitizing), a standard fluoride dentifricewith no specific 
anti-sensitivity, anti-gingivitis and anti-plaque activity (Chinese marketed Colgate Triple 
Protection) will be included as the negative control.A Chinese marketed positive control 
dentifrice with sensitivity benefits (Crest 7-Effects Strengthen Dental Enamel toothpaste, 
containing stannous chloride(SnCl
2)) will also be included in this study design as a 
benchmark of performance in the Chinese population.
4
SUBJECT SELECTION
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 nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol.  
4.1
Inclusion Criteria
Subject eligibility should be reviewed anddocumented by an appropriate member of the 
investigator’s study team before subjects are included in the study
.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consentindicating the subjecthas 
been informed of all pertinent aspects of the study before any assessment is performed.
2. Male and female subjects who, at the time of screening
, are between the ages of 18 and 70 
years, inclusive.
3. Subjects whoare willing and able to comply with scheduled visits, treatment plan,and 
other study procedures.
 
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4. Good general and mental health, in the opinion of the investigator or medically qualified 
designee.
5. Male subjects able to father children and female subjectsof childbearing potential and at 
risk for pregnancy must agree to use a highly effective method of contraception 
throughout the study and for at least 5 days after the last dose of assigned treatment, refer 
to Section 4.4.2 for guidance. Female subjects who are not of childbearing potential must 
meet requirements in Section 4.4.2.
6. The following oral and dental inclusions will apply at Screening (Visit 1):
a) Self-reported history of dentinal hypersensitivitylasting 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 Modified Gingival Index (MGI)score =0 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)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 evaporativeair assessment (Schiff sensitivity score ≥2). The 
two selected test teeth must have also qualified at Screeningfor this criteria.
Note: The Investigator will select two Test Teethfrom those which meet boththe tactile 
threshold andSchiff sensitivity score criteria, in addition to meeting all other criteria. Test 
Teethshould not be adjacent to each other and preferably in different quadrants.  
4.2
Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the study:
1. Subjects who are investigational site staff members directly involved in the conduct of 
the study and their family members, site staff members otherwise supervised by the 
investigator, or subjects who are GSK employees directly involved in the conduct of 
the study.
2. Participation inanother clinical study (including cosmetic studies), or receipt of an 
investigational drug within 30 days prior to the Screening visit and/or during study 
participation.
 
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Stannous fluoride
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3. Participation in another tooth desensitizing treatment study within 8 weeks of the 
Screening visit.
4. Acute or chronic medical or psychiatric condition that may increase the risk associated 
with study participation or investigational product administration or may interfere with 
the interpretation of study results and, in the judgment of the investigator, would make 
the subject inappropriate for entry into this study.
5. Pregnant female subjects.This will be confirmed verbally at Screening and confirmed 
by Urine pregnancy testing (carried out on all female subjects of child bearing 
potential)at the Baseline visit.
6. Breastfeeding female subjects.
7. Known or suspected intolerance or hypersensitivity to the study materials (or closely 
related compounds) or any of their stated ingredients. 
8. Recenthistory (within the last year) of alcohol or other substance abuse.
9. Unwilling or unable to comply with the lifestyle guidelines described in this protocol. 
10.Subjects who have previously been enrolled in this study. 
11.General oral and dental exclusions:
a) Dental prophylaxis within 4 weeks of Screening.
b) Tongue or lip piercing or presence of dental implants.
c) Gross periodontal disease, treatment of periodontal disease (including surgery) 
within 12 months of Screening, scaling or root planning within 3 months of 
Screening.
d) Teeth bleaching within 8 weeks of Screening.
e) Use of an over-the-counter (OTC) desensitizing product (eg. dentifrice) and/or 
professional desensitizing 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.
12.Specific dental exclusions for test teeth:
a) Sensitive tooth not expected to respond to treatment with an over-the-counter 
dentifrice in the opinion of the investigator.
b) Tooth with exposed 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. Sensitive teeth with 
contributingaetiologies other than erosion, abrasion or recession of exposed 
dentine.
c) Tooth with evidence of current or recent caries, or reported treatment of decay 
within 12 months of Screening.
13.Concomitant Medication:
a) Daily 
doses 
of 
medication/treatments 
or 
traditional 
herbal 
ingredients/treatments which, in the opinion of the investigator, could interfere 
 
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Stannous fluoride
Protocol Number 208153
Final 1.0 Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential
Template Version Effective: 22-Jun-2017
Page 18of 60
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.
b) Currently taking antibiotics or has taken antibiotics within 2 weeks of 
Screeningand/or Baseline.
c) Daily dose of a medication which, in the opinion of the investigator, is causing 
xerostomia.
d) Individuals who require antibiotic prophylaxis for dental procedures.
14.Any subject who, in the judgment of the investigator, should not participate in the 
study.
4.3
Randomization Criteria
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria.
4.4
Lifestyle Guidelines
For the duration of the study (Screening toLSLV):
Eligible subjects will be asked to stop using their regular oral care products 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 use any other oral care products (i.e., oral rinses, tongue 
cleaners, whitening/bleaching products, inter-dental brushes) other than those provided to 
themin this study.
Subjects will not be permitted to use any other dental products(other than those provided 
to themin this study), including home remedies, intended for treating sensitive teeth.
Subjects will not be permitted to chew gum.
Prior to study days (Baseline to Week 8):
Subjects will be asked to refrain from all oral hygiene procedures for at least 8 hoursin 
order to standardize oral hygiene practices.
4.4.1
Dietary and Alcohol Restrictions
Prior to study days (Baseline to Week 8):
 
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Subjects will be asked to refrain from eating and drinking for at least 4 hours.Before
each visit small sips of water will be allowed for the purpose of taking medication, but 
subjects will be asked to refrain from doing this 1 hour before attending the study site. 
Subjects will be requested to refrain from excessive alcohol consumption for 24 hours 
prior to the Baseline, Week 4 and Week 8 visits. If in the opinion of the Investigator the 
subject has consumed an excessive amount of alcohol prior to the visit, every effort will 
be made to reappoint them to the next day.If this is not possible then the subject should 
betreated as per Section 6.4.
4.4.2
Contraception
All male subjects and female subjects who are of childbearing potential and are sexually 
active and at risk for pregnancy must agree to use a highly effective method of contraception 
consistently and correctly for the duration of the active study period and for at least 5 days 
after the last dose of investigational product.The investigator or his or her designee, in 
consultation with the subject, will confirm that the subject will selectan appropriate method 
of contraception for the individual subject from the permitted list of contraception methods 
(see below) and instruct the subject in its consistent and correct use. Subjects need to affirm 
that they meet the criteria for the correct use of at least 1 of the selected methods of 
contraception. The investigator or his or her designee will discuss with the subject the need to 
use highly effective contraception consistently and correctly according to the schedule of 
activities and document such conversation in the subject’s chart.In addition, the investigator 
or his or her designee will instruct the subject to call immediately if the selected contraception 
method is discontinued or if pregnancy is known or suspected in the subject orthe subject’s 
partner. 
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (i.e., perfect use) 
and include the following:
1. Established use of oral, inserted, injected, transdermal, or implanted hormonal methods of 
contraception is allowed provided the subject plans to remain on the same treatment 
throughout the entire study and has been using that hormonal contraceptive for an 
adequate period of time to ensure effectiveness as deemed appropriate by the investigator.
2. Correctly placed copper-containing intrauterine device (IUD). 
3. Male condom or female condom used WITH a spermicide (i.e., foam, gel,film, cream, or 
suppository). For countries where spermicide is not available or condom plus spermicide 
is not accepted as highly effective contraception, this option is not appropriate.
4. Male sterilization with absence of sperm in the post-vasectomy ejaculate.
5. Bilateral tubal ligation / bilateral salpingectomyor bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label).
6. Female who meets the criteria for non-childbearing potential as described below.  
 
