An 8-week, Randomised, Controlled, Examiner-Blind, Proof of Principle Study Investigating the Ability of a 3% Methyl Vinyl Ether/Maleic Anhydride Co-Polymer (PVM/MA) + 5% Potassium Nitrate (KNO3) Combination Toothpaste to Protect From Dentine Hypersensitivity
Phase: NA
Conditions: Dentin Sensitivity
Sponsor: HALEON

GSK Consumer Healthcare 
Confidential 
Clinical Protocol 
Protocol Number: 218220 
Property of GSK Consumer Healthcare – Confidential 
May not be used, divulged, published or otherwise disclosed without the consent of GSK 
SP1963/ 
 Template Version:28-Sep-2018 (CCR #11475) 
Page 1 of 100 
CLINICAL PROTOCOL 
An 8-week, randomised, controlled, examiner-blind, proof of principle 
study investigating the ability of a 3% methyl vinyl ether/maleic 
anhydride co-polymer (PVM/MA) + 5% potassium nitrate (KNO3) 
combination toothpaste to protect from dentine hypersensitivity 
Protocol Number: 
218220 
Compound/Product Name: 
3% PVM/MA + 5% KNO3 
United States (US) Investigational New 
Drug (IND) Number: 
Not applicable (N/A) 
European Clinical Trials Database 
(EudraCT) Number: 
N/A 
Other Regulatory Agency Identified 
Number: 
N/A 
Phase: 
Exploratory 
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This document contains confidentiality statements that are not relevant for this publicly
available version
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Clinical Protocol 
 
 
Protocol Number: 218220 
 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of 
GSKCH 
 Clinical Protocol Template v7.0 
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Sponsor Information 
 
Sponsor Name & Legal 
Registered Address 
 
GlaxoSmithKline Consumer Healthcare 
(UK) Trading Limited 
980 Great West Road, 
Brentford, 
Middlesex, 
TW8 9GS, 
United Kingdom (UK) 
Sponsor Contact Details 
 
GlaxoSmithKline Consumer Healthcare 
(GSK CH) 
St. George’s Avenue 
Weybridge 
KT13-0DE 
United Kingdom  
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Clinical Protocol 
 
 
Protocol Number: 218220 
 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of 
GSKCH 
 Clinical Protocol Template v7.0 
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Document History 
 
Document 
Version 
Summary of Changes  
Protocol 
1.0 
Not applicable (N/A) 
Amendment 1 
2.0 
• Addition of Supervised Brushing with Study Toothpaste 
for all the Visits (2-6) in the schedule of activities 
• Change of toothbrush in the sundry items table 
(Aquafresh, flat trim, medium toothbrush (Germany)) 
• Amendment of Schiff score units in the Samples Size 
section 
Amendment 2 
 
 
 
 
 
Amendments incorporate all revisions to date, including amendments made at the request 
of country health authorities, research ethics committees (RECs), etc.   
 
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Clinical Protocol 
 
 
Protocol Number: 218220 
 
 
Property of GSK Consumer Healthcare - Confidential  
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 Clinical Protocol Template v7.0 
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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 
 
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Clinical Protocol 
 
 
Protocol Number: 218220 
 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of 
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 Clinical Protocol Template v7.0 
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Table of Contents 
Sponsor Information .............................................................................................2 
Document History .................................................................................................3 
Principal Investigator Protocol Agreement Page ..................................................4 
Table of Contents ..................................................................................................5 
1 
PROTOCOL SUMMARY ..................................................................................12 
1.1 
Synopsis ..................................................................................................12 
1.2 
Schedule of Activities .............................................................................16 
2 
INTRODUCTION ..............................................................................................18 
2.1 
Study Rationale .......................................................................................18 
2.2 
Background .............................................................................................18 
2.3 
Benefit/Risk Assessment.........................................................................20 
2.4 
Mechanism of Action/Indication ............................................................21 
3 
STUDY OBJECTIVES AND ENDPOINTS ......................................................22 
4 
STUDY DESIGN ...............................................................................................23 
4.1 
Overall Design ........................................................................................23 
4.2 
Scientific Rationale for Study Design .....................................................25 
4.3 
Justification for Product Usage Regimen................................................26 
4.4 
End of Study Definition ..........................................................................26 
5 
STUDY POPULATION .....................................................................................27 
5.1 
Type and Planned Number of Subjects ...................................................27 
5.2 
Inclusion Criteria.....................................................................................27 
5.3 
Exclusion Criteria. ..................................................................................29 
5.4 
Randomisation Criteria ...........................................................................32 
5.5 
Lifestyle Considerations .........................................................................32 
5.5.1 
Oral Hygiene Restrictions ......................................................33 
5.5.2 
Dietary and Alcohol, Restrictions ..........................................33 
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Protocol Number: 218220 
 
 
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5.5.3 
Contraception (Hatcher and Nelson, 2007) ............................33 
5.6 
Screen Failures ........................................................................................35 
5.7 
Sponsor’s Qualified Medical Personnel ..................................................35 
5.8 
Clinical Assessor Qualifications .............................................................36 
6 
STUDY PRODUCTS .........................................................................................36 
6.1 
Study Product Supplies ...........................................................................37 
6.1.1 
Product Form and Packaging..................................................38 
6.1.2 
Product Dispensing .................................................................39 
6.2 
Administration ........................................................................................40 
6.2.1 
Product Usage Errors ..............................................................40 
6.2.2 
Overdose .................................................................................41 
6.3 
Study Product Storage .............................................................................41 
6.4 
Study Product Accountability .................................................................42 
6.4.1 
Destruction of Study Product Supplies...................................43 
6.5 
Blinding and Allocation/Randomisation .................................................43 
6.6 
Breaking the Blind ..................................................................................44 
6.7 
Compliance .............................................................................................44 
6.8 
Concomitant Medication/Treatment(s) ...................................................45 
7 
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL ..........................................................46 
7.1 
Subject Discontinuation/Withdrawal ......................................................46 
7.2 
Lost to Follow up ....................................................................................47 
8 
STUDY PROCEDURES ....................................................................................48 
8.1 
Screening: Day -28 to Day -14 (Visit 1) .................................................48 
8.1.1 
Informed Consent ...................................................................48 
8.1.2 
Demographics .........................................................................49 
8.1.3 
Inclusion/Exclusion Criteria ...................................................49 
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Protocol Number: 218220 
 
 
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8.1.4 
Medical History and Prior Medication/Treatment .................49 
8.1.5 
Subject Eligibility ...................................................................50 
8.1.6 
Screening Procedures .............................................................50 
8.1.7 
Supervised Use of Acclimatisation Toothpaste ......................51 
8.2 
Study Period ............................................................................................51 
8.2.1 
Baseline: Visit 2 (Day 0) ........................................................51 
8.2.2 
Visits 3-5 (Day 3±1 day, Week 2±1 day and Week 4 ±2 days)
 ................................................................................................53 
8.2.3 
Visit 6 (Week 8 ±2 days) ........................................................54 
8.3 
Diary Review ..........................................................................................55 
8.4 
Study Conclusion ....................................................................................56 
8.5 
Follow-up Visit/Phone Call ....................................................................56 
9 
STUDY ASSESSMENTS ..................................................................................56 
9.1 
Screening Assessments ...........................................................................57 
9.1.1 
Erosion, Abrasion and Recession (EAR) ...............................57 
9.1.2 
Modified Gingival Index (MGI) .............................................57 
9.1.3 
Tooth Mobility Assessment ....................................................58 
9.1.4 
Qualifying Tactile Sensitivity (Visit 1) ..................................58 
9.1.5 
Qualifying Evaporative Air Sensitivity (Visit 1) ....................60 
9.2 
Product Performance Assessments .........................................................60 
9.2.1 
Dentine Hypersensitivity Experience Questionnaire (DHEQ)
 ................................................................................................60 
9.2.2 
Self-Perceived Sensitivity Discomfort Assessment ...............61 
9.2.3 
Tactile Sensitivity Assessment ...............................................62 
9.2.4 
Evaporative (Air) Sensitivity Assessment ..............................62 
9.2.5 
Selection of Test Teeth ...........................................................63 
9.3 
Safety and Other Assessments ................................................................63 
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Protocol Number: 218220 
 
 
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9.3.1 
Oral Soft Tissue (OST) Examination .....................................63 
9.3.2 
Oral Hard Tissue (OHT) Examination ...................................63 
9.3.3 
Pregnancy Testing ..................................................................64 
10 ADVERSE EVENT AND SERIOUS ADVERSE EVENTS .............................64 
10.1 
Definition of an Adverse Event (AE) .....................................................64 
10.2 
Definition of a Serious Adverse Event (SAE) ........................................66 
10.3 
Time Period and Frequency for Collecting AE and SAE Information ...67 
10.4 
Reporting Procedures ..............................................................................68 
10.4.1 
Reporting of an Adverse Event ..............................................69 
10.4.2 
Reporting of a Serious Adverse Event ...................................69 
10.5 
Evaluating Adverse Events .....................................................................71 
10.5.1 
Assessment of Intensity ..........................................................71 
10.5.2 
Assessment of Causality .........................................................71 
10.6 
Follow-up of AEs and SAEs ...................................................................72 
10.7 
Withdrawal Due to an Adverse Event .....................................................73 
10.8 
Regulatory Reporting Requirements for SAEs .......................................73 
10.9 
Pregnancy ................................................................................................74 
10.9.1 
Time Period for Collecting Pregnancy Information ...............74 
10.9.2 
Action to be Taken if Pregnancy Occurs ................................74 
11 DATA MANAGEMENT ...................................................................................75 
11.1 
Case Report Form ...................................................................................76 
11.2 
Data Handling .........................................................................................76 
11.2.1 
Data Queries ...........................................................................77 
11.3 
Processing Subject Reported Outcomes .................................................77 
11.4 
External Data...........................................................................................78 
12 STATISTICAL CONSIDERATIONS AND DATA ANALYSES ....................78 
12.1 
Sample Size Determination .....................................................................78 
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Protocol Number: 218220 
 
 
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12.2 
Populations for Analysis .........................................................................79 
12.3 
Statistical Analyses .................................................................................79 
12.3.1 
Primary Analyses....................................................................79 
12.3.2 
Secondary Analyses................................................................80 
12.3.3 
Safety Analyses ......................................................................81 
12.3.4 
Exclusion of Data from Analysis ...........................................82 
12.3.5 
Demographic and Baseline Characteristics ............................82 
12.3.6 
Study Drug/Product Compliance and Use of Other Therapies
 ................................................................................................83 
12.3.7 
Handling of Dropouts and Missing Data ................................83 
12.3.8 
Interim Analysis .....................................................................83 
13 STUDY GOVERNANCE CONSIDERATIONS ...............................................83 
13.1 
Quality Control .......................................................................................83 
13.2 
Quality Assurance ...................................................................................84 
13.3 
Regulatory and Ethical Considerations ...................................................85 
13.3.1 
Research Ethics Committee (REC) ........................................85 
13.3.2 
Ethical Conduct of the Study ..................................................85 
13.3.3 
Subject Information and Consent ...........................................85 
13.3.4 
Subject Recruitment ...............................................................86 
13.3.5 
Reporting of Safety Issues and Serious Breaches of the 
Protocol or ICH GCP..............................................................86 
13.4 
Posting of Information on Publicly Available Clinical Trial Registers ..87 
13.5 
Provision of Study Results to Investigators ............................................87 
13.6 
Records Retention ...................................................................................88 
13.7 
Conditions for Terminating the Study ....................................................89 
14 REFERENCES ...................................................................................................90 
15 APPENDICIES ...................................................................................................93 
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Clinical Protocol 
 
 
Protocol Number: 218220 
 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of 
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 Clinical Protocol Template v7.0 
Page 10 of 100 
 
15.1 
ABBREVIATIONS ................................................................................93 
15.2 
Dentine Hypersensitivity Experience Questionnaire (Example) ............95 
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Clinical Protocol 
 
 
Protocol Number: 218220 
 
 
Property of GSK Consumer Healthcare - Confidential  
May not be used, divulged, published or otherwise disclosed without the consent of 
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 Clinical Protocol Template v7.0 
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List of in text tables 
Table 1-1 
Schedule of Activities.............................................................16 
Table 3-1 
Study Objectives and Endpoints .............................................22 
Table 6-1 
Investigational/Study Product Supplies ..................................37 
Table 6-2 
Sundry Items ...........................................................................38 
Table 15-1 
Abbreviations .........................................................................93 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Clinical Protocol 
 
