Randomized Controlled Examiner-Blind Phase II Exploratory Clinical Study to Characterize the Efficacy Profile of an Experimental Dual Active Combination Dentifrice for the Relief of Dentin Hypersensitivity, in Subjects With Clinically Diagnosed Dentin Hypersensitivity
Phase: PHASE2
Conditions: Dentin Hypersensitivity, Dentin Sensitivity
Sponsor: GlaxoSmithKline

Author(s) 
APPROVALS
Name
Reason for Approval
Approval Date CET*(MM/DD/YYYY)
10/14/2018 3:01:09 PM
10/15/2018 8:15:15 AM
10/15/2018 10:45:57 AM
10/16/2018 9:34:18 AM
Document Name 
Scope 
Document Type 
Document Subtype 
Document ID 
Version 
Approved Date in CET* 
Pages 
*CET: Central European Time
2.0
98
209723_Clinical Protocol
0900c35380fa4d66
Oct 16,2018  9:34:00 AM
209723-Clinical Protocol-209723_Clinical Protocol
Clinical Protocol
Studies
003 Study protocol and Amendment
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5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
Protocol Number 209723
Clinical Protocol
This document contains confidentiality statements that are not relevant for this publicly 
available version
GlaxoSmithKline Consumer Healthcare Confidential
May not be used, divulged, published or otherwise disclosed without the consent of GSK CH 
Template Version Effective: 18-May-18 (CCR #11475)
Page 1 of 97
CLINICAL PROTOCOL
RANDOMIZED CONTROLLED EXAMINER-BLIND PHASE II 
EXPLORATORY CLINICAL STUDY TO CHARACTERIZE THE 
EFFICACY PROFILE OF AN EXPERIMENTAL DUAL ACTIVE 
COMBINATION DENTIFRICE FOR THE RELIEF OF DENTIN 
HYPERSENSITIVITY, IN SUBJECTS WITH CLINICALLY DIAGNOSED 
DENTIN HYPERSENSITIVITY
Protocol Number:
209723
Compound/Product Name:
Potassium nitrate 5% weight/weight (w/w) and 
stannous fluoride 0.454% (w/w) dentifrice
United States (US) Investigational 
New Drug (IND) Number:
Not applicable (N/A)
European Clinical Trials Database 
(EudraCT) Number:
N/A
Phase:
II
Sponsor Information
Sponsor Name & Legal 
Registered Address
GlaxoSmithKline Research & Development Limited
980 Great West Road, 
Brentford, 
Middlesex, TW8 9GS,
United Kingdom (UK)
Sponsor Contact Details
GlaxoSmithKline Consumer Healthcare Holdings (US)
LLC
184 Liberty Corner Rd., 
Warren, New Jersey (NJ) 07059, 
United States (US)

Author(s) 
APPROVALS
Name
Reason for Approval
Approval Date CET*(MM/DD/YYYY)
3/18/2019 1:21:25 PM
Document Name 
Scope 
Document Type 
Document Subtype 
Document ID 
Version 
Approved Date in CET* 
Pages 
*CET: Central European Time
1.0
4
209723_Clinical Protocol Administrative Change Letter_02
Mar 18,2019  1:21:00 PM
209723-Clinical Protocol Administrative Change Letter-209723_Clinical
Protocol Administrative Change Letter_02
Clinical Protocol Administrative Change Letter
Studies
003 Study protocol and Amendment
PPD
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Development of Clinical Protocols 
and Protocol Amendments 
Protocol number: 209723
GlaxoSmithKline Consumer Healthcare Confidential
SP1963 Appendix 8.2f v01
Page 1 of 3
GlaxoSmithKline Consumer Healthcare
184 Liberty Corner Road
Warren, NJ 07059
Unites States of America
March 18, 2019
RE: Protocol Administrative Changes #02 for Study 209723 
RANDOMIZED CONTROLLED EXAMINER-BLIND PHASE II EXPLORATORY 
CLINICAL STUDY TO CHARACTERIZE THE EFFICACY PROFILE OF AN 
EXPERIMENTAL DUAL ACTIVE COMBINATION DENTIFRICE FOR THE 
RELIEF OF DENTIN HYPERSENSITIVITY, IN SUBJECTS WITH CLINICALLY 
DIAGNOSED DENTIN HYPERSENSITIVITY
Dear Investigator,
This letter is being sent to notify you of the following clarifications and administrative 
changes to the 209723 protocol; version 2.0, dated 16 Oct 2018.
Points of Clarification:

Section 6.7 Subject Compliance, the following statement is added for 
clarification.
As this is an exploratory study, no specific thresholds for compliance/non-
compliance have been defined. Compliance will be assessed at the Blind Data 
Review Meeting (Section 12.2.2 Exclusion of Data from Analysis), prior to 
database lock, to identify subjects with protocol deviations which would warrant 
exclusion of data from the mITT analysis population.

Section 10.7.1 Sponsor’s Reporting Requirements to Regulatory Authorities 
and Ethics Committees, the following statement is added for clarification.
SAEs and SUSARs will be reported in an expedited manner to Health Canada as 
per the NNHPD Clinical Trials for NHPs guidance document 
(https://www.canada.ca/en/health-canada/services/drugs-health-
products/natural-non-prescription/legislation-guidelines/guidance-
documents/clinical-trials.html). 
 
 
 
 
 
 

Development of Clinical Protocols 
and Protocol Amendments 
Protocol number: 209723
GlaxoSmithKline Consumer Healthcare Confidential
SP1963 Appendix 8.2f v01
Page 2 of 3

Section 12.1 Sample Size Determination, the following statement
Approximately 104 subjects will be randomized to study treatment (approximately 
52 per treatment group) 
is changed to 
Approximately 104 subjects will be randomized to study treatment (approximately 
52 per treatment group) to achieve approximately 50 evaluable subjects per 
treatment group, allowing for a dropout rate of approximately 4%. 
for clarification.
Minor Administrative Changes:

Protocol Administrative Change Letter #01 for Study 209723 referenced Section 
9.9.2 in error, this is corrected to Section 9.2.2; stated NJ 07094 as ZIP code for 
the sponsor address in error, this is corrected to NJ 07059.

Section 1.1 Schedule of Activities, Table 1-1, Procedure/Assessment at Visit 6, 
Day 28 (± 2 days), the following statement is removed.
Provide Subject with New Diary 
The diary provided at Visit 2 (Day 0, Baseline) will cover the entire 8-week 
treatment period; subjects will not be re-supplied with a diary at Visit 6.

Section 8.2.1 Baseline: Day 0 (Visit 2), the following statement is removed. 
Clinical examiner completes an OHT examination. Record findings in the CRF.
OHT (oral hard tissue) examinations will be completed at Visit 1 (Screening) and 
Visit 7 (Day 56) only, as per Table 1.1 Schedule of Activities.

Section 9.1.4 Qualifying Tactile Sensitivity, the following statement
The subject may respond "yes" if they feel pressure as the probe is applied to their 
tooth. The examiner will remind them they should only respond ‘yes’ if they feet 
PAIN or DISCOMFORT. 
is corrected to 
The subject may respond "yes" if they feel pressure as the probe is applied to their 
tooth. The examiner will remind them they should only respond ‘yes’ if they feel 
PAIN or DISCOMFORT.
 
 
 
 
 
 

Development of Clinical Protocols 
and Protocol Amendments 
Protocol number: 209723
GlaxoSmithKline Consumer Healthcare Confidential
SP1963 Appendix 8.2f v01
Page 3 of 3
NO ADDITIONAL CHANGES HAVE BEEN MADE TO THE STUDY 
DOCUMENTATION.
Sincerely,
__
___________           
   18 Mar 2019
Clinical Research
    
    Date
cc: Trial Master File, IRB/EC
 
 
 
 
 
 
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5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
Protocol Number 209723
Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential 
Template Version Effective: 18-May-18 (CCR #11475)
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Document History
Document
Version
Summary of Changes 
Original protocol
2.0
N/A
Amendments incorporate all revisions to date, including amendments made at the request of 
country health authorities, institutional review boards/ethics committees (IRBs/ECs), etc.  

5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
Protocol Number 209723
Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential 
Template Version Effective: 18-May-18 (CCR #11475)
Page 3 of 97
Principal Investigator Protocol Agreement Page

I confirm agreement to conduct the study in compliance with the protocol and any 
amendments according to the current International Conference on Harmonisation Good 
Clinical Practice (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:
Investigator Qualifications:
Investigator Signature:
Date of Signature/Agreement:
DD-MMM-YYYY
PPD
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5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
Protocol Number 209723
Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential 
Template Version Effective: 18-May-18 (CCR #11475)
Page 4 of 97
Table of Contents
Sponsor Information ............................................................................................................1
Document History................................................................................................................2
Principal Investigator Protocol Agreement Page.................................................................3
Table of Contents.................................................................................................................4
1
PROTOCOL SUMMARY...................................................................................................9
1.1
Schedule of Activities............................................................................................12
2
INTRODUCTION .............................................................................................................14
2.1
Study Rationale......................................................................................................14
2.2
Background............................................................................................................15
2.3
Mechanism of Action/Indication ...........................................................................17
3
STUDY OBJECTIVES AND ENDPOINTS.....................................................................18
4
STUDY DESIGN ..............................................................................................................19
4.1
Overall Design .......................................................................................................19
4.2
Rationale for Study Design....................................................................................20
4.3
Justification for Dose .............................................................................................21
4.4
End of Study Definition.........................................................................................22
5
STUDY POPULATION....................................................................................................22
5.1
Type and Planned Number of Subjects..................................................................22
5.2
Inclusion Criteria....................................................................................................23
5.3
Exclusion Criteria ..................................................................................................24
5.4
Randomization Criteria..........................................................................................26
5.5
Lifestyle Considerations ........................................................................................26
5.5.1
Oral Hygiene Restrictions .....................................................................27
5.5.2
Dietary and Alcohol Restrictions ..........................................................28
5.5.3
Contraception ........................................................................................28
5.6
Screen Failures.......................................................................................................30
5.7
Sponsor’s Qualified Medical Personnel.................................................................30
5.8
Rater/Clinical Assessor Qualifications ..................................................................31
6
INVESTIGATIONAL/STUDY PRODUCTS...................................................................31
6.1
Investigational/Study Product Supplies .................................................................31
6.1.1
Dosage Form and Packaging.................................................................33
6.1.2
Preparation and Dispensing...................................................................34
6.2
Administration .......................................................................................................34
6.2.1
Medication/Dosing Errors .....................................................................34
6.3
Investigational/Study Product Storage...................................................................35
6.4
Investigational/Study Product Accountability .......................................................36
6.4.1
Destruction of Investigational/Study Product Supplies.........................36
6.5
Blinding and Allocation/Randomization ...............................................................37
6.6
Breaking the Blind .................................................................................................37

5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
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6.7
Subject Compliance ...............................................................................................38
6.8
Concomitant Medication/Treatment(s)..................................................................38
7
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL .........................................................................39
7.1
Subject Discontinuation/Withdrawal.....................................................................39
7.2
Lost to Follow up...................................................................................................40
8
STUDY PROCEDURES...................................................................................................41
8.1
Screening: Day -28 to Day -14 (Visit 1)................................................................41
8.1.1
Informed Consent..................................................................................41
8.1.2
Demographics........................................................................................42
8.1.3
Medical History and Prior Medication/Treatment ................................42
8.1.4
Screening Procedures ............................................................................42
8.1.5
Inclusion/Exclusion Criteria..................................................................43
8.1.6
Subject Eligibility..................................................................................43
8.1.7
Supervised Use of Acclimatization Dentifrice......................................44
8.2
Study Period...........................................................................................................44
8.2.1
Baseline: Day 0 (Visit 2).......................................................................44
8.2.2
Day 3, Day 7 (+1 day), Day 14 (±1 day) and Day 28 (±2 days)   
(Visits 3-6).............................................................................................45
8.2.3
Day 56 (±2 days) (Visit 7).....................................................................47
8.3
Diary Review .........................................................................................................48
8.4
Study Conclusion...................................................................................................48
8.5
Follow-up Visit/Phone Call ...................................................................................48
9
STUDY ASSESSMENTS .................................................................................................48
9.1
Screening Assessments ..........................................................................................49
9.1.1
Erosion, Abrasion and Recession (EAR) ..............................................49
9.1.2
Modified Gingival Index (MGI)............................................................49
9.1.3
Tooth Mobility Assessment...................................................................50
9.1.4
Qualifying Tactile Sensitivity................................................................50
9.1.5
Qualifying Evaporative Air Sensitivity.................................................52
9.2
Efficacy Assessments.............................................................................................53
9.2.1
Dentine Hypersensitivity Experience Questionnaire (DHEQ-15) ........53
9.2.2
Tactile Sensitivity..................................................................................53
9.2.3
Evaporative Air Sensitivity ...................................................................54
9.2.4
Selection of Test Teeth..........................................................................54
9.3
Safety and Other Assessments...............................................................................54
9.3.1
Oral Soft Tissue (OST) Examination ....................................................54
9.3.2
Oral Hard Tissue (OHT) Examination ..................................................55
9.3.3
Pregnancy Testing .................................................................................55
10 ADVERSE EVENT AND SERIOUS ADVERSE EVENTS............................................55

5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
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GlaxoSmithKline Consumer Healthcare Confidential 
Template Version Effective: 18-May-18 (CCR #11475)
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10.1
Definition of an Adverse Event (AE) ....................................................................55
10.2
Definition of a Serious Adverse Event (SAE) .......................................................57
10.3
Reporting of Adverse Events.................................................................................58
10.3.1
Reporting Period....................................................................................58
10.4
Reporting Procedures.............................................................................................58
10.4.1
Reporting of an Adverse Event .............................................................59
10.4.2
Reporting of a Serious Adverse Event ..................................................60
10.5
Evaluating Adverse Events....................................................................................61
10.5.1
Assessment of Intensity.........................................................................61
10.5.2
Assessment of Causality........................................................................61
10.6
Follow-up of Adverse Events ................................................................................62
10.7
Withdrawal Due to an Adverse Event....................................................................63
10.7.1
Sponsor’s Reporting Requirements to Regulatory Authorities and 
Ethics Committees.................................................................................63
10.8
Pregnancy...............................................................................................................64
10.8.1
Time Period for Collecting Pregnancy Information..............................64
10.8.2
Action to be Taken if Pregnancy Occurs...............................................64
10.9
Definition of and Procedure for Reporting Medical Device Incidents..................64
10.9.1
Definition of an Incident .......................................................................65
10.9.2
Reporting of Incidents and Malfunctions..............................................65
10.9.3
Follow-up of Medical Device Incidents................................................67
10.9.4
Regulatory and Ethics Reporting Requirements for Incidents..............67
11 DATA MANAGEMENT ..................................................................................................67
11.1
Case Report Form ..................................................................................................68
11.2
Data Handling ........................................................................................................68
11.2.1
Data Queries..........................................................................................69
11.3
Processing Patient Reported Outcomes .................................................................69
11.4
External Data..........................................................................................................70
12 STATISTICAL CONSIDERATIONS AND DATA ANALYSES...................................70
12.1
Sample Size Determination....................................................................................70
12.2
Statistical Methods and Analytical Plan ................................................................70
12.2.1
Definition of Analysis Populations .......................................................71
12.2.2
Exclusion of Data from Analysis ..........................................................71
12.2.3
Demographic and Baseline Characteristics...........................................71
12.2.4
Study Drug/Product Compliance and Use of Other Therapies .............71
12.2.5
Primary Analysis ...................................................................................72
12.2.6
Secondary Analysis ...............................................................................72
12.2.7
Safety Analyses .....................................................................................73
12.2.8
Other Analyses ......................................................................................74
12.2.9
Handling of Dropouts and Missing Data...............................................74

5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
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GlaxoSmithKline Consumer Healthcare Confidential 
Template Version Effective: 18-May-18 (CCR #11475)
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12.2.10
Interim Analysis ....................................................................................74
13 STUDY GOVERNANCE CONSIDERATIONS..............................................................75
13.1
Quality Control ......................................................................................................75
13.2
Quality Assurance..................................................................................................75
13.3
Regulatory and Ethical Considerations..................................................................76
13.3.1
Institutional Review Board/ Ethics Committee.....................................76
13.3.2
Ethical Conduct of the Study.................................................................76
13.3.3
Subject Information and Consent..........................................................76
13.3.4
Subject Recruitment ..............................................................................77
13.3.5
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP ...............................................................................................77
13.4
Posting of Information on Publicly Available Clinical Trial Registers.................78
13.5
Provision of Study Results to Investigators...........................................................78
13.6
Records Retention..................................................................................................78
13.7
Conditions for Terminating the Study ...................................................................79
14 REFERENCES ..................................................................................................................81
15 APPENDICES ...................................................................................................................91
15.1
Abbreviations.........................................................................................................91
15.2
Dentine Hypersensitivity Experience Questionnaire (Example) ...........................93

5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
Protocol Number 209723
Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential 
Template Version Effective: 18-May-18 (CCR #11475)
Page 8 of 97
List of in text tables
Table 1-1
Schedule of Activities............................................................................12
Table 3-1
Study Objectives and Endpoints............................................................18
Table 6-1
Investigational/Study Product Supplies.................................................31
Table 6-2
Sundry Items..........................................................................................32
Table 15-1
Abbreviations ........................................................................................91

5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
Protocol Number 209723
Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential 
Template Version Effective: 18-May-18 (CCR #11475)
Page 9 of 97
1
PROTOCOL SUMMARY 
Background and Rationale
GlaxoSmithKline Consumer Healthcare (GSK CH) has developed an anhydrous 5% 
potassium nitrate (KNO3) and 0.454% stannous fluoride (SnF2) combination dentifrice for the 
relief of dentin hypersensitivity (DH).  It is hypothesized that the combination of two anti-
sensitivity active ingredients with complementary modes of action (KNO3: nerve 
desensitization; SnF2: dentin tubule occlusion) will deliver superior anti-sensitivity efficacy, 
compared to either active alone. Published clinical studies report DH efficacy for KNO3/SnF2 
combination dentifrices and indicate greater clinical benefit for dual active formulations, 
compared to KNO3 only formulations, with 4-8 weeks treatment. They do not provide any 
information regarding performance versus SnF2 only formulations (no SnF2 only dentifrices 
were evaluated). This exploratory study will characterize the efficacy profile of an 
experimental 5% KNO3 and 0.454% SnF2 combination dentifrice, compared to a 0.454% SnF2 
single active desensitizing dentifrice, across an 8-week treatment period. 
Objectives and Endpoints
Objectives
Endpoints
Primary
To characterize the efficacy profiles of an 
experimental 5% w/w KNO3 and 0.454% w/w SnF2 
combination dentifrice and a 0.454% w/w SnF2 only 
dentifrice in reducing DH, with twice daily use for 8 
weeks. 
At Baseline, Days 3, 7, 14, 28, 56; 
Schiff sensitivity score 
Tactile threshold (grams [g])
Number of sensitive teeth (Schiff 
sensitivity score ≥ 1) 
Secondary
To investigate the clinical efficacy of an experimental 
5% w/w KNO3 and 0.454% w/w SnF2 combination 
dentifrice in reducing DH to an evaporative air 
stimulus (Schiff sensitivity score), compared to a 
0.454% w/w SnF2 only dentifrice, after 8 weeks twice 
daily use.
Change from Baseline in Schiff 
sensitivity score at Day 56 
To investigate the clinical efficacy of an experimental 
5% w/w KNO3 and 0.454% w/w SnF2 combination 
dentifrice in reducing DH to a tactile stimulus (tactile 
threshold), compared to a 0.454% w/w SnF2 only 
dentifrice, after 8 weeks twice daily use. 
Change from Baseline in tactile 
threshold (g) at Day 56 
Safety
To assess the safety and tolerability of an experimental 
5% w/w KNO3 and 0.454% w/w SnF2 combination 
dentifrice with twice daily use for 8 weeks.
Treatment emergent adverse 
events
Other 
To investigate the clinical efficacy of an experimental 
5% w/w KNO3 and 0.454% w/w SnF2 combination 
At Days 3, 7, 14 & 28; 
Change from Baseline in Schiff 