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Stannous fluoride
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Final 1.0 Clinical Protocol
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Female subjects of non-childbearing potential must meet at least one of the following 
criteria:
a. Achieved postmenopausal status, defined as follows: cessation of regular 
menses for at least 12consecutive months with no alternative pathological or 
physiological cause; and have a serum follicle-stimulating hormone (FSH) 
level confirming the post-menopausal state;  
b. Have undergone a documented hysterectomy and/or bilateral oophorectomy;
c. Have medically confirmed ovarian failure.
All other female subjects (including females with tubal ligations) willbe considered to be 
of childbearing potential.
4.5
Screen Failures
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not subsequently randomized.In order 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, and any serious adverse events
(SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) may not
be re-screened.
4.6
Sponsor’s Qualified Medical Personnel
The contact information for the sponsor
's appropriately qualified medical/dental personnel for 
the study is documented in thestudy contact listlocated in thestudy file.
The contact number can be used by investigational staff if they are seeking advice on 
medical/dental questions or problems; however, it should be used only in the event that the 
established communication pathways between the investigational site and thestudy team are 
not available. It is therefore intended to augment, but not replace, the established 
communication pathways between the investigational site and the study team for advice on 
medical/dental questions or problems that may arise during the study.The contact number is 
not intended for use by the subject directly, and if a subject calls that number, he or she will 
be directed back to the investigational site.
To facilitate access to appropriately qualified medical/dental personnel on study-related
medical/dental questions or problems, subjects are provided with a contact card.The contact 
card contains, at a minimum, protocol identifiers, subject study numbers, contact information 
for the investigational site, and contact details in the event thatthe investigational site staff 
cannot be reached to provide advice on a medical question or problem identified from the 
subject’s healthcare professional other than the investigator.
 
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Stannous fluoride
Protocol Number 208153
Final 1.0 Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential
Template Version Effective: 22-Jun-2017
Page 21of 60
5
STUDY TREATMENTS
5.1
Blinding and Allocation to Treatment/Randomization
This study is described as examiner blind, however, to minimize the potential of unblinding
the study statistician, other employees of the sponsor, and vendors acting on behalf of the 
sponsor, whomay influence study outcomes are blinded to the product allocation of subjects.
The examiner will be blinded to the treatment received. To ensure the examinerremains 
blinded throughout the study, the examiner is not permitted in the room whilst product is 
dispensed, and subjects will be asked not to remove study products from their bags outside of 
the dispensing room and until they are home. In addition, subjects shouldbe treated in a 
separate area. The dispensing staff will not be involved in any efficacy assessments during the 
study.
InVentiv Healthwill create the randomization schedules and provide to Global Clinical 
Supplies (GCS). GCS will print the randomization schedules and supply the clinical study site 
with two versions of the randomization schedule, each in a sealed envelope and clearly 
marked as either “For Dispensing” or “Emergency Use Only”. 
The “For Dispensing” schedule will contain the list of randomization numbers only and will 
not include any coded description, just a letter A, B or C.
The ‘Emergency Use Only’ randomization schedule will only be removed from the sealed 
envelope in an emergency situation. This schedule will have a randomization number 
followed by the letter A, B or C. The schedule will have a footnote with a key for A, B and C 
identifying the three treatments arms. However, to maintain the blinding of the study as far as 
possible, all treatment allocations for all randomization numbers on this randomization 
schedule will be masked with scratch-off panels. 
Subjects will bestratified according to their maximum baseline Schiff sensitivity score of the 
two selected teeth (sensitivity score of 2 or 3) with randomization numbers within each 
stratum assigned 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 two selected test teeth.
Stratum 2: Maximum Schiff=3. These are subjects with the maximum baseline Schiff 
sensitivity score of 3 for the two selected test teeth.
In accordance with the randomization numbers, the subject will receive the study treatment 
assigned to the corresponding randomization number.
5.2
Breaking the Blind
At the initiation of the study, the study site will be instructed on the method for breaking the 
blind. The method will be a manual process, wherebyonly scratch-off panels will be removed 
 
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for subjectsthat require unblinding.Blinding codes should be broken only in emergency 
situations for reasons of subject safety. Whenever possible, the investigator or sub-
investigator should consult with a member of the study team prior to breaking the blind unless 
the delay would endanger the subject’s health. When the blinding code is broken, the reason 
must be fully documented and entered in the CRF.
Any AE or SAEassociated with breaking the blind must be recorded and reported as specified 
in this protocol. The study site is required to inform the EC if the blind is broken. 
5.3 
Subject Compliance
Subjects will be asked to bring all tubes of study dentifrice to each study visit for a visual 
compliance check of each product.Any suspected product over use, or under use will be 
documented in the CRF and subjects will be re-educated on the correct dosing amount and 
instructions.
Subjects will be provided with a diary at Screening and again at the Baselineand Week 4 
visits,which they will return at their following visit to the study site. The number of missed or 
extra brushings will be recorded in the CRF.  
5.4
Investigational Product Supplies
The following study products will be supplied by GCS, GSKCH: 
Testproduct:Experimental dentifrice containing 0.454% SnF
2and 0.072% NaF
(1450ppm fluoride in total); 
.
Control product 1:Colgate Triple Protection dentifrice containing 1400ppm fluoride 
as sodium monofluorophosphate (SMFP); Chinese Marketplace.
Controlproduct 2: Crest 7-Effects Strengthen Dental Enamel dentifrice containing 
SnCl2 and 0.15% NaF(1450ppm fluoride in total); Chinese marketplace.
Other items to be supplied by the Clinical Supplies Department, GSKCH:
Acclimatization dentifrice: Colgate Strengthen Fresh Dentifrice containing 1400ppm 
fluoride as SMFP(Chinese Marketplace).
Aquafresh Clean Control Toothbrush (UK market place).
Countdown timers.
Subject diaries (including product usage instructions) willbe supplied by GSKCH China.
Urine pregnancy test kits (to test for pregnancy on female subjects of child bearing potential) 
will be provided by the site.
 
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Stannous fluoride
Protocol Number 208153
Final 1.0 Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential
Template Version Effective: 22-Jun-2017
Page 23of 60
5.4.1
Dosage Form and Packaging
All investigational dentifrices are intended for oral use, and will be administered as detailed in 
Section 5.5.
The controland acclimatizationdentifrices (Colgate Triple Protection, Crest 7-Effectsand 
Colgate Strengthen Fresh)will be sourced from the Chinesemarket. The test dentifrice will be
manufactured and filled into whitealuminum barrier laminate(ABL)tubes and supplied by 
GSK CH. 
The test and controldentifrices 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 acclimatizationdentifrice will be supplied in its commercial 
packaging with a study label affixed. The contents of the dentifrice labelswill be in 
accordance with all applicable regulatory requirements and will be the responsibility ofGCS,
GSKCH.Each subject will receive a sufficient number ofacclimatization and investigational 
dentifricetubes to cover usage during the treatment phase.The investigational dentifrice will 
be dispensed at the Baseline and Week 4 visits.
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.
5.4.2
Preparation and Dispensing 
The examiner will be blinded to the treatment received. To ensure the examiner remains 
blinded throughout the study, the examiner will not be permitted in the room where the test 
products are stored or dispensed. The product dispensing area will be separate from the 
subjects’ examination area. All study dentifrices will be dispensed by qualified site personnel
who are not involved in any study efficacy assessments.The investigational products will be 
dispensed in blinded fashion to the subject.A second member of site personnel will verify that 
the correct dentifrice has been dispensed to each subject. A record of the product dispensed to 
each subject will be recorded in a treatment dispensing log, and assigned against each subject 
number.
5.5
Administration
A record of the administration of the study products will be kept using a dispensing log and 
the CRF.
Subjects will be instructed to self-administer their investigational product 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 
the date and time of each brushing occasion during the treatment period(Appendix I). 
 
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Subjects will also be asked to note any missed brushings, and to use the diary to record any 
illness, medication or significant changes 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) at the Screening, Baseline and Week 4 visits,and subjects 
will conduct a supervised brushing. Subjects will brush in their usual manner with a full brush 
head of their assigned dentifrice for 1 timed minute and expectorate.
5.5.1
Medication Errors
Medication errors may result, in this study, from the administration or consumption of: 
the wrong product,
by the wrong subject, 
at the wrong time, 
or the wrong dosage amount
Such medication errors occurring to a study participant are to be captured in thesubject diary 
and later transcribed by the site into theCRF. 
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:
Medication errors involving subject exposure to the investigational product;
Potential medication errors or uses outside of what is foreseen in the protocol that 
do or do not involve the participating subject.
Whether or not a medication error is accompanied by an AE, as determined by the 
investigator, the medication error and, if applicable, any associated AE(s) is captured on an 
AECRF page.
5.6
Investigational Product Storage
The investigator, or an approved representative, will ensure that all investigational products 
including any comparator, marketed and acclimatization products arestored in a secured area 
with controlled access under required storage conditions and in accordance with applicable 
regulatory requirements and product label.
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products). This should be 
captured from the time of investigational productreceipt 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. 
 