 
Protocol Number: 218220 
 
 
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 Clinical Protocol Template v7.0 
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1 
PROTOCOL SUMMARY  
1.1 
Synopsis 
Short Title: 
A proof of principle (PoP) study to evaluate the ability of an experimental combination 
toothpaste formulation to protect sensitive teeth from dentine hypersensitivity. 
Background and Rationale: 
GlaxoSmithKline Consumer Healthcare (GSK CH) has developed a new combination 
toothpaste containing 3% poly vinyl methyl ether/maleic anhydride (PVM/MA) co-
polymer and 5% potassium nitrate (KNO3). It is hypothesised that the combination of these 
2 ingredients with different modes of action (PVM/MA: dentin tubule occlusion; KNO3: 
nerve desensitisation) will deliver superior protection for sensitive teeth from dentine 
hypersensitivity, compared to toothpastes containing either PVM/MA or KNO3 alone.  
Toothpastes containing co-polymers such as PVM/MA are reported to alleviate tooth 
sensitivity. None of the studies reported to date investigated PVM/MA+KNO3 
formulations compared to the single ingredients. This PoP will evaluate and compare the 
ability of the three products - a PVM/MA+KNO3 combination toothpaste, a PVM/MA only 
toothpaste and a KNO3 only toothpaste to provide sensitivity protection across an 8-week 
usage period. A regular fluoride toothpaste will be included as negative control. 
Objectives and Endpoints: 
Objectives 
Endpoints 
Product performance  
Primary 
To characterise the sensitivity protection profile of an 
experimental 3% PVM/MA + 5% KNO3 combination 
toothpaste, a 3% PVM/MA only toothpaste, a 5% 
KNO3 and a regular fluoride toothpaste (negative 
control) over 8 weeks (with twice daily use).  
 
At Day 0 (Baseline), Day 3 and Weeks 2, 4 & 8: 
- Schiff sensitivity score  
- Tactile threshold (grams [g])  
- Number of sensitive teeth (Schiff sensitivity 
score ≥ 1) 
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Protocol Number: 218220 
 
 
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Secondary 
To investigate the ability of an experimental 3% 
PVM/MA + 5% KNO3 combination toothpaste to 
provide sensitivity protection , in response to an 
evaporative (air) stimulus (Schiff sensitivity score), 
compared to a 3% PVM/MA only toothpaste, a 5% 
KNO3 only toothpaste and a regular fluoride toothpaste 
(negative control), after 3 days and 2, 4 and 8 weeks 
twice daily use. 
At Day 3 and Weeks 2, 4 & 8: 
Change from Baseline in Schiff sensitivity score  
To investigate the ability of an experimental 3% 
PVM/MA + 5% KNO3 combination toothpaste to 
provide sensitivity protection, in response to a tactile 
stimulus (tactile threshold), compared to a 3% 
PVM/MA only toothpaste, a 5% KNO3 only toothpaste 
and regular fluoride toothpaste (negative control), after 
3 days and 2, 4 and 8 weeks twice daily use. 
At Day 3 and Weeks 2, 4 & 8: 
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 3 days and 2, 4 and 8 weeks twice daily use of a 
3% PVM/MA + 5% KNO3 combination toothpaste, a 
3% PVM/MA only toothpaste, a 5% KNO3 only 
toothpaste and a regular fluoride toothpaste (negative 
control).  
At Day 3 and Weeks 2, 4 & 8: 
Change from Baseline in 
- Responses to DHEQ Section 1, Questions 7-9 
- Total Score; responses to DHEQ Section 2, 
Questions 1-15 
- Restrictions, Adaptation, Social Impact, 
Emotional Impact & Identity Domains 
To explore changes in self-perceived discomfort 
associated with tooth sensitivity, as measured by a 
numeric rating scale (NRS), after 3 days and 2, 4 and 8 
weeks twice daily use of a 3% PVM/MA + 5% KNO3 
combination toothpaste, a 3% PVM/MA only 
toothpaste, a 5% KNO3 only toothpaste and a regular 
fluoride toothpaste (negative control). 
At Baseline, Day 3 and Weeks 2, 4 & 8: 
- NRS score 
At Day 3 and Weeks 2, 4 & 8: 
- Change from Baseline in NRS score  
Safety 
To assess the safety and tolerability of study products 
with twice daily use for 8 weeks. 
Treatment emergent adverse events 
 
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Study Design: 
This will be a PoP, single centre, 8-week, randomised, controlled, examiner blind, parallel 
design, stratified (by maximum Baseline Schiff sensitivity score of the two selected test 
teeth) clinical study, investigating the ability of a 3% PVM/MA + 5% KNO3 combination 
toothpaste to protect sensitive teeth from dentine hypersensitivity.  
In line with widely recommended oral hygiene practice and typical consumer habit, study 
subjects will be requested to brush their teeth twice daily (morning and evening) with their 
assigned study toothpaste for the duration of the 8-week study period.  
Tooth sensitivity will be assessed at Screening (Visit 1), Baseline (Day 0), Day 3 and 
Weeks 2, 4 and 8 using two independent stimulus-based (tactile and evaporative (air)) 
measures will be employed, in line with published recommendations for the design and 
conduct of sensitivity clinical studies.  
Oral Health Related Quality of Life (OHRQoL) will be evaluated using the validated 
Dentine Hypersensitivity Experience Questionnaire (DHEQ-15), completed by study 
subjects after 3 days and 2-, 4- and 8-weeks product use. In addition, a Numeric Rating 
Scale (NRS) will be also used to explore changes in self-perceived discomfort associated 
to tooth sensitivity after 3 days and 2-, 4- and 8-weeks product use. 
Safety and oral tolerability of the study products will be monitored over the 8-week usage 
period by review of reported AEs. 
Study Products: 
Product 
Description 
Acclimatisation 
Product 
Test Product 
Comparator 1 
Comparator 2 
Negative 
control 
Regular fluoride 
toothpaste 
3% PVM/MA + 
5% KNO3 
combination 
toothpaste 
3% PVM/MA 
only toothpaste 
5% KNO3 only 
toothpaste 
Regular fluoride 
toothpaste 
Fluoride 
Content 
1450 parts per million 
(ppm) fluoride as 
sodium fluoride (NaF) 
1450 ppm 
fluoride as NaF 
1450 ppm 
fluoride as NaF 
1450 ppm 
fluoride as NaF 
1450 ppm 
fluoride as NaF 
Product  
Name 
Colgate Cavity 
Protection 
Not applicable 
(N/A) 
N/A 
N/A 
 Colgate Cavity 
Protection 
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Protocol Number: 218220 
 
 
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Type and Planned Number of Subjects: 
The study will be conducted in male and female subjects in good general health, aged 18-
65 years inclusive, 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) visits.  
 
Sufficient subjects will be screened to ensure approximately 120 subjects are randomised 
to study product (approximately 30 subjects per product arm); approximately 30 evaluable 
subjects per product group is considered sufficient to provide reliable estimates of 
performance for the purposes of this study and to aid in the design of future clinical studies. 
Statistical Analyses: 
A modified Intent-To-Treat population (mITT) (all randomised subjects who complete at 
least one use of study product and have at least one post baseline clinical performance 
assessment) will be used for product performance analyses. The primary statistical 
analyses will descriptively and visually present the performance of the study products over 
time. Summary statistics (mean, median, standard error (SE), standard deviation (SD), 
minimum, maximum) will be presented for each primary end point at each assessment time 
point. Raw means (average score of the two test teeth) ± SE will be plotted for Schiff 
sensitivity score and tactile threshold (g) at each timepoint by product group; the number 
of sensitive teeth will also be plotted at each timepoint by product group. 
 
Secondary end points include change from Baseline in Schiff sensitivity score and tactile 
threshold (g). Change from Baseline will be analysed at each assessment time point using 
use of Analysis of Covariance (ANCOVA), comparing the Test Product to Comparator 1, 
Comparator 2 and the negative control. Adjusted mean change from Baseline, along with 
95% confidence intervals (CIs) will be reported by product; p-values testing for non-zero 
change from Baseline will be presented for all products.  
 
Summary of statistics (mean, median, SE, SD, minimum, maximum) will be presented for 
each secondary endpoint by product group and assessment time point. Significance testing 
will be conducted at the two-sided 5% significance level with no adjustments for multiple 
testing. 
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1.2 
Schedule of Activities 
The schedule of activities table provides an overview of the subject visits and study 
procedures.  The investigator may schedule visits (unplanned visits) in addition to those 
listed on the schedule of activities, to conduct evaluations or assessments required to 
protect the well-being of the subject. 
Table 1-1 
Schedule of Activities 
Procedure/Assessment 
Screening 
 
Study Visits 
Visit 1 
Day -28  
to -14 
Visit 2 
Baseline 
Day 0 
Visit 3 
Day 3 
(± 1 day)  
Visit 4 
Week 2 
Day 14 
(± 1 day)   
Visit 5 
Week 4 
Day 28 
(± 2 day)  
Visit 6 
Week 8 
Day 56 
(± 2 day)   
Informed Consent 
X 
Acclimatisation Period (2-4 weeks) 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
Medical History & Current/Prior Concomitant 
Medication/Treatment Review 
X 
 
 
 
 
 
Changes in Health & Medications/ Treatments 
 
X 
X 
X 
X 
X 
Urine Pregnancy Test (UPT)1 
X 
 
 
 
 
X 
Oral Soft Tissue (OST) Examination 
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) 2 
X 
X 
 
 
 
 
Qualifying Evaporative (Air) Sensitivity Assessment 
(Schiff sensitivity score)3  
X 
X 
 
 
 
 
Inclusion / Exclusion Criteria  
X 
X 
 
 
 
 
Subject Eligibility 
X 
X 
 
 
 
 
Dispense Acclimatisation Toothpaste, Toothbrush, 
Timer & Diary 
X 
 
 
 
 
 
Supervised Brushing with Acclimatisation 
Toothpaste  
X 
 
 
 
 
 
Return Acclimatisation Toothpaste, Toothbrush & 
Diary4 
 
X 
 
 
 
 
Stratification/Randomisation 
 
X 
 
 
 
 
Dispense Study Toothpaste, Toothbrush & Diary 
 
X 
 
 
 
 
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Procedure/Assessment 
Screening 
 
Study Visits 
Visit 1 
Day -28  
to -14 
Visit 2 
Baseline 
Day 0 
Visit 3 
Day 3 
(± 1 day)  
Visit 4 
Week 2 
Day 14 
(± 1 day)   
Visit 5 
Week 4 
Day 28 
(± 2 day)  
Visit 6 
Week 8 
Day 56 
(± 2 day)   
Supervised Brushing with Study Toothpaste 
 
X 
X 
X 
X 
X 
Return Study Toothpaste, Toothbrush & Diary4 
 
 
 
 
 
X 
Compliance Checks5 
 
X 
X 
X 
X 
X 
Clinical Examiner Selects Two ‘Test Teeth’ (Eligible 
Subjects Only) 
 
X 
 
 
 
 
Tactile Sensitivity Assessment (Yeaple Probe): Two 
Test Teeth Only2 
 
 
X 
X 
X 
X 
Evaporative (Air) Sensitivity (Schiff sensitivity 
score): Two Test Teeth Only3 
 
 
X 
X 
X 
X 
Evaporative (Air) Sensitivity (Schiff sensitivity 
score): All Remaining Eligible Teeth Identified at 
Screening3 
 
 
X 
X 
X 
X 
DHEQ 6 
 
X6 
X6 
X6 
X6 
X6 
NSR Self- Perceived Discomfort Questions 
 
X 
X 
X 
X 
X 
Study Conclusion 
 
 
 
 
 