5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
Protocol Number 209723
Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential 
Template Version Effective: 18-May-18 (CCR #11475)
Page 10 of 97
dentifrice in reducing DH to evaporative air (Schiff 
sensitivity score) and tactile (tactile threshold) stimuli, 
compared to a 0.454% w/w SnF2 only dentifrice, after 
3, 7, 14 & 28 days twice daily use.
sensitivity score 
Change from Baseline in tactile 
threshold (g)
To monitor Oral Health Related Quality of Life 
(OHRQoL) as measured by the Dentine 
Hypersensitivity Experience Questionnaire (DHEQ) 
after 4 and 8 weeks treatment with an experimental 5% 
w/w KNO3 and 0.454% w/w SnF2 combination 
dentifrice and a 0.454% w/w SnF2 only dentifrice
At Days 28 & Day 56; 
Change from Baseline in 
- responses to Questions 7-9, 
DHEQ Section 1
- Total Score, Questions 
1-15, DHEQ Section 2 
- Restrictions, Adaptation, 
Social Impact, Emotional 
Impact & Identity Domains
Study Design
This will be a single center, 8-week, randomized, controlled, examiner-blind, two treatment 
arm, parallel design, stratified (by maximum Baseline Schiff sensitivity score of the two 
selected test teeth), Phase II, exploratory study to evaluate the DH efficacy of an experimental 
5% KNO3 and 0.454% SnF2 combination dentifrice (Test), compared to a marketed 0.454% 
SnF2 desensitizing dentifrice (Control). Study dentifrices will be applied twice daily, by 
toothbrushing, over the 8-week treatment period. 
DH to tactile and evaporative air stimuli will be assessed at Screening (Visit 1) and Baseline 
(Visit 2), and after 3, 7, 14, 28 and 56 days treatment (Visits 3-7). Eligible subjects will 
complete an acclimatization phase (2-4 weeks) between the Screening and Baseline visits and 
will be randomized to study dentifrice following Baseline assessments. The safety and oral 
tolerability of the study products will be monitored over the treatment period by review of 
reported adverse events (AEs). 
Study Products
Acclimatization 
Dentifrice
Test 
Dentifrice
Control 
Dentifrice
Treatment 
Description
Dentifrice containing 
1000 parts per million 
(ppm) fluoride as 
sodium monofluoro-
phosphate (SMFP)
Dentifrice containing 
5% w/w KNO3 and 
0.454% w/w SnF2 
(1100 ppm fluoride)
Dentifrice containing 
0.454% SnF2 (1100 
ppm fluoride)
Product Name
Colgate Cavity 
Protection 
(Canadian market)
Experimental 
dentifrice
Sensodyne Rapid 
Relief Regular 
(registered as a Non-
prescription Natural 
Health Product 
[NNHP] in Canada)

5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
Protocol Number 209723
Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential 
Template Version Effective: 18-May-18 (CCR #11475)
Page 11 of 97
Type and Planned Number of Subjects
The study will be conducted in male and female subjects in good general health, aged 18-65 
years, with pre-existing self-reported tooth sensitivity, and at least two sensitive teeth 
(confirmed clinically) that meet all study criteria at both the Screening (Visit 1) and Baseline 
(Visit 2, pre-treatment) visits. Sufficient subjects will be screened (approximately 150 
subjects) to enter approximately 125 subjects into the acclimatization phase to ensure 
approximately 104 subjects are randomized to study treatment (approximately 52 subjects per 
treatment arm).
Statistical Analyses 
A modified Intent-To-Treat (mITT) population will be used for efficacy analyses. 
The primary efficacy variables are Schiff sensitivity score and tactile threshold (g), both 
calculated as the average score of the two test teeth, and the number of sensitive teeth (Schiff 
sensitivity score ≥ 1) at Day 0 (Baseline), Day 3, Day 7, Day 14, Day 28 and Day 56. Summary 
statistics (mean, median, standard error (SE), standard deviation (SD), minimum, maximum) 
will be presented for each outcome variable at each assessment time point.  Raw means (± SE) 
of Schiff sensitivity score, tactile threshold (g) and number of sensitive teeth at each timepoint 
will be plotted by treatment group. 
The secondary efficacy variables are change from Baseline in Schiff sensitivity score and the 
change from Baseline in tactile threshold (g), at Day 56. Change from Baseline in Schiff 
sensitivity score will be analysed at Day 56 using an analysis of covariance (ANCOVA) 
model which will include treatment as a factor and Baseline Schiff sensitivity score as a 
covariate. Change from Baseline in tactile threshold (g) will be analysed at Day 56 using an 
ANCOVA model with treatment and Baseline Schiff stratification included as factors and 
Baseline tactile threshold included as a covariate. Adjusted mean change from Baseline, along 
with 95% confidence intervals (CIs) will be reported by treatment group. P-values testing for 
non-zero change from baseline will be presented for both treatment groups. The mean 
difference between treatment groups, 95% CIs and p-values will be provided. Significance 
testing will be conducted at the two-sided 5% significance level with no adjustments for 
multiple testing. 

5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
Protocol Number 209723
Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential 
Template Version Effective: 18-May-18 (CCR #11475)
Page 12 of 97
1.1
Schedule of Activities
The schedule of activities table provides an overview of the subject visits and study procedures.  
The investigator may schedule visits (unplanned visits) in addition to those listed on the schedule of activities, in order to conduct evaluations or assessments 
required to protect the well-being of the subject.
Table 1-1
Schedule of Activities
Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Day 0
Day 3
Day 7
Day 14
Day 28 
Day 56
Procedure/ Assessment
Visit 1
Day -28 to -14 
Screening
Baseline
(+1day)
(±1day)
(±2days)
(±2days)
Informed Consent
X
Demographics
X
Medical History
X
Prior/Current Medications and Treatments
X
Review Subject’s Current Oral Care Products 
X
Subject Returns with Acclimatization Dentifrice, Toothbrush and Completed Diary1
X
Subject Returns with Study Treatment, Toothbrush and Completed Diary1 
X
X
X
X
X
Compliance Checks2
X
X
X
X
X
X
Concomitant Medications and Treatments
X
X
X
X
X
X
Urine Pregnancy Test (UPT)3 
X
X
Subject Continuance
X
X
X
X
X
Dentine Hypersensitivity Experience Questionnaire (DHEQ)4 
X
X
X
Oral Soft Tissue (OST) Examination
X
X
X
X
X
X
X
Oral Hard Tissue (OHT) Examination
X
X
Eligible Teeth Assessments (Dentition Exclusions, Erosion/Abrasion/Recession 
[EAR], Modified Gingival Index [MGI], Tooth Mobility)
X
Qualifying Tactile Sensitivity Assessment (Tactile Threshold)5
X
X
Qualifying Evaporative Air Sensitivity Assessment (Schiff sensitivity score)6
X
X
Inclusion / Exclusion Criteria
X
Acclimatization Period (2-4 Weeks)
X

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Visit 2
Visit 3
Visit 4
Visit 5
Visit 6
Visit 7
Day 0
Day 3
Day 7
Day 14
Day 28 
Day 56
Procedure/ Assessment
Visit 1
Day -28 to -14 
Screening
Baseline
(+1day)
(±1day)
(±2days)
(±2days)
Subject Eligibility
X
X
Clinical Examiner Selects Two ‘Test Teeth’ Eligible Subjects Only
X
Stratification/Randomization
X
Dispense Acclimatization dentifrice, Toothbrush, Diary and Timer
X
Supervised Brushing with Acclimatization Dentifrice
X
Dispense Study Treatment, Toothbrush and Diary
X
Tactile Sensitivity Assessment (Yeaple Probe)5 Test Teeth Only 
X
X
X
X
X
Evaporative Air Sensitivity (Schiff sensitivity score)6 Test Teeth Only
X
X
X
X
X
Evaporative Air Sensitivity (Schiff sensitivity score)6 
Remaining Eligible Teeth from Screening
X
X
X
X
X
X
Supervised Brushing with Study Treatment
X
X
X
X
X
Return Study Treatment/Toothbrush and Diary to Subject 
X
X
X
X
Provide Subject with New Diary
X
Adverse Events/Incidents7
X
X
X
X
X
X
X
Study Conclusion
X
Footnotes:
1.
Subject will be required to bring their study supplies (minus timer) to every visit. 
2.
Perform visual check of returned study supplies and review diary (Visit 2: compliance with use of acclimatization dentifrice; Visits 3-7: compliance with use of study treatment).
Check compliance with Lifestyle Guidelines/Medication Requirements. 
3.
Female subjects of child bearing potential only.
4.
DHEQ must be completed prior to OST examination/clinical assessments. 
5.
Visits 1-2: maximum force 20 g (Screening and Baseline); Visits 3-7: maximum force 80 g. 
6.
Evaporative air assessment will follow tactile assessment, with minimum 5 minutes between last tactile assessment and first evaporative (air) assessment (to allow tooth recovery).
Visits 3-7: Complete evaporative (air) assessments for 2 test teeth first, before assessing remaining eligible teeth from Screening.
7.
AEs, and therefore all Serious Adverse Events (SAEs), and incidents will be recorded from immediately after a subject consents to participate in the study (by the completion of the 
Informed Consent Form [ICF]) until 5 days after last dose of study treatment.

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2
INTRODUCTION
2.1
Study Rationale
GSK CH has developed a dual active dentifrice containing 5% KNO3 and 0.454% SnF2.  
Product development has been targeted at providing an effective dual active desensitizing 
formulation with improved efficacy compared to each single active ingredient, in an 
anhydrous toothpaste format.    
A number of published clinical studies report DH efficacy for combination KNO3/SnF2 
dentifrices, delivered from a dual chambered tube (Bae et al. 2015, Conforti et al. 2000, 
Schiff et al. 2000a, Schiff et al. 2000b, Sowinski et al. 2001, Sowinski et al. 2000a, 
Sowinski et al. 2000b). While the data would indicate greater clinical efficacy for the 
dual active formulations compared to KNO3 alone (after 4 and 8 weeks treatment), they 
do not provide any information regarding performance of a combination dentifrice versus 
a SnF2 only formulation.  This exploratory study will investigate the efficacy profile of 
an experimental dual active KNO3 and SnF2 combination dentifrice (single chamber 
tube) for the relief of DH, compared to a SnF2 only desensitizing dentifrice. Efficacy will 
be assessed at multiple time points over an 8-week treatment period, with a focus on Day 
56 (primary time point).  The data generated will provide an initial indication of the 
potential clinical benefit of a dual active formulation over a ‘stannous only’ formulation 
and will inform the design of future clinical studies investigating the efficacy of dual 
active anti-sensitivity dentifrices.
Complete information for the experimental KNO3 and SnF2 combination dentifrice may 
be found in the single reference safety document (SRSD), which for this study is the 
Investigator’s Brochure (IB). Seven clinical studies evaluating the efficacy of a 
combination KNO3/SnF2 dentifrice (delivered from a dual chambered tube) are reported 
in the scientific literature. In each study, subjects brushed twice daily with their assigned 
study dentifrice for the duration of the treatment period  [Short Term (14 days): (Conforti 
et al. 2000). Longer Term (8 weeks):(Schiff et al. 2000a, Schiff et al. 2000b, Sowinski et 
al. 2001, Sowinski et al. 2000a, Sowinski et al. 2000b). Only four of the seven studies 
reported safety outcomes (Conforti et al. 2000, Schiff et al. 2000a, Sowinski et al. 2000a, 
Sowinski et al. 2000b).  There were no adverse events in the 2-week study (Conforti et 
al. 2000); there were no adverse events which could be ascribed to use of the 
combination dentifrice in the three 8-week studies (Schiff et al. 2000a, Sowinski et al. 
2000a, Sowinski et al. 2000b). Based on the available non-clinical and clinical 
information, the combination of 5% KNO3 and 0.454% SnF2 is considered generally safe 
for topical oral use, when delivered from a dentifrice with twice daily brushing, under 

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controlled conditions of a clinical trial.  
2.2
Background
Dentin 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 et al. 1985, Canadian Advisory 
Board on Dentin Hypersensitivity 2003).  The hydrodynamic theory of DH hypothesizes 
that a stimulus external to the tooth (for example, a temperature/osmotic differential, 
pressure) causes movement of the fluid resident within exposed dentinal tubules 
(Brännström 1963). This movement may stimulate nerve processes in the dental pulp 
(Addy 2002, Hall et al. 2000), resulting in the characteristic short, sharp pain of DH. 
Currently there are two approaches for the management of DH: nerve desensitization and 
the occlusion of exposed dentin tubules. 
Nerve desensitizing agents, such as potassium nitrate (KNO3), generally require a period 
of use (e.g. 2-4 weeks) before their benefit is established. Delivery of potassium ions into 
exposed dentin tubules is believed to result in desensitization of pulpal nerve fibers 
thereby blocking the pain response (Addy and Smith 2010). KNO3 has been incorporated 
into oral hygiene products indicated for the relief of DH since the 1970s (Markowitz 
2009). In the United States (US), the Monograph for Oral Health Care Drug Products for 
Over-the-Counter Human Use recognizes the cumulative clinical efficacy of KNO3 in the 
relief of DH - ‘potassium nitrate’s effectiveness as a tooth desensitizer is cumulate...as it 
may take two or three weeks before significant therapeutic relief is obtained’ (Oral 
Health Care Drug Products for Over-the-Counter Human Use 1991). Many clinical 
studies (typically 4-12 weeks treatment) have been published demonstrating the efficacy 
of KNO3 for the relief of DH [for example, (Acharya et al. 2013, Ayad et al. 1994, 
Gallob et al. 2017, Gillam et al. 1996, Hu et al. 2004, Jeandot et al. 2007, Jiang et al. 
2009, Konekeri et al. 2015, Kumari et al. 2013, Kumari et al. 2016, Leight et al. 2008a, 
Li et al. 2013, Liang et al. 2011, Nagata et al. 1994, Orsini et al. 2010, Parkinson et al. 
2017, Pradeep et al. 2012, Pradeep and Sharma 2010, Salian et al. 2010, Salvato et al. 
1992, Satyapal et al. 2014, Schiff et al. 2000a, Schiff et al. 1994, Schiff et al. 2000b, 
Sharma et al. 2010, Shen et al. 2009, Silverman 1985, Silverman et al. 1996, Silverman 
et al. 1994, Sowinski et al. 2001, Sowinski et al. 2000a, Sowinski et al. 2000b, Surve et 
al. 2012, Wara-aswapati et al. 2005, West et al. 1997, Yates et al. 2005, Young et al. 
2017, Zhuang and Cao 2011). Although one literature review of DH studies describes the 
effectiveness of potassium-containing treatments as unproven (West et al. 2015), 
numerous clinical studies and a meta-analysis of randomized controlled trials (RCTs) 
(Bae et al. 2015) report potassium-containing desensitizing dentifrices to be clinically 
effective in the treatment of DH.

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Dentin tubule occluding agents, such as strontium salts, stannous salts, bioglasses or 
silicas serve to physically block or narrow the exposed ends of dentin tubules, reducing 
dentinal fluid movement, and thereby decreasing the effect of external stimuli.  Tubule 
occlusion can be favored over nerve desensitization, due to the more rapid onset of relief 
from DH (Gillam et al. 1996). Stannous fluoride (SnF2) has been incorporated into oral 
hygiene products indicated for the reduction of DH since the 1960s (Schiff et al. 2006).  
Its mechanism of action is thought to be via the chemical precipitation of tin salts which 
occlude exposed dentin tubules (Burnett 2013, Burnett et al. 2013, Earl and Langford 
2013).  Published clinical studies demonstrate the efficacy of stannous fluoride in 
providing both early onset (within days) and longer term (weeks) relief of DH [for 
example, Short Term (typically 1-14 days treatment): (Cepeda-Bravo et al. 2014, Creeth 
et al. 2017a, Creeth et al. 2017b, Goyal et al. 2017, He et al. 2014a, He et al. 2011a, He et 
al. 2011b, He et al. 2011c, He et al. 2011d, Parkinson et al. 2016, Seong et al. 2017, 
Sharma et al. 2011); Longer Term (typically 4-12 weeks treatment): (Chaknis et al. 2011, 
Day et al. 2010, Du et al. 2011, Gallob et al. 2017, Hazen et al. 1968, He et al. 2014b, Ni 
et al. 2011, Ni et al. 2010, Parkinson et al. 2013, Parkinson et al. 2015, Schiff et al. 2006, 
Schiff et al. 2005, Sharma et al. 2010, Vinaya et al. 2010)]. Review and meta-analyses of 
RCTs report desensitizing dentifrices containing stannous fluoride to be clinically 
effective in the treatment of DH (Bae et al. 2015, Gerlach and Sagel 2017, West et al. 
2015, Yang et al. 2016).
It can be hypothesized that the combination of these two anti-sensitivity active 
ingredients with complementary modes of action (KNO3 and SnF2) will deliver superior 
anti-sensitivity efficacy, compared to either active alone. 

SnF2 does not form a ‘wholly protective’ layer over the dentin (Mason et al. 
2009), as evidenced by longer term clinical studies in the literature which at no 
time report complete resolution of DH. 

Occlusion is a dynamic process - occlusive deposits are formed, lost through acid 
dissolution/physical wear processes within the oral cavity (e.g. dietary acid 
challenge, tooth brushing, mastication), and then replaced/maintained with 
repeated, twice daily treatment (Markowitz 2009). 