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Stannous fluoride
Protocol Number 208153
Final 1.0 Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential
Template Version Effective: 22-Jun-2017
Page 25of 60
Any excursions from the product-label storage conditions should be reported upon discovery.  
The site should actively pursue options for returning the product to the storage conditions as 
described in the labeling, as soon as possible. Deviations from the storage requirements, 
including any actions taken, must be documented and reported to the Sponsor.
Once an excursion is identified, the investigational product must be quarantined and not used 
until the Sponsor provides documentation of permission to use the investigational product. It 
will not be considered a protocol deviation if the sponsor approves the use of the 
investigational product after the temperature excursion.Use of the investigational product 
prior to sponsor approval will be considered a protocol deviation. Specific details regarding 
information the site should report for each excursion will be provided to the site. 
Site staff will instruct subjects on the proper storage requirements for take-home 
investigational products. 
5.7
Investigational Product Accountability
All products supplied are for use only in this clinical study and should not be used for any 
other purpose.
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 treatments should be stored according to the instructions specified on the 
treatment labels. Clinical supplies are to be dispensed only in accordance with the protocol.
The clinical study site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies. All investigational product will be 
accounted for using an investigational product accountability form/record. 
At the end of the study subjects will return all study products back to the clinical study site, 
which will be verified by the monitor. Study product supplies will then be either collected by 
the study monitor or returned by the investigator or designee to GCS, GSK CH,or designated 
vendor.
The inventory must be available for inspection by the study monitor during the study. 
Monitoring of treatments accountability will be performed by the field monitor during site 
visits and at the completion of the study.
5.7.1
Destruction of Investigational Product Supplies 
At the conclusion of the study, the Principal Investigator or an appropriate designee, and a 
representative of GSK CH will inventory all used and unused investigational study treatment. 
The study treatment inventory record for returned study treatment will then be completed. All 
investigationaland acclimatizationdentifrices for this clinical study (empty containers), as 
well as all unused study product will be returned to the GSK CHdesignated vendor using the 
return instructions provided.
 
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Stannous fluoride
Protocol Number 208153
Final 1.0 Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential
Template Version Effective: 22-Jun-2017
Page 26of 60
5.8
Concomitant Treatment(s)
Details of any relevantdental, medical or surgical history (within the last yearprior to 
Screening),including allergies or drugsensitivity, will be recorded in the CRF.
All concomitant treatments taken during the study must be recorded with indication, unit 
dose, daily dose, and start and stop dates of administration.All subjects will bequestioned 
about concomitant treatment at each clinic visit.
Treatments taken within 30 days before the first dose of acclimatization product will be 
documented as a prior treatment. Treatments taken after the first dose of acclimatization 
product will bedocumented as concomitant treatments.
During the entire study (Screening -LSLV):
Subjects who enter the study will be requested to delay having any non-emergency, 
elective dental treatment until after study completion (including prophylaxis).
If concomitant medications/treatments ortraditional herbal ingredients/treatments are 
used during the study, their identity, as well as their dosage and frequency, start and stop 
dates must be reported to the Investigator and recorded in the Case Report Form(CRF).
Should a randomised subject start a course of treatment during the study which includes 
the daily or intermittent use of an analgesic, the identity of that medication/treatment, 
dosage and frequency and start date will be recorded. The subject willnot be withdrawn.  
Should a subject take an analgesic within 8 hoursof a scheduled visit, every effort will 
be made to reappoint them to the next day.  If this is not possible then the subject should 
be treated as per Section 6.4.
Subjects should notparticipate in another clinical study (including cosmetic studies),or 
be in receipt of an investigational drug.
6
STUDY PROCEDURES
6.1
Screening-Visit 1(FSFV)
The following procedures/assessmentswill take place in the order listed below(where 
possible)and recorded in the CRF:
Obtain written informed consent.
Collect demographyand ethnicity. The following demographic parameters will be 
captured by the Investigator or designee: year of birth, gender and race.
Obtain medical history, including history of illegal drug, alcohol and tobacco use. 
Obtain complete medication history of all prescription or nonprescription drugs, and 
dietary and herbal supplements taken within 30 daysprior tothe Screening visit.
Review of the oral care products the subject is currently using to confirmthatthey do 
not contain any ingredients intended for treating sensitive teeth. Subjects will be 
 
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Protocol Number 208153
Final 1.0 Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential
Template Version Effective: 22-Jun-2017
Page 27of 60
asked to bring these to the clinical study site to enable a member of the clinical study
staffto check the ingredients list.
Full oral soft tissue (OST)examination conducted by a qualified dental examiner.
Full oral hard tissue (OHT) examination conducted by a qualified dental examiner.
Eligible teeth assessments (dentition exclusions, Erosion, Abrasion, Recession (EAR), 
modified gingival index (MGI), tooth mobility) conducted by a qualified dental 
examiner.All teeth that satisfy these criteriawill thenbe assessed for the following:
i.
Qualifying tactile threshold conducted by a qualified dental examiner. To ease 
subject flow, scores may be recorded on a score sheet and then transcribed 
into the CRF.
ii.
Qualifying evaporative air sensitivityof all teeth qualifying on tactile 
threshold (≤20g), conducted by a qualified dental examiner.The examiner 
should allow at least 5 minutes between completion of all tactile assessments 
and thenstart the evaporative air assessment.To ease subject flow, scores may 
be recorded on a score sheet and then transcribed into the CRF.
Review Inclusion and Exclusion criteria.Pregnancy status will be confirmed verbally 
by the subject.
Confirmation of subject eligibility.
Dispensation of acclimatization dentifrice, toothbrush, diary with usage instructions 
and timer.
Supervised brushing with acclimatization dentifrice.Site staff must observe subjects 
for the entire dosing and brushing period.
Adverse Events (AEs) will be documented from completion of the supervised 
brushing with acclimatisation dentifrice.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 instructed on the use of the 
Lifestyle Guidelines(Section 4.4) and Concomitant Treatment(s)(Section 5.8) 
sections of the protocol.
6.2
Study Period
6.2.1
Day1;Baseline-Visit 2
Subjects will be admitted to the clinicalstudysite 2-6weeks after the Screening visit,having 
refrained from eating or drinking for at least 4hours, and from all oral hygiene procedures for 
at least 8 hours. Prior to randomization the following procedures will be completed in the 
following order(where possible), and recorded in the CRF:
Review of concomitant medications, AEs. 
 
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Urine pregnancy testing will be carried out on all female subjects of child bearing 
potential. 
Return of acclimatization dentifrice, toothbrush and diary. 
Review of completed diary and visual check of acclimatization dentifrice by study site 
staff to determine usage compliance.Any potential dentifrice underuse or overuse will be 
noted in the CRF and subjects will be re-educated on the correct dose amount.
Confirmation of subjectadherenceand continuance. 
Full OST examination conducted by a medically qualified dental examiner.
Tactile sensitivity assessment of eligible teeth identified at screening (all 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)). Assessments will be carried out by a qualified dental examiner.To ease subject 
flow, scores may be recorded on a paper score sheet andthen transcribed into the CRF.
Evaporative air sensitivity assessment of eligible teeth thatmeet the tactile sensitivity at 
Baseline.Assessments will be carried out by a qualified dental examiner.The examiner 
should allow at least 5 minutes between completion of all tactile assessments and then
start the evaporative air assessment.To ease subject flow, scores may be recorded on a 
score sheet and then transcribed into the CRF.
Inclusion criteria 6d and exclusion criteria 13b.
Selection of two test teethfor all subsequent assessmentsby a qualified dental examiner.
Confirmation of subject eligibility.
Stratification and randomization.
Following randomization,the following procedures/assessments will be completed in the 
following order(where possible)and recorded in the CRF, unless stated otherwise:
Dispensation of allocated study dentifrice, toothbrush and diary, usage instructions.
Supervised brushing with allocated studydentifrice.Site staff must observe subjects for 
the entire dosing and brushing period.
AEs captured. Assess symptoms by spontaneous reporting of adverse events and by 
asking the subjects to respond to a non-leading question such as “How do you feel?”
6.2.2
Day 29 (±3days)-Visit 3
Subjects will be admitted to the clinical site 4 weeks (±3days) after the Baseline visit,having 
refrained from eating or drinking for at least 4 hours, and from all oral hygiene procedures for 
at least 8 hours.The following procedures will be completed after admission to the clinical 
study site, in the following order(where possible), and recorded in the CRF:
Review of concomitant medications and AEs. 
Return of study dentifrice, toothbrushand diary. 
 