 
X 
Monitor Adverse Events (AEs)7 
 
 
X 
X 
X 
X 
X 
Footnotes:  
1. 
Female subjects of child-bearing potential only.  
2. 
Visits 1-2: maximum force 20g (Screening and Baseline); Visits 3-6: maximum force 80g.  
3. 
Evaporative (air) assessment will follow tactile assessment, with minimum 5 minutes between last tactile assessment and first 
evaporative (air) assessment (to allow tooth recovery).  
Visit 1: assess the evaporative (air) sensitivity of teeth with tactile threshold ≤ 20 g.  
Visit 2: assess the evaporative (air) sensitivity of all eligible teeth identified at Screening.  
Visits 3-6: assess the evaporative (air) sensitivity of the 2 test teeth first, then assess the evaporative (air) sensitivity of all other 
eligible teeth identified at Screening. 
4. 
Subject will be required to bring their study supplies (minus timer) to every visit.  
5. 
Perform visual check of returned study supplies, review diary & evaluate compliance.  
Visit 2: check compliance with use of acclimatisation toothpaste.  
Visits 3-6: check compliance with use of study product.  
Visits 2-6: check compliance with Lifestyle Guidelines/Medication requirements.  
6. 
DHEQ must be completed before the NRS question is asked; DHEQ & NRS question must be completed prior to OST 
examination/clinical assessments.  
DHEQ Visit 2: complete all questions 
DHEQ Visits 3-6: complete Section 1 Q7-9 & Section 2 all questions.  
7. 
Record AEs from signing of informed consent until 5 days after last use of study product  
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2 
INTRODUCTION 
2.1 
Study Rationale 
GlaxoSmithKline Consumer Healthcare (GSK CH) has developed a new combination 
toothpaste containing 3% PVM/MA and 5% KNO3 with potential to protect sensitive teeth 
from dentine hypersensitivity. It is hypothesised that the combination of these 2 ingredients 
with different modes of action (PVM/MA: dentin tubule occlusion; KNO3: nerve 
desensitisation) will deliver superior protection from sensitive teeth, compared to the 
toothpastes containing either PVM/MA or KNO3 alone.  
Several clinical studies evaluating the ability of PVM/MA toothpaste to protect teeth from 
sensitivity are reported in the scientific literature (Schiff et al., 1994, Ayad et al., 1994, 
Chaknis et al., 2011), however, none of the studies reported to date investigated the 
performance of a toothpaste formulated with PVM/MA+KNO3 in comparison with the 
single ingredients.  
This PoP clinical study will evaluate and compare the ability of a daily use 3% PVM/MA+ 
5% KNO3 combination toothpaste, a 3% PVM/MA only toothpaste, a 5% KNO3 only 
toothpaste and regular fluoride toothpaste (negative control) to provide sensitivity 
protection over 8 weeks, with twice daily brushing. Data generated will aid in the design 
of future clinical studies investigating this combination toothpaste.  
2.2 
Background 
Dentine hypersensitivity (DH) is a common oral condition (Addy, 2000, West et al., 2014), 
with the peak incidence occurring at the end of the third decade and decreasing during the 
fourth and fifth decades of life (Irwin and McCusker, 1997, Bartold, 2006, West et al., 
2014).  
Reduced levels of DH in older individuals are most likely a result of reparative processes, 
such as the formation of reparative dentine, which decrease permeability and reduce 
hydraulic conductance (West, 2006). But, as individuals retain their teeth and complete 
functionality for longer (due to caries and periodontal disease prevention) and as diets 
change (with an increased consumption of acidic drinks and foods) it is reasonable to 
expect a higher incidence of oral discomfort related to DH (Drisko, 2002, West et al., 2014) 
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and with that an increase in use of oral care products which can help protect sensitive teeth 
from DH.  
Epidemiological studies on the prevalence of DH in the general population have shown 
conflicting results and it is not simple to estimate a precise percentage (%) of incidence. 
This is likely due to several factors such as different sample populations, different 
diagnostic approaches, and whether the source data is based on clinical evaluation or 
patient-based questionnaires (West et al., 2014, Favaro Zeola et al., 2019, Splieth and 
Tachou, 2013). It is noted that individuals who have received periodontal therapy are four 
times more at risk for developing DH than the general population (Drisko, 2002). 
In a normal tooth, dentine is covered by enamel over the crown, and by cementum 
(connective tissue) and the periodontal tissues over the root. Aetiologic factors such as 
gingival recession, tooth erosion and/or abrasion that result in loss of enamel or cementum 
and exposure of underlying dentine with patent dentinal tubules (Orchardson and Collins, 
1987) are believed to be responsible for DH onset. 
Once the dentine is exposed, the most common triggers of DH are evaporative (such as 
cold air), thermal (hot and cold drinks/foods), tactile (adding pressure e.g. from 
toothbrushing) and osmotic (sugary foods and drinks) stimuli. It is hypothesised that these 
stimuli can cause movement in the fluid within patent dentine tubules, triggering the intra-
dental nerves (Brännström, 1963).  
There are currently two ways to protect against DH. The first is to use desensitising agents, 
such as KNO3. It is postulated that potassium ions, delivered into exposed dentine tubules, 
are able to depolarise the intra-dental nerves, thereby reducing the discomfort from tooth 
sensitivity (Addy and Smith, 2010). Numerous longer-term studies (typically 4-12 weeks) 
have been published demonstrating the clinical efficacy of KNO3 in protecting sensitive 
teeth from DH (Silverman, 1985, Nagata et al., 1994, Gillam, 1996, West et al., 1997, 
Wara‐aswapati et al., 2005, Kakar and Kakar, 2013, Bae et al., 2015). 
The second approach, with more rapid effects (Gillam et al., 1996), is to use an occlusion 
technology. 
Occluding 
agents 
(such 
as 
strontium/stannous 
salts, 
bioglasses, 
arginine/calcium carbonate, silicas) act to seal or narrow the dentine tubules, thereby 
reducing fluid movement, pulpal irritation and the subsequent sensitivity response.  
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It has been reported that co-polymers such as PVM/MA, already extensively employed as 
excipients in oral care formulations such as toothpastes, denture adhesives and 
mouthwashes, may also act to occlude exposed dentine and help protect sensitive teeth 
(Schiff et al., 1994, Ayad et al., 1994, Chaknis et al., 2011). A 12-week clinical study 
demonstrated the ability of a combination toothpaste containing  PVM/MA to alleviate 
sensitivity, compared to a placebo toothpaste (Schiff et al., 1994). In addition, Chaknis et 
al., showed the greater ability of a PVM/MA toothpaste, compared to a stannous fluoride 
only  toothpaste, to protect sensitive teeth (Chaknis et al., 2011). None of the clinical DH 
studies reported to date investigated the combination of PVM/MA+KNO3 compared to the 
single ingredients.  
This PoP clinical study will evaluate and compare the ability of a daily use 3% PVM/MA+ 
5% KNO3 combination toothpaste, a 3% PVM/MA only toothpaste, a 5% KNO3 only 
toothpaste and regular fluoride toothpaste (negative control) to protect sensitive teeth from 
DH over 8 weeks, with twice daily brushing. Given occluding toothpastes are reported to 
provide fast protection from the discomfort of DH, the clinical study will include clinical 
assessments at a range of time points across the 8-week usage period. 
Safety and tolerability of the study toothpastes will be assessed by review of treatment 
emergent adverse events. 
Data generated from this study will provide an initial indication of the clinical benefits of 
the new combination toothpaste, compared to its’ individual components alone, and will 
be used to direct any future clinical evaluations.  
2.3 
Benefit/Risk Assessment  
Complete information for the combination toothpaste may be found in the single reference 
safety document (SRSD), which for this study is the Safety Statement (SS).  
Three clinical studies evaluating the ability of a toothpaste formulated with PVM/MA 
polymer (in combination with various other ingredients) to protect sensitive teeth are 
reported in the scientific literature. In these studies, subjects brushed twice daily with their 
assigned study toothpaste for the duration of the treatment period. No adverse events which 
could be ascribed to use of the combination toothpaste were reported. 
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• 8-Week Study: Toothpaste containing 2.0% PVM/MA copolymer, 0.3 % 
triclosan, 0.243% NaF (Chaknis et al., 2011). 
• 12-Week Study: Toothpaste containing 1.5% PVM/MA+ 5% KNO3 (Ayad et al., 
1994, Schiff et al., 1994).  
• 12-Week Study: Toothpaste containing 1.5% PVM/MA+ 5% KNO3 (Ayad et al., 
1994, Schiff et al., 1994). 
The combination of 3% PVM/MA+ 5% KNO3 is considered generally safe for topical oral 
use, when delivered from a toothpaste with twice daily brushing, under the controlled 
conditions of a clinical trial.     
2.4 
Mechanism of Action/Indication 
Potassium nitrate has been found to be an effective desensitising ingredient. It is postulated 
that after each brushing with a potassium ion (K+) containing toothpaste, the concentration 
of K+ ions at the tooth surface is raised. K+ ions move into the dentine through the tubules, 
gradually desensitising the nerves inside the tooth and thereby providing protection from 
DH. Potassium salts generally require a period of use (for example, 14 to 28 days) before 
their benefit is established (Parkinson et al., 2017, West et al., 1997, Jeandot et al., 2007, 
Schiff et al., 2000). 
Occlusion agents act by physically blocking or narrowing the exposed ends of the dentine 
tubules, thereby reducing dentinal fluid movement and decreasing the effect of external 
stimuli and consequent discomfort. Tubule occlusion can be favored over nerve 
desensitisation, due to the more rapid onset of relief from DH (Gillam, 1996).  
PVM/MA is an occluding polymer that has been shown to be effective in protecting 
sensitive teeth when delivered from a daily use toothpaste (Chaknis et al., 2011, Schiff et 
al., 1994).  
In this exploratory study, it is hypothesised that the combination of these two ingredients 
(PVM/MA+KNO3) with complementary modes of action should deliver greater protection 
for sensitive teeth, compared to either PVM/MA or KNO3 alone. 
 
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3 
STUDY OBJECTIVES AND ENDPOINTS 
Table 3-1 
Study Objectives and Endpoints 
Objectives 
Endpoints 
Product performance  
Primary 
To characterise the sensitivity protection profile of an 
experimental 3% PVM/MA + 5% KNO3 combination 
toothpaste, a 3% PVM/MA only toothpaste, a 5% 
KNO3 and a regular fluoride toothpaste (negative 
control) over 8 weeks (with twice daily use).  
 
At Day 0 (Baseline), Day 3 and Weeks 2, 4 & 8: 
- Schiff sensitivity score  
- Tactile threshold (grams [g])  
- Number of sensitive teeth (Schiff sensitivity 
score ≥ 1) 
Secondary 
To investigate the ability of an experimental 3% 
PVM/MA + 5% KNO3 combination toothpaste to 
provide sensitivity protection, in response to an 
evaporative (air) stimulus (Schiff sensitivity score), 
compared to a 3% PVM/MA only toothpaste, a 5% 
KNO3 only toothpaste and a regular fluoride toothpaste 
(negative control), after 3 days and 2, 4 and 8 weeks 
twice daily use. 
At Day 3 and Weeks 2, 4 & 8: 
Change from Baseline in Schiff sensitivity score  
To investigate the ability of an experimental 3% 
PVM/MA + 5% KNO3 combination toothpaste to 
provide sensitivity protection, in response to a tactile 
stimulus (tactile threshold), compared to a 3% 
PVM/MA only toothpaste, a 5% KNO3 only toothpaste 
and regular fluoride toothpaste (negative control), after 
3 days and 2, 4 and 8 weeks twice daily use. 
At Day 3 and Weeks 2, 4 & 8: 
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 3 days and 2, 4 and 8 weeks twice daily use of a 
3% PVM/MA + 5% KNO3 combination toothpaste, a 
3% PVM/MA only toothpaste, a 5% KNO3 only 
toothpaste and a regular fluoride toothpaste (negative 
control).  
At Day 3 and Weeks 2, 4 & 8: 
Change from Baseline in 
- Responses to DHEQ Section 1, Questions 7-9 
- Total Score; responses to DHEQ Section 2, 
Questions 1-15 
- Restrictions, Adaptation, Social Impact, 
Emotional Impact & Identity Domains 
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To explore changes in self-perceived discomfort 
associated with tooth sensitivity, as measured by a 
numeric rating scale (NRS), after 3 days and 2, 4 and 8 
weeks twice daily use of a 3% PVM/MA + 5% KNO3 
combination toothpaste, a 3% PVM/MA only 
toothpaste, a 5% KNO3 only toothpaste and a regular 
fluoride toothpaste (negative control). 
At Baseline, Day 3 and Weeks 2, 4 & 8: 
- NRS score 
At Day 3 and Weeks 2, 4 & 8: 
- Change from Baseline in NRS score  
Safety 
To assess the safety and tolerability of study products 
with twice daily use for 8 weeks. 
Treatment emergent adverse events 
 
No formal success criterion has been defined for this exploratory study; however, if the 
combination toothpaste provides greater sensitivity protection, it would be expected that 
the performance profiles (plots of Schiff sensitivity score, tactile threshold (g) and number 
of sensitive teeth) for the 3% PVM/MA + 5% KNO3 toothpaste would show a consistent 
improvement in sensitivity with 8 weeks twice-daily use, directionally superior to the  
respective component formulations (PVM/MA alone and KNO3 alone) and the negative 
control. 
 