With a dual active KNO3/SnF2 anti-sensitivity system, it can be envisaged that 
sensitivity arising from any un-occluded/re-exposed areas of the dentin could be 
treated by the ingress of potassium ions into patent tubules and subsequent 
desensitization of the intra-dental nerves. 
Several clinical studies report DH efficacy for combination 5% KNO3/0.454-0.590% 
SnF2 dentifrices, delivered from a dual chambered tube [Short Term (14 days): (Conforti 

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et al. 2000). Longer Term (8 weeks): (Bae et al. 2015, Schiff et al. 2000a, Schiff et al. 
2000b, Sowinski et al. 2001, Sowinski et al. 2000a, Sowinski et al. 2000b)].  While these 
studies are not directly comparable, due to differences in study design (differing 
assessment time points; differing control products, different marketed potassium nitrate 
formulations), they indicate greater clinical benefit for dual active anti-sensitivity 
formulations, compared to KNO3 only formulations, with 4-8 weeks treatment.  They do 
not provide any information regarding performance versus SnF2 only formulations (no 
SnF2 only dentifrices were evaluated). 
The aim of the current exploratory clinical study is therefore to investigate the efficacy 
profile of an experimental dual active (KNO3 and SnF2) dentifrice for the relief of DH at 
multiple time points over an 8-week treatment period, compared to a single active (SnF2 
only) desensitizing dentifrice.  Data generated will aid in the design of future clinical 
studies investigating the efficacy of dual active anti-sensitivity dentifrice formulations.
2.3
Mechanism of Action/Indication
Potassium ions (K+) are thought to relieve DH by reducing the excitability of the intra-
dental nerves.  After each brushing with a K+ containing toothpaste, the concentration of 
K+ ions at the tooth surface is raised.  K+ ions move into the dentin through the tubules, 
gradually desensitizing the nerves at the center of the tooth and thereby providing relief 
from DH.  
Occlusion agents act by physically blocking or narrowing the exposed ends of the dentin 
tubules, thereby reducing dentinal fluid movement and decreasing the effect of external 
stimuli. SnF2 is known to rapidly oxidize (from Sn [II] to Sn[IV]) and hydrolyze in the 
presence of water (saliva) and saliva-derived ions to form insoluble tin compounds 
(hydroxides, oxides and phosphates) (Makin 2013, Miller et al. 1994). Stannous ions 
have been shown in vitro to form insoluble precipitates on the dentin surface and within 
dentin tubules (at the oral cavity end of the tubule) through combination with formulation 
excipients and saliva-derived ions (Ellingsen and Rolla 1987, Miller et al. 1994, 
Parkinson and Willson 2011, Shi et al. 2012, White et al. 2007, Zsiska et al. 2012, Zsiska 
et al. 2011), thereby providing relief from DH.
The combination of these two active ingredients (KNO3 and SnF2) in a dentifrice format 
will be investigated in subjects with DH.

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3
STUDY OBJECTIVES AND ENDPOINTS
Table 3-1
Study Objectives and Endpoints
Objectives
Endpoints
Primary
To characterize the efficacy profiles of an 
experimental 5% w/w KNO3 and 0.454% w/w 
SnF2 combination dentifrice and a 0.454% w/w 
SnF2 only dentifrice in reducing DH, with twice 
daily use for 8 weeks. 
At Baseline, Days 3, 7, 14, 28, 56; 
Schiff sensitivity score 
Tactile threshold (grams [g])
Number of sensitive teeth (Schiff 
sensitivity score ≥ 1) 
Secondary
To investigate the clinical efficacy of an 
experimental 5% w/w KNO3 and 0.454% w/w 
SnF2 combination dentifrice in reducing DH to 
an evaporative air stimulus (Schiff sensitivity 
score), compared to a 0.454% w/w SnF2 only 
dentifrice, after 8 weeks twice daily use.
Change from Baseline in Schiff 
sensitivity score at Day 56 
To investigate the clinical efficacy of an 
experimental 5% w/w KNO3 and 0.454% w/w 
SnF2 combination dentifrice in reducing DH to a 
tactile stimulus (tactile threshold), compared to a 
0.454% w/w SnF2 only dentifrice, after 8 weeks 
twice daily use. 
Change from Baseline in tactile 
threshold (g) at Day 56 
Safety
To assess the safety and tolerability of an 
experimental 5% w/w KNO3 and 0.454% w/w 
SnF2 combination dentifrice with twice daily use 
for 8 weeks.
Treatment emergent adverse events
Other 
To investigate the clinical efficacy of an 
experimental 5% w/w KNO3 and 0.454% w/w 
SnF2 combination dentifrice in reducing DH to 
evaporative air (Schiff sensitivity score) and 
tactile (tactile threshold) stimuli, compared to a 
At Days 3, 7, 14 & 28; 
Change from Baseline in Schiff 
sensitivity score 
Change from Baseline in tactile 
threshold (g)

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0.454% w/w SnF2 only dentifrice, after 3, 7, 14 
& 28 days twice daily use.
To monitor Oral Health Related Quality of Life 
(OHRQoL) as measured by the Dentine 
Hypersensitivity Experience Questionnaire 
(DHEQ) after 4 and 8 weeks treatment with an 
experimental 5% w/w KNO3 and 0.454% w/w 
SnF2 combination dentifrice and a 0.454% w/w 
SnF2 only dentifrice
At Days 28 & Day 56; 
Change from Baseline in 
- responses to Questions 7-9, 
DHEQ Section 1
- Total Score, Questions 
1-15, DHEQ Section 2 
- Restrictions, Adaptation, Social 
Impact, Emotional Impact & 
Identity Domains
This exploratory study will be considered successful if the efficacy profiles of both study 
products indicate a reduction in sensitivity. In addition to this reduction, a statistically 
significant difference in change from Baseline in Schiff sensitivity score at Day 56 
between the Test and Control dentifrices, in favour of the Test dentifrice would be 
viewed as success. 
4
STUDY DESIGN 
4.1
Overall Design
This will be a single center, 8-week, randomized, controlled, examiner-blind, two 
treatment arm, parallel design, stratified (by maximum Baseline Schiff sensitivity score 
of the two selected test teeth), Phase II, exploratory clinical study in healthy subjects with 
DH. Eligible subjects will enter a 2-4 week acclimatization phase between the Screening 
and Baseline assessments. Subjects who meet all study criteria at both Screening and 
Baseline visits will be randomized to study treatment.
DH to tactile and evaporative air stimuli will be assessed at Screening (Visit 1) and then 
at multiple time points across the 8-week treatment period - for all qualifying teeth at 
Baseline (Day 0) and then for two ‘test teeth’ only from Day 3 onwards (Days 3, 7, 14, 
28 and 56).  In addition, the remaining qualifying teeth identified at Screening will be 
assessed for evaporative air sensitivity from Day 3 onwards (Days 3, 7, 14, 28 and 56). A 
single clinical examiner will be responsible for the conduct of both clinical measures of 
DH for the duration of the study for all study subjects. 
Safety and oral tolerability of the study products will be monitored over the 8-week 
treatment period by review of reported AEs and incidents. 

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4.2
Rationale for Study Design
In line with published recommendations for the design and conduct of DH clinical trials 
(Holland et al. 1997), two independent stimulus-based efficacy measures will be 
employed (tactile and thermal [evaporative air] sensitivity) to assess the efficacy of the 
study dentifrices.  

A tactile stimulus will be administered using a constant pressure probe (Yeaple 
Probe (Polson et al. 1980)).  Subject response to this stimulus will be recorded as 
tactile threshold in g.  

An evaporative (air) stimulus will be administered using a dental air syringe. 
Subject response to this stimulus will be evaluated using the Schiff sensitivity 
scale (Schiff et al. 1994).  
On completion of the Baseline assessments, the clinical examiner will select two ‘test 
teeth’ from those that qualified at Screening and Baseline, for assessment of tactile and 
evaporative air sensitivity at all subsequent visits.  The selection of two ‘test teeth’ to 
evaluate changes in DH is common practice in sensitivity studies (Schiff et al. 1994). 
Eligible subjects will be stratified after the Baseline assessments according to the 
maximum Schiff sensitivity score of their two selected ‘test teeth’ to ensure treatment 
groups are balanced for sensitivity severity. 
Study subjects will be recruited between 18 and 65 years of age (DH is most frequently 
diagnosed between the ages of 20 and 40 years and is known to decrease with age above 
40 years (Dababneh et al. 1999, West 2006).  
The Investigational Product (IP) is an experimental dual active (KNO3/SnF2) dentifrice. 
The Control is a single active (SnF2 only) dentifrice, selected as a representative 0.454% 
SnF2 desensitizing formulation, and is registered as a Non-prescription Natural Health 
Product (NNHP) in Canada. The two dentifrices will be identical in visual appearance 
(white pastes, packaged in plain white laminate tubes) and flavour, but may differ in 
rheology. The level of blindness for this study is therefore described as ‘examiner-blind’. 
For a study to be classed as truly double blind, not only does the examiner (and any 
member of staff involved in the dispensing of products, analysis of data etc.) need to be 
blind to the treatment received, but the products under test should be identical (in color, 
flavor, rheology, appearance and packaging). Study dentifrices will be dispensed in a 
blinded fashion to the subject, by trained site personnel who are not involved in clinical 
efficacy assessment procedures, in a separate area from the clinical examination area.
Clinical trials evaluating clinical end points relating to pain can be prone to ‘placebo 
effects’ (Addy et al. 1985, West et al. 1997). Such effects are frequently observed in DH 

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studies. A clinical study conducted to evaluate the natural history of the DH condition 
also highlighted the existence of a ‘no treatment’ effect, characterized by an 
improvement in sensitivity simply as a result of study participation (Leight et al. 2008b). 
To help minimize the potential impact of such effects, it is relatively common to include 
a lead-in (acclimatization) period prior to Baseline assessments, and to randomize only 
subjects whose signs or symptoms remain above a pre-specified entry level value. This 
helps to ensure that subjects who would show improvement for reasons other than a 
response to study treatment (spontaneous improvement, ‘placebo effect’, their own 
expectations or clinical observation) are not randomized (i.e. subjects incapable of 
showing a treatment response). During the acclimatization period subjects will be 
provided with a marketed, regular fluoride toothpaste and toothbrush to use in place of 
their own oral hygiene products. Use of these products will also help provide the study 
population with a standardized oral hygiene regimen prior to the Baseline visit and 
familiarize them with completion of a product usage diary after each brushing. 
DH is an episodic condition; symptoms are known to vary spontaneously (West 2008, 
West et al. 2013). Baseline clinical values that would support enrolment may represent 
random highs in the condition that will be followed by regression to the mean, leaving 
the subject or a particular sensitive tooth without the condition under investigation during 
the treatment period. To help minimize the potential for this to occur on the current 
study, subjects will be required to demonstrate consistency in response at both the 
Screening and the Baseline visits (qualifying responses to tactile and evaporative air 
stimuli must be met at Screening and Baseline).  
With the growing acknowledgment of the value of information gleaned directly from the 
subject, self-reported outcome measures have become increasingly important barometers 
of the benefit of medical interventions. The dentine hypersensitivity questionnaire 
(DHEQ) is a validated, condition specific measure of impacts on everyday life for DH 
sufferers which has been shown to have good psychometric properties in both the general 
population and in a clinical sample of DH sufferers (Baker et al. 2014, Boiko et al. 2010). 
A short form of the DHEQ has also been developed and validated (Machuca et al. 2014), 
and will be included in this study to evaluate treatment impacts in a clinically diagnosed 
DH population.
4.3
Justification for Dose
The study products are dentifrices, intended for topical oral use, and will be applied by 
toothbrushing using a manual toothbrush. 
The dosage regimen of twice daily treatment (morning and evening) will be the same for 
all subjects and is based on widely recommended oral hygiene practice/typical consumer 

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habit. Study subjects will be required to brush for at least 1 timed minute with their 
assigned study dentifrice on each brushing occasion. To align with the usage instructions 
of the marketed, stannous-only dentifrice, subjects will brush their two selected sensitive 
‘test teeth’ first, followed by their whole mouth. After 8 weeks (Day 56 ±2 days) twice-
daily treatment, each subject should complete between 108-116 treatments.
Each subject will complete a supervised brushing with their assigned study dentifrice at 
the end of each study visit (while still at the study site) to enable staff to check correct 
dosing and encourage compliance with product usage throughout the study.    
4.4
End of Study Definition
A subject is considered to have completed the study if he or she has completed all phases 
of the study including the last visit or the last scheduled procedure shown in the Schedule 
of Activities.
The end of this study is defined as the date of the last scheduled procedure shown in the 
Schedule of Activities for the last subject in the trial. 
5
STUDY POPULATION
5.1
Type and Planned Number of Subjects
The study will be conducted in male and female subjects in good general health, with pre-
existing self-reported tooth sensitivity, and at least two sensitive teeth (DH confirmed 
clinically) that meet all study criteria at both the Screening (Visit 1) and Baseline (Visit 2 
- pre-treatment) visits. Sufficient subjects will be screened (approximately 150 subjects) 
to enter approximately 125 subjects into the acclimatization phase to ensure approximately 
104 subjects are randomized to study treatment (approximately 52 subjects per treatment 
arm). Subjects will be recruited primarily from the study site’s database.
This study can fulfill its objectives only if appropriate subjects are enrolled.  The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate.  All relevant medical and non-medical conditions should be taken 
into consideration when deciding whether a subject is suitable for this protocol.  
Subject eligibility to participate in the clinical study should be reviewed and documented 
by an appropriate member of the investigator’s study team before subjects are included in 
the study.

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5.2
Inclusion Criteria
An individual must meet all of the following inclusion criteria to be eligible for enrollment 
into the study.
1. Subject provision of a signed and dated informed consent document indicating that 
the subject has been informed of all pertinent aspects of the study before any 
assessment is performed.
2. Male or female subject who, at the time of screening, is between the ages of 18 and 
65 years, inclusive.
3. Subject who is willing and able to comply with scheduled visits, treatment plan, and 
other study procedures.
4. Subject in good general, oral and mental health with, in the opinion of the 
investigator or medically qualified designee, no clinically significant/relevant 
abnormalities in medical history, or upon oral examination, or condition that would 
impact the subject’s safety, wellbeing or the outcome of the study, if they were to 
participate in the study, or affect the individual’s ability to understand and follow 
study procedures and requirements.
5. Male subject able to father children or female subject of child-bearing 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.  A 
female subject who is of child-bearing potential must meet requirements in Section 
5.5.3.
6. AT VISIT 1 (Screening): 
Subject must have
a) a self-reported history of DH lasting more than six months but not more than 10 
years.
b) a minimum of 20 natural teeth.
c) a minimum of 2 accessible, non-adjacent teeth (incisors, canines, pre-molars), 
preferably in different quadrants, with clinically diagnosed DH; each tooth must 
meet the following criteria:
- exposed dentin due to facial/cervical erosion, abrasion or gingival recession 
(EAR).
- MGI score = 0 adjacent to the test area (exposed dentin) only (Lobene et al. 
1986) 

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- clinical mobility ≤ 1 (Laster et al. 1975)
- DH, as evidenced by qualifying levels of tactile and evaporative air sensitivity 
(tactile threshold ≤ 20 g; Schiff sensitivity score ≥ 2).
7. AT VISIT 2 (Baseline): 
Subject must have a minimum of two, non-adjacent accessible teeth (incisors, 
canines, pre-molars), preferably in different quadrants, with DH, as evidenced by 
qualifying tactile and evaporative air sensitivity (each tooth must have a tactile 
threshold ≤ 20 g and a Schiff sensitivity score ≥ 2) at the Screening and Baseline 
visits.
Note: All teeth which meet the sensitivity criteria (tactile threshold ≤ 20g; Schiff 
sensitivity score ≥ 2) at Screening (Visit 1) should be assessed by tactile and 
evaporative air stimuli at Baseline (Visit 2). 
The examiner will select two ‘Test Teeth’ from those which meet the tactile threshold 
and Schiff sensitivity score inclusion criteria at Screening and Baseline. Test Teeth 
should not be adjacent to each other and preferably in different quadrants.
5.3
Exclusion Criteria
An individual who meets any of the following exclusion criteria will not be eligible for 
enrollment into the study.
1. Subject who is an employee of the investigational site, either directly involved in the 
conduct of the study or a member of their immediate family; or an employee of the 
investigational site otherwise supervised by the investigator; or a GSK CH employee 
directly involved in the conduct of the study or a member of their immediate family.
2. Subject who has participated in other studies (including non-medicinal studies) 
involving investigational product(s) within 30 days prior to study entry and/or during 
study participation.
3. Subject with, in the opinion of the investigator or medically qualified designee, an 
acute or chronic medical, oral, psychiatric condition or laboratory abnormality that 
may increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator or medically qualified designee, would make the subject 
inappropriate for entry into this study.
4. Subject with any condition which, in the opinion of the investigator or medically 
qualified designee, causes xerostomia.

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5. Subject who is a pregnant female (as evidenced by a positive UPT at Screening).
6. Subject who is a breast-feeding female.
7. Subject with known or suspected intolerance or hypersensitivity to the study 
materials (or closely related compounds) or any of their stated ingredients. 
8. Subject who is unwilling or unable to comply with the Lifestyle Considerations 
described in this protocol (Section 5.5).
9. Subject with a recent history (within the last year) of alcohol or other substance 
abuse.
10. Subject who has participated in another tooth desensitizing treatment study within 8 
weeks Screening.
11. Subject who has used an oral care product indicated for the relief of DH within 8 
weeks of Screening (subject 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. Subject who has had dental prophylaxis within 4 weeks of Screening.
13. Subject who has had a teeth bleaching procedure within 8 weeks of Screening.
14. Subject who has had treatment for periodontal disease (including surgery) within 12 
months of Screening
15. Subject who has had scaling or root planning within 3 months of Screening.
16. Subject with gross periodontal disease
17. Subject with evidence of gross intra-oral neglect or the need for extensive dental 
therapy.
18. Subject with a tongue or lip piercing or presence of multiple dental implants.
19. Subject with fixed or removable partial dentures.
20. Subject with fixed or removable orthodontic braces/bands or a fixed orthodontic 
retainer.
21. SPECIFIC DENTITION EXCLUSIONS FOR ‘TEST TEETH’:
a) Tooth with evidence of current or recent caries or reported treatment of decay 
within 12 months of Screening.
b) Tooth with exposed dentin but with deep, defective or facial restorations.
c) Tooth with full crown or veneer.

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d) Sensitive tooth with contributing etiologies other than erosion, abrasion or 
recession to exposed dentin.
e) Sensitive tooth not expected to respond to treatment with an over-the-counter 
dentifrice in the opinion of the investigator.
22. Subject taking daily doses of medication/treatments which, in the opinion of the 
investigator or medically qualified designee, could interfere with the perception of 
pain (examples of such medications include analgesics, anticonvulsants, 
antihistamines that cause marked or moderate sedation, sedatives, tranquilizers, anti-
depressants, mood-altering and anti-inflammatory drugs).
23. AT VISIT 1 (Screening): 
Subject who has taken antibiotics in the 2 weeks prior to the Screening visit.
24. AT VISIT 2 (Baseline): 
Subject who has taken antibiotics in the 2 weeks prior to the Baseline visit, during the 
acclimatization period.
25. Subject taking daily doses of a medication which, in the opinion of the investigator or 
medically qualified designee, is causing xerostomia.
26. Subject who requires antibiotic prophylaxis for dental procedures.
27. Subject who has previously been enrolled in this study.
28. Subject who, in the opinion of the investigator or medically qualified designee, 
should not participate in the study.
5.4
Randomization Criteria
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria.
Subjects will be stratified according to the maximum Baseline Schiff sensitivity score of 
their two selected ‘test teeth’. The stratification factor will give rise to two strata.

Stratum 1: maximum Schiff sensitivity score = 2. 

Stratum 2: maximum Schiff sensitivity score = 3. 
5.5
Lifestyle Considerations
If, in the opinion of the investigator or medically qualified designee, a subject has not 
complied with a study restriction (oral hygiene, dietary or alcohol-related) prior to a 

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study visit, every effort will be made to reappoint them (within permitted visit tolerances, 
see Schedule of Activities (Table 1-1)). The reason for re-appointment will be 
documented in the CRF. If this is not possible, the following visit specific actions should 
be taken. 

Screening (Visit 1): if the subject cannot be reappointed, they will be withdrawn 
from the study (Section 7.1). No clinical efficacy assessments will be performed. 
The subject may be replaced.

Baseline (Visit 2): if the subject cannot be reappointed, they will be withdrawn 
from the study (Section 7.1). No clinical efficacy assessments will be performed. 
The subject will not be replaced.