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Review of completed diary and visual check of dentifrice by study site staff to determine 
usage compliance.Any potential dentifrice underuse or overuse will be noted in the CRF 
and subjects will be re-educated on the correct dose amount.
Confirmation of subject adherence and continuance. 
Full OST examination conducted by a qualified dental examiner.
Tactile sensitivity assessment of the two selected test teethby a qualified dental 
examiner.To ease subject flow, scores may be recorded on a score sheet and then 
transcribed into the CRF.
Evaporative air sensitivity assessmentof the two selected test teeth by a qualified dental 
examiner.The examiner should allow at least 5 minutes between completion of all tactile 
assessments and thenstart the evaporative air assessment.To ease subject flow, scores 
may be recorded on a score sheet and then transcribed into the CRF.
Return study products to subject.Subjects will also be re-dispensed new tubes of their 
allocated dentifrice. 
Supervised brushing by subject with allocated study dentifrice after all assessments
completed.Site staff must observesubjects for the entire dosing and brushing period.
AEs captured. Assess symptoms by spontaneous reporting of adverse events and by 
asking the subjects to respond to a non-leading question such as “How do you feel?”
6.2.3
Day 57 (±3 days) -Visit 4
Subjects will be admitted to the clinical site 8weeks (±3days) after the Baseline visit,having 
refrained from eating or drinking for at least 4 hours, and from all oral hygiene procedures for 
at least 8 hours. The following procedures will be completed after admission to the clinical 
study site, in the following order(where possible), and recorded in the CRF:
Review of concomitant medications and AEs. 
Return of study dentifrice, toothbrushand diary. 
Review of completed diary and visual check of dentifrice by study site staff to determine 
usage compliance.Any potential dentifrice underuse or overuse will be noted in the CRF 
and subjects will be re-educated on the correct dose amount.
Confirmation of subject adherence and continuance. 
Full OST examination conducted by a qualified dental examiner.
Tactile sensitivity assessment of the two selected test teethby a qualified dental 
examiner.To ease subject flow, scores may be recorded on a score sheet and then 
transcribed into the CRF.
Evaporative air sensitivity assessmentof the two selected test teeth by a qualified dental 
examiner.The examiner should allow at least 5 minutes between completion of all tactile 
assessments and thenstart the evaporative air assessment.To ease subject flow, scores 
may be recorded on a score sheet and then transcribed into the CRF.
 
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AEs captured. Assess symptoms by spontaneous reporting of adverse events and by 
asking the subjects to respond to a non-leading question such as “How do you feel?”. AEs 
will be recorded for 5 days after last treatment.Subjects will be asked to contact the site if 
they feel unwell in the 5 days following their last visit.
Study conclusion.
6.3
Follow-up Phone Call
Where applicable, the clinical study site will contact any subject(s)with AEsand in some 
circumstances request that theyreturn for a final follow-up visit. If deemed to be required,an 
OST may be conducted by a qualified dental examiner at this visit.
6.4
Subject Withdrawal
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety or, behavioral 
reasons, or the inability of the subject to comply with the protocol-required schedule of study 
visits or procedures at a given studysite.  
The following circumstances require discontinuation of study treatment and/or premature 
subject withdrawal:
Protocol violation that may impact the outcome of the subject’s safety
Withdrawal of informed consent
Subject lost to follow-up 
Unblindingof the subject 
Pregnancy
Death
If a subject is discontinued or prematurely withdraws from the study, reasons for 
discontinuation or withdrawal and associated date must be documented in the relevant 
section(s)of the CRF. 
If a subject does not return fora scheduled visit, every effort should be made to contact the 
subject. The Investigator or clinical study site staff should attempt to contact the subject twice.
After two attempts, clinical study site staffmust send a registered letter.If no response is 
received from the subject, the subject will beconsidered lost to follow up. All attempts to 
contact the subject and information received during contact attempts must be documented in 
theCRF.In any circumstance, every effort should be made to documentsubject outcome, if 
possible. The investigator should inquire about the reason for withdrawal, and request that the 
subject return all used and unused investigational productsrequest and where applicable, 
 
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Protocol Number 208153
Final 1.0 Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential
Template Version Effective: 22-Jun-2017
Page 31of 60
return for a final visit and follow-up with the subject regarding any unresolved adverse events 
(AEs).
It may be appropriate for the subject to return to the clinical site for final safety assessments. 
Subjects shouldbe questioned regarding their reason for withdrawal. An OST may be 
conducted at the investigator’s discretion.
7
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 perform 
the test.In these cases, the investigator must take all steps necessary to ensure the safety and 
well-being of the subject. When a protocol-required test cannot be performed, the investigator 
will document thereason for the missed test 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 
study team must be informed of these incidents in a timely manner.
7.1
Screening
7.1.1
InformedConsent
The investigator, or designee, must obtain written (signed and dated by the subject) informed 
consent from each subject participating in this study after adequate explanation of the aims, 
methods, objectives, and potential hazards of the study.
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 written consent will be provided by the investigator or by GSKCH.  The 
investigator, or designee, should sign and date the consent form to confirm that the consent 
process was completed correctly.  The subject, will be provided with a copy of their signed 
and dated consent form and any other written information which they should be instructed to 
retain.
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. Subjects will be 
provided with a copy of the signed and dated amended consent form.
7.1.2
Eligible Tooth Assessments
Eligible tooth assessment will include an OHTexaminationto evaluate dentition exclusions; 
erosion, abrasion and/or gingival recession; modified gingival index; tooth mobility and 
qualifying tactile and evaporative air assessments. Assessments will be carried out by the 
 
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Investigator or qualified designee against the inclusion/exclusion criteria and recorded in the 
CRF.
7.1.2.1 Erosion, Abrasion and Recession (EAR) assessment
The presence of cervical erosion, abrasion and/or gingival recession(EAR)[Addy, 2000]will 
be determined onthe facial surfaces of individual teeth. Teeth which donot meet any of the 
general dentition exclusion criteria and the specific dentition exclusion criteria for eligible 
teeth will be assessed for EAR.
7.1.2.2 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) of teeth exhibiting facial cervical erosion, abrasion and/or recession. MGI = 
0 is required for eligible teeth.
Score
Description
0 
Absence ofinflammation
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.
7.1.2.3 Tooth Mobility Assessment
The clinical mobility assessment will only be performed on teeth exhibiting facial cervical 
EAR and with a MGI = 0. 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
Mobilityof 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.
7.1.2.4 Qualifying Tactile Threshold
Only teeth that do not meet any of the dentition exclusion criteria and meet the EAR, MGI
andmobilitycriteriawill be tested. The same qualified dental examiner will be used for all
tactile assessmentsthroughout the duration of the study.
Prior to the conduct of any tactile assessments the yeaple probe must be calibrated (Section 
7.2.1.1). This assessment will be made by placing the probe tip perpendicularto the buccal 
surface and movingin a slow motion whilebeingdrawn across the tooth surface in order to 
ensure application of the stimulus across the sensitive area of the exposed dentine. After each 
challenge, 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" ifthey 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 gram setting, which elicits the two consecutive “yes” 
responses, will be recorded as the thresholdon the score sheet.Where scores are recorded on 
a score sheet they must be transcribed into the CRF at a later point in time.At this visit the 
upper test limit is 20g.If no pain response is found, the threshold will be recorded as >20 g 
and the tooth will be disqualifiedfrom further testing. 
7.1.2.5 Qualifying Evaporative Air Sensitivity
Evaporative air sensitivitywill be assessed a minimum of 5 minutes after the tactile threshold 
stimulus. The qualified dental examiner will assess evaporative air sensitivityby a simple air 
blast on the facial surface of all teeth that do not meet any of the dentition exclusion criteria 
and meet the EAR, MGI, mobilityand tactile threshold criteria.The same dental examiner 
will be used for all evaporative air assessments throughout the duration of the study.This 
assessment is made by directing a one second application of air from a standard dental syringe 
held perpendicular to thetooth surface approximately 1-2mm coronal to the free gingival 
margin and from a distance of approximately 1cm. The examiner should take appropriate 
measures to isolate the tooth surface to prevent stimulation of adjacent teeth or surrounding 
soft tissue.
Response to this stimulus willbe evaluated using the Schiff sensitivity scale(Section 7.2.2.1). 
In order for a tooth to qualify it must have a Schiff score ≥2. The qualifying score will be 
recordedon the score sheet.Where scores are recorded on a score sheet they must be 
 