4 
STUDY DESIGN  
4.1 
Overall Design 
This will be a PoP, single centre, 8-week, randomised, controlled, examiner blind, parallel 
design, stratified (by maximum Baseline Schiff sensitivity score of the two selected test 
teeth) clinical study in healthy subjects with sensitive teeth.   
To help minimise the potential impact of ‘placebo’/‘no treatment’ effects, and to 
standardise oral hygiene practices, an acclimatisation period (2-4 weeks) will be included 
between the Screening and Baseline assessments. Subjects who meet all study criteria at 
both Screening and Baseline visits will be randomised to one of the 4 study products. 
In line with widely recommended oral hygiene practice and typical consumer habit, study 
subjects will be requested to brush their teeth for one timed minute twice daily (morning 
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and evening) with their assigned study toothpaste, covering the toothbrush head with full 
ribbon of toothpaste (approximately 1.5 g) on each brushing occasion.  
Two independent stimulus-based (tactile and evaporative) measures of tooth sensitivity 
will be employed. 
• A tactile stimulus will be administered using a constant pressure probe (Yeaple 
Probe (Polson et al., 1980)). Subject response will determine the tactile threshold 
in grams (g). 
• An evaporative (air) stimulus will be administered using a dental air syringe. 
Subject response will be evaluated using the Schiff sensitivity scale (Schiff et al., 
1994). 
Sensitivity to tactile and evaporative (air) stimuli will be assessed at Screening (Visit 1) 
and then at various time points across the 8-week usage period - Baseline (Day 0), Day 3 
and Weeks  2, 4 and 8. A single clinical examiner will assess both measures for the duration 
of the study for all study subjects. 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. In 
addition, the remaining ‘eligible teeth’ identified as sensitive to both tactile and 
evaporative (air) stimuli at Screening will be assessed for evaporative (air) sensitivity only 
at Day 3 and Weeks 2, 4 and 8. 
Oral Health Related Quality of Life (OHRQoL) will be evaluated using the validated 
Dentine Hypersensitivity Experience Questionnaire (short version DHEQ-15); this will be 
completed by study subjects at Baseline (Day 0), and after 3 days and 2, 4 and 8-weeks 
product use. A Numeric Rating Scale (NRS) will be also used to explore changes in self-
perceived discomfort associated with tooth sensitivity after 3 days and 2-, 4- and 8-weeks 
product use. 
Safety and oral tolerability of the study products will be monitored over the 8-week usage 
period by review of reported AEs. 
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4.2 
Scientific Rationale for Study Design 
The study will investigate the ability of an experimental combination toothpaste containing 
3% weight/weight (w/w) PVM/MA + 5% w/w KNO3 (Test Product), a 3% w/w PVM/MA 
only toothpaste (Comparator 1), a 5% w/w KNO3 only toothpaste (Comparator 2) and a 
regular fluoride toothpaste with no known anti-sensitivity properties (negative control) to 
protect sensitive teeth from DH. Trends in sensitivity measures over time (from Baseline 
to 8 weeks) will be investigated for each product group as the primary objective. Inter-
product comparisons will be investigated as secondary objectives; comparisons between 
the Test and Comparator toothpastes will be of particular interest to explore if the 
combination toothpaste provides enhanced sensitivity protection.  
The randomised, controlled, examiner-blind, parallel design selected for this study follows 
the recommended approach for investigating the performance of sensitivity products.  
Use of two independent stimulus-based (tactile and evaporative (air)) measures of tooth 
sensitivity is in line with published recommendations for the design and conduct of 
sensitivity clinical studies. The selection of two ‘test teeth’ to evaluate changes in DH is 
also 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 product groups are balanced for sensitivity 
severity. 
Study subjects will be aged between 18 and 65 years; DH most frequently occurs between 
the ages of 20 and 40 years and is known to decrease with age above 40 years (Bartold, 
2006, West et al., 2014, Dababneh et al., 1999). 
According to ICH guidelines, for a study to be classed as truly double blind, not only does 
the examiner (and any appropriate member of staff who may be involved in the dispensing 
of products, analysis of data etc.) need to be blinded as to the product the subject receives, 
but the products under test must be identical in every way (colour, flavour, appearance, 
packaging). Given it is almost impossible to ensure identical appearance, taste and 
packaging for the toothpastes evaluated in oral care studies, the level of product blinding 
for this study is described as ‘examiner blind’. Study toothpastes will be supplied in over-
wrapped tubes. The blind will be maintained by staff involved in dispensing, brushing 
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instruction and supervised brushings not being involved in the clinical examinations and 
study products being provided to subjects in blinded packs. 
The DHEQ is a validated, condition-specific measure of the impacts of tooth sensitivity on 
everyday life; it has been shown to have good psychometric properties in both the general 
population and in a clinical sample of subjects with sensitive teeth (Boiko et al., 2010, 
Baker et al., 2014). A short form of the DHEQ (DHEQ-15) has also been developed and 
validated (Machuca et al., 2014) and will be included in this study to evaluate product 
performance in a clinically diagnosed DH population. In addition, an NRS will be used to 
monitor changes in the level of subject-perceived discomfort associated to tooth sensitivity 
at the same time points as the DHEQ. 
4.3 
Justification for Product Usage Regimen 
The study products are toothpastes, intended for topical oral use, and will be applied by 
toothbrushing using a manual toothbrush. 
The usage regimen of twice daily brushing (morning and evening) will be the same for all 
subjects and is based on widely recommended oral hygiene practice/typical consumer 
habit. Study subjects will be required to brush for at least 1 timed minute with their 
assigned study toothpaste on each brushing occasion. Subjects will brush their two selected 
sensitive ‘test teeth’ first, followed by their whole mouth. After 8 weeks (Day 56 ±2 days) 
twice daily usage, each subject should complete between 108-116 brushings. 
Each subject will complete a supervised brushing with their assigned study toothpaste at 
the end of each study visit (while still at the study site) to enable staff to check correct 
usage and to encourage compliance with the required  usage regimen for the duration of 
the study. 
4.4 
End of Study Definition 
A subject is considered to have completed the study if they complete 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. 
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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 (clinically confirmed 
DH) that meet all study criteria at both the Screening (Visit 1) and Baseline (Visit 2) visits. 
Sufficient subjects will be screened and entered into the acclimatisation phase to ensure 
approximately 120 subjects are randomised to study product (approximately 30 subjects 
per product arm). Subjects will be recruited primarily from the study site 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 or not a subject is suitable.   
Eligibility to participate should be reviewed and documented by an appropriate member of 
the study site team before each subject is included in the study. 
5.2 
Inclusion Criteria 
An individual must meet all the following inclusion criteria to be eligible to be included in 
the study: 
1. Provision of a signed and dated informed consent indicating the subject has been 
informed of all pertinent aspects of the study before any study procedures are 
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, product usage 
requirements and other study procedures. 
 
 
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4. Subject in good general, oral and mental health with, in the opinion of the investigator 
or medically qualified designee, no clinically significant or relevant abnormalities in 
medical history, or upon oral examination, that would impact the subject’s safety or 
wellbeing, or the outcomes of the study, if they were to participate in the study, or 
affect the subject’s ability to understand and follow study procedures and requirements. 
5. Female subject of child-bearing potential and at risk for pregnancy who agrees to use 
a highly effective method of contraception throughout the study and for at least 5 days 
after the last use of assigned study product.   
6. AT VISIT 1 (Screening): 
Subject must have 
a) a self-reported history of tooth sensitivity 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 confirmed DH; each tooth must 
meet the following criteria: 
- 
exposed dentine due to facial/cervical erosion, abrasion or gingival recession 
(EAR). 
- 
MGI score = 0 adjacent to the test area (exposed dentine) only (Lobene et al., 
1986) 
- 
clinical mobility = 0  (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) with DH, as evidenced by qualifying levels of tactile and evaporative (air) 
sensitivity (tactile threshold ≤ 20 g; Schiff sensitivity score ≥ 2) at the Screening and 
Baseline visits. 
 
 
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Note: All teeth which meet the eligibility criteria 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 both 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 be excluded from the 
study: 
1. Subject who is an employee of the study site, either directly involved in the conduct of 
the study or a member of their immediate family; or an employee of the study 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 of 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 or psychiatric condition or laboratory abnormality that may 
increase the risk associated with study participation or study 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. Female subject who is pregnant (as evidenced by a positive urine pregnancy test (UPT) 
at Screening) or intending to become pregnant during the study. 
5. Female subject who is breastfeeding. 
6. Subject with known or suspected intolerance or hypersensitivity to the study products 
or any of their stated ingredients (or closely related compounds). 
7. Subject who is unwilling or unable to comply with the Lifestyle Considerations 
described in the protocol (Section 5.5).  
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8. Subject with a recent history (within the last year) of alcohol or other substance abuse. 
9. Subject who has participated in another tooth sensitivity study within 8 weeks of 
Screening. 
10. Subject who has used an oral care product indicated for the relief of DH or care of 
sensitive teeth within 8 weeks of Screening (subjects will be required to verbally 
confirm the name of  their current oral care products  to enable site staff to verify the 
absence of known sensitivity ingredients). 
11. Subject who has had dental prophylaxis within 4 weeks of Screening. 
12. Subject who has had a teeth bleaching procedure within 8 weeks of Screening. 
13. Subject who has had treatment for periodontal disease (including surgery) within 12 
months of Screening. 
14. Subject who has had scaling or root planning within 3 months of Screening. 
15. Subject with gross periodontal disease. 
16. Subject with evidence of gross intra-oral neglect or the need for extensive dental 
therapy. 
17. Subject with a tongue or lip piercing.  
18. Subject with a fixed or removable partial prosthesis which, in the opinion of the 
investigator, would impact study outcomes. 
19. Subject with multiple dental implants which, in the opinion of the investigator, would 
impact study outcomes. 
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 dentine but with deep, defective or facial restorations. 
c) Tooth with full crown or veneer. 
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d) Tooth adjacent to a bridge abutment or crown which, in the opinion of the 
investigator, would impact study outcomes. 
e) Sensitive tooth with contributing etiologies other than erosion, abrasion or 
recession to exposed dentine. 
f) Sensitive tooth not expected to benefit from use of a sensitivity toothpaste 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 their perception of 
tooth sensitivity (examples of such medications include analgesics, anticonvulsants, 
antihistamines that cause marked or moderate sedation, sedatives, tranquilisers, 
antidepressants, 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 
acclimatisation period. 
25. Subject who is 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. 
 
 
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5.4 
Randomisation Criteria 
Subjects will be randomised into the study provided they have satisfied all subject selection 
criteria.  
Subjects will be stratified (by 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 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 eCRF. 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 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 assessments will be performed. The 
subject will not be replaced. 
• Day 3 (Visit 3): the subject will continue in the study. No clinical assessments will 
be performed. 
• Weeks 2 and 4 (Visits 4-5): if the subject cannot be reappointed (within the visit 
tolerance for Visits 4-6), they will continue in the study. No clinical assessments 
will be performed. 
• Week 8 (Visit 6): if the subject cannot be reappointed, they will be withdrawn from 
the study (Section 7.1). No clinical assessments will be performed. The subject will 
not be replaced. 
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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, toothpastes, 
toothbrushes, oral rinses, tongue cleaners, whitening/bleaching products, 
interdental 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 or caring 
for sensitive teeth (including herbal remedies) than those provided during the study. 
• Subjects should not chew gum. 
Before a Clinical Assessment Visit: Baseline (Visit 2) to Week 8 (Visit 6) 
• Subjects will refrain from all oral hygiene procedures for at least 8 hours before a 
study visit. 
5.5.2 
Dietary and Alcohol, Restrictions 
Before a Clinical Assessment Visit: Baseline (Visit 2) to Week 8 (Visit 6) 
• 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 (Hatcher and Nelson, 2007) 
All 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 
use of assigned study product. 
 