Day 3 (Visit 3): the subject will continue in the study. No clinical efficacy 
assessments will be performed.

Days 7, 14 & 28 (Visits 4-6): if the subject cannot be reappointed (within the 
visit tolerance for Visits 4-6), they will continue in the study. No clinical efficacy 
assessments will be performed.

Day 56 (Visit 7): if the subject cannot be reappointed, they will be withdrawn 
from the study (Section 7.1). No clinical efficacy assessments will be performed. 
The subject will not be replaced.
5.5.1
Oral Hygiene Restrictions 
For the Duration of the Study: Screening (Visit 1) to the Subject’s Last Study Visit

Subjects should not use any other oral care products (for example, dentifrices, 
toothbrushes, oral rinses, tongue cleaners, whitening/bleaching products, inter-
dental cleaning products) than those provided during the study.
Note: dental floss can be used to remove impacted food.

Subjects should not use any other dental products intended for treating sensitive 
teeth (including herbal remedies) than those provided during the study.

Subjects should not chew gum.
Before a Clinical Efficacy Assessment Visit: Baseline (Visit 2) to Day 56 (Visit 7)

Subjects will refrain from all oral hygiene procedures for at least 8 hours before a 
study visit.

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5.5.2
 Dietary and Alcohol Restrictions 
Before a Clinical Efficacy Assessment Visit: Baseline (Visit 2) to Day 56 (Visit 7)

Subjects should not eat or drink for at least 4 hours before a study visit. 
Small sips of room-temperature water will be permitted to take medications or to 
relieve a dry mouth up to 1 hour before attending the study site (but not within 1 
hour of the visit). 

Subjects should refrain from excessive alcohol consumption for 24 hours before a 
study visit. 
5.5.3
Contraception
All male subjects able to father children and female subjects who are of child-bearing 
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 assigned treatment. 
Female subjects of non-childbearing potential must meet at least one of the following 
criteria (subject-reported):

female who has achieved post-menopausal status, defined as cessation of regular 
menses for at least 12 consecutive months with no alternative pathological or 
physiological cause;  

female who has undergone a documented hysterectomy and/or bilateral 
oophorectomy;

female who has undergone one of the following procedures: bilateral tubal 
ligation or salpingectomy; hysteroscopic tubal occlusion procedure with follow-
up confirmation of bilateral tubal occlusion;

female who has medically confirmed ovarian failure;

female who is pre-menarcheal.
The investigator or their 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 addition, the investigator or their 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 or the subject’s partner. 
The following is the all-inclusive list of the highly effective methods for avoiding 
pregnancy that meets the GSK definition (i.e., have a failure rate of less than 1% per year 

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when used consistently and correctly and, when applicable, in accordance with the 
product label) (Guidance on Reproductive Issues in Clinical Studies GSK Cross-Business 
). 
The list does not apply to females of reproductive potential with same sex partners or for 
subjects who are and will continue to be abstinent from penile-vaginal intercourse on a 
long term and persistent basis, when this is their preferred and usual lifestyle. Periodic 
abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and 
withdrawal are not acceptable methods of contraception.
1. Contraceptive subdermal implant
2. Intrauterine device (IUD) or intrauterine system
3. Combined estrogen and progestogen oral contraceptive 
4. Injectable progestogen 
5. Contraceptive vaginal ring 
6. Percutaneous contraceptive patches 
7. Male partner sterilization with documentation of azoospermia prior to the female 
subject's entry into the study, and this male is the sole partner for that subject. The 
documentation on male sterility can come from site personnel review of subject’s 
medical records, medical examination and/or semen analysis, or medical history 
interview provided by her or her partner.
These allowed methods of contraception are only effective when used consistently, 
correctly and in accordance with the product label. The investigator will confirm that 
subjects have had instruction in how to properly use these methods of contraception from 
an appropriately trained health care professional and will document such conversation. 
Male subjects with female partners of child-bearing potential must comply with the 
following contraception requirements from the time of first dose of study medication 
until at least 5 days after the last dose of assigned treatment [Guidance on Reproductive 
Issues in Clinical Studies GSK Cross-Business 
1. Vasectomy with documentation of azoospermia. The documentation on male 
sterility can come from site personnel: review of subject’s medical records, 
medical examination and/or semen analysis, or medical history interview.
2. Male condom plus partner use of one of the contraceptive options below that 
meets the effectiveness criteria including a less than 1% rate of failure per year, 
as stated in the product label:
CCI
CCI

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- Contraceptive subdermal implant
- IUD or intrauterine system
- Combined estrogen and progestogen oral contraceptive 
- Injectable progestogen 
- Contraceptive vaginal ring 
- Percutaneous contraceptive patches 
These allowed methods of contraception are only effective when used consistently, 
correctly and in accordance with the product label. The investigator will confirm that 
subjects have had instruction in how to properly use these methods of contraception from 
an appropriately trained health care professional and will document such conversation.
5.6
Screen Failures
Screen failures are defined as subjects who consent to participate in the clinical study but 
are not subsequently randomized. To ensure transparent reporting of screen failure 
subjects, a minimal set of screen failure information will include demography, screen 
failure details (e.g. withdrawal of consent), eligibility criteria, and any adverse events or 
incidents as applicable. 
Individuals who do not meet the criteria for participation in this study (screen failure) 
may not be re-screened.
5.7
Sponsor’s Qualified Medical Personnel
Contact information for the sponsor's appropriately qualified medical/dental personnel 
for the study is documented in the Study Contact List located in the investigator study 
master file held at the study site.
The contact number is only to be used by investigational staff seeking advice on medical/ 
dental questions or problems in the event that the established communication pathways 
between the investigational site and the study team are not available.  
The contact number is not intended for direct use by study subjects.  To facilitate access 
to appropriately qualified medical/dental personnel on study-related medical/dental 
questions or problems, subjects will be provided with a contact card.  The contact card 
will provide, as a minimum, protocol identifiers, the subject’s study identification 
number, contact information for the investigational site, and contact details in the event 
that the investigational site cannot be reached to provide advice on a medical question or 
problem identified by a healthcare professional other than the investigator.  

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5.8
Rater/Clinical Assessor Qualifications 
Clinical examiners involved in screening and efficacy assessment procedures will be 
qualified dentists, registered to practice in Canada. Oral examinations to determine 
subject eligibility and all safety/efficacy (tactile threshold/ Schiff sensitivity scale) 
assessments will be performed by appropriately trained clinical examiners. No additional 
qualifications are required for the clinical examiners involved in this study.
6
INVESTIGATIONAL/STUDY PRODUCTS
For the purposes of this study, per International Conference on Harmonization (ICH) 
guidelines, and GSK policy, investigational product is defined as a pharmaceutical form 
of an active ingredient, a non-medicinal product (marketed or investigational), or a 
placebo, being tested or used as a reference (positive or negative control), in a clinical 
trial. This includes a product with a marketing authorization when used or assembled 
(formulated or packaged) in a way different from the approved form, or when used for an 
unapproved indication, or when used to gain further information about an approved use. 
6.1
Investigational/Study Product Supplies
The following study products will be supplied by the Clinical Supplies Department, GSK 
CH.
Table 6-1
Investigational/Study Product Supplies
Acclimatization 
Dentifrice
Test 
Dentifrice
Control 
Dentifrice
Treatment 
Description
Dentifrice containing 
1000 ppm fluoride as 
SMFP
Dentifrice containing 5% 
w/w potassium nitrate 
and 0.454% w/w 
stannous fluoride 
(1100 ppm fluoride)
Dentifrice containing 
0.454% stannous fluoride 
(1100 ppm fluoride)
Product Name
Colgate Cavity 
Protection 
(Canadian market)
Experimental dentifrice
Sensodyne Rapid Relief 
Regular (registered as 
NNHP in Canada)
Pack Design
One carton containing 
two tubes
One carton containing 
two tubes
One carton containing 
two tubes
Dispensing 
Details
One carton (two tubes) at 
Screening 
Two cartons (four tubes) 
at Baseline 
Two cartons (four tubes) 
at Baseline

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Product Master 
Formulation 
Code (MFC)
Commercial Product
Dose/Application
Subjects will dose the 
toothbrush provided with 
a strip of dentifrice (a full 
brush head) on each 
brushing occasion
Subjects will dose the 
toothbrush provided with 
a strip of dentifrice (a full 
brush head) on each 
brushing occasion
Subjects will dose the 
toothbrush provided with 
a strip of dentifrice (a full 
brush head) on each 
brushing occasion
Route of 
Administration
Oral topical use
Oral topical use
Oral topical use
Usage 
Instructions
Subjects will brush for at 
least one timed minute, 
twice daily (morning and 
evening); subjects will be 
permitted to rinse with 
water post-brushing.
Subjects will brush their 
two selected ‘test teeth’ 
first, followed by the 
whole mouth for at least 
one timed minute, twice 
daily (morning and 
evening); subjects will be 
permitted to rinse with 
water post-brushing.
Subjects will brush their 
two selected ‘test teeth’ 
first, followed by the 
whole mouth for at least 
one timed minute, twice 
daily (morning and 
evening); subjects will be 
permitted to rinse with 
water post-brushing.
Return 
Requirements
All used/unused samples 
to be returned
All used/unused samples 
to be returned
All used/unused samples 
to be returned
Table 6-2
Sundry Items
Return/Disposal Details
Item
Supplied 
By
Pack Design
Dispensing Details
Used Samples
Unused 
Samples
Oral B 
Sensi-soft 
toothbrush 
(Canadian 
market)
GSK CH
Individual 
toothbrush in 
commercial 
pack 
One toothbrush at 
Screening for use with 
acclimatization product
One toothbrush at 
Baseline for use with 
assigned study dentifrice
Destroy at site 
using site 
disposal 
procedures
Return to 
3rd party 
vendor 
Countdown 
Timer
GSK CH
Individual timer 
in commercial 
pack 
One timer at Screening
Subject to keep 
or destroy at 
site using site 
disposal 
procedures
Return to 
3rd party 
vendor 
CCI
CCI

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Pregnancy 
Tests 
(Canadian 
market)
GSK CH
Commercial 
pack
Use as per study 
schedule
Destroy at site 
using site 
disposal 
procedures
Return to 
3rd party 
vendor 
For further information, please refer to the Global Clinical Supplies (GCS) Packaging 
and Labelling Proposal.
GSK CH will ensure copies of the diary (which will also include dentifrice usage 
instructions), the clinical assessment score sheets, the DHEQ and the Subject Contact 
Cards are provided to the study site.
Detailed instructions for the return of study product/study supplies for the accountability 
checks and subsequent destruction will be provided by GSK CH during the course of the 
study in time for study close out visit.
6.1.1
Dosage Form and Packaging
All study products are dentifrices, intended for topical oral use, and will be applied by 
toothbrushing using a manual toothbrush.
The IP and the Control dentifrice will be manufactured and filled into plain white tubes 
by GSK CH with a study label affixed. The acclimatization dentifrice will be supplied in 
its’ commercial pack and overwrapped in white vinyl (to mask its’ identity and obscure 
any branding) with a study label affixed. The content of the product labels will be in 
accordance with all applicable regulatory requirements and will be the responsibility of 
the GSK CH GCS group. Each study label will contain, but not be limited to, protocol 
number, directions for use and storage requirements.
Each subject will receive sufficient tubes of the acclimatization dentifrice and their 
assigned study dentifrice to cover usage during the acclimatization and treatment periods, 
respectively. Acclimatization dentifrice will be dispensed at Screening (Visit 1); study 
dentifrice will be dispensed at Baseline (Visit 2).  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 will be instructed to not remove or deface any part of 
a product label. 
All products supplied are for use only in this clinical study and should not be used for 
any other purpose.

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6.1.2
Preparation and Dispensing 
Subjects will be assigned to products in accordance with the randomization schedule 
generated by an approved GSK CH vendor, prior to the start of the study, using validated 
software.
The product dispensing area will be separate from the clinical examination area. Study 
dentifrices will be dispensed in blinded fashion to the subject, by trained site personnel. 
These staff members will not be involved in any safety/efficacy assessments or other 
aspects of the study that could be influenced by the knowledge of product a subject has 
been assigned to. An additional member of the site staff will verify the dispensing 
procedure has been completed accurately for each subject. 
A record of product dispensing to each subject will be maintained in the dispensing log; 
completion of the dispensing procedure will be recorded in the case report form (CRF).
6.2
Administration
Subjects will be instructed to self-administer the acclimatization dentifrice and their 
assigned study dentifrice according to the usage instructions provided at the study site 
and detailed in the diary.  To help ensure subjects fully understand the dose of dentifrice 
to be used each time they brush and the usage instructions:

staff will demonstrate dispensing a full ribbon of dentifrice along the length of the 
toothbrush head to each eligible subject and supervise their first brushing with the 
acclimatization dentifrice/diary completion at the end of the Screening visit (Visit 
1), after all clinical assessments have been completed;

staff will supervise the first brushing with study dentifrice/diary completion at the 
end of the Baseline visit (Visit 2), after all clinical assessments have been 
completed;

staff will supervise a brushing with study dentifrice/diary completion at the end of 
the Day 3, Day 7, Day 14 and Day 28 visits (Visits 2-6), after all clinical 
assessments have been completed.
On-site administration of study products will be recorded in the dispensing log and the 
CRF.
6.2.1
Medication/Dosing Errors
Study product/dosing errors may result, in this study, from the administration or 
consumption of the wrong product, by the wrong subject, at the wrong time, or at the 
wrong dosage. 

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Such study product/dosing errors occurring to a study subject are to be captured in the 
CRF.  In the event of study product dosing error, the sponsor should be notified 
immediately.
Study product/dosing errors are reportable irrespective of the presence of an associated 
AE, including:

study product/dosing errors involving subject exposure to any of the study 
products;

potential study product/dosing errors or uses outside of what is foreseen in the 
protocol that do or do not involve the participating subject.
If a study product/dosing error is accompanied by an AE, as determined by the 
investigator, the study product/dosing error and any associated adverse event(s) are to be 
captured in the CRF AE form. 
6.3
Investigational/Study Product Storage 
The investigator, or designee, will ensure that all study products are stored in a secured 
area with controlled access under required storage conditions and in accordance with 
applicable regulatory requirements and the product label.  
Site systems must be capable of measuring and documenting (for example, via a log), at 
a minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated and/or room-temperature products).  This 
should be captured from the time of first product receipt until product is returned to the 
3rd party vendor.  Even for continuous monitoring systems, a log or site procedure that 
ensures active daily evaluation for excursions should be available.  The operation of the 
temperature-monitoring device and storage unit (for example, refrigerator), as applicable, 
should be regularly inspected to ensure it is maintained in working order. 
Any excursions from the product-label storage conditions should be reported to 
appropriate site staff upon discovery and communicated to sponsor as soon as possible.  
The site should actively pursue options for returning the product to the storage conditions 
as described in the labeling, as soon as possible.  Excursions from the storage 
requirements, including any actions taken, must be documented as a protocol deviation 
and reported to the Sponsor.  
Once an excursion is identified, the affected product (or products) must be quarantined 
and not used until the sponsor provides documentation of permission to use. Use of any 
of the affected product(s) prior to sponsor approval will be considered a protocol 
deviation.  

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Site staff will instruct subjects on the proper storage requirements for all take-home 
products. 
6.4
Investigational/Study Product Accountability
All products supplied are for use only in this clinical study and should not be used for 
any other purpose.
All study products must be received by a designated person at the study sites, handled 
and stored safely and properly, and kept in a secured location to which only the staff 
have access. Upon receipt, all study products should be stored according to the 
instructions specified on the product labels. Study products are to be dispensed only to 
subjects enrolled in the study in accordance with the protocol, by authorized site staff.
The investigator site must maintain adequate records documenting the receipt, use, loss, 
or other disposition of all the product supplies. All study products will be accounted for 
using the investigational/study product accountability form/record. The investigator is 
responsible for study product accountability, reconciliation, and record maintenance. 
Subjects will return used and unused tubes of the acclimatization dentifrice to the 
investigator site at their Baseline visit (Visit 2). Subjects will return used and unused 
tubes of their assigned study dentifrice to the investigator site at their last visit (for most 
subjects this will be Visit 7). Study product return will be documented using the 
investigational/study product accountability form/record. 
The accountability records must be available for inspection by the study monitor during 
the study. Monitoring of product accountability will be performed by the monitor during 
site visits and at the completion of the study. 
6.4.1
Destruction of Investigational/Study Product Supplies 
At the conclusion of the study, the Principal Investigator (PI) or an appropriate designee, 
and a representative of GSK CH (study monitor) will inventory all used and unused study 
products and sundry items.  The investigational/study product accountability record for 
returned study products will then be completed. All study product (used and unused) for 
this clinical study (including empty containers) will be returned for destruction to the 
GSK CH designated vendor using the return instructions provided. 
Return and destruction instructions for sundry items are provided in Table 6-2.

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6.5
Blinding and Allocation/Randomization
All subjects will be centrally randomized to one of the two study treatments using an 
Interactive Response Technology (IRT). Before the study is initiated, training, login 
information and directions for the IRT will be provided to each site. Study products will 
be dispensed according to the instruction received through the IRT at the appropriate 
study visits.
Returned study products should not be re-dispensed to any subject.
This study is described as examiner-blind (the subjects, investigator, clinical examiner(s) 
and monitor will be blinded to product received). Site staff, the study statistician, data 
management staff, other employees of the Sponsor and vendors acting on behalf of the 
sponsor, who may influence study outcomes will also be blinded to the product 
allocation. 
To ensure the examiner remains blinded throughout the study:

site staff involved in the dispensing of study treatment and the supervision of on-
site product usage will work in a separate area;

the examiner will not be permitted in any area where study product is stored, 
dispensed, or in use; 

study subjects will be instructed not to remove study product from the opaque 
bags provided outside of the dispensing room, while at the study site;

dispensing staff will not be involved in any safety/efficacy assessment procedure 
during the study.
6.6
Breaking the Blind
At the initiation of the study, the study site will be instructed in the method for breaking 
the blind.  The method will be an electronic process.
The electronic system will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has sole responsibility for determining if unblinding of a 
subject’s product assignment is warranted. Subject safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding 
is warranted, the investigator should make every effort to contact the sponsor prior to 
unblinding a subject’s product assignment unless this would delay emergency treatment 
of the subject.

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If a subject’s product assignment is unblinded, the sponsor must be notified within 24 
hours of breaking the blind. The date and reason that the blind was broken must be 
recorded in the source documentation and CRF, as applicable.
Any AE associated with breaking the blind must be recorded and reported as specified in 
this protocol. The study site may also be required be required to inform the IRB/EC if the 
blind is broken. 
6.7
Subject Compliance
To facilitate compliance with product usage, subjects will be provided with a diary at 
Screening (Visit 1) and at Baseline (Visit 2) to record each brushing with study product 
throughout their study participation. They will also use the diary to note any 
missed/additional brushings, the reasons for any missed/additional brushings, any issues 
with the dentifrice used, oral problems, illnesses and any new medications/treatments. 
Subjects will attend each study visit with all tubes of dentifrice provided (used and 
unused) for a visual check of product usage, and with their completed diary for review by 
study staff. 
Any suspected over or under use, and the number of any missed or additional brushings, 
will be documented in the CRF. Subjects will be re-instructed in the correct dosing, 
usage requirements and diary completion as needed.
Supervised brushings will be carried out at the study site at the end of Visits 2-6 to 
facilitate subject compliance with dosing and brushing instructions.
6.8
Concomitant Medication/Treatment(s)
Any medications, treatments or vaccine (including over-the-counter or prescription 
medicines, vitamins, and/or herbal supplements) taken during the study, from signing the 
informed consent, must be recorded in the CRF with indication, reason for use, unit dose, 
daily dose, and start and stop dates of administration.  All subjects will be questioned 
about concomitant medication/treatments at each site visit.
Medication/treatments taken within 30 days of signing the informed consent form will be 
documented as a prior medication/treatment.  Medications/treatments taken after signing 
the informed consent form will be documented as concomitant medication/treatments.
For the Duration of the Study: Screening (Visit 1) to Subject’s Last Study Visit

Subjects should delay any non-emergency, elective dental treatment until after 
study completion (including dental prophylaxis).