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transcribed into the CRF at a later point in time.If no pain response is found, the score will be 
recorded as <2 andthe tooth will be disqualified from further testing.
7.2
Efficacy
The following efficacy assessments will be performed at times defined in the Study 
Procedures(Section 6) section of this protocol.  
7.2.1
TactileSensitivityAssessment (Yeaple probe)
Tactile assessments will be performed by a single trained examiner.The same qualified dental 
examiner will be used for all tactile assessments throughout the duration of the study.Prior to 
the conduct of any tactile assessments the yeaple probe must be calibrated (Section 7.2.1.1).
This assessment will be made by placing the probe tip perpendicularto the buccal surface and 
movingin a slow motion while beingdrawn across thetooth surface in order to ensure 
application of the stimulus across the sensitive area of the exposed dentine. After each 
challenge, 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 asnecessary, that they will feel pressure but to only respond "yes" ifthey feel 
pain or discomfort. Testing shall begin at 10g and increase by 10g with each successive 
challenge until a "yes" response is recorded. The force setting which elicited the “yes”
response will be repeated. If a second "yes" is not obtained, the force setting will be increased 
by 10g and continue until a force is found which elicits two consecutive "yes" responses.The 
gram setting, which elicits the two consecutive “yes” responses, will be recorded as the 
threshold.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 nextstep in the upward 
direction. If no sensitivity is found below the session maximum, the tooth is disqualified from 
further testing.
At Baseline (Visit 2) all teeth that qualified for evaporative air sensitivity at Screening will be 
tested; 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. 
At Visits 3 and4 the tactile assessmentswill be conducted as described on the two selected 
test teeth only, the upper force setting will be 80g.If no sensitivity is found, the threshold will 
be recorded as >80g.
The recording/calibration assistant/examiner will make adjustments and record the 
micro-amperage force setting and subject
's responses onto the source document. The assistant 
will not give verbal cues to the examiner (the individual applying the probe tip to the tooth) 
other than when it is okay to proceed as this may bias the subject
's response. For example, if 
the assistant feels that the subject did not give a true response, they may then elect to repeat 
 
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the same force settingwithout telling the examiner. In this respect the examiner is also 
blinded, to avoid investigator bias. Since this places more responsibility on the assistant, it is 
imperative that the assistant be well trained in this procedure.It is also possible that the 
investigator may be unsure of the reliability of the subject
's response. In this case, the 
investigator may then 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).
7.2.1.1 Calibration of the Yeaple Probe
The Yeaple probe will be calibrated before use on each day subjects are assessed. The 
microamp settings will vary from day to day (partly due to battery power consumption), but 
the difference should not be significant. Thus, previous probe settings will serve as a guide.  
Calibration should start at the lowest microamp setting and then increase.
The proceduredescribedbelow ispreferred; however other comparable procedures may be 
acceptable.
The Yeaple probe is fixed to a clamp attached to a ring stand so that the probe tip is vertical. 
A small paper cup attached with cotton thread is balanced over the end of the Yeaple probe, 
without the probe tripping. The probe dial is set to the microamp setting and water is fed into 
the paper cup using a dropper until the probe trips. The gram setting is recorded and the 
Yeaple probe reset to the next microamp value. The procedure is repeated until data has been 
collected to more than 80 grams. 
The data are plotted and the points connected with line segments in order tointerpolate the 
micro-amp values equivalent to 10, 20, 30, 40, 50, 60, 70 and 80 grams. This calibration 
should be repeated three times, and the average of the three used for the day’s settings.
The settings will be recorded on the Yeapleprobe calibration record. This form must also be 
dated and initialled by whoever performs the calibration. For convenience a separate form 
should be used for each probe (record the unit’s serial number on the form). This record will 
serve as the guide for the force setting for that day’s examinations.
7.2.2
Evaporative Air Sensitivity Assessment 
This assessment will be conducted by a single examiner for all subjects at each visit by 
directing a maximum one second application of air from a dental air syringe to the exposed 
dentine surface from a distance of approximately 1 cm. The examiner should take appropriate 
measures to isolate the test tooth surface in order to prevent stimulus exposure to adjacent 
tooth or surrounding soft tissue. Response to this stimulus will be evaluated using the Schiff 
sensitivity scale.The evaporative air stimulus (with Schiff sensitivity score) should follow the 
tactile assessment, with a minimum of five minutes in between each assessment type to allow 
recovery time.
The examiner will assess the evaporative air sensitivity of all clinically eligible teeth 
identified atScreening (teeth that qualified on EAR, MGI and tooth mobility criteria, and had 
 
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none of the dentition exclusions). At Baseline only those teeth which meet the tactile 
threshold inclusion criterion (tactile threshold ≤20g) will be assessed. Two test teethwill be 
selected according to specific eligibility criteria in an individual subject. At Visits 3 and 4 
only the eligible test teeth will be assessed. 
7.2.2.1 Subject Response -Schiff Sensitivity Scale
This is an examiner based index [Schiff, 1994], 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 
andmay 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.  
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
7.3
Safety
The following safety assessments will be performed at times defined in the Study Procedures
(Section 6) section of this protocol.  
7.3.1
Oral Soft Tissue (OST) Examination
Where possible, this procedure should be conducted by a single trained dental examiner. 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. A brief description of any abnormality observed by the examiner 
or reported by the subject at the application site following theadministration of the 
acclimatisation or treatment dentifrices will be recorded as an AE. 
An OST examination will be conducted at every study visit prior to any clinical assessments. 
To ensure consistency in evaluations, every effort should be made to use the same OST 
 
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examiner throughout the study, however if this is not achievable e.g. because of examiner 
illness, OST examinations may be carried out by different examiners.
7.3.2
Full Oral Hard Tissue (OHT) Examination
Where possible, this procedure should be conductedby a single dental examiner or clinically 
qualified designee for all subjects. Subjects with evidenceof gross intraoral neglect or the 
need for extensive dental therapy will be excluded.
The OHT examination will assess grossly carious lesions orsigns of erosive wear,enamel 
irregularities, tooth fracture, gross decay, decalcification and faultyrestorations.
Observations will be listed as “Absent” or “Present” and conditions noted as presentwill be 
described. Examination findings will be described and documented in theeCRF. Any 
observation that changes from “Absent” to “Present” from the screeningassessment must be 
recorded as an AE.
7.3.3
Urine Pregnancy Test
Urine pregnancy testing will be performed on females of child bearing potential at Baseline 
(Visit 2) according to the test kit manufacturer’s instructions. Urine collected for urine 
pregnancy testing will be disposed of as appropriate immediately following the test result. 
Female subjects of non-childbearing potential must meet at least one of the following criteria:
Achieved postmenopausal status, defined as follows: cessation of regular 
menses for at least 12consecutive months with no alternative pathological or 
physiological cause; and have a serum follicle-stimulating hormone (FSH) 
level confirming the post-menopausal state;  
Have undergone a documented hysterectomy and/or bilateral oophorectomy;
Have medically confirmed ovarian failure.
All other female subjects (including females with tubal ligations) will be considered to be of 
childbearing potential.
8
ADVERSE EVENT AND OTHER EVENTS OF SPECIAL 
INTEREST REPORTING
8.1
Definitions of Adverse Events and Serious Adverse Events
8.1.1
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of an investigational or acclimatization product, whether or not 
considered related to the investigational or acclimatization product.
 
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NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a study treatment.
Events Meeting the AE Definition:  
Any abnormal safety assessments (eg, OST findings, including those that worsen 
from baseline, considered clinically significant in the medical and scientific judgment 
of the investigator (ie, not related to progression of underlying disease).
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study.
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae.
"Lack of efficacy" per se will not be reported as an AE or SAE. Such instances will be 
captured in the efficacy assessments. However, the signs, symptoms, and/or clinical 
sequelae resulting from lack of efficacy will be reported as AE or SAE if they fulfill 
the definition of an AE or SAE. 
Events NOTmeeting the AE definition: 
Any 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 symptomsof 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.
8.1.2
Serious Adverse Event
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
 
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A serious adverseevent 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 participant was at risk of death at the time of the event. It does not refer to an 
event, which hypothetically might have caused death, if it were more severe;
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.
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 (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption
Results in congenital anomaly/birth defect
Other situations
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse.
 