 
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Female subjects of non-child-bearing 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 methods for avoiding pregnancy that meets the 
GSK definition of highly effective (i.e., have a failure rate of less than 1% per year when 
used consistently and correctly and, when applicable, in accordance with the product label)  
The list does not apply to females of reproductive potential with same sex partners or to 
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 considered acceptable methods of contraception. 
• Contraceptive subdermal implant 
• Intrauterine device (IUD) or intrauterine system 
• Combined estrogen and progestogen oral contraceptive 
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• Injectable progestogen 
• Contraceptive vaginal ring 
• Percutaneous contraceptive patches 
• Male partner sterilisation 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. 
5.6 
Screen Failures 
Screen failures are defined as subjects who consent to participate in the clinical study but 
are not subsequently randomised. To ensure transparent reporting of screen failure 
subjects, a minimal set of screen failure information will include demography, screen 
failure details (e.g. withdrawal of consent), eligibility criteria, and any adverse events  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 or 
clinical research scientist 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 study staff seeking advice on medical/dental 
questions or problems in the event that the established communication pathways between 
the study site and the study team are not available.   
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The contact number is not intended for direct use by study subjects.  To facilitate access to 
appropriately experienced GSK CH 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 study site, and contact details in the event that the study site cannot be 
reached to provide advice on a medical question or problem identified by a healthcare 
professional other than the investigator.   
5.8 
Clinical Assessor Qualifications  
Examiners involved in screening and clinical assessment procedures will be qualified 
dentists, registered to practice in the UK. Oral examinations to determine subject eligibility 
and all safety/product performance (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 
STUDY PRODUCTS 
For the purposes of this study, per International Conference on Harmonisation (ICH) 
guidelines, and GSK policy, study intervention is defined as any investigational 
intervention(s), marketed product(s), placebo, or medical device(s) intended to be 
administered to a study participant according to the study protocol. 
This includes a product with a marketing authorisation 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.  
 
 
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6.1 
Study Product Supplies 
The following study products will be supplied by Clinical Supplies Department, GSK CH. 
Table 6-1 
Investigational/Study Product Supplies 
Product 
Description 
Acclimatisation 
Product 
Test Product 
Comparator 1 
Comparator 2 
Negative control 
Regular fluoride 
toothpaste  
3% PVM/MA 
+ 5% KNO3 
combination 
toothpaste 
3% PVM/MA 
only toothpaste 
5% KNO3 only 
toothpaste 
Regular fluoride 
toothpaste  
Fluoride content 
1450ppm fluoride as 
NaF 
1450ppm 
fluoride as NaF  
1450ppm 
fluoride as NaF 
1450ppm 
fluoride as NaF  
1450ppm fluoride 
as NaF 
Product Name 
 Colgate Cavity 
Protection 
N/A 
N/A 
N/A 
 Colgate Cavity 
Protection 
Pack Design 
One carton containing 2 overwrapped tubes of toothpaste 
Dispensing 
Details 
Visit 1 (Screening):  
1 carton 
Visit 2 (Baseline): 2 cartons 
Product Master 
Formulation 
Code (MFC) 
Commercial 
Product 
 
 
 
Commercial 
Product 
Product 
Application 
Subjects will dose the toothbrush provided with a strip of dentifrice (a full brush head) on each 
brushing occasion 
Route of 
Administration 
Topical Oral Use 
Usage 
Instructions 
Subjects will brush 
for 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 one timed minute, twice daily (morning and evening); 
subjects will be permitted to rinse with water post-brushing. 
Return 
Requirements 
All used/unused product to be returned to GSK 
 
 
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Table 6-2 
Sundry Items 
 
Item 
Supplied 
By 
Pack Design 
Dispensing Details 
Return/Disposal Details 
Used Samples 
Unused Samples 
Aquafresh, flat 
trim, medium 
toothbrush 
(Germany) 
GSK CH 
Individual 
toothbrush in 
commercial 
pack 
One toothbrush at 
Screening for use with 
acclimatisation 
toothpaste  
One toothbrush at 
Baseline for use with 
assigned study toothpaste 
Destroy at site 
using site disposal 
procedures 
Return to GSK 
Countdown Timer 
GSK CH 
Individual timer 
in commercial 
pack 
 
One timer at Screening 
visit 
Subject to keep or 
destroy at site 
using site disposal 
procedures 
Return to GSK 
Pregnancy Tests  
(UK Market) 
GSK CH 
Commercial 
pack 
Use as per study schedule 
Destroy at site 
using site disposal 
procedures 
Return to GSK 
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 
toothpaste usage instructions), the clinical assessment score sheets, the DHEQ-15, the NRS 
question 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 prior to the study close 
out visit. 
6.1.1 
Product Form and Packaging 
All study products are toothpastes, intended for topical oral use, and will be applied by 
toothbrushing using a manual toothbrush. 
The test product and comparator toothpastes will be manufactured and filled into plain 
white tubes by GSK CH with a study label affixed; the acclimatisation and control 
toothpastes will be supplied in their commercial packs. All study toothpastes (including 
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the acclimatisation product) will be overwrapped in white vinyl (to mask their 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 acclimatisation toothpaste and their 
assigned study toothpaste to cover usage during the acclimatisation and treatment periods, 
respectively. Acclimatisation toothpaste will be dispensed at Screening (Visit 1); study 
toothpaste 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 to ensure 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. 
6.1.2 
Product Dispensing  
Subjects will be assigned to study product in accordance with the randomisation 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 
toothpastes will be dispensed in blinded fashion to the subject, by trained site personnel. 
These staff members will not be involved in any safety/product performance 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 (eCRF). 
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6.2 
Administration 
Subjects will be instructed to self-administer the acclimatisation toothpaste and their 
assigned study toothpaste according to the usage instructions provided at the study site and 
detailed in the diary. To help ensure subjects fully understand the amount of toothpaste to 
be used each time they brush and the usage instructions: 
• staff will demonstrate dispensing a full ribbon of toothpaste along the length of the 
toothbrush head to each eligible subject and supervise their first brushing with the 
acclimatisation toothpaste/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 toothpaste/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 toothpaste/diary completion at the end of 
the Day 3, Week 2, 4 and 8 visits (Visits 3-6), after all clinical assessments have 
been completed. 
On-site administration of study products will be recorded in the dispensing log and the 
eCRF. 
6.2.1 
Product Usage Errors 
Study product usage errors may result, in this study, from the administration or 
consumption of the wrong product, by the wrong subject, at the wrong time, in the wrong 
way. 
Such study product usage errors occurring to a study subject are to be captured in the eCRF. 
In the event of study product usage error, the sponsor should be notified immediately. 
Study product usage errors are reportable irrespective of the presence of an associated AE, 
including: 
• study product usage errors involving subject exposure to any of the study products; 
• potential study product usage errors or uses outside of what is foreseen in the 
protocol that do or do not involve the participating subject. 
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If a study product usage error is accompanied by an AE, as determined by the investigator, 
the study product usage error and any associated adverse event(s) are to be captured in the 
eCRF AE form. 
6.2.2 
Overdose 
Overdose is not likely to occur in this study. Limited quantities of the study products will 
be supplied and closely monitored by the site for each subject. 
Overdose per se is not an AE. However, any clinical sequelae of an overdose should be 
reported as an AE (and serious adverse event (SAE), if appropriate). For reporting, follow 
the AE and SAE reporting instructions. 
6.3 
Study Product Storage  
The investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study products received and any discrepancies are reported 
and resolved before use according to the supplied shipping documentation. 
The investigator, or designee, will ensure that all study products are stored in a secured 
area with controlled access under required storage conditions and in accordance with 
applicable regulatory requirements, the product label and Clinical Study Supplies 
Checklist.   
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products).  This should 
be captured from the time of first product receipt throughout the study. Even for continuous 
monitoring systems, a log or site procedure that ensures active daily evaluation for 
excursions should be available. The operation of the temperature-monitoring device and 
storage unit (for example, refrigerator), as applicable, should be regularly inspected to 
ensure it is maintained in working order.  
Any excursions from the product-label storage conditions should be reported to appropriate 
site staff upon discovery and communicated to sponsor as soon as possible.  The site should 
actively pursue options for returning the product to the storage conditions as described in 
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the labeling, as soon as possible. Excursions from the storage requirements, including any 
actions taken, must be documented as a protocol deviation and reported to the Sponsor.   
Once an excursion is identified, the affected product (or products) must be quarantined and 
not used until the sponsor provides documentation of permission to use. Use of any of the 
affected product(s) prior to sponsor approval will be considered a protocol deviation.   
Site staff will instruct subjects on the proper storage requirements for all take-home 
products.  
6.4 
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 secure location to which only permitted staff have 
access. Upon receipt, all study products should be stored according to the instructions 
specified on the product labels. Study products are to be dispensed only to subjects enrolled 
in the study in accordance with the protocol, by authorised site staff. 
The investigative site must maintain adequate records documenting the receipt, use, loss, 
or other disposition of all the product supplies. All study products will be accounted for 
using the study product accountability form/record. The investigator is responsible for 
study product accountability, reconciliation, and record maintenance.  
Subjects will return used and unused tubes of the acclimatisation toothpaste to the study 
site at their Baseline visit (Visit 2). Subjects will return used and unused tubes of their 
assigned study toothpaste to the study site at their last visit (for most subjects this will be 
Visit 6). Study product return will be documented using the 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.  
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6.4.1 
Destruction of Study Product Supplies  
At the conclusion of the study, the investigator or an appropriate designee, and a 
representative of GSK CH (study monitor) will inventory all used and unused study 
products and sundry items. The 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 Clinical 
Supplies Department or designated vendor using the return instructions provided. 
Return and destruction instructions for sundry items are provided in Table 6-2. 
6.5 
Blinding and Allocation/Randomisation 
All subjects will be centrally randomised to one of the four study products using an 
Interactive Response Technology (IRT). Before the study is initiated, training, login 
information and directions for the IRT will be provided to the study site. Study products 
will be dispensed according to the instruction received through the IRT at the appropriate 
study visits. 
Returned study products should not be re-dispensed to any subject. This study is described 
as examiner-blind (the subjects, investigator, clinical examiner 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 clinical examiner remains blinded throughout the study: 
• site staff involved in the dispensing of study product and the supervision of onsite 
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 
it is provided in outside of the dispensing room, while at the study site; 
• dispensing staff and on-site brushing supervisors will not be involved in any 
safety/product performance assessments during the study. 
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6.6 
Breaking the Blind 
At the initiation of the study, the study site will be instructed on the method for breaking 
the blind. The method will be an electronic process. 
The electronic system will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has the sole responsibility for determining if unblinding of a 
subject’s product assignment is warranted. Subject safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding 
is warranted, the investigator should make every effort to contact the sponsor prior to 
unblinding a subject’s product assignment unless this could delay emergency treatment of 
the subject. 
If a subject’s product assignment is unblinded, the sponsor must be notified within 24 hours 
after breaking the blind. The date and reason that the blind was broken must be recorded 
in the source documentation and case report form, as applicable. 
Any AE associated with breaking the blind must be recorded and reported as specified in 
this protocol. The study site may also be required be required to inform the REC if the 
blind is broken.  
6.7 
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 the 
acclimatisation toothpaste and their assigned 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 toothpaste used, oral 
problems, illnesses and any new medications/treatments. 
Subjects will attend each study visit with all tubes of toothpaste 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 eCRF. Subjects will be re-instructed in the correct product usage 
requirements and diary completion as needed. 
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Supervised brushings will be carried out at the study site at the end of Visits 2-5 to facilitate 
subject compliance with product usage 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 eCRF 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. 
Medications taken and treatments within 30 days of signing the informed consent form 
will be documented as a prior medication/treatment. Medications taken and treatments 
started 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). 
• 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 their perception of sensitivity (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 
eCRF. 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 tooth sensitivity assessments will be performed. 
The subject may be replaced. 
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Baseline (Visit 2): if the subject cannot be reappointed, they will be withdrawn 
from the study (Section 7.1). No tooth sensitivity assessments will be performed. 
The subject will not be replaced. 
Day 3 (Visit 3): the subject will continue in the study. Tooth sensitivity 
assessments will be performed. 
Week 2, 4 & 8 (Visits 4-6): if the subject cannot be reappointed (within the visit 
tolerance for Visits 4-6), they will continue in the study. Tooth sensitivity 
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 their own request or may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety, behavioral 
reasons, or the inability of the subject to comply with the protocol-required schedule of 
study visits or procedures.   
The following circumstances require discontinuation of study product and/or premature 
subject withdrawal: 
• Protocol violation that may impact the subject’s safety 
• Withdrawal of informed consent 
• Subject lost to follow-up  
• Unblinding of the subject  
• Pregnancy 
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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 eCRF.  
7.2 
Lost to Follow up 
If a subject fails to return to the site for a required study visit the site must attempt to 
contact the subject and reschedule the missed visit as soon as possible and counsel the 
subject on the importance of maintaining the assigned visit schedule and ascertain whether 
the subject wishes to and/or should continue in the study. 
A subject will be considered lost to follow up if they repeatedly fail to return for scheduled 
visits and cannot be contacted by the study site. Before a subject is deemed lost to follow 
up, the investigator or designee must make every effort to regain contact with the subject 
(where possible, 3 telephone calls and, if necessary, a certified letter to the subject’s last 
known mailing address or local equivalent methods). These contact attempts should be 
documented. If contact is made with the subject, the investigator should inquire about the 
reason for withdrawal, request that the subject return all study products provided and, if 
appropriate, request the subject return for a final visit and follow-up with the subject 
regarding any unresolved adverse events (AEs). 
Final safety assessments may be carried out when the subject returns to the study site, at 
the investigator’s discretion, which could include the following: an oral examination. 
Should the subject continue to be unreachable, they will be considered to have withdrawn 
from the study and lost to follow up.  
Lack of completion of all or any of the early termination procedures will not be viewed as 
protocol deviations so long as the subject’s safety was preserved. 
If the subject withdraws from the study and withdraws consent for future disclosure of 
their information, no further evaluations should be performed, and no additional data 
should be collected.  The sponsor may retain and continue to use any data collected before 
such withdrawal of consent. 
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8 
STUDY PROCEDURES 
This section lists the procedures to be completed at each planned study visit.  The timing 
of each procedure is listed in the Schedule of Activities section. 
Adherence to the study design requirements, including all procedures are essential and 
required for study conduct. 
8.1 
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 toothpastes 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 be captured as this is the point 
from which all Adverse Events will be captured. The date and time of consent will be 
captured in the eCRF. 
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 
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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 on the eCRF. 
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, the subject is considered enrolled 
in the study. 
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 eCRF: year of birth, gender 
and race.  
 