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
Should a randomised subject start a course of treatment which includes daily or 
intermittent use of an analgesic, details of that medication/treatment will be 
recorded as outlined above. The investigator or designee will decide if the subject 
should continue on the study or be withdrawn.

Should a subject take a medication which, in the opinion of the investigator or 
their medically qualified designee, could impact subject perception of pain (for 
example, an analgesic) within 8 hours of a scheduled study visit, every effort will 
be made to reappoint them (within permitted visit tolerances, see Schedule of 
Activities (Table 1-1)). The reason for re-appointment will be documented in the 
CRF. If this is not possible, the following visit specific actions should be taken.
Screening (Visit 1): if the subject cannot be reappointed, they will be withdrawn 
from the study (Section 7.1). No clinical efficacy assessments will be performed. 
The subject may be replaced.
Baseline (Visit 2): if the subject cannot be reappointed, they will be withdrawn 
from the study (Section 7.1). No clinical efficacy assessments will be performed. 
The subject will not be replaced.
Day 3 (Visit 3): the subject will continue in the study. Clinical efficacy 
assessments will be performed.
Days 7, 14, 28 & 56 (Visits 4-7): if the subject cannot be reappointed (within the 
visit tolerance for Visits 4-7), they will continue in the study. Clinical efficacy 
assessments will be performed.

Subjects should not participate in any other clinical study (including cosmetic 
studies) or be in receipt of another IP.
7
DISCONTINUATION OF STUDY INTERVENTION AND 
SUBJECT DISCONTINUATION/WITHDRAWAL
7.1
Subject Discontinuation/Withdrawal 
A subject may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of either the investigator or the sponsor for safety 
or behavioral reasons, or the inability of the subject to comply with the protocol-required 
schedule of study visits or procedures.  
The following circumstances require discontinuation of study product and/or premature 
subject withdrawal:

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
Protocol violation that may impact the subject’s safety

Withdrawal of informed consent

Subject lost to follow-up 

Unblinding of the subject 

Pregnancy
If a subject is discontinued or prematurely withdraws from the study, the reason(s) for 
discontinuation or withdrawal and the associated date must be documented in the 
relevant section(s) of the CRF. 
7.2
Lost to Follow up
A subject will be considered lost to follow up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
If a subject fails to return to the site for a required study visit, the site must attempt to 
contact the subject to reschedule the missed visit as soon as possible, to counsel the 
subject on the importance of maintaining the assigned visit schedule and to ascertain 
whether or not the subject wishes to and/or should continue in the study.
Before a subject is deemed lost to follow up, the investigator or designee must make 
every effort to regain contact with the subject (where possible, 3 telephone calls and, if 
necessary, a certified letter to the subject’s last known mailing address or local equivalent 
methods). These contact attempts should be documented. If contact is made with the 
subject, the investigator should inquire about the reason for withdrawal, request that the 
subject return all products dispensed to them and, if appropriate, request that the subject 
return for a final visit and follow-up with the subject regarding any unresolved AEs.
Final safety assessments may be carried out when the subject returns to the study site, at 
the investigator’s discretion, which could include the following: an oral examination.
Should the subject continue to be unreachable, he/she will be considered to have 
withdrawn from the study and lost to follow up. 
Lack of completion of all or any of the early termination procedures will not be viewed 
as protocol deviations so long as the subject’s safety was preserved.
If the subject withdraws from the study and also withdraws consent for disclosure of 
future information, no further evaluations should be performed, and no additional data 
should be collected.  The sponsor may retain and continue to use any data collected 
before such withdrawal of consent.

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8
STUDY PROCEDURES
This section lists the procedures to be completed at each planned study visit.  The timing 
of each procedure is listed in the Schedule of Activities section.
Adherence to the study design requirements, including all procedures, is essential and 
required for study conduct.
8.1
Screening: Day -28 to Day -14 (Visit 1)
Screening procedures will be conducted by the Investigator, or suitably qualified 
designee.
8.1.1
Informed Consent
The investigator, or designee, must obtain informed consent from each subject 
participating in this study after adequate explanation of the aims, methods, objectives, 
and potential hazards of the study. A list of ingredients in the dentifrices to be used 
during the study will be provided to each subject during the consent process to enable 
them to confirm they are not aware of any allergy or hypersensitivity to any of the 
ingredients listed. Two copies of the informed consent form (ICF) will be signed and 
dated by the subject, the subject will retain one copy and the other will be kept at site.
The investigator, or designee, must also explain to the subjects that they are completely 
free to refuse to enter the study or to withdraw from it at any time.  Appropriate forms for 
documenting a signed and dated consent will be provided by either the investigator or by 
GSK CH. The investigator, or designee, should sign and date each copy of the ICF to 
confirm that the consent process was completed correctly after the subject has signed.  
The time the subject signed the informed consent form will also be captured on the ICF 
as this is the point from which all AEs will be captured. The date and time of consent 
will be transcribed to the CRF.
If, during a subject’s participation in the study, any new information becomes available 
that may affect the subject’s willingness to participate in the study, each ongoing subject 
should receive a copy of this new information and be re-consented into the study (2 
copies as before). Each subject should be provided with a copy of the signed and dated 
amended consent form. The date of re-consent will be recorded in the CRF.
After signing the ICF, subjects will undergo the screening assessments to confirm that 
they meet all the inclusion criteria and none of the exclusion criteria. If the subject is 
confirmed eligible by the investigator (or designee) to participate in the study the subject 
is considered enrolled in the study.

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e-Consent is a tool that assists in the consent process by using multimedia components 
delivered by an electronic system (e.g. iPad/tablet). The multimedia components consist 
of video, audio, knowledge review, dictionary and electronic signature.
The site staff can use the system to consent the subject with the benefit of helping the 
subject understand the research they are taking part in and to control the consent process.
The system will allow for a copy of the consent to be printed and given to the subject and 
for consent documents to be retained by the site in PDF format.
A GSK CH approved vendor will be used to provide the system and training and help 
desk will be provided as needed.
If the country and/or site does not have approval to use the e-Consent system, or the 
subject does not want to use the e-Consent system, then the conventional paper process 
will be followed. It is possible to use the e-Consent system to educate the subject while 
using paper to obtain signatures.
8.1.2
Demographics
The following demographic information will be recorded in the CRF: year of birth, 
gender, ethnicity and race.
Data from this study may be submitted to the US Food and Drug Administration (FDA) 
at a later date as part of a New Drug Application (NDA) for a dual active DH dentifrice; 
the FDA require ethnicity and race to be reported in clinical studies submitted in support 
of an NDA. Ethnicity and race of subjects will be recorded in accordance with FDA 
Guidance for Industry: Collection of Race and Ethnicity Data in Clinical Trials (FDA 
2016).
8.1.3
Medical History and Prior Medication/Treatment
Details of relevant medical and surgical history, including allergies or drug sensitivity, will 
be documented in the CRF.
Prior medications/treatments, including prescription and non-prescription drugs, dietary 
supplements and herbal remedies, taken in the last 30 days and prior to signing the ICF, 
will be documented in the CRF.
8.1.4
Screening Procedures
The following procedures will be completed, and data recorded in the CRF.

The oral care products the subject is currently using will be reviewed to confirm 
that they do not contain any ingredients intended for treating sensitive teeth. 

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Subjects will be required to bring the products to the study site to enable study 
staff to check ingredient listings.

Female subjects of child-bearing potential only will complete a UPT. 

An OST examination will be completed by a clinical examiner as described in 
Section 9.3.1.

An OHT examination will be completed by a clinical examiner as described in 
Section 9.3.2.

Eligible teeth assessments for incisors, canines and pre-molars, including 
dentition exclusions and assessments of EAR, MGI (gingiva adjacent to the 
exposed dentin only) and tooth mobility will be completed by a clinical examiner 
as described in Section 5.3, Section 9.1.1, Section 9.1.2 and Section 9.1.3 
respectively. 

The sensitivity of each tooth that meets the eligibility criteria, first to a tactile 
stimulus and then to an evaporative air stimulus will be evaluated by the clinical 
examiner as described in Section 9.1.4 and Section 9.1.5 respectively.  
Evaporative air sensitivity will only be assessed for teeth with a qualifying tactile 
threshold of ≤ 20 g. The examiner will allow at least 5 minutes between the 
completion of the tactile assessments and the start the evaporative air 
assessments. To ease subject flow, assessments may be recorded on a score sheet 
and later transcribed into the CRF. The same examiner will be responsible for 
completing both clinical measures of DH (tactile and evaporative air sensitivity) 
for the duration of the study.
8.1.5
Inclusion/Exclusion Criteria
Inclusion and exclusion criteria information will be documented in the CRF.
8.1.6
Subject Eligibility
The investigator and/or medically qualified designee will review the medical history, 
prior medications and inclusion/exclusion criteria to confirm subject eligibility to 
participate in the clinical trial. This will be documented in the CRF.
To prepare for study participation, subjects will be instructed in the Lifestyle Guidelines 
(Section 5.5) and any Concomitant Medication/Treatment(s) requirements (Section 6.8) 
of the protocol.

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8.1.7
Supervised Use of Acclimatization Dentifrice
Eligible subjects will be provided with the acclimatization dentifrice, toothbrush, diary 
and timer to use during the acclimatization period (2-4 weeks). Dentifrice usage 
instructions will be described to the subject and dosing of a full brush head with 
dentifrice will be demonstrated. Staff will supervise the subject carrying out first 
dosing/brushing with acclimatization dentifrice and recording first use in their diary. 
Completion of all procedures will be documented in the CRF. 
Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed. Any 
AEs/incidents reported on completion of the supervised brushing with the acclimatization 
dentifrice will be recorded in the CRF.
8.2
Study Period
8.2.1
Baseline: Day 0 (Visit 2)
Changes in health, concomitant medication or non-drug treatments/procedures will be 
documented in the CRF. 
Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed and any AEs 
recorded in the CRF.
The following procedures will then be completed. 

Complete visual checks of returned acclimatization dentifrice tubes and review 
completed diary. Record any suspected over or under use, and the number of any 
missed or additional brushings, in the CRF. 
Do not return acclimatization dentifrice/toothbrush/diary to subject.

Female subjects of child-bearing potential only complete a UPT. Record the result 
in the CRF. 

Subject completes a DHEQ (source document), for later transcription into the 
CRF. 

Clinical examiner completes an OST examination. Record findings in the CRF.

Clinical examiner completes an OHT examination. Record findings in the CRF. 

Clinical examiner completes sensitivity assessments for each eligible tooth 
identified at Screening (eligible incisors, canines, pre-molars, with a tactile 
threshold of ≤ 20 g and a Schiff sensitivity score ≥ 2), first to a tactile stimulus 

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and then to an evaporative air stimulus. The examiner will allow at least 5 
minutes between the completion of the tactile assessments and the start the 
evaporative air assessments for tooth recovery. Record clinical assessment scores 
in the CRF or using source documentation for later transfer to the CRF. The same 
examiner will be responsible for completing both clinical measures of DH (tactile 
and evaporative air sensitivity) for the duration of the study.

Clinical examiner reviews inclusion and exclusion criteria and confirms subject 
eligibility in the CRF.  Subjects with at least 2 sensitive teeth (tactile threshold ≤ 
20 g; Schiff sensitivity score ≥ 2 at Screening and Baseline) will continue.

Clinical examiner selects the two ‘test teeth’ for sensitivity assessment at 
subsequent study visits. Record in the CRF.

Complete stratification and randomization.

Dispense allocated study dentifrice, toothbrush and diary. Record in the CRF.

Describe dentifrice usage instructions and diary completion to subject; supervise 
their first dosing and brushing with study dentifrice and recording of brushing in 
the diary. Record in the CRF.

Spontaneous reporting of adverse events and those elicited by asking subjects to 
respond to a non-leading question such as “How do you feel?” will be assessed. 
Any AEs/incidents reported on completion of the supervised brushing with the 
assigned study dentifrice will be recorded in the CRF.

Remind the subject of the Lifestyle Guidelines (Section 5.5) and any Concomitant 
Medication/Treatment(s) requirements (Section 6.8) of the protocol. Record in 
the CRF.
8.2.2
Day 3, Day 7 (+1 day), Day 14 (±1 day) and Day 28 (±2 days)   
(Visits 3-6)
Changes in health, concomitant medication or non-drug treatments/procedures will be 
documented in the CRF. 
Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed and any AEs 
recorded in the CRF.
The following procedures will then be completed at each visit. 

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
Complete visual checks of returned study dentifrice tubes and review completed 
diary. Record any suspected over or under use, and the number of any missed or 
additional brushings, in the CRF. Re-instruct the subject in the correct dosing, 
usage requirements and diary completion as needed. 
Return dentifrice/toothbrush/diary to subject.

Confirm subject adherence to the requirements of the protocol and continuance. 
Record in the CRF.

Day 28 (Visit 6) only: Subject completes a DHEQ (source document), for later 
transcription into the CRF. 

Clinical examiner completes an OST examination. Record findings in the CRF.

Clinical examiner completes sensitivity assessments for the two ‘test teeth’ 
selected at Baseline, first to a tactile stimulus and then to an evaporative air 
stimulus. The examiner will allow at least 5 minutes between the completion of 
the tactile assessments and the start the evaporative air assessments for tooth 
recovery. Record clinical assessment scores in the CRF or using source 
documentation for later transfer to the CRF. 
Clinical examiner completes evaporative air sensitivity assessments (Schiff 
Sensitivity Scale only) on remaining eligible teeth identified at Screening. Record 
clinical assessment scores in the CRF or using source documentation for later 
transfer to the CRF.
The same examiner will be responsible for completing both clinical measures of 
DH (tactile and evaporative air sensitivity) for the duration of the study.

Remind subject of dentifrice usage instructions; supervise dosing and brushing 
with study dentifrice and recording of brushing in the diary. Record in the CRF.

Spontaneous reporting of adverse events and those elicited by asking subjects to 
respond to a non-leading question such as “How do you feel?” will be assessed. 
Any AEs/incidents reported on completion of the supervised brushing with the 
assigned study dentifrice will be recorded in the CRF.

Remind the subject of the Lifestyle Guidelines (Section 5.5) and any Concomitant 
Medication/Treatment(s) requirements (Section 6.8) of the protocol. Record in 
the CRF.

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8.2.3
Day 56 (±2 days) (Visit 7)
Changes in health, concomitant medication or non-drug treatments/procedures will be 
documented in the CRF. 
Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to a non-leading question such as “How do you feel?” will be assessed and any AEs 
recorded in the CRF.
The following procedures will then be completed at each visit. 

Complete visual checks of returned study dentifrice tubes and review completed 
diary. Record any suspected over or under use, and the number of any missed or 
additional brushings, in the CRF. Do not return dentifrice/toothbrush/diary to 
subject.

Confirm subject adherence to the requirements of the protocol and continuance. 
Record in the CRF.

Subject completes a DHEQ (source document), for later transcription into the 
CRF. 

Clinical examiner completes an OST examination. Record findings in the CRF.

Clinical examiner completes an OHT examination. Record findings in the CRF. 

Clinical examiner completes sensitivity assessments for the two ‘test teeth’ 
selected at Baseline, first to a tactile stimulus and then to an evaporative air 
stimulus. The examiner will allow at least 5 minutes between the completion of 
the tactile assessments and the start the evaporative air assessments for tooth 
recovery. Record clinical assessment scores in the CRF or using source 
documentation for later transfer to the CRF.
Clinical examiner completes evaporative air sensitivity assessments (Schiff 
Sensitivity Scale only) on remaining eligible teeth identified at Screening. Record 
clinical assessment scores in the CRF or using source documentation for later 
transfer to the CRF.
The same examiner will be responsible for completing both clinical measures of 
DH (tactile and evaporative air sensitivity) for the duration of the study.

Remind the subject to inform the site if they experience any untoward medical 
occurrence or use any medications in the next 5 days (that is, in the 5 days 
following their last dose of study treatment).

Study conclusion.

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8.3
Diary Review
The diary should be reviewed at every visit by the investigator, or suitably qualified 
designee, and the subject. Any subject comment captured in the diary which is 
considered an adverse event or incident will be assessed and reported as per the defined 
procedures in this protocol. Adverse event reporting procedures are summarized in 
Adverse Event and Serious Adverse Events (Section 10). Incident reporting procedures 
are summarized in Definition of and Procedure for Reporting Medical Device Incidents 
(Section 10.9).
Any additional comments relating to medications/treatments provided in the diary will be 
reviewed by the investigator or medically qualified designee with the subject and entered 
into the CRF as appropriate. 
Additional and missed product applications will be considered deviations from the 
protocol and will be recorded on the Deviations Log.
8.4
Study Conclusion
The Study Conclusion page of the CRF will be completed for all subjects whether they 
completed all study procedures or if they were discontinued from the study early.  If the 
subject discontinued early, at any point during the study, the primary reason for 
withdrawal should be recorded on the Study Conclusion page.
If a subject has any clinically significant, study-related abnormalities, AEs or incidents at 
the conclusion of the study, the GSK CH medical monitor (or designated representative) 
should be notified and, the subject may be asked to remain at the clinical site or be asked 
to return for a follow-up visit to ensure any issue is resolved or deemed not clinically 
significant. 
8.5
Follow-up Visit/Phone Call
The study site may contact a subject to follow up an AE post-study completion/ 
withdrawal and, in some circumstances, request they return to the site for additional 
follow-up visits (final safety assessments). If needed, additional oral examinations may 
be carried out at such visits.
9
STUDY ASSESSMENTS
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described.  However, it is anticipated that from time to time there may be 
circumstances, outside the control of the investigator that may make it unfeasible to 

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complete an assessment. In these cases, the investigator must take all steps necessary to 
ensure the safety and well-being of the subject. When a protocol-required assessment 
cannot be performed, the investigator (or designee) will document the reason for the 
missed assessment as a protocol deviation and any corrective and preventative actions 
that he or she has taken to ensure that required processes are adhered to as soon as 
possible. The Sponsor must be informed of any missed assessments in a timely manner.
To ensure the clinical examiner/staff involved in efficacy and safety assessments remain 
blind to product received, throughout the study: site staff involved in the dispensing of 
study treatment and the supervision of on-site product usage will work in a separate area; 
the examiner will not be permitted in any area where study product is stored, dispensed, 
or in use; study subjects will be instructed not to remove study product from the opaque 
bags provided outside of the dispensing room, while at the study site; dispensing staff 
will not be involved in any safety/efficacy assessment procedure during the study.
9.1
Screening Assessments
Screening assessments to identify eligible teeth will be performed by appropriately 
trained clinical examiners at the times, and in the order, defined in the Study Procedures 
section of this protocol (Section 8). A single examiner will be responsible for the conduct 
of the clinical measures of DH (tactile and evaporative air sensitivity) for the duration of 
the study (at Screening and all subsequent visits).
Eligible tooth assessments will be accomplished by oral examination and will evaluate 
dentition exclusions, EAR, MGI, tooth mobility and sensitivity to tactile and evaporative 
air stimuli. Assessments will be carried out by the investigator, or qualified designee, 
against the inclusion/exclusion criteria. Ineligible subjects will not be re-screened.
9.1.1
Erosion, Abrasion and Recession (EAR) 
The facial surfaces of all incisor, canine and pre-molar teeth that do not present any of 
the general dentition exclusion criteria, or specific dentition exclusion criteria for eligible 
teeth, will be examined for signs of cervical EAR (Addy 2002).
9.1.2
Modified Gingival Index (MGI) 
The MGI is a non-invasive, visual assessment of gingival health (Lobene et al. 1986). 
MGI will be assessed for incisor, canine and pre-molar teeth exhibiting none of the 
dentition exclusions and facial/cervical EAR. MGI will be scored for the facial gingiva 
only, adjacent to the test area (exposed dentine). Eligible teeth will have a MGI score of 
zero.