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8.2
Reporting Period
8.2.1
Adverse Event
AEs will be collected from thetimeofthe first supervised brushing with the acclimatization 
dentifriceand until 5days following last administration of the investigational product.
Medical occurrences that begin before the start of study treatment but after obtaining 
informed consent will be recorded on the Medical History/Current Medical Conditions section 
of the case report form (CRF) not the AE section.
8.2.2
Serious Adverse Event
SAEs assessed asnot relatedorrelatedto study participation (e.g., investigational product, 
protocol mandated procedures, invasive tests, or change in existing therapy),or related/not 
relatedto a GSK concomitant medication will be recorded from the time a subjectsigns the 
ICF, which is obtained prior to the subject’s participation in the study
, i.e., prior to undergoing 
any study-related procedure and/or receiving investigational product and until 5days 
following last administration of the investigational product.
8.3
Reporting Procedures
The investigator and anydesigneesareresponsible for detecting, documenting and reporting 
events that meet the definition of an AE or SAEand remain responsible for following up on 
AEs that are serious, considered related to the study treatmentand/or the study, or that caused 
the participant to discontinue thestudy treatment. 
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subjectwill be questioned about AEs. 
Each AE is to be assessed to determine if it meets the criteria for SAEs.If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, 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/SAE in 
the CRF.
It is notacceptable for the investigator to send photocopies of the participant’s medical 
records to GSK inlieu of completion of the GSK AE/SAECRF page.
There may be instances when copies of medical records for certain cases are requested by 
GSK.  In this instance, all subject identifiers, with the exception of the subject number, will be 
blinded on the copies of the medical records prior to submission to GSK.
The investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. In such cases, the diagnosis will be documented as the 
 
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AE/SAE and not the individual signs/symptoms. Clinical AEs will be described by diagnosis 
and not by symptoms when possible (e.g., upper respiratory tract infection, seasonal allergy, 
etc. instead of runny nose).
Medical conditions reported prior to the time period for reporting AEs/SAEs should be 
recorded as part of the subject’s medical history.
AEs elicited by the investigator in a standard manner at the study visits should also be 
recorded in the AE section of the CRF. Care will be taken not to introduce bias when 
detecting AE and/or SAE. Open-ended and non-leading verbal questioning of the participant 
is the preferred method to inquire about AEoccurrence.
8.3.1
Adverse Event
All AEs will be reported on the AE page(s) of the CRFby 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 forms must be completed in a consistent manner. 
For example, the same AE termshould be used on both forms. AE should be reported using 
concise medical terminology on the CRF as well as on the form for collection of SAE 
information.
8.3.2
Serious Adverse Event
A paper copy of the SAE form provided in the investigator study master file should be 
completed as fully as possible. 
It is essential to enter the following information: 
Protocol and subject identifiers
Subject’s demography
Description of events, with diagnosis if available
Investigator opinion of relationship to study product 
Criterion for seriousness.
The following are desirable and are of particular relevance for investigator and GSK CH 
assessment of the SAEreport:
Date of onset of AE 
Date AE stopped, if relevant
Study product start date
Study product end date if relevant
Action taken on study product
Outcome if known
The SAE form, completed as fully as possible, must be e-mailed to the GSK CH Clinical 
Operations Safety Reporting email box with the study number and subject numberin the 
 
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subject line of the email immediately and under no circumstance should this exceed 24 
hoursafter study site personnel learn of the event. The investigator will submit any updated 
SAE data to the sponsor, immediately andunder no circumstance should this exceed 24 
hours of it being available. The GSK CH Study Manager should also be notified of the 
situation by telephone or email.
EmailSerious Adverse Events to:
The GSK CH Study Manager or designee will be responsible for forwarding the SAE form to 
the Case Management Group, Global Clinical Safety and Pharmacovigilance mailbox 
The initial report will be followed up with more information as relevant, or as requested by 
the GSK CH study manager.
8.3.3
Sponsor’s Reporting Requirements to Regulatory Authorities and 
Ethics Committees
GSK has a legal responsibility to notify, as appropriate, the local regulatory authority and 
other regulatory authorities about the safety of a productunder clinical investigation. Prompt 
notification of SAEs by the investigator to GSK is essential so that legal obligations and 
ethical responsibilities towards the safety of subjects are met.
GSK will comply with country specific regulatory requirements relating to safety reporting to 
the regulatory authority, IEC and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describinga SAE or other specific 
safety information eg, summary or listing of SAE) from the sponsor will review and then file 
it along with the Safety Statement and will notify the IEC, if appropriate according to local 
requirements.
8.4
Evaluating Adverse Events and Serious Adverse Events
8.4.1
Severity Assessment
The investigator or designee will make an assessment of severity for each AE and SAE 
reported during the study and will assign it to one of the following categories:
Mild:  An event that is easily tolerated by thesubject, causing minimal discomfort and 
not interfering with everyday activities.
 
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Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities
Severe:  An event that prevents normal everyday activities. 
Note: An AE that is assessed as severe will not be confused with an SAE. Severity is a 
category utilized for rating the intensity of an event; and both AEs and SAEs can be assessed 
as severe. For example, a headache may be severe (interferes significantly with the subject
's 
usual function) but would not be classified as serious unless it met one of the criteria for 
SAEs, listed above. 
8.4.2
Causality Assessment
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.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 theCRF, as appropriate, and report such 
an assessment in accordance with the SAE reporting requirements if 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 Safety Statement and/or 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.
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. The investigator may change his/her opinion of 
causality in light of follow-up informationand send an SAE follow-up report with the updated 
causality assessment. 
8.5
Withdrawal Due to an Adverse Event and Serious Adverse 
Events
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on theappropriate AE CRF
page. 
When a subject withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below.
 
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8.6
Pregnancy
8.6.1
Time Period for Collecting Pregnancy Information
Pregnancy information will be collected on all pregnancies reported following administration 
of any investigational productor acclimatization product and until 5 days after the last dose.
8.6.2
Action to be Taken if Pregnancy Occurs
The investigator will collect pregnancy information on any subject who becomes pregnant 
while participating in the study after administration of the investigational productor washout 
product. The investigator will record pregnancy information on the appropriate form and e-
mail itto the GSK CH Clinical Operations Safety Reporting email box 
 within 24 hours of learning of the subject becoming pregnant. The GSK 
CH Study Manager or designee will be responsible for forwarding the pregnancy information 
formto the Case Management Group, Global Clinical Safety and Pharmacovigilance mailbox 
The subject will be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and infant / neonate (including concomitant medications taken by the 
mother during the pregnancy) will be forwarded by the investigator to the GSK CH Clinical 
Operations Safety Reporting email boxand the GSK CH Study Manager or designee will 
forward this information to the Case Management Group, Global Clinical Safety and 
Pharmacovigilance group mailbox at GSK
 Generally, follow-up will 
be no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported.
While pregnancy itself is not considered to be an AE, abnormal pregnancy outcomes (eg, 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered tobe and should be recorded as an SAE.
Any female participant who becomes pregnant while participating will discontinue study 
treatment.
8.7
Follow-up of Adverse Events and Serious Adverse Events
After the initial report, the investigator is required to proactively follow up with each subject 
and provide further information on the subject’s condition.
All AEs/SAEs will be followed until resolution, until the condition stabilizes, until the event 
is otherwise explained, or until the subject is lost to follow-up. 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as may be indicated or as requested by GSK to elucidate as 
fully as possible the nature and/or causality of the AE or SAE.This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals.
 
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New or updated information will be recorded in the originally completed CRF.
The investigator will submit any updated SAE data to GSK within 24 hours of receipt of the 
information.
Investigators are not obliged to actively seek AEs or SAEs in former subjects.  However, if 
the investigator learns of any SAE, including the death, at any time after a subject has been 
discharged from the study, and considers the event reasonably related to the investigational 
product or study participation, the investigator will promptly notify GSK by emailing the 
information to the GSK CH Clinical Operations Safety Reporting email box 
. The GSK CH Study Manager or designee will be responsible for 
forwarding theinformation to theCase Management Group, Global Clinical Safety and 
Pharmacovigilance group mailbox at GSK
The investigator will submit any updated SAE data to GSK within the designated reporting 
time frames.
9
DATA MANAGEMENT
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study. 
For this study subject data will be entered into an electronicCRF using a validated data 
system.
9.1
Source Documents/ Data
The source documents (eg. Score cards)which contain the source of data recorded in the CRF 
should be specified in Section 6. The CRF and diarycan be used as a source document at the 
discretion of data management.
Each subject will be assigned and identified by a unique Number. Any reference made to an 
individual subject within the study must be done using the unique Screening Number.
9.2
Case Report Form
A CRF is a printed, optical, or electronic document designed to record all of the protocol 
required information to be reported to the sponsor on each trial subject.
For each subject who has given informed consent/assent and has been screened, CRF must be 
completed and signed by the Principal Investigator (or authorized designee) to certify that the 
data are complete and correct.  
Management of clinical data will be performed in accordance with applicable GSK CH 
standards and data cleaning procedures to ensure the integrity of the data e.g. removing errors 
and inconsistencies in the data. 
 