Ethnicity and race of subjects will be recorded in accordance with FDA Guidance for 
Industry: Collection of Race and Ethnicity Data in Clinical Trials, 2005. 
8.1.3 
Inclusion/Exclusion Criteria 
Inclusion and exclusion criteria information will be documented in the eCRF. 
8.1.4 
Medical History and Prior Medication/Treatment 
Details of relevant medical and surgical history, including allergies and drug sensitivities, 
will be documented in the eCRF. 
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Prior medications/treatments, including prescription and non-prescription drugs, dietary 
supplements and herbal remedies, taken in the last 30 days will be documented in the 
eCRF. 
8.1.5 
Subject Eligibility 
The investigator and/or medically qualified designee will review inclusion/exclusion 
criteria, medical history, prior medications to confirm subject eligibility to participate in 
the clinical trial. This will be documented in the eCRF. 
To prepare for study participation, subjects will be instructed in the Lifestyle Guidelines 
(Section 5.5) and any Concomitant Medication/Treatment(s) (Section 6.8) requirements of 
the protocol. 
8.1.6 
Screening Procedures 
The following procedures will be completed, and data recorded in the eCRF. 
• Review the oral care products the subject is currently using (subject will provide 
the names of their current oral care products) to confirm they do not contain any 
ingredients intended for treating sensitive teeth.  
• Female subjects of child-bearing potential only complete a UPT. 
• Clinical examiner completes an OST examination as described in Section 9.3.1. 
• Clinical examiner completes as OHT examination as described in Section 9.3.2. 
• Clinical examiner completes eligible teeth assessments for incisors, canines and 
pre-molars, including dentition exclusions and assessments of EAR, MGI and tooth 
mobility as described in Section 5.3, Section 9.1.1, Section 9.1.2 and Section 9.1.3 
respectively. 
• Clinical examiner assesses the sensitivity of each tooth that meets the above 
eligibility criteria, first to a tactile stimulus and then to an evaporative (air) 
stimulus, 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.  
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To facilitate subject flow, clinical assessments may be recorded on a paper score sheet 
(source document) and later transcribed into the eCRF.  
The same examiner will be responsible for completing both sensitivity measures (tactile 
and evaporative (air) sensitivity) for the duration of the study. 
8.1.7 
Supervised Use of Acclimatisation Toothpaste 
Eligible subjects will be provided with the acclimatisation toothpaste, a toothbrush, diary 
and timer to use during the acclimatisation period (2-4 weeks). Toothpaste usage 
instructions will be described to the subject and covering the full brush head with 
toothpaste will be demonstrated. Staff will supervise the subject carrying out first their first 
use of acclimatisation toothpaste and recording first use in their diary. 
Completion of all procedures will be documented in the eCRF.  
Spontaneous reporting of AEs and those elicited by asking subjects to respond to a non-
leading question such as “How do you feel?” will be assessed. Any AEs reported on 
completion of the supervised brushing with the acclimatisation toothpaste will be recorded 
in the eCRF. 
8.2 
Study Period 
8.2.1 
Baseline: Visit 2 (Day 0) 
Changes in concomitant medication or non-drug treatments/procedures will be 
documented in the eCRF. Spontaneous reporting of AEs and those elicited by asking 
subjects to respond to a non-leading question such as “How do you feel?” will be assessed 
and any AEs recorded in the eCRF. 
The following procedures will then be completed, and data recorded in the eCRF. 
• Complete visual checks of returned acclimatisation toothpaste tubes and review 
completed diary. Record any suspected over or under use and the number of any 
missed or additional brushings. 
Do not return acclimatisation toothpaste/toothbrush/diary to subject. 
• Confirm subject adherence to the requirements of the protocol and continuance. 
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• Female subjects of child-bearing potential only to self-report pregnancy status.  
• Subject completes a DHEQ Sections 1 and 2 (source document) for later 
transcription into the eCRF. 
• Subject completes the NRS question (source document) for later transcription into 
the eCRF 
• Clinical examiner completes an OST examination. 
• Clinical examiner completes sensitivity assessments for each eligible tooth 
identified at Screening, first to a tactile stimulus and then to an evaporative (air) 
stimulus.  
Eligible teeth are defined as incisors, canines and pre-molars with none of the 
study-specific dentition exclusions (Section 5.3) which meet the EAR, MGI and 
mobility inclusion criteria (Section 5.2) and had a tactile threshold ≤ 20 g and a 
Schiff sensitivity score ≥ 2 at Screening (Visit 1). 
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. To 
facilitate subject flow, assessments may be recorded on a paper score sheet (source 
document) and later transcribed into the eCRF.  
• Clinical examiner reviews inclusion and exclusion criteria and confirms subject 
eligibility. Subjects who meet all the inclusion criteria and none of the exclusion 
criteria with at least 2 eligible sensitive teeth (tactile threshold ≤ 20 g and Schiff 
sensitivity score ≥ 2 at Screening and Baseline) will continue. 
• Clinical examiner selects the two ‘test teeth’.  
• Complete stratification and randomisation. 
• Dispense allocated study toothpaste, toothbrush and diary. 
• Describe toothpaste usage instructions and diary completion to subject; supervise 
their first use of study toothpaste and recording of brushing in the diary. 
• 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. 
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Any AEs reported on completion of the supervised brushing with the assigned 
study toothpaste will be recorded. 
• Remind the subject of the Lifestyle Guidelines (Section 5.5) and any Concomitant 
Medication/Treatment(s) requirements (Section 6.8) of the protocol. 
8.2.2 
Visits 3-5 (Day 3±1 day, Week 2±1 day and Week 4 ±2 days) 
Changes in health, concomitant medication or non-drug treatments/procedures will be 
documented in the eCRF. Spontaneous reporting of AEs and those elicited by asking 
subjects to respond to a non-leading question such as “How do you feel?” will be assessed 
and any AEs recorded in the eCRF. 
The following procedures will then be completed at each visit, and data recorded in the 
eCRF. 
• Complete visual checks of returned study toothpaste tubes and review completed 
diary. Record any suspected over or under use and the number of any missed or 
additional brushings. Re-instruct the subject in the correct dosing, usage 
requirements and diary completion as needed. 
Return toothpaste/toothbrush/diary to subject. 
• Confirm subject adherence to the requirements of the protocol and continuance. 
• Female subjects of child-bearing potential only to self-report pregnancy status.  
• Subject completes a DHEQ Section 1 Questions 7-9 only and Section 2 all 
questions (source document) for later transcription into the eCRF. 
• Subject completes the NRS question (source document) for later transcription into 
the eCRF  
• Clinical examiner completes an OST examination.  
• 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. 
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Record clinical assessment scores using source documentation for later transfer to 
the eCRF. 
• Clinical examiner then assesses the evaporative (air) sensitivity (Schiff Sensitivity 
Scale only) of all remaining eligible teeth identified at Screening.  
Record clinical assessment scores using source documentation for later transfer to 
the eCRF. 
• Remind subject of toothpaste usage instructions; supervise brushing with study 
toothpaste and recording of brushing in the diary.  
• 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 reported on completion of the supervised brushing with the assigned 
study toothpaste will be recorded. 
• Remind the subject of the Lifestyle Guidelines (Section 5.5) and any Concomitant 
Medication/Treatment(s) requirements (Section 6.8) of the protocol. 
8.2.3 
Visit 6 (Week 8 ±2 days) 
Changes in health, concomitant medication or non-drug treatments/procedures will be 
documented in the eCRF. Spontaneous reporting of AEs and those elicited by asking 
subjects to respond to a non-leading question such as “How do you feel?” will be assessed 
and any AEs recorded in the eCRF. 
The following procedures will then be completed, and data recorded in the eCRF. 
• Complete visual checks of returned study toothpaste tubes and review completed 
diary. Record any suspected over or under use and the number of any missed or 
additional brushings.  
Do not return toothpaste/toothbrush/diary to subject. 
• Confirm subject adherence to the requirements of the protocol and continuance. 
• Female subjects of child-bearing potential only complete a UPT. 
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• Subject completes a DHEQ Section 1 Questions 7-9 only and Section 2 all 
questions (source document) for later transcription into the eCRF. 
• Subject completes the NRS question (source document) for later transcription into 
the eCRF 
• Clinical examiner completes an OST examination, then an OHT examination.  
• 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 eCRF or using source documentation for 
later transfer to the eCRF. 
• Clinical examiner then assesses the evaporative (air) sensitivity (Schiff Sensitivity 
Scale only) of all remaining eligible teeth identified at Screening.  
Record clinical assessment scores in the eCRF or using source documentation for 
later transfer to the eCRF. 
• 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 use of study product). 
• Study conclusion. 
8.3 
Diary Review 
The diary should be reviewed at every visit by the investigator, or suitably qualified 
designee, and the subject. Any subject-recorded comment captured in the diary considered 
an AE will be assessed and reported as described in Section 10. 
Any additional comments relating to medications/treatments captured in the diary will be 
reviewed by the investigator, or medically qualified designee, with the subject and 
recorded in the eCRF as appropriate. Additional and missed product applications will be 
considered deviations from the protocol and will be recorded on the Deviations Log and 
captured as a deviation in the eCRF. 
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8.4 
Study Conclusion 
The Study Conclusion page of the eCRF will be completed for all subjects whether they 
completed all study procedures or were discontinued early.  If the subject was discontinued 
at any point during the study, the primary reason for withdrawal should be recorded on the 
Study Conclusion page. 
If a subject has any clinically significant, study-related abnormalities or AEs at the end of 
the study, the GSK CH medical monitor (or designated representative) should be notified; 
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 clinical examinations may be carried out 
at such visits. 
9 
STUDY ASSESSMENTS 
Every effort should be made to ensure that protocol-required assessments are completed 
as described.  However, it is anticipated there may be circumstances, outside the control 
of the investigator, that may make it unfeasible to complete an assessment.  In these cases, 
the investigator must take all steps necessary to ensure the safety and well-being of the 
subject.  When a protocol-required assessment cannot be performed, the investigator (or 
designee) will document the reason for the missed assessment as a protocol deviation and 
any corrective and preventative actions they have taken to ensure the required procedures 
were 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 safety/product performance assessments 
remain blind to product received throughout the study, site staff involved in the dispensing 
of study product 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 
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provided, outside of the dispensing room, while at the study site; dispensing staff will not 
be involved in any safety/product performance assessment procedures during the study. 
9.1 
Screening Assessments 
Screening assessments will be performed by appropriately trained staff/clinical examiners 
at the times, and in the order, defined in the Study Procedures section of this protocol 
(Section 8). 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. Eligibility 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, 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. 
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. 
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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 MGI = 0, using a modification of the 
Miller Index (Laster et al., 1975). Eligible teeth will have clinical mobility = 0. 
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 (Visit 1) 
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 experienced 
any sensitivity 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 feel sensitivity 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 eCRF. 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 
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(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 the subject's 
responses in a source document. 
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 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. 
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9.1.5 
Qualifying Evaporative Air Sensitivity (Visit 1) 
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 criteria, with a tactile threshold (≤ 20 g) criteria; assessment will 
commence 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. 
9.2 
Product Performance Assessments 
The following product performance assessments will be performed by appropriately 
trained staff/clinical examiners (who are blind to product received), at the times and in the 
order defined in the Study Procedures section of this protocol (Section 8). 
9.2.1 
Dentine Hypersensitivity Experience Questionnaire (DHEQ) 
A ‘short form’ DHEQ (Appendix I: Example DHEQ-15) will be completed by each study 
subject at Baseline (Visit 2), Day 3 (Visit 3), Week 2 (Visit 4), Week 4 (Visit 5) and Week 
8 (Visit 6), prior to the OST examination and clinical 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. 
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• 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 3, Week 2, Week 4 and Week 8, Section 1 (Q7-9 only) and Section 2 (Q1-15) will 
be answered. 
9.2.2 
Self-Perceived Sensitivity Discomfort Assessment 
The 11-item Numeric Rating Scale (NRS) is a segmented numeric version of the visual 
analog scale (VAS) in which a respondent selects the number (0–10) that best reflects the 
intensity of the discomfort caused by their sensitivity (Hawker et al., 2011, Rocha et al., 
2020). Similar to the VAS, the NRS is anchored by terms describing discomfort extremes 
and ranges from 0 = no discomfort to 10 = worst discomfort imaginable. 
An NRS (example below) will be completed by each study subject at Baseline (Visit 2), 
Day 3 (Visit 3), Week 2 (Visit 4), Week 4 (Visit 5) and Week 8 (Visit 6), after the DHEQ 
but prior to the OST examination and clinical assessments. 
No 
Discomfort 
Moderate 
Discomfort 
Worst 
Discomfort 
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9.2.3 
Tactile Sensitivity Assessment 
Visit 2: The tactile sensitivity of all qualifying teeth from Screening (i.e., teeth that 
exhibited none of the dentition exclusions, met the EAR, MGI, clinical mobility and 
qualifying tactile threshold/Schiff sensitivity score criteria) will be assessed at Baseline. 
Visits 3-6: The tactile sensitivity of the two ‘test teeth’ selected by the clinical examiner 
at Baseline will be assessed for randomised subjects. 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 
3-6), 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 Day 3, Week 2, 4 
and 8. 
9.2.4 
Evaporative (Air) Sensitivity Assessment 
Visit 2: The evaporative (air) sensitivity of all qualifying teeth from Screening will be 
assessed at Baseline.  
Visits 3-6: The evaporative (air) sensitivity of the two ‘test teeth’ selected at Baseline will 
be assessed first for all randomised subjects; this will followed by the assessment of 
evaporative (air) sensitivity for all remaining eligible teeth identified at Screening. 
The evaporative (air) stimulus will be administered, and subject response recorded, as 
described in Section 9.1.5. On every occasion, the evaporative (air) assessment of the two 
test teeth will begin a minimum of 5 minutes after the last tactile assessment has been 
completed (to allow tooth recovery time). 
Score 
Description 
0 
Subject does not respond to stimulus 
1 
Subject responds to stimulus but does not request discontinuation of stimulus 
2 
Subject responds to stimulus and requests discontinuation of, or moves from stimulus 
3 
Subject responds to stimulus, considers it uncomfortable and requests discontinuation of stimulus 
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9.2.5 
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 first at all subsequent visits. The 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 staff/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 and salivary 
glands. The results of the examination will be recorded in the eCRF 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 eCRF. 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. 
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9.3.3 
Pregnancy Testing 
For female subjects of child-bearing potential, a UPT will be performed at Screening (Visit 
1) and at Week 8 (Visit 6); the results must be obtained prior to first use of the 
acclimatisation toothpaste (Visit 1) and before the end of the study. They will also be asked 
to self-report their pregnancy status at the start of all other visits (Visits 2-5). 
The investigator and site personnel will remind female subjects of child-bearing potential 
at each visit to inform site personnel if their menstrual cycle has changed or if they have 
any other reason to suspect they could be pregnant (e.g. had unprotected intercourse since 
the last visit). 
A negative pregnancy test result is required before the subject receives the acclimatisation 
toothpaste.  Pregnancy tests will also be done should one menstrual cycle be missed during 
the active study period (or when pregnancy is otherwise suspected). Pregnancy tests may 
also be repeated as per request of the Research Ethics Committee (REC) or if required by 
local regulations. 
In the case of a positive confirmed pregnancy, the subject will be withdrawn from 
administration of acclimatisation or 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 acclimatisation, washout or lead-
in product (or medical device), whether or not considered related to the study product, 
including any acclimatisation, 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 acclimatisation, washout or lead-
in product (or medical device). 
 