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Score
Description
0
Absence of inflammation
1
Mild inflammation; slight change in colour, little change in colour; little 
change in texture of any portion of the marginal or papillary gingival unit.
2
Mild inflammation; criteria as above but involving the entire marginal or 
papillar gingival unit.
3
Moderate inflammation; glazing, redness, edema, and/or hypertrophy of 
the marginal or papillary gingival unit.
4
Severe inflammation; marked redness, edema and/or hypertrophy of the 
marginal or papillary gingival unit, spontaneous bleeding, congestion, or 
ulceration.
9.1.3
Tooth Mobility Assessment
Clinical mobility will be assessed for incisor, canine and pre-molar teeth exhibiting none 
of the dentition exclusions, facial/cervical EAR and a MGI = 0, using a modification of 
the Miller Index (Laster et al. 1975). Eligible teeth will have clinical mobility ≤ 1.
Degree
Description
0
No movement or mobility of the crown of the tooth < 0.2 millimeter 
(mm) in a horizontal direction.
1
Mobility of the crown of the tooth 0.2 – 1 mm in a horizontal direction
2
Mobility of the crown of the tooth exceeding 1 mm in a horizontal 
direction
3
Mobility of the crown of the tooth in a vertical direction as well.
9.1.4
Qualifying Tactile Sensitivity
The tactile sensitivity of incisor, canine and pre-molar teeth exhibiting none of the 
dentition exclusions, and meeting the EAR, MGI and clinical mobility criteria, will be 
assessed using a constant pressure probe (Yeaple probe (Polson et al. 1980). The probe 
tip will be placed perpendicular to the facial surface of the tooth and drawn slowly across 
the exposed dentine to ensure application of the stimulus across the potentially ‘sensitive’ 
area. After each application, the subject will be asked to indicate whether they 

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experienced any pain or discomfort (yes/no response only). The subject may respond 
"yes" if they feel pressure as the probe is applied to their tooth. The examiner will remind 
them they should only respond ‘yes’ if they feet PAIN or DISCOMFORT. The gram 
setting which elicits the two consecutive ‘yes’ responses will be recorded as the tactile 
threshold (g). At Screening, the upper force setting will be 20 g. For a tooth to qualify at 
Screening, it must have a tactile threshold ≤ 20 g. If no sensitivity is found at the upper 
setting, the tactile threshold will be recorded as > 20 g and the tooth will be disqualified 
from further testing. 
If a subject fails to give a definite answer, the examiner will re-prompt them to provide 
response. If uncertainty continues, this will be indicated on the clinical assessment score 
sheet/in the CRF. If the subject continues to be unsure, or the examiner is unsure of the 
reliability of their response, the examiner may opt to re-probe at the same force setting 
(indicated to the assistant by a non-verbal signal, i.e. a hand gesture), or move to the next 
force setting (10 g increase). 
The examiner will generally make the pressure setting adjustments (may be carried out 
by an assistant/scribe); the scribe will record the micro-amperage setting and subject's 
responses.
Calibration of the Yeaple Probe: 
The Yeaple probe will be calibrated by an appropriately trained member of the study 
staff (typically the clinical examiner or their assistant/scribe) before use on each day 
subjects are assessed. The microamp settings may vary from day to day (partly due to 
battery power consumption), but the difference should not be significant. Thus, previous 
probe settings can serve as a guide. Calibration should start at the lowest microamp 
setting and then increase. Either calibration method described below is acceptable.

Method 1 (‘Water Cup’): 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 g. 

Method 2: The Yeaple probe is fixed to a clamp attached to a ring stand so that 
the top is perpendicular to the pan of an ohaus dial-o-gram® balance or 
equivalent. The probe tip is positioned to just touch the pan when the balance is 
set at zero grams. The probe dial is set to the microamp setting and the gram 

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setting is increased on the balance until the probe trips. The gram setting is 
recorded and the Yeaple probe reset to the next microamp value.
The data are plotted, and the points connected with line segments in order to interpolate 
the micro-amp values equivalent to 10, 20, 30, 40, 50, 60, 70 and 80 g. 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 Yeaple probe calibration record (along the probe’s 
serial number) which will serve as the force setting guide for that day’s examinations.
9.1.5
Qualifying Evaporative Air Sensitivity
Evaporative air sensitivity will be assessed on the facial surfaces of incisor, canine and 
pre-molar teeth exhibiting none of the dentition exclusions, and meeting the EAR, MGI, 
clinical mobility and tactile threshold (≤ 20 g) criteria, a minimum of 5 minutes after the 
tactile assessments have been completed. The assessment will be made by directing a one 
second application of air from a standard dental syringe held perpendicular to the tooth 
surface, approximately 1-2 mm coronal to the gingival margin, and from a distance of 
approximately 1 centimeter. The examiner will take appropriate measures to isolate the 
tooth surface to prevent stimulation of adjacent teeth or surrounding soft tissue.  
Subject response to the stimulus will be evaluated using the Schiff sensitivity scale 
(Schiff et al. 1994).  This is an examiner-based index, scored immediately following 
administration of the evaporative air stimulus. This scale focuses on a combination of 
specific, observable, physical, behavioural and verbal responses from the subject, which 
may facilitate discrimination. For a tooth to qualify at screening, it must have a Schiff 
sensitivity score ≥ 2. If Schiff sensitivity score = 0 or 1, the tooth will be disqualified 
from further testing.
Score
Description
0
Subject does not respond to air stimulation
1
Subject responds to air stimulus but does not request discontinuation of 
stimulus
2
Subject responds to air stimulus and requests discontinuation or moves from 
stimulus
3
Subject responds to stimulus, considers stimulus to be painful, and requests 
discontinuation of the stimulus

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9.2
Efficacy Assessments
The following efficacy assessments will be performed by an appropriately trained 
clinical examiner/staff (who are blind to product received), at the times and in the order 
defined in the Study Procedures section of this protocol (Section 8).
A single examiner will be responsible for the conduct of both clinical measures of DH 
(tactile and evaporative air sensitivity) for the duration of the study and the selection of 
the two ‘test teeth’ for all study subjects.
9.2.1
Dentine Hypersensitivity Experience Questionnaire (DHEQ-15) 
A ‘short form’ DHEQ (Appendix I Example DHEQ) will be completed by each study 
subject at Baseline (Visit 2), Day 28 (Visit 3) and Day 56 (Visit 4), prior to the OST 
examination and the clinical efficacy assessments. 
The DHEQ is divided into two sections - Section 1 asks questions about ‘your sensitive 
teeth and the impact it has on your everyday life’; Section 2 asks questions about ‘the 
ways in which the sensations in your teeth affect you in your daily life’ grouped into the 
following domains.

Restrictions (Section 2, Q1-3)

Adaptation (Section 2, Q4-6)

Social Impact (Section 2, Q7-9)

Emotional Impact (Section 2, Q10-12)

Identity (Section 2, Q13-15)
At Baseline, all questions will be answered - Section 1 (Q1-9) and Section 2 (Q1-15); at 
Day 28 and Day 56, Section 1 (Q7-9 only) and Section 2 (Q1-15) will be answered. 
9.2.2
Tactile Sensitivity 
The tactile sensitivity of all teeth that exhibited none of the dentition exclusions, and met 
the EAR, MGI, clinical mobility and qualifying tactile threshold/Schiff sensitivity score 
criteria at Screening, will be assessed at Baseline (Visit 2). Teeth with a Baseline tactile 
threshold of ≤ 20 g will also be assessed for evaporative air sensitivity. The tactile 
sensitivity of the two ‘test teeth’ selected by the clinical examiner at Baseline will be 
assessed for randomised subjects at all subsequent visits (Visits 3-7).

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The tactile stimulus will be administered, and subject response recorded, as described in 
Section 9.1.4.  The gram setting which elicits the two consecutive ‘yes’ responses will be 
recorded as the tactile threshold (g).  
At Baseline (Visit 2), the upper force setting will be 20 g; at all subsequent visits (Visits 
3-7), the upper force setting will be 80 g. If no sensitivity is found at the upper setting, 
the tactile threshold will be recorded as > 20 g at Baseline, and as > 80 g on Days 3, 7, 
14, 28 and 56. 
9.2.3
Evaporative Air Sensitivity 
The evaporative air sensitivity of all clinically eligible teeth from Screening will be 
assessed at Baseline (Visit 2). The evaporative air sensitivity of the two ‘test teeth’ 
selected at Baseline, followed by the remaining eligible teeth identified at Screening, will 
be assessed for all randomised subjects at subsequent visits (Visits 3-7).
The evaporative air stimulus will be administered, and subject response recorded, as 
described in Section 9.1.5.  On every occasion, evaporative air assessment will begin a 
minimum of 5 minutes after the last tactile assessment has been completed (to allow 
tooth recovery time). 
9.2.4
Selection of Test Teeth
On completion of the Baseline clinical assessments, the clinical examiner will select two 
‘test teeth’ for each eligible subject, to be evaluated at all subsequent visits. Test teeth 
will exhibit none of the dentition exclusions and meet all the inclusion criteria for eligible 
teeth (including Screening and Baseline tactile threshold ≤ 20 g; Screening and Baseline 
Schiff sensitivity score ≥ 2). 
Test teeth should not be adjacent to each other and preferably in different quadrants.
9.3
Safety and Other Assessments
The following safety assessments will be performed by appropriately trained clinical 
examiners, at the times and in the order defined in the Study Procedures section of this 
protocol (Section 8).  
9.3.1
Oral Soft Tissue (OST) Examination
The OST examination will be accomplished by direct observation and palpation, using 
retraction aids as appropriate, and will include examination of the labial mucosa 
(including lips), buccal mucosa, and mucogingival folds, gingival mucosa, hard palate, 
soft palate, tonsillar area, pharyngeal area, tongue, sublingual area, submandibular area 

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and salivary glands. The results of the examination will be recorded in the CRF as either 
normal or abnormal with details of any abnormalities. Any abnormality or worsening of a 
pre-existing condition observed by the clinical examiner or reported by the subject from 
the OST examination carried out at Screening will be recorded as an AE. 
9.3.2
Oral Hard Tissue (OHT) Examination 
The OHT examination will be accomplished by direct observation, using retraction aids 
as appropriate and will identify any grossly carious lesions or signs of erosive wear, 
enamel irregularities, tooth fracture, gross decay, decalcification and faulty restorations. 
The presence of any implants, fixed or removable dentures, fixed or removable 
orthodontic braces/bands, fixed orthodontic retainers, full crowns or veneers will be 
recorded. Observations will be listed as either absent or present, and conditions noted as 
present will be described in the CRF. Any change observed by the clinical examiner or 
reported by the subject from the OHT examination carried out at Screening will be 
recorded as an AE.
9.3.3
Pregnancy Testing
For female subjects of childbearing potential, a UPT will be performed at Screening 
(Visit 1) and Baseline, and the results obtained prior to first use of acclimatization 
dentifrice (Visit 1) and first use of study dentifrice (Visit 2) respectively.  
The investigator and site personnel will remind subjects at each visit to inform site 
personnel if their menstrual cycle has changed or if they have any other reason to suspect 
they may be pregnant (e.g. had unprotected intercourse since the last visit).
A negative pregnancy result is required before the subject may receive study product.  
Pregnancy tests will also be done whenever one menstrual cycle is missed during the 
active study period (or when potential pregnancy is otherwise suspected). Pregnancy tests 
may also be repeated as per request of the IRB/EC or if required by local regulations.
In the case of a positive confirmed pregnancy, the subject will be withdrawn from 
administration of study product and from the study.
10
ADVERSE EVENT AND SERIOUS ADVERSE EVENTS
10.1
Definition of an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study subject, temporally 
associated with the use of a study product including any washout or lead-in product (or 

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medical device), whether or not considered related to the study product, including any 
washout or lead-in product (or medical device).
NOTE: An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally 
associated with the use of a study product including any washout or lead-in product (or 
medical device).
Events Meeting the AE Definition:  

Any abnormal laboratory test results (hematology, clinical chemistry, or 
urinalysis) or other safety assessments (e.g. ECG, radiological scans, vital sign 
measurements), including those that worsen from baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not 
related to progression of underlying disease).

Exacerbation of a chronic or intermittent pre-existing condition including either 
an increase in frequency and/or intensity of the condition.

New conditions detected or diagnosed after study product administration even 
though it may have been present before the start of the study.

Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.

Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
product or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-
harming intent. Such overdoses should be reported regardless of sequelae.

"Lack of efficacy" or "failure of expected pharmacological action" per se will not 
be reported as an AE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms, and/or clinical sequelae resulting from lack of 
efficacy will be reported as AE if they fulfill the definition of an AE. 
Events NOT meeting the AE definition: 

Any clinically significant abnormal laboratory findings (if applicable) or other 
abnormal safety assessments which are associated with the underlying disease, 
unless judged by the investigator to be more severe than expected for the 
subject’s condition. 

The disease/disorder being studied or expected progression, signs, or symptoms 
of the disease/disorder being studied, unless more severe than expected for the 
subject’s condition. 

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
Medical or surgical procedure (e.g. endoscopy, appendectomy) is not the AE. The 
condition that leads to the procedure is an AE (e.g. appendicitis).

Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).

Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen. 
10.2
Definition of a Serious Adverse Event (SAE)
A Serious Adverse Event (SAE) is a particular category of an adverse event where the 
adverse outcome is serious. If an event is not an AE per definition above, then it cannot be 
an SAE even if serious conditions are met (e.g. hospitalization for signs/symptoms of the 
disease under study, death due to progression of disease).
A serious adverse event is any untoward medical occurrence at any dose that:

Results in death

Is life-threatening 

The term 'life-threatening' in the definition of 'serious' refers to an event in 
which the subject was at risk of death at the time of the event. It does not 
refer to an event, which hypothetically might have caused death, if it were 
more severe;

Requires inpatient hospitalization or prolongation of existing hospitalization 

In general, hospitalization signifies that the subject has been detained 
(usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate 
in the physician’s office or outpatient setting. Complications that occur 
during hospitalization are AEs. If a complication prolongs hospitalization or 
fulfills any other serious criteria, the event is serious. When in doubt as to 
whether “hospitalization” occurred, or was necessary, the AE should be 
considered serious.

Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.

Results in persistent or significant disability/incapacity

The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions.

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
This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption

Results in congenital anomaly/birth defect

Other situations:

Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events 
that may not be immediately life-threatening or result in death or 
hospitalization but may jeopardize the subject or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious.

Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development 
of drug dependency or drug abuse.
Note: Classification of an AE as ‘serious’ is based on the outcome of the event, and is a 
factor in determining reporting requirements.
10.3
Reporting of Adverse Events
10.3.1
Reporting Period 
All AEs, and therefore all SAEs will be collected immediately after a subject consents to 
participate in the study by the completion (signature) of the ICF and until 5 days 
following last administration of the study product (or last procedure). 
Medical occurrences that began before obtaining informed consent will be recorded in 
the Medical History/Current Medical Conditions section of the CRF not the AE section.
Details recorded by the subject on a diary or similar document that meet the definition of 
an AE must also be discussed with the subjects and transcribed in the AE section of the 
CRF. 
10.4
Reporting Procedures
The investigator and any designees are responsible for detecting, documenting and 
reporting events that meet the definition of an AE and remain responsible for following 

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up on AEs that are serious, considered related to the study product(s), participation in the 
study, or a study procedure, or that caused the subject to discontinue the study product or 
study. 
The investigator (or medically qualified designee) is to report all directly observed AEs 
and all AEs spontaneously reported by the study subject. In addition, each study subject 
will be questioned about AEs. 
Each AE is to be assessed to determine if it meets the criteria for a SAE.  If an SAE 
occurs, expedited reporting will follow local and international regulations, as appropriate.
When an AE occurs, it is the responsibility of the investigator (or medically qualified 
designee) to review all documentation (e.g. hospital progress notes, laboratory, and 
diagnostics reports) related to the event.
The investigator or site staff will then record all relevant information regarding an AE in 
the CRF and all details relating to an SAE in the paper SAE Form provided.
It is not acceptable for the investigator (or medically qualified designee) to send 
photocopies of the subject’s medical records to GSK CH in lieu of completion of the AE 
CRF page/SAE form.
There may be instances when copies of medical records for certain cases are requested by 
GSK CH.  In this instance, all subject identifiers, with the exception of the subject 
number, will be redacted on the copies of the medical records prior to submission to GSK 
CH.
The investigator (or medically qualified designee) will attempt to establish a diagnosis of 
the event based on signs, symptoms, and/or other clinical information.  The diagnosis 
will be the documented as the AE/SAE where known and not the individual 
signs/symptoms. (e.g. upper respiratory tract infection, seasonal allergy, etc. instead of 
runny nose).
AEs elicited by the investigator (or medically qualified designee) in a standard manner at 
the study visits should also be recorded in the AE section of the CRF and/or using the 
SAE form (subject to the classification of the AE). Care will be taken not to introduce 
bias when questioning a subject about any changes in their health. Open-ended and non-
leading verbal questioning should be used.
10.4.1
Reporting of an Adverse Event
All AEs will be reported on the AE page of the CRF by the investigator or site staff.  It 
should be noted that the form for collection of SAE information is not the same as the 
AE CRF.  Where the same data are collected, the AE CRF page and the SAE form must 

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be completed in a consistent manner.  For example, the same AE term should be used on 
both.  AEs should be reported using concise medical terminology on the CRF as well as 
on the form for collection of SAE information.
10.4.2
Reporting of a Serious Adverse Event
In addition to recording the details of each AE on the AE CRF page, an SAE form should 
be completed, as fully as possible. Hard copies of the ‘paper’ SAE form will be provided 
in the investigator study master file. Original SAE forms will be retained in the 
investigator study master file.
It is essential to enter the following information: 

Protocol and subject identifiers

Subject demography

Description of events, with diagnosis if available

Investigator opinion of relationship to study product (or study procedure, if 
appropriate)

Criterion for seriousness.
The following are desirable and are of particular relevance for investigator and GSK CH 
assessment of the SAE report:

Date of onset of AE 

Date AE stopped, if relevant

Study product start date

Study product end date if relevant

Action taken in relation to the study product

Outcome if known
The SAE form, completed as fully as possible, must be scanned and e-mailed to the GSK 
CH Clinical Operations Safety Reporting email box with the study number and subject 
number in the subject line of the email immediately and under no circumstance 
should this exceed 24 hours after study site personnel learn of the event. The 
investigator will submit any updated SAE data to the sponsor, immediately and under 
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.