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In order to protect the privacy of subjects, no Personally Identifiable Information (PII) 
(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 hasbeen 
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 at the completion of the 
study. 
9.3
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. 
Anycorrections to the entries made to the paper source documents must be dated, initialed, 
and explained (if necessary) and should not obscure the original entry. 
Adverse events will be coded using MedDRA (Medical Dictionary for Regulatory Activities) 
and concomitant medications terms (if applicable) using an internal validated medication 
dictionary, GSKDrug.  
9.3.1
Queries
Programmed edit checks will be generated automatically, as the data is being entered into the 
system. Data Management will also run reports and listings on the CRF data, 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 (Adverse Events and 
Drugs) appropriately. 
The study monitor at the study site will review the CRFs in accordance with the monitoring 
plan, and 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.
9.4
Processing Patient Reported Outcomes
Patient reported outcome (PRO) data may be collected from diary cards, questionnaires, etc, 
and entered into the sponsor’s clinical data management system (DMS). In instances where 
the PRO data is entered into the DMS by GSK CH, the PROs will be anonymized as agreed 
 
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and documented prior to study initiation. PROs that are source will be retained by the 
investigator and certified copies will be sent to GSK CH. 
In order to protect the privacy of subjects, no Personally Identifiable Information (PII) 
(including the subject
's name or initials or birth date) is to be recorded on all PRO’s that will 
be forwarded to GSK CH.
10
STATISTICAL CONSIDERATIONS AND DATA ANALYSES
10.1
Sample Size Determination
Change from baseline in Schiff sensitivity score will be used to evaluate treatmenteffects 
with regard to the primary objective. With 55evaluable subjects per group, the study will 
have 80% powerto detect a mean differenceof 0.33 (SD=0.619) in change from baseline in 
Schiff sensitivityscore after 8 weeks of treatment.
The estimate of SD wasobtained from GSKCH study 205794. The sample size is based on 
carrying out two-tailed two sample t-test at a5% significance level.
Therefore, to allowfor dropouts a sufficient amount of subjects will be screened to randomize 
approximately 180 subjects toensure 165 subjects (approximately 55per arm) complete the 
study.
10.2
Statistical Methods and Analytical Plan
Additional details of the proposed statistical analysis will be documented in the statistical 
analysis plan (SAP), which will be written following finalization of the protocol and prior to 
study unblinding.
10.2.1
Demographic and Baseline Characteristics
Descriptive statistics (percentages, means and standard deviations) of demographic baseline 
characteristics, medical history, current/concomitant medication and compliancewill be 
tabulated.
10.2.2
Primary Analysis
The primary efficacy variable is the change from baseline in Schiff sensitivity score at 8 
weeks. The primary comparison is between the Experimental formulation 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 two test teeth. The change 
from baseline is derived from the individual teeth first before calculating the average change 
of the two test teeth.
 
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The change from baseline in Schiff sensitivity score will be analysed using analysisof 
covariance (ANCOVA) with treatment as factor and baseline Schiff sensitivityscore as a 
covariate. Note that since the baseline Schiff sensitivity score will beincluded as a covariate, 
the baseline Schiff stratification value will not be included inthe model.
The assumption of normality and homogeneity of variance in the ANCOVA modelwill 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 andresults will be compared with the ANCOVA results. 
If the inferences from the twoanalyses are similar,then both sets of results will be reported 
and emphasis will bemade on the ANCOVA results. If there are differences between the 
inferences, then the emphasis will be on the non-parametric analysis.
10.2.3
Secondary Analyses
The secondary efficacy variable is change from baseline in Tactile threshold at 8 weeks (Test 
Product vs Control Product 1).
Tactile score includingthe change is derived in the same manner as for the Schiff score.
The change from baseline in tactile threshold will be analysed using ANCOVA with treatment 
and baseline Schiff stratification included as factors and baseline tactile threshold 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.
10.2.4
Exploratory Analyses
The exploratory efficacy variables are:
Change from baseline in Schiff sensitivity at8 weeks (Test Product vs Control Product 
2and Control Product 2 vs Control Product 1).
Change from baseline in Tactile threshold at 8 weeks (Test Product vs Control Product 
2 and Control Product 2 vs Control Product 1).
Change from baseline in Schiff sensitivity at 4 weeks (Test Product vs Control Product
1,Test Product vs Control Product 2and Control Product 2 vs Control Product 1).
Change from baseline in Tactile threshold at 4 weeks (Test Product vs Control Product
1,Test Product vs Control Product 2and Control Product 2 vs Control Product 1).
Schiff and tactile score is derived as per the primaryanalysis including the change.
Both change from baseline in Schiff and tactile sensitivity will be analysed in the same way as 
per the primary and secondary analyses.
 
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10.2.5
Safety Analyses
Safety population will be used for safety assessments. Safety analyses will beperformed 
according to the treatment that the subject received (using variable ATRT).All AEswill be 
reviewed by the Clinical Research Scientist orDesignee prior to database lock and unblinding 
and will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). During 
this review stage, AEs willbe further categorized as oral or non-oral. AEs will be listed and 
summarized bytreatmentreceived. Serious AEs will also be listed. AEs will be regarded as 
treatmentemergent if they occur on or after the first treatment application at the baseline visit.
The following AEs tables split by treatment will be produced:
Listing of all AEs (including Non-treatment emergent AEs from all subjects)
Listing of all AEs for screened subjects
Treatment emergent AEs by Oral/Non-Oral Preferred Term (PT)
Treatment emergent AEs by System Organ Class (SOC) and PT
Treatment emergent AEs by SOC, PTand intensity
Treatment emergent treatment related AEs by Oral/Non-Oral
Treatment emergent treatment related AEs by SOCand PT
Listing of SAEs (if there are none a null listing will be produced; ifthere are more 
than 5 treatment emergent serious SAEs a table will beproduced instead by SOC and 
PT)
Non-serious treatment emergent AEs by SOC and PT (only produced if thereare more 
than 5 SAEs)
OSTabnormalities will be listed and tabulated.The tabulation will show changes in 
abnormality from baseline to each follow-up assessment.
Exposure to study product will also be tabulated and listed by treatment group.
10.2.6
Definition of Analysis Populations
The safety population includes all subjects who are randomized and receive 
investigational productand analysed as per treatment received
The ITT population includes all randomized subjects who receive at least one dose of 
investigational productand analysed as randomized.
The PP population includes all subjects who fully comply with all study procedures 
and restrictionsand is a sub-set of the ITT population. Any protocol deviations that 
would lead to subjects/databeing excluded will be removed from the PP population. 
 
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10.2.7
Exclusion of Data from Analysis 
Any of the following will be considered a protocol violation which may warrant exclusion of 
data or the subject from efficacy analysis:
Violation of inclusion or exclusion criteria that are deemed to affect efficacy.
Medical history which is deemed to affect efficacy.
Use of prohibited treatment or medication before or during the study, which is felt to 
affect the assessment of efficacy. 
Not receiving randomised treatment.
Treatment non-compliance.
Assessments outside the scheduled time windows.
Protocol deviations.
Any other reason identified likely to affect efficacy.
Exclusion of any data from the analyses will be determined during a Blind Data Review 
Meeting prior to database lock. Any reasons for exclusion from an analysis population will be 
listed, if applicable.
10.2.8
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.
10.2.9
Interim Analysis
No interim analysis is planned for this study.
10.2.10 Other Analyses
To cover the Chinese requirement to demonstrate a 15% difference betweenthe Test Product 
and Control product 1,the difference between treatments in the raw means of the actual score 
(note not change from baseline) will be calculated and presented. This will be done for Schiff 
and tactile at weeks 4 and 8.  The calculation is: -
100*(Test-Ref1)/Ref1
11
STUDY GOVERNANCE CONSIDERATIONS
11.1
Quality Control 
In accordance with applicable regulations includingGCP, and GSK procedures, GSK or 
designee (i.e. third party vendor) monitors will contact the site prior to the start of the study to 
 
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review with the site staff the protocol, study requirements, and their responsibilities to satisfy 
regulatory, ethical, and GSK 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 or designee will monitor the study and site activity to verify that the:
Data are authentic, accurate, and complete.
Safety and rights of subjects are being protected.
Study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements.
The extent and nature of monitoring will be described in a written monitoring plan on file at 
GSK CH. The investigator (or designee) agrees to allow the monitor direct access to all 
relevant documents and agrees to co-operate with the monitor to ensure that any problems 
detected in the course of these monitoring visits are resolved.
11.2
Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK 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 investigatorwill 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.
 