 
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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 the 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" per se will not be reported as an AE. Such instances will be 
captured in the product performance assessments. However, the signs, 
symptoms, and/or clinical sequelae resulting from lack of performance will be 
reported as AE if they fulfill the definition of an AE.  
Events NOT meeting the AE definition:  
• Any clinically significant abnormal laboratory findings (if applicable) or other 
abnormal safety assessments which are associated with the underlying disease, 
unless judged by the investigator to be more severe than expected for the subject’s 
condition.  
• The disease/disorder being studied or expected progression, signs, or symptoms of 
the disease/disorder being studied, unless more severe than expected for the 
subject’s condition.  
• Medical or surgical procedure (e.g. endoscopy, appendectomy) is not the AE. The 
condition that leads to the procedure is an AE (e.g. appendicitis). 
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• Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 
• Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.  
10.2 
Definition of a Serious Adverse Event (SAE) 
A Serious Adverse Event (SAE) is a particular category of an adverse event where the 
adverse outcome is serious. If an event is not an AE per definition above, then it cannot be 
an SAE even if serious conditions are met (e.g. hospitalisation for signs/symptoms of the 
disease under study, death due to progression of disease). 
A serious adverse event is any untoward medical occurrence at any dose that: 
• Results in death 
• Is life-threatening  
▪ The term 'life-threatening' in the definition of 'serious' refers to an event in 
which the subject was at risk of death at the time of the event. It does not 
refer to an event, which hypothetically might have caused death, if it were 
more severe; 
• Requires inpatient hospitalisation or prolongation of existing hospitalisation  
▪ In general, hospitalisation signifies that the subject has been detained 
(usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate 
in the physician’s office or outpatient setting. Complications that occur 
during hospitalisation are AEs. If a complication prolongs hospitalisation or 
fulfills any other serious criteria, the event is serious. When in doubt as to 
whether “hospitalisation” occurred, or was necessary, the AE should be 
considered serious. 
▪ Hospitalisation for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
 
 
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• Results in persistent or significant disability/incapacity 
▪ The term disability means a substantial disruption of a person’s ability to 
conduct normal life functions. 
▪ This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere with or prevent everyday life functions but do not constitute a 
substantial disruption 
• Results in congenital anomaly/birth defect 
• Other situations: 
▪ Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events 
that may not be immediately life-threatening or result in death or 
hospitalisation but may jeopardise the subject or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These events should usually be considered serious. 
▪ Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalisation, or development 
of drug dependency or drug abuse. 
Note: Classification of an AE as ‘serious’ is based on the outcome of the event and is a 
factor in determining reporting requirements. 
10.3 
Time Period and Frequency for Collecting AE and SAE Information 
All AEs, and therefore all SAEs, will be collected immediately after a subject provides 
consent to participate in the study by the completion (signature) of the ICF until 5 days 
following last use 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 eCRF not the AE section. 
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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 
eCRF.  
All SAEs will be recorded and reported to the sponsor, or designee, immediately and under 
no circumstance should this exceed 24 hours. The investigator will submit any updated 
SAE data to the sponsor within 24 hours of it being available. 
Investigators are not obligated to actively seek AEs or SAEs after the conclusion of the 
study participation. However, if the investigator learns of any SAE, including a death, at 
any time after a subject has been discharged from the study, and considers the event to be 
reasonably related to the study product or study participation, the investigator must 
promptly notify the sponsor. 
10.4 
Reporting Procedures 
The investigator and any designees are responsible for detecting, documenting and 
reporting events that meet the definition of an AE and remain responsible for following up 
on AEs that are serious, considered related to study product(s), participation in the study 
or a study procedure, or that caused the subject to discontinue the study product or study 
participation.  
Spontaneous reporting of adverse events and those elicited by asking subjects to respond 
to non-leading such as “How do you feel” will be assessed and any AEs recorded in the 
eCRF and reported appropriately. 
The investigator (or medically qualified designee) is to report all directly observed AEs 
and all AEs spontaneously reported by the study subject. In addition, each study subject 
will be questioned about AEs.  
Each AE is to be assessed to determine if it meets the criteria for a SAE.  If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate. 
When an AE occurs, it is the responsibility of the investigator (or medically qualified 
designee) to review all documentation (e.g. hospital progress notes, laboratory, and 
diagnostics reports) related to the event. 
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The investigator or site staff will then record all relevant information regarding an AE in 
the eCRF 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 
eCRF page/SAE form. 
There may be instances when copies of medical records for certain cases are requested by 
GSK CH.  In this instance, all subject identifiers, except for the subject number, will be 
redacted on the copies of the medical records prior to submission to GSK CH. 
The investigator (or medically qualified designee) will attempt to establish a diagnosis of 
the event based on signs, symptoms, and/or other clinical information.  The diagnosis will 
be the documented as the AE/SAE, where known, and not the individual signs/symptoms 
(e.g., upper respiratory tract infection, seasonal allergy, not cough, 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 eCRF 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 eCRF 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 
eCRF.  Where the same data are collected, the AE eCRF page and the SAE form must be 
completed in a consistent manner (e.g., the same AE term should be used on both).  AEs 
should be reported using concise medical terminology on the eCRF and the SAE form. 
10.4.2 
Reporting of a Serious Adverse Event 
In addition to recording the details of each AE on the AE eCRF 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. 
 