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Email Serious 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.
10.5
Evaluating Adverse Events 
10.5.1
Assessment of Intensity
The investigator or medically qualified designee will make an assessment of intensity for 
each AE reported during the study and will assign it to one of the following categories:

Mild:  An event that is easily tolerated by the subject, causing minimal discomfort 
and not interfering with everyday activities.

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 should not be confused with an SAE. Severe is a 
category utilized for rating the intensity of an event; and both non-serious 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. An event is defined as ‘serious’ 
when it meets at least 1 of the predefined outcomes as described in the definition of an 
SAE, NOT when it is rated as severe.
10.5.2
Assessment of Causality
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. For each AE (serious and non-serious), the investigator (or 
medically qualified designee) must provide an assessment of causality on the AE CRF 
page and the SAE form (subject to the classification of the AE). The investigator will 
also document in the medical notes that he/she has reviewed the AE and assessed 
causality, where applicable. 
PPD
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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 Investigator Brochure (IB), 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.
For each AE/SAE, the investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality.
The investigator’s assessment of causality must be provided for all AEs (serious and non-
serious); the investigator must record the causal relationship in the CRF, as appropriate, 
and report such an assessment in accordance with the SAE reporting requirements if 
applicable.
There may be situations when an SAE has occurred and the investigator has minimal 
information to include in the initial report to GSK.  However, it is very important that 
the investigator always make an assessment of causality for every event prior to the 
initial transmission of the SAE data to GSK CH. The investigator may change his/her 
opinion of causality in light of follow-up information and send an SAE follow-up report 
with the updated causality assessment. 
10.6
Follow-up of 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 (serious and non-serious) will be followed until resolution, until the condition 
stabilizes, until the event is otherwise explained, or until the subject is lost to follow-up.  
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as may be indicated or as requested by GSK CH to 
elucidate as fully as possible the nature and/or causality of the AE. This may include 
additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals.
New or updated information will be recorded on the AE CRF page and on the SAE form 
(subject to the classification of the AE).

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The investigator will submit any updated SAE data to GSK CH within 24 hours of 
receipt of the information.
Investigators are not obliged to actively seek AEs in former subjects.  However, if the 
investigator learns of a SAE, including death, at any time after a subject has been 
discharged from the study, and considers the event reasonably related to the study 
product or study participation, the investigator will promptly notify GSK CH 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 the information to the Case Management Group, Global 
Clinical Safety and Pharmacovigilance group mailbox at GSK 
).
The investigator will submit any updated SAE data to GSK CH within the designated 
reporting time frames.
10.7
Withdrawal Due to an Adverse Event 
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of an AE noted earlier, and recorded on the appropriate AE 
CRF page. 
When a subject withdraws because of an SAE, the SAE must be reported in accordance 
with the reporting requirements defined.
10.7.1
Sponsor’s Reporting Requirements to Regulatory Authorities and 
Ethics Committees
GSK CH has a legal responsibility to notify, as appropriate, the local regulatory authority 
and other regulatory authorities about the safety of a product under clinical investigation.  
Prompt notification of SAEs by the investigator to GSK CH is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects are met.
GSK CH will comply with country specific regulatory requirements relating to safety 
reporting to the regulatory authority, IRB/EC 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 describing a SAE or other 
specific safety information e.g. summary or listing of SAE from the sponsor will review 
and then file it along with the Investigator’s Brochure in the investigator study master 
file, and will notify the IRB/IEC, if appropriate according to local requirements.
PPD
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10.8
Pregnancy
10.8.1
Time Period for Collecting Pregnancy Information
Pregnancy information will be collected on all pregnancies reported while a female 
subject is participating in the study from the signing of informed consent until 5 days 
after last administration of study product.
10.8.2
Action to be Taken if Pregnancy Occurs
The investigator will record pregnancy information on the appropriate form scan and e-
mail it to 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 
form to the Case Management Group, Global Clinical Safety and Pharmacovigilance 
mailbox 
). Original pregnancy information forms will be retained 
in the investigator study master file. 
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 box and 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 
(e.g. spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic 
pregnancy) are, and should be recorded as an SAE.
Any female subject who becomes pregnant while participating will discontinue study 
treatment and/or be withdrawn from the study. 
10.9
Definition of and Procedure for Reporting Medical Device 
Incidents
Medical devices are being provided by GSK CH for use in this study; the medical device 
in this study is the toothbrush Oral B Sensi-soft toothbrush (Canadian market). 
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10.9.1
 Definition of an Incident
A medical device incident is any malfunction or deterioration in the characteristics and/or 
performance of a device as well as any inadequacy in the labeling or the instructions for 
use which, directly or indirectly, might lead to or might have led to the death of a 
subject/user/other person or to a serious deterioration in his/her state of health.
Not all incidents lead to death or serious deterioration in health. The nonoccurrence of 
such a result might have been due to other fortunate circumstances or to the intervention 
of health care personnel.
It is sufficient that:
An incident associated with a device happened and

The incident was such that, if it occurred again, might lead to death or a serious 
deterioration in health.

A serious deterioration in state of health can include any of the following:

Life-threatening illness

Permanent impairment of body function or permanent damage to body structure

Condition necessitating medical or surgical intervention to prevent one of the 
above 

Fetal distress, fetal death, or any congenital abnormality or birth defects
Examples of incidents:

A subject, user, caregiver, or healthcare professional is injured as a result of a 
medical device failure or its misuse.

A subject’s study treatment is interrupted or compromised by a medical device 
failure.

A misdiagnosis due to medical device failure leads to inappropriate treatment.

A subject’s health deteriorates due to medical device failure.
10.9.2
Reporting of Incidents and Malfunctions
All incidents must be reported to GSK CH within 24 hours (or sooner if possible) of the 
investigator or designee becoming aware of the situation.
Any medical device incident occurring during the study will be documented in the 
subject's medical records, if in accordance with the investigator's normal clinical practice, 

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and on the appropriate Incident Report Form.  In addition, for incidents fulfilling the 
definition of an AE (serious and non-serious), the appropriate AE CRF page and SAE 
form will be completed and reported as per the AE and SAE reporting sections.
The Incident Report Form will be completed as thoroughly as possible and signed by the 
investigator before transmittal to GSK CH.  It is very important that the investigator 
describes any corrective or remedial actions taken to prevent recurrence of the incident.
The completed Incident Report Form should be scanned and emailed to the GSK CH 
Clinical Operations Safety Reporting email box with the study number and subject 
number in the subject line of the email as soon as possible, but not more than 24 hours 
after study site personnel learn of the event. If there is an SAE, the completed SAE form 
should be sent together with this report form.  However, if a copy of the SAE report is 
sent with this form, this does not replace the procedure to report an SAE.  The original 
Incident Report Form will be retained in the investigator study master file. 
The GSK CH Study Manager should be notified of the situation by telephone or email.
Email the Incident Report Forms to:
The GSK CH Study Manager or designee will be responsible for forwarding the Incident 
Report Form to the Case Management Group, Global Clinical Safety and 
Pharmacovigilance group mailbox (
), responsible for the study and 
other GSK CH personnel as appropriate.
The initial report will be followed up with more information as relevant, or as requested 
by the GSK CH study manager.
The investigator will follow the following directions regarding the reporting of a device 
failure (malfunction):

Notify GSK CH immediately (by following the process described above).

Schedule the subject to return to the site promptly to return the failed device.

Record any incidents on the CRF and Incident Report Form following 
instructions given in the section above.

Return the failed device to the sponsor as soon as possible, including 
documentation of the details of the failure 
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10.9.3
Follow-up of Medical Device Incidents
Medical device incidents involving an AE will be followed and reported in the same 
manner as other AEs. This applies to all subjects, including those who discontinue study 
product or are withdrawn from the study.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the incident.
New or updated information will be recorded on the originally completed Incident Report 
form with all changes signed and dated by the investigator.
10.9.4
Regulatory and Ethics Reporting Requirements for Incidents
To fulfill regulatory reporting obligations worldwide, the investigator is responsible for 
the detection and documentation of events meeting the definitions of incident or 
malfunction that occur during all periods of the study in which the medical device is 
used. 
The investigator will promptly report all incidents occurring with any medical device 
provided for use in the study in order for the sponsor to fulfill the legal responsibility to 
notify appropriate regulatory authorities and other entities about certain safety 
information relating to medical devices being used in clinical studies.
The investigator, or responsible person according to local requirements (e.g. the head of 
the medical institution), will comply with the applicable local regulatory requirements 
relating to the reporting of incidents to the IRB/IEC.
11
DATA MANAGEMENT
As used in this protocol, the term CRF is understood to refer to either a paper form or an 
electronic data record or both, depending on the data collection method. 
For this study, subject data will be entered into an electronic CRF (eCRF), using a 
validated system. Data relating to SAEs, pregnancy and incidents will also be collected 
on paper forms.
The investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF.
The source documents (e.g. hospital records, clinical and office charts, laboratory notes, 
memoranda, subject diaries, questionnaires, evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, microfiches, photographic negatives, 
microfilm or magnetic media, x-rays, subject files and records kept at the pharmacy, at 

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the laboratory and at the medico-technical departments involved in the clinical study) 
which contain the source of data recorded in the CRF should be specified in Sections 8 
and 9.  The CRF and/or diary can be used as a source document at the discretion of data 
management.
Each subject will be assigned and identified by a unique Screening Subject Number. Any 
reference made to an individual subject within the study must be done using their unique 
Screening Subject Number.
11.1
Case Report Form
A CRF is a printed, optical or electronic document designed to record the protocol 
required information to be reported to the sponsor on each trial subject.
For each subject who has given informed consent/assent the CRF must be completed and 
signed by the PI (or authorized designee) to certify that the data are complete and correct.  
The investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF.
Management of clinical data will be performed in accordance with Third Party 
Biostatistics and Data Management (BDM) Vendor applicable standards and data 
cleaning procedures with oversight by GSK CH to ensure integrity of the data, for 
example, to remove errors and inconsistencies in the data. 
To protect the privacy of subjects, no 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 has been 
designated as the source.  Data that is sourced elsewhere should be entered into the CRF 
in an agreed upon timeframe between the Investigator and Sponsor.  
GSK CH will obtain and retain all CRFs and associated study data as applicable at the 
completion of the study. 
11.2
Data Handling
Documentation of all data management activities should allow step-by-step retrospective 
assessment of data quality and study performance. 
Any changes or corrections to data will be performed in the Electronic Data Capture 
(EDC) System, and it will include rationale for changes. The EDC system has an audit 
trail, which will provide a complete record of the changes and corrections endorsed by 
the Investigator.

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Adverse events will be coded using Medical Dictionary for Regulatory Activities 
(MedDRA) and any concomitant medications terms (if applicable) using an internal 
validated medication dictionary, GSKDrug.  
11.2.1
Data Queries
Programmed edit checks will be generated automatically, as the data are being entered 
into the system. Reports and listings on the CRF data will also be run, in addition to the 
queries already programmed and generated by the system, to raise manual queries as 
needed for site clarification or correction. The Clinical Dictionary Development and 
Management Group will raise queries as needed on safety data to code the terms (AEs 
and Drugs or concomitant medication) appropriately. 
The study monitor will perform ongoing review the of the CRFs in accordance with the 
monitoring plan, to confirm that data entered into the CRF by authorized site personnel 
are accurate, complete, and verifiable from source documents; that the safety and rights 
of participants are being protected; and that the study is being conducted in accordance 
with the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements.
Any queries will be generated in the EDC System to the Investigator or designee, 
enabling the errors to be addressed in parallel with Data Management review. The study 
monitor can also run reports and listings on the CRFs, to raise manual queries as needed 
for site clarification or correction.
11.3
Processing Patient Reported Outcomes
Paper based patient reported outcome (PRO) data may be collected from a diary, 
questionnaire, or other specified document, etc. and entered into the data management 
system (DMS).  
Electronic Patient reported outcome (ePRO) data may be collected using electronic 
devices and transferred electronically to GSK CH or Third-party BDM vendor.
All PRO source data should be reviewed by the study staff and the study monitor in order 
to ensure accurate transcription of data and that any potential AEs or concomitant 
medications reported on these documents are discussed with the subject and transcribed 
accurately to the CRF and/or DMS.  PROs that are classed as source data will be retained 
by the investigator and true/certified copies may be sent to a designated vendor or GSK 
CH as required.

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To protect the privacy of subjects, no PII (including the subject's name or initials or birth 
date) is to be recorded on any PRO/ePRO that will be forwarded to GSK CH or Third-
Party BDM Vendor.
11.4
External Data 
External Data are subject data obtained externally to the CRF. These data are generated 
from laboratory instruments, computers or other sources and then transcribed into a file 
and format agreed upon by GSK CH to identify the subject and time point referenced in 
the CRF and/or protocol. 
An agreed quality control process will be performed against the transcribed data to the 
source to ensure the accuracy of the transcription. The transcribed data is transmitted in 
an agreed upon format to GSK CH. 
Reconciliation will be performed between the transcribed data and the clinical database 
to ensure subject and time point referenced in the Clinical Database match before 
Clinical Database Freeze (locking of the database) can occur.
12
STATISTICAL CONSIDERATIONS AND DATA ANALYSES
12.1
Sample Size Determination
No formal sample size has been produced for this exploratory clinical study to 
characterize the DH efficacy profile of the IP, as measured by Schiff sensitivity score and 
tactile threshold, over time. Based on previous GSK CH studies evaluating DH efficacy 
of 0.454% w/w SnF2 dentifrices (for example, (GSK CH Study 205794 2017, GSK CH 
Study RH01325 2013, GSK CH Study RH01685 2013), approximately 50 evaluable 
subjects per treatment group is considered sufficient to provide reliable estimates of 
treatment effect for the purposes of this study and to aid in the design of future clinical 
studies. Approximately 104 subjects will be randomized to study treatment 
(approximately 52 per treatment group).
12.2
Statistical Methods and Analytical Plan
Additional details of the proposed statistical analysis will be documented in the statistical 
reporting and analysis plan (RAP), which will be written following finalization of the 
protocol and prior to study unblinding/analysis (as appropriate).
Treatment differences in the study variables will be tested under the null hypothesis:

H0: there is no treatment difference versus the alternate hypothesis;

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
H1: there is a treatment difference.
12.2.1
Definition of Analysis Populations
The Safety population will include all randomized subjects who receive at least one dose 
of study product. This population will be based on the product the subject received.
The modified Intent-To-Treat (mITT) population will include all randomized subjects 
who receive at least one dose of study product and have at least one post baseline 
efficacy measurement. This population will be based on the study product to which the 
subject was randomized. Any subject who receives a randomization number will be 
considered to have been randomized.
The Per-Protocol (PP) population will include all randomized subjects who do not have 
any protocol deviations that could confound the interpretation of analyses conducted on 
the mITT.
12.2.2
Exclusion of Data from Analysis 
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. A PP analysis will be performed only if 10% or more of the 
subjects from the mITT population are excluded from the PP population. 
12.2.3
Demographic and Baseline Characteristics
Demographic and baseline characteristics summaries will be produced for the mITT and 
safety populations.
Categorical demographic variables include gender, race, ethnicity, baseline Schiff 
stratification score. These variables will be summarized by the number and percentage of 
subjects with each relevant characteristic in each treatment group. Age will be 
summarized by the mean, standard deviation, median, minimum and maximum values in 
each treatment group.  
12.2.4
Study Drug/Product Compliance and Use of Other Therapies
12.2.4.1 Study Drug/Product Compliance
Compliance with study product use (number of brushings) will be listed and summarized 
for the mITT population.

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12.2.4.2 Prior and Concomitant Medications
Prior medications, concomitant medications and significant non-drug therapies taken 
during treatment will be listed for the Safety population.
12.2.5
Primary Analysis 
The mITT population will be used for efficacy analyses. 
The primary efficacy variables are:

Schiff sensitivity score at Days 0 (Baseline), 3, 7, 14, 28 and 56;

Tactile threshold (g) at Days 0 (Baseline), 3, 7, 14, 28 and 56;

Number of sensitive teeth (Schiff sensitivity score ≥ 1) at Days 0 (Baseline), 3, 7, 
14, 28 and 56.
Schiff sensitivity score is derived as the average score of the two test teeth; tactile 
threshold (g) is derived in the same way.  Summary statistics (mean, median, standard 
error (SE), standard deviation (SD), minimum, maximum) will be presented for each 
outcome variable at each assessment time point.  Raw means (± SE) of Schiff sensitivity 
score, tactile threshold (g) and number of sensitive teeth at each timepoint will be plotted 
by treatment group. 
12.2.6
Secondary Analysis
The secondary efficacy variables are:

change from Baseline in Schiff sensitivity score at Day 56;

change from Baseline in tactile threshold (g) at Day 56.  
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.  The change in Schiff sensitivity score will be 
analysed at Day 56 timepoint using an ANCOVA model which will include treatment as 
a factor and Baseline Schiff sensitivity score as a covariate.  Note that since the Baseline 
Schiff sensitivity score will be included as a covariate, the Baseline Schiff stratification 
value will not be included in the model.
Tactile threshold (g) and change from Baseline will be derived as for the Schiff 
sensitivity score. The change in tactile threshold (g) will be analysed at Day 56 timepoint 
using an ANCOVA model with treatment and Baseline Schiff stratification included as 
factors and Baseline tactile threshold included as a covariate.  

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Using the above models, adjusted mean change from Baseline, along with 95% CIs will 
be reported by treatment group.  P-values testing for non-zero change from baseline will 
also be presented for both treatment groups.  Mean difference between treatment groups, 
95% CIs and p-values will also be provided.  Significance testing will be conducted at 
the two-sided 5% significance level; no adjustment for multiple comparisons will be 
made.
The assumption of normality and homogeneity of variance in the ANCOVA models will 
be investigated, and if violated, an appropriate data transformation or non-parametric 
method, for example, the van Elteren test, adjusting for the maximum baseline Schiff 
Sensitivity scores, will be performed.
12.2.7
Safety Analyses
The Safety population will be used for safety analyses.  Safety analyses will be 
performed according to treatment received.  All AEs will be reviewed by the Clinical 
Research Scientist or Designee prior to database lock and unblinding and will be coded 
using the MedDRA. During this review stage, AEs will be further categorized as oral or 
non-oral.  AEs will be listed and summarized by treatment received.  SAEs will also be 
listed.  AEs will be regarded as treatment emergent if they occur on or after the first 
treatment application at the Baseline visit.  The following AEs tables will be produced, 
presented by treatment group:

listing of all AEs (randomized subjects and non-randomized subjects);

summary of AEs;

treatment emergent AEs by Oral/Non-Oral and Preferred Term (PT);

treatment emergent AEs by System Organ Class (SOC) and PT;

treatment emergent treatment related AEs by Oral/Non-Oral and PT;

listing of serious AEs (if there are no SAEs, a null listing will be produced; if 
there are more than 5 treatment emergent serious AEs (SAEs), a table will be 
produced in place of the listing by SOC and PT);

non-serious treatment emergent AEs by SOC and PT (only produced if there are 
more than 5 SAEs); 

listing of incidents (if there are no incidents, a null listing will be produced).
The results of the OST and OHT examinations will be listed and the results of the OST 
examinations will be tabulated.