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11.3
Regulatory and Ethical Considerations
11.3.1
Ethics Committee 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, safety statement (including any updates) 
and other relevant documents, e.g.,recruitment advertisements, if applicable, from the IEC. 
All correspondence with the IEC should be retained in the investigator file.Copies of IEC
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 anamendment may be initiated prior to IEC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.In that 
event, the investigator must notify the IEC and GSK CH in writing immediately after the 
implementation.
11.3.2
Ethical Conduct of the Study
The study will be conducted in accordance with 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), guidelines for GCP (ICH 1996and 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 guidelineon 
GCP, and applicable local regulatory requirements and laws.
11.3.3
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 otherdisclosures, except where 
required by laws. 
When study data are compiled for transfer to GSK CH and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by GSK CH in order to de-identify study subjects.  
The study site will maintain a confidential list of subjects who participated in the study, 
linking each subject’s numerical codeto 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 consentdocuments must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws.
The informed consentdocuments used during the informed consent process must be reviewed 
and approved by the sponsor, approved by the IECbefore use, and available for inspection.
 
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The investigator must ensure that each study subject,is fully informed about the nature and 
objectives of the study and possible risks associated with participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consentfrom each subjectbefore any study-specific activity is performed.  The investigator 
will retain the original of each subject
's signedinformed consentdocument.
11.3.4
Subject Recruitment 
Advertisements approved by IECsand investigator databases may be used as recruitment 
procedures.Use of IECapproved, generic, prescreening questionnaire to assess basic subject 
characteristics to determine general eligibility for this study is allowed.This generic 
questionnaire may be used by sites as a phone script and/or to review internal databases to 
identify subjects.  
GSK CH will have an opportunity to review and approve the content of any study recruitment 
materials directed to potential study subjects before such materials are used. 
11.3.5
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 humansubject 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.
11.4
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 processes.
11.5
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 site or other mutually-agreeable 
location.
 
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GSK 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 theresults summary and for development 
of a manuscript for publication will be in accordance with GSK Policy.
A manuscript will be progressed for publication in the scientific literature if the results 
provide important scientific or medical knowledge.
11.6
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 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 shouldnot be identified by their names or 
initials, but by an identification code. The investigator should keep a separate log of subjects’ 
codes, names and addresses. Documents not for submission to GSK CH, e.g. subjects’ written 
consent forms, should be maintained by the investigator in strict confidence.
Records and documents, including signed ICF, pertaining to the conduct of this study must be 
retained by the investigator for 25 years from the issue of the final Clinical Study Report 
(CSR)/ equivalent summaryunless 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 local laws or regulations, GSK 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 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.
 
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11.7
Conditions for Terminating the Study 
Premature termination of this study may occur because of a regulatory authority decision,
change in opinionof the IEC, or investigational product safety problems, or at the discretion 
of GSK CH. In addition, GSK CH retains the right to discontinue development of SnF2
dentifricesat any time. 
If a study is prematurely terminated, GSK CH will promptly notify the investigator.After 
notification, the investigator must promptly contact all participating subjects and should 
assure appropriate therapy/ follow-up for the subjects. As directed by GSK CH, all study 
materials must be collected and all CRFscompleted 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 IEC and provide the IECa 
detailed written explanation of the termination or suspension. 
If the IECterminates 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 GSKCH Standard Operating Procedures.
11.8
Definition of Study End/End of Study 
The end of the study will be the date of the Last Subject Last Visit (LSLV). For this study the 
LSLV will be the primary completion date (PCD).
12
REFERENCES
Addy M., Mostafa P., AbsiE., 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.
Dababneh R. H., Khouri A. T., Addy M., Dentine hypersensitivity -an enigma? A review of 
terminology, mechanisms, aetiology and management. Br. Dent. J.1999, 187, 606–611; 
discussion 603.
 
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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.
Graf H., Galasse R., Morbidity, prevalence and intraoral distribution of hypersensitive teeth. 
J. Dent. Res.1977, 56, A162.
Hall R., Embery G., Shellis R., Biological and structural features of enamel and dentin: 
current conceptsrelevant to erosion and dentin hypersensitivity. In Tooth Wear and 
Sensitivity; Addy, M., Embery, G., Edgar, W., Orchardson, R., Eds.; Martin Dunitz Ltd, 
London, 2000; pp 3–19.
Holland G. R., Narhi M. N., Addy M., Gangarosa L., Orchardson R., Guidelines for the 
design and conduct of clinical trials on dentine hypersensitivity. J. Clin. Periodontol.1997, 
24, 808–813.
Irwin C. R., McCusker P., Prevalence of dentine hypersensitivity in a general dental 
population. J. Ir. Dent. Assoc.1997, 43, 7–9.
Laster L., Laudenbach K. W., Stoller N. H., An evaluation of clinical tooth mobility 
measurements. J. Periodontol.1975, 46, 603–607.
Leight R., Bowman J., Barlow A., Dentinal Hypersensitivity: Evidence for a “No Treatment” 
Effect. J. Dent. Res.2008, 87, Abstract No 3498.
Lobene R. R., Weatherford T., Ross N. M., Lamm R. A., Menaker L., A modified gingival 
index for use in clinical trials. Clin. Prev. Dent.1986, 8, 3–6.
Makin S. A., Stannous fluoride dentifrices. Am. J. Dent.2013, 26 Spec No, 3A –9A.
Ministry ofHealth, 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.
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.
 
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Parkinson C. R., Willson R. J., A comparative in vitro study investigating the occlusion and 
mineralization properties of commercial toothpastes in a four-day dentin disc model. J. Clin. 
Dent.2011, 22, 74–81.
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 Dent2008, 
29, 1–35.
Polson A. M., Caton J. G., Yeaple R. N., Zander H. A., Histological determination of probe 
tip penetration into gingival sulcus of humans using an electronic pressure-sensitive probe. J. 
Clin. Periodontol.1980, 7, 479–488.
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., Efficacy of a dentifrice containing potassium nitrate, soluble 
pyrophosphate, PVM/MA copolymer, and sodium fluoride on dentinal hypersensitivity: a 
twelve-week study. J. Clin. Dent.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.
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. 
13
APPENDIX
13.1
Appendix I–Instructions
INSTRUCTIONS
Brush twice a day (morning and evening) for 1 timed minute.
Each time you brush:
Dispense a ribbon of toothpaste covering the length of the toothbrush head (see below 
picture).
Set your timer for 1 minute, and then brush all the teeth in your mouth in your usual 
manner for 1 timed minute.
Record each brushing in the diary. Note any changes to these brushing procedures and 
reasons for changes (e.g. missed brushings, extra brushings) too.
 
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Stannous fluoride
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Record any changes in your smoking habits, health, medications (prescription and over 
the counter medications) or treatments in the diary. 
Bring your diary card (completed and not completed), toothpaste and toothbrush to the 
next study visit.
Please do not remove or deface any part of the study label.
Please do not share your study toothpaste with anybody and do not discuss with the 
examiner your experience with your assigned toothpaste (taste, color and smell).
13.2
Appendix II -Abbreviations
The following is a list of abbreviations that may be used in the protocol.
Table 13-1
Abbreviations
Abbreviation
Term
ABL
aluminum barrier laminate
AE
adverse event
ANCOVA
analysis of covariance
CI
confidence interval
CRF
case report form
DMS
data management system 
DH
dentinehypersensitivity
EAR
erosion, abrasion, recession
EDC
electronic data capture
EDP
exposure during pregnancy
FSFV
first subject firstvisit
FSH
follicle stimulating hormone
 
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Stannous fluoride
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Final 1.0 Clinical Protocol
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Abbreviation
Term
GCP
Good Clinical Practice
GCS 
Global Clinical Supplies
GSK CH
GlaxoSmithKline Consumer Healthcare
IB
investigator’s brochure
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee 
ITT
intent to treat
IUD
intrauterine device
LSLV
last subject last visit 
MedDRA
medical Dictionary for Regulatory Activities
MoH
Ministry of Health
MGI
Modified Gingival Index
NaF
sodium fluoride 
N/A
not applicable
OHT
oral hard tissue 
OST
oral soft tissue 
OTC
over-the-counter
P&G
Proctor and Gamble
PI
principal investigator
PII
personally identifiable information
PP
per protocol
PT
preferred term
PRO
patient reported outcome
SAE
serious adverse event
SAP
statistical analysis plan
SnF2
stannous fluoride 
SnCl2
stannous chloride
SMFP
sodium monofluorophosphate 
SOC
system organ class
SOP
standard operating procedure
SUSAR
suspected unexpected serious adverse reactions
SS
safety statement
 
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Stannous fluoride
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Abbreviation
Term
SSRD
single reference safety document
TMF
trial master file
 
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SIGNATURE PAGE 
 
  
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
23-Aug-2017 05:58:16
 
Approved
Approved
21-Aug-2017 10:22:45
Biostatistics Approval
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PPD
PPD
PPD