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12.2.8
Other Analyses
Other efficacy variables include:

Change from Baseline in Schiff sensitivity at Days 3, 7, 14 and 28; 

Change from Baseline in tactile threshold (g) at Days 3, 7, 14 and 28.
Change from Baseline in Schiff sensitivity score and tactile threshold at Days 3, 7, 14 
and 28 will be analysed as per the secondary analyses: adjusted mean change from 
Baseline, along with 95% CIs will be reported by treatment group.  Treatment 
differences and 95% CIs will also be presented.  No p-values will be reported. 
Change from Baseline in DHEQ (Short Form) at Day 28 (Week 4) and Day 56 
(Week 8) 
The following DHEQ endpoints will be reported:

Responses to Questions 7, 8 and 9, DHEQ Section 1 (as separate questions);

Total Score for Questions 1 to 15, DHEQ Section 2;

Restrictions Domain (total score for Questions 1 to 3, DHEQ Section 2);

Adaptation Domain (total score for Questions 4 to 6, DHEQ Section 2);

Social Impact Domain (total score for Questions 7 to 9, DHEQ Section 2);

Emotional Impact Domain (total score for Questions 10 to 12, DHEQ Section 
2);

Identity Domain (total score for Questions 13 to 15, DHEQ Section 2);

Change from Baseline at Day 28 and Day 56 for each DHEQ endpoint.  
Summary statistics (mean, median, SE, SD, minimum, maximum) will be presented for 
each DHEQ endpoint by treatment group.
12.2.9
Handling of Dropouts and Missing Data 
Subjects who withdraw from the study early will be included in the study analysis up to 
the point of withdrawal. Subjects who withdraw will not be replaced. No data will be 
imputed in the case of dropouts or missing data.
12.2.10
Interim Analysis 
No interim analysis is planned for this study.

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13
STUDY GOVERNANCE CONSIDERATIONS
13.1
Quality Control 
In accordance with applicable regulations including GCP, and GSK CH procedures, GSK 
CH or designee (i.e. third-party vendor) monitors will contact the site prior to the start of 
the study to review with the site staff the protocol, study requirements, and their 
responsibilities to satisfy regulatory, ethical, and GSK CH requirements.
When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the CRF will serve as the source 
document.
GSK CH or designee will monitor the study and site activity to verify that the:

Data are authentic, accurate, and complete.

Safety and rights of subjects are being protected.

Study is conducted in accordance with the currently approved protocol and any 
other study agreements, GCP, and all applicable regulatory requirements.
The extent and nature of monitoring will be described in a written monitoring plan on file 
at GSK CH. The investigator (or designee) agrees to allow the monitor direct access to 
all relevant documents and agrees to co-operate with the monitor to ensure that any 
problems detected in the course of these monitoring visits are resolved.
13.2
Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK CH 
may conduct a quality assurance assessment and/or audit of the site records, and the 
regulatory agencies may conduct a regulatory inspection at any time during or after 
completion of the study. 
In the event of an assessment, audit or inspection, the investigator (and institution) must 
agree to grant the advisor(s), auditor(s) and inspector(s) direct access to all relevant 
documents and to allocate their time and the time of their staff to discuss the conduct of 
the study, any findings/relevant issues and to implement any corrective and/or 
preventative actions to address any findings/issues identified.
The investigator(s) will notify GSK CH or its agents immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will 
cooperate with GSK CH or its agents to prepare the study site for the inspection and will 
allow GSK CH or its agent, whenever feasible, to be present during the inspection. The 

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investigator will promptly apply copies of the inspection finding to GSK CH or its agent. 
Before response submission to the regulatory authority, the investigator will provide 
GSK CH or its agents with an opportunity to review and comment on responses to any 
such findings. 
The sponsor will be available to help investigators prepare for an inspection.
13.3
Regulatory and Ethical Considerations
13.3.1
Institutional Review Board/ Ethics Committee 
It is the responsibility of the investigator to have prospective approval of the study 
protocol, protocol amendments, informed consent documents, investigator 
brochure/safety statement (including any updates) and other relevant documents, 
e.g. recruitment advertisements, if applicable, from the IRB/EC.  All correspondence 
with the IRB/EC should be retained in the investigator file.  Copies of IRB/EC approvals 
should be forwarded to GSK CH prior to the initiation of the study, and also when 
subsequent amendments to the protocol are made.
The only circumstance in which an amendment may be initiated prior to IRB/EC 
approval is where the change is necessary to eliminate apparent immediate hazards to the 
subjects.  In that event, the investigator must notify the IRB/EC and GSK CH in writing 
immediately after the implementation.
13.3.2
Ethical Conduct of the Study
The study will be conducted in accordance with legal and regulatory requirements, as 
well as the general principles set forth in the International Ethical Guidelines for 
Biomedical Research Involving Human Subjects (Council for International Organizations 
of Medical Sciences 2002), International Ethical Guidelines for Health-Related Research 
Involving Humans (Council for International Organizations of Medical Sciences 2016), 
guidelines for GCP (ICH 2016), and the Declaration of Helsinki (World Medical 
Association 2013).
In addition, the study will be conducted in accordance with the protocol, the ICH 
guideline on GCP, and applicable local regulatory requirements and laws.
13.3.3
Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject 
names or other identifiable data in any reports, publications, or other disclosures, except 
where required by laws. 

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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 code to his or her actual identity.  In case of data 
transfer, GSK CH will maintain high standards of confidentiality and protection of 
subjects’ personal data consistent with applicable privacy laws.
The informed consent documents must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws.
The informed consent documents used during the informed consent process must be 
reviewed and approved by the sponsor, approved by the IRB/EC before use, and 
available for inspection.
The investigator must ensure that each study subject is fully informed about the nature 
and objectives of the study and possible risks associated with participation. 
13.3.4
Subject Recruitment 
Advertisements approved by IRBs/ECs and investigator databases may be used as 
recruitment procedures.  Use of ethics committee approved, generic, prescreening 
questionnaire to assess basic subject characteristics to determine general eligibility for 
this study is allowed.  This generic questionnaire may be used by sites as a phone script 
and/or to review internal databases to identify subjects.  
GSK CH will have an opportunity to review and approve the content of any study 
recruitment materials directed to potential study subjects before such materials are used. 
13.3.5
Reporting of Safety Issues and Serious Breaches of the Protocol 
or ICH GCP 
Within GSK CH a serious breach is defined as a breach likely to affect to a significant 
degree the safety and rights of a subject or the reliability and robustness of the data 
generated in GSK CH-sponsored human subject research studies. 
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. 

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In addition, the investigator will inform GSK CH immediately of any urgent safety 
measures taken by the investigator to protect the study subjects against any immediate 
hazard, and of any serious breaches of this protocol or of ICH GCP that the investigator 
becomes aware of.
13.4
Posting of Information on Publicly Available Clinical Trial 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins in accordance with applicable GSK CH 
processes.
GSK intends to make anonymized subject-level data from this trial available to external 
researchers for scientific analyses or to conduct further research that can help advance 
medical science or improve patient care. This helps ensure the data provided by trial 
participants are used to maximum effect in the creation of knowledge and understanding
13.5
Provision of Study Results to Investigators
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.  The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK CH site or other mutually-
agreeable location.
GSK CH will also provide the investigator with the full summary of the study results.  
The investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK CH Policy.
A manuscript will be progressed for publication in the scientific literature if the results 
provide important scientific or medical knowledge.
13.6
Records Retention
Following closure of the study, the investigator must maintain all site study records 
(except for those required by local regulations to be maintained elsewhere), in a safe and 
secure location.  
The records (study/ site master file) must be maintained to allow easy and timely 
retrieval, when needed (e.g. for a GSK CH audit or regulatory inspection) and must be 

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available for review in conjunction with assessment of the facility, supporting systems, 
and relevant site staff.
Where permitted by local laws/regulations or institutional policy, some or all of these 
records can be maintained in a format other than hard copy (e.g. microfiche, scanned, 
electronic); however, caution needs to be exercised before such action is taken. 
The investigator must ensure that all reproductions are legible and are a true and accurate 
copy of the original and meet accessibility and retrieval standards, including re-
generating a hard copy, if required.  Furthermore, the investigator must ensure there is an 
acceptable back-up of these reproductions and that an acceptable quality control process 
exists for making these reproductions.
The investigator must assure that the subject’s anonymity will be maintained.  On CRFs 
or other documents submitted to GSK CH, subjects should not be identified by their 
names or initials, but by an identification code. The investigator should keep a separate 
log of subjects’ codes, names and addresses.  Documents not for submission to GSK CH, 
e.g. subjects’ written consent forms, should be maintained by the investigator in strict 
confidence.
Records and documents, including signed ICF, pertaining to the conduct of this study 
must be retained by the investigator for 25 years from the issue of the final Clinical Study 
Report (CSR) or equivalent summary, unless local regulations or institutional policies 
require a longer retention period. The minimum retention time will meet the strictest 
standard applicable to that site for the study, as dictated by any institutional requirements 
or local laws or regulations, GSK CH standards/procedures, and/or institutional 
requirements.  
No study document should be destroyed without a prior written agreement between GSK 
CH and the investigator. The investigator must notify GSK CH of any changes in the 
archival arrangements, including, but not limited to, archival at an off-site facility or 
transfer of ownership of the records in the event the investigator is no longer associated 
with the site.
13.7
Conditions for Terminating the Study 
Premature termination of this study may occur because of a regulatory authority decision, 
change in opinion of the IRB/EC, or study product safety problems, or at the discretion 
of GSK CH.  In addition, GSK CH retains the right to discontinue development of the 
investigational product at any time. For multicenter studies (if applicable), this can occur 
at one or more or at all sites.  

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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 CRFs completed to the greatest extent 
possible. Where required by the applicable regulatory requirements, GSK CH should 
inform the regulatory authority(ies) and the investigator should promptly inform the 
IRB/EC and provide the IRB/EC a detailed written explanation of the termination or 
suspension. 
If the IRB/EC terminates or suspends its approval/favorable opinion of a trial, the 
investigator should promptly notify the GSK CH and provide GSK CH with a detailed 
written explanation of the termination or suspension.
Upon completion or premature discontinuation of the study, the GSK CH monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in 
accordance with applicable regulations including GCP, and GSK CH Standard Operating 
Procedures.

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[West, N. X., Sanz, M., Lussi, A., et al. (2013)] Prevalence of dentine hypersensitivity 
and study of associated factors: a European population-based cross-sectional 
study. Journal of dentistry, 41(10), 841-851.

5% Potassium Nitrate and 0.454% Stannous Fluoride Combination Dentifrice
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[West, N. X., Seong, J. & Davies, M. (2015)] Management of dentine hypersensitivity: 
efficacy of professionally and self‐administered agents. Journal of clinical 
periodontology, 42(Suppl.16), S256-S302.
[White, D. J., Lawless, M., Fatade, A., et al. (2007)] Stannous fluoride/sodium 
hexametaphosphate dentifrice increases dentin resistance to tubule exposure in 
vitro. Journal of Clinical Dentistry, 18(2), 55-59.
[World Medical Association (2013)] Declaration of Helsinki, 64th General Assembly. 
Fortaleza.
[Yang, S., Ying, K., Wang, F., et al. (2016)] Desensitizing effect of stannous fluoride-
containing toothpaste for patients with dentine hypersensitivity: a Meta-analysis. 
West China Journal of Stomatology, 34(2), 150-155.
[Yates, R., Ferro, R., Newcombe, R., et al. (2005)] A comparison of a reformulated 
potassium citrate desensitising toothpaste with the original proprietary product. 
Journal of dentistry, 33(1), 19-25.
[Young, S., Wang, N., Mason, S., et al. (2017)] A Randomized Clinical Study to 
Evaluate the Efficacy of an Experimental 3.75%(w/w) Potassium Chloride 
Dentifrice for the Relief of Dentin Hypersensitivity. The Journal of clinical 
dentistry, 28(2), 9-15.
[Zhuang, W. & Cao, D. (2011)] Efficacy of a dentifrice containing 5% potassium nitrate 
on dental hypersensitivity. Shanghai journal of stomatology, 20(6), 638-640.
[Zsiska, M., Gibbs, M., Moore, J. A., et al. (2012)] Dentinal tubule occlusion with 
stannous fluoride and KNO3/Gantrez dentifrices. Journal of dental research, 
91(-), 744.
[Zsiska, M., White, D. J. & Moore, J. A. (2011)] Acid Durability of Rapid-Onset Smear 
Layers Produced by Dentifrices (Abstract #2635). IADR/AADR/CADR General 
Session. San Diego, California.

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15
APPENDICES
15.1
Abbreviations
The following is a list of abbreviations that may be used in the protocol. 
Table 15-1
Abbreviations
Abbreviation
Term
AE
Adverse event
ANCOVA
Analysis of covariance
BDM
Biostatistics and Data Management
CI
Confidence interval
CRF
Case report form
CSR
Clinical study report
DH
Dentinal hypersensitivity
DHEQ
Dentinal hypersensitivity experience questionnaire
DMS
Data management system
EAR
Erosion abrasion recession
EC
Ethics committee
EDC
Electronic data capture
ECG
Electrocardiogram
eCRF
Electronic case report form
ePRO
Electronic patient reported outcome
FDA
Food and Drug Administration (United States)
FSH
Follicle-stimulating hormone
g
Gram
GCP
Good Clinical Practice
GCS
Global clinical supplies
GSK CH
GlaxoSmithKline Consumer Healthcare
IB
Investigator’s brochure
ICF
Informed consent form
ICH
International Conference on Harmonisation
IND
Investigational new drug application
IP
Investigational product
IRB
Institutional review board
IRT
Interactive response technology
ITT
Intent-to-treat

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Abbreviation
Term
IUD
Intrauterine device
K+
Potassium ion
KNO3
Potassium nitrate
MedDRA
Medical Dictionary for Regulatory Activities
MFC
Master formulation code
MGI
Modified gingival index
mITT
Modified intent-to-treat
N/A
Not applicable
NDA
New drug application
NNHP
Non-prescription natural health product
OHRQOL
Oral health related quality of life
OHT
Oral hard tissue
OST
Oral soft tissue
PI
Principal investigator
PII
Personally identifiable information
PP
Per protocol
ppm
Parts per million
PRO
Patient reported outcome
PT
Preferred term
RAP
Reporting and analysis plan
RCT
Randomized controlled trial
SAE
Serious adverse event
SD
Standard deviation
SE
Standard error
SOC
System organ class
SMFP
Sodium monofluorophosphate
SnF2
Stannous fluoride
Sn
Tin
SRSD
Single reference study document
SUSAR
Suspected unexpected serious adverse reaction
UPT
Urine pregnancy test
US
United States
w/w
Weight/weight

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2) How long have you been experiencing any sensations in your teeth? (tick only one response)
Less than six months (1)
More than six months but less than a year (2)
More than a year but less than five years (3)
More than five years but less than 20 years (4)
More than 20 years (5)
None (0)
15.2
Dentine Hypersensitivity Experience Questionnaire 
(Example)
SECTION ONE
The following questions are about your sensitive teeth, and the impact it has on your everyday life.
From now on in this questionnaire we are going to call what you feel as ‘sensations in your 
teeth’ or ‘sensations’.
3) Which parts of your mouth have been affected? (tick all that apply)
Top front (1)
Top back (2)
Bottom front (3)
Bottom back (4)
None (5)
1) Which of the following best describe any sensations that you may have felt in your teeth (tick all 
that apply)
Itchy (1)
Aching (2)
Shooting (3)
Piercing (4)
Tingling (5)
Sharp (6)
Dull (7)
Flashing (8)
Shivery (9)
Lingering (10)
Twinging (11)
Flickering (12)
Stabbing (13)
Shattering (14)
Freezing (15)
Fleeting (16)
Quivering (17)
Pricking (18)
Pain (19)
Discomfort (20)
Twinges (21)
Sensitivity (22)
Other (please specify) (23)
None of the Above (24)

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5) How often do you have any sensations? (tick only one response)
Several times a day (7)
Once a day (6)
Several times a week (5)
Once a week (4)
Several times a month (3)
Once a month (2)
Less than once a month (1)
Never (0)
6) If you have any sensations, on average how long do these sensations last? (tick only one response)
A few seconds (5)
About a minute (4)
Several minutes (3)
About half an hour (2)
Longer than half an hour (Please specify) (1) 
Don’t have them (0)
4) Which of the following cause you to have sensations? (tick all that apply)
Cold fluids (1)
Salty foods (2)
Cold foods (3)
Tooth brushing (4)
Hot fluids (5)
Acidy fruits (e.g. oranges) (6)
Hot foods (7)
Sweet things (8)
Having teeth cleaned at the dentist (9) 
Hard foods (10)
Sticky foods (11)
Tooth Whitening Products (12)
Cold air (13)
Ice Cream (14)
Metals touching my teeth (15)
Other (Please Specify) (16) 
None (17)

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The following questions are about your sensitive teeth, and the impact it has on your everyday life.
7) On a scale of 1 to 10 how intense are the sensations? (Please circle your answer) 
1
2
3
4
5
6
7
8
9
10
Not at all intense
Worst imaginable
1
2
3
4
5
6
7
8
9
10
8) On a scale of 1 to 10 how bothered are you by any sensations? (Please circle your answer)
1
2
3
4
5
6
7
8
9
10
Not at all bothered
Extremely bothered
1
2
3
4
5
6
7
8
9
10 
        
9) On a scale of 1 to 10 how well can you tolerate sensations? (Please circle your answer)
1
2
3
4
5
6
7
8
9
10
Can easily tolerate
Can’t tolerate at all
1
2
3
4
5
6
7
8
9
10

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SECTION TWO
The following questions are about the ways in which any sensations in your teeth affect you in 
your daily life.  Thinking about yourself over the last 4 weeks to what extent would you agree or 
disagree with the following statements (Please tick only one response for each question) 
Strongly 
agree
(7)
Agree
(6)
Agree a 
little
(5)
Neither 
agree nor 
disagree
(4)
Disagree a 
little
(3)
Disagree
(2)
Strongly 
disagree
(1)
1) Having sensations 
in my teeth takes a lot 
of the pleasure out of 
eating and drinking.
2) It takes a long time 
to finish some foods 
and drinks because of 
sensations in my 
teeth.
3) There have been 
times when I have had 
problems eating ice 
cream because of 
these sensations.
4) I have to change 
the way I eat or drink 
certain things.
5) I have to be careful 
how I breathe on a 
cold day.
6) When eating some 
foods I have made 
sure they don’t touch 
certain teeth.
7) Because of the 
sensations I take 
longer than others to 
finish a meal.

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8) I have to be careful 
what I eat when I am 
with others because of 
the sensations in my 
teeth.
9) Going to the dentist 
is hard for me 
because I know it is 
going to be painful as 
a result of sensations 
in my teeth.
10) I’ve been anxious 
that something I eat or 
drink might cause 
sensations in my 
teeth.
11) The sensations in 
my teeth have been 
irritating.
12) The sensations in 
my teeth have been 
annoying.
13) Having these 
sensations in my teeth 
makes me feel old.
14) Having these 
sensations in my teeth 
makes me feel 
damaged.
15) Having these 
sensations in my teeth 
makes me feels as 
though I am 
unhealthy.