 
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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. 
Email Serious Adverse Events to: 
 
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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 utilised 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 pre-defined 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 eCRF page and the SAE form (subject 
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to the classification of the AE). The investigator will also document in the medical notes 
that they have reviewed the AE and assessed causality, where applicable.  
A “reasonable possibility” of a relationship conveys that there are facts, evidence and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
Generally, the facts (evidence) or arguments to suggest a causal relationship should be 
provided. 
The investigator will use clinical judgment to determine the relationship and will also 
consult the Investigator Brochure (IB), Safety Statement and/or Product Information for 
marketed products, in the determination of their 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 they have 
reviewed the AE/SAE and 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 eCRF, 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 their 
opinion of causality in light of follow-up information and send an SAE follow-up report 
with the updated causality assessment.  
10.6 
Follow-up of AEs and SAEs  
After the initial AE/SAE report, the investigator is required to proactively follow up with 
each subject and provide further information on the subject’s condition. 
All AEs (serious and non-serious) will be followed until resolution, until the condition 
stabilises, until the event is otherwise explained or until the subject is lost to follow-up.   
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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 eCRF page and on the SAE form 
(subject to the classification of the AE). 
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 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 an AE should be distinguished from withdrawal due to other causes, 
according to the definition of an AE noted earlier, and recorded on the appropriate AE 
eCRF page.  
When a subject withdraws because of an SAE, the SAE must be reported in accordance 
with the reporting requirements defined. 
10.8 
Regulatory Reporting Requirements for SAEs 
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.  
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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, EC and the investigator. 
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 RIEC, if appropriate according to local requirements. 
10.9 
Pregnancy 
10.9.1 
Time Period for Collecting Pregnancy Information 
Pregnancy information will be collected on all pregnancies reported while a female subject 
of child-bearing potential is participating in the study from the signing of informed consent 
until 5 days after last use of study product. 
10.9.2 
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 
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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 
product and/or be withdrawn from the study. 
11 
DATA MANAGEMENT 
As used in this protocol, the term eCRF 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. To facilitate subject flow during Visits 1-6, clinical assessments (including tactile 
and evaporative (air) sensitivity) may be recorded on a paper score sheet (source 
document) and later transcribed into the eCRF; subjects will self-record each brushing 
occasion in paper diaries (source document); data relating to SAEs and pregnancy will also 
be collected on paper forms (source documents).  
The investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF. 
All source documents (e.g., hospital records, clinical and office charts, laboratory notes, 
memoranda, subject diaries, questionnaires, evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, microfiches, photographic negatives, 
microfilm or magnetic media, x-rays, subject files and records kept at the pharmacy, at the 
laboratory and at the medico-technical departments involved in the clinical study) which 
contain the source of data recorded in the eCRF should be specified.  The eCRF can be 
used as a source document at the discretion of data management. 
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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 this unique 
number. 
11.1 
Case Report Form 
An eCRF is a printed, optical, or electronic document designed to record the protocol 
required information to be reported to the sponsor on each study subject. 
For each subject who has given informed consent the eCRF must be completed and signed 
by the investigator (or authorised designee) to certify the data are complete and correct.  
Where the eCRF is not the source document, the investigator must maintain accurate 
documentation (source data) to support information entered in the eCRF. 
Management of clinical data will be performed in accordance with Third Party Biostatistics 
and Data Management Vendor applicable standards and data cleaning procedures with 
oversight by GSK CH to ensure integrity of the data, for example, to correct/remove errors 
and inconsistencies in the data.  
To protect the privacy of subjects, no Personal Information (PI) (including the subject's 
name or initials or full birth date) is to be recorded in the eCRF or as part of the query text. 
All eCRF pages should be completed during a subject assessment when the eCRF has been 
designated as the source.  Data that is sourced elsewhere should be entered into the eCRF 
in an agreed upon timeframe between the Investigator and Sponsor.   
GSK CH will obtain and retain all eCRFs 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 WHODrug.   
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 eCRF data will also be run, in addition to the queries 
already programmed and generated by the system, to raise manual queries as needed for 
site clarification or correction. A query should be issued to update the verbatim towards a 
codable description. 
The study monitor will perform ongoing review  of the eCRFs in accordance with the 
monitoring plan, to confirm that data entered into the eCRF by authorised site personnel 
are accurate, complete and verifiable from source documents; that the safety and rights of 
participants are being protected; and that the study is being conducted in accordance with 
the currently approved protocol and any other study agreements, ICH GCP and all 
applicable regulatory requirements. 
Any queries will be generated in the EDC System to the investigator or designee, enabling 
the errors to be addressed in parallel with Data Management review. The study monitor 
can also run reports and listings on the eCRFs, to raise manual queries as needed for site 
clarification or correction. 
11.3 
Processing Subject Reported Outcomes 
Paper-based subject reported outcome (SRO) data will be collected from the product usage 
diary and DHEQ and entered into the eCRF.   
All SRO source data should be reviewed by the study staff and the study monitor to ensure 
accurate transcription of data and that any potential AEs or concomitant medications 
reported on these documents are discussed with the subject and transcribed accurately to 
the eCRF.  SROs that are classed as source data will be retained by the investigator and 
true/certified copies may be sent to a designated vendor or GSK CH as required. 
To protect the privacy of subjects, no Personal Information (PI) (including the subject's 
name or initials or full birth date) is to be recorded on any SRO that will be forwarded to 
GSK CH or Third-Party Vendor. 
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11.4 
External Data  
Subject data generated externally to the eCRF from laboratory instruments, computers or 
other sources and then transcribed into a file and format agreed upon by GSK CH is termed 
external data. No external data will be generated during the conduct of this study. 
 
12 
STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES 
12.1 
Sample Size Determination 
No formal sample size has been produced for this PoP clinical study to investigate changes 
in sensitivity measures (Schiff sensitivity score, tactile threshold and number of sensitive 
teeth) over time with twice-daily use of a novel combination toothpaste. Based on previous, 
similar GSK CH studies evaluating the sensitivity protection provided by daily-use 
toothpastes, approximately 30 evaluable subjects per product group is considered 
sufficient to provide reliable estimates of performance for the purposes of this study and 
to aid in the design of future clinical studies. Approximately 120 subjects will be 
randomised to study product.  
From a previous, similar GSK CH study (GSKCH Clinical Study 209723, 2020), change 
in Schiff sensitivity score at Week 8 had an SD of 0.7 units and the degree of 
variability (SD) in the test and control groups remained roughly consistent with each other 
over time. A similar trend was observed for the tactile threshold and number of sensitive 
teeth endpoints.  
A sample size of 30 evaluable subjects per product group is expected to provide 95% CIs 
with a width of ± 0.261 units for the Schiff sensitivity score. This level of precision is 
considered sufficient for the purposes of this study. Approximately 120 subjects will be 
randomised to study treatment.  
 
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12.2 
Populations for Analysis 
The Safety population will include all randomised subjects who complete at least one use 
of study product. This population will be based on the product the subject received. 
The modified Intent-To-Treat (mITT) population will include all randomised subjects who 
complete at least one use of study product and have at least one post baseline clinical 
performance assessment. This population will be based on the study product to which the 
subject was randomised. Any subject who receives a randomisation number will be 
considered to have been randomised. 
The Per-Protocol (PP) population will include all randomised subjects who do not have 
any protocol deviations that could confound the interpretation of analyses conducted on 
the mITT. 
12.3 
Statistical Analyses 
Additional details of the proposed statistical analysis will be documented in the statistical 
reporting and analysis plan (RAP), which will be written following finalisation of the 
protocol and prior to study unblinding/analysis (as appropriate). 
Where a hypothesis test between products is conducted, product differences in the study 
variables will be tested under the null hypothesis, H0: there is no product difference, versus 
the alternate hypothesis (H1) that there is a product difference. 
12.3.1 
Primary Analyses  
The modified Intent-to-Treat (mITT) population will be used for the primary analyses.  
The primary analysis variables are:  
• Schiff sensitivity score at Day 0 (Baseline), Day 3, Weeks 2, 4 and 8;  
• Tactile threshold (g) at Days 0 (Baseline), Day 3, Weeks 2, 4 and 8;  
• Number of sensitive teeth (Schiff sensitivity score ≥ 1) at Day 0 (Baseline), Day 3, 
Weeks 2, 4 and 8. 
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, SE, SD, minimum, 
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maximum) will be presented for each outcome variable at each assessment time point. Raw 
means (± SE) of Schiff sensitivity score and tactile threshold (g) and the number of 
sensitive teeth at each timepoint will be plotted by product group.  
12.3.2 
Secondary Analyses 
Summary statistics (mean, median, SE, SD, minimum, maximum) will be presented for 
each secondary analysis variable by product group at each assessment time point, including 
Baseline assessments. Raw means (± SE) at each timepoint will be plotted by product 
group. 
Change from Baseline in Schiff sensitivity score at Day 3, Weeks 2, 4 and 8 
The Schiff sensitivity score is derived as the average score of the two test teeth. The change 
from Baseline is derived for the individual teeth first before calculating the average change 
of the two test teeth. The change in Schiff sensitivity score will be analysed at each time 
point using an ANCOVA model which will include product 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.  
Change from Baseline in tactile threshold (g) at Day 3, Weeks 2, 4 and 8  
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 each time point using an 
ANCOVA model with product and Baseline Schiff stratification included as factors and 
Baseline tactile threshold included as a covariate.  
For both Change from Baseline in Schiff sensitivity score and Change from Baseline in 
tactile threshold, using the above models, adjusted mean change from Baseline, along with 
95% CIs will be reported by product group. P-values testing for non-zero change from 
Baseline will also be presented for each product group. Mean difference between product 
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.  
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In each case, the assumptions of the ANCOVA model will be investigated. An appropriate 
data transformation or non-parametric method may be performed in case of strong model 
violations.  
Change from Baseline in DHEQ at Day 3, Weeks 2, 4 and 8  
The following DHEQ-15 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 3, and Week 2, 4 and 8 for each DHEQ endpoint.  
Summary statistics (mean, median, SE, SD, minimum, maximum) will be presented for 
Change from Baseline for each DHEQ endpoint by product group at each assessment 
time point. 
Change from Baseline in Numeric Rating Scale (NRS) at Day 3, Weeks 2, 4 and 8 
Summary statistics (mean, median, SE, SD, minimum, maximum) will be presented for 
Change from Baseline in NRS by product group at each assessment time point. 
12.3.3 
Safety Analyses 
The Safety population will be used for safety analyses. Safety analyses will be performed 
according to product 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 categorised as oral or non-oral. AEs will be 
listed and summarised by product received. SAEs will also be listed. AEs will be regarded 
as ‘treatment’ emergent if they occur on or after the first product use at the Baseline visit.  
 
 
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The following AEs tables will be produced, presented by product group:  
• listing of all AEs (randomised subjects and non-randomised 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). 
The results of the OST and OHT examinations will be listed and the results of the OST 
examinations will be tabulated. 
12.3.4 
Exclusion of Data from Analysis  
Exclusion of any data from the analyses will be determined during Blind Data Review 
(BDR) prior to database lock. Any reasons for exclusion from an analysis population will 
be listed, if applicable.  
12.3.5 
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 summarised by the number and percentage of 
subjects with each relevant characteristic in each product group. Age will be summarised 
by the mean, standard deviation, median, minimum and maximum values in each product 
group. 
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12.3.6 
Study Drug/Product Compliance and Use of Other Therapies 
12.3.6.1 Study Drug/Product Compliance 
Compliance with study product use (number of brushings) will be listed and summarised 
for the mITT population. 
12.3.6.2 Prior and Concomitant Medications 
Prior medications, concomitant medications and significant non-drug therapies taken 
during the active study period will be listed for the Safety population. 
12.3.6.3 Other Therapy/Rescue Medication (if applicable) 
N/A 
12.3.7 
Handling of Dropouts and Missing Data  
Subjects who withdraw from the study early will be included in the statistical analysis up 
to the point of withdrawal. Subjects who withdraw will not be replaced. No data will be 
imputed in the case of dropouts or missing data. 
12.3.8 
Interim Analysis  
No interim analysis is planned for this study. 
13 
STUDY GOVERNANCE CONSIDERATIONS 
13.1 
Quality Control  
In accordance with applicable regulations including GCP and 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 the protocol, study requirements and staff responsibilities with the 
study staff 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 eCRF will serve as the source 
document. Other documentation will be identified and agreed. 
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GSK CH, or designee, will monitor the study and site activity to verify: 
• Data are authentic, accurate and complete. 
• Safety and rights of subjects are being protected. 
• Study is being 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 during 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 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 will notify GSK CH, or its agents, immediately of any regulatory 
inspection notification in relation to the study. Furthermore, the investigator will cooperate 
with GSK CH, or its agents, to prepare the study site for the inspection and will allow GSK 
CH, or its agent, whenever feasible, to be present during the inspection. The investigator 
will promptly provide copies of the inspection findings 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 the investigator prepare for an inspection. 
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13.3 
Regulatory and Ethical Considerations 
13.3.1 
Research Ethics Committee (REC) 
It is the responsibility of the investigator to have prospective approval of the study 
protocol, protocol amendments, informed consent, investigator brochure/safety statement 
(including any updates) and other relevant documents (e.g., recruitment advertisements), 
if applicable, from the REC.  All correspondence with the REC should be retained in the 
investigator file.  Copies of REC approvals should be forwarded to GSK CH prior to the 
initiation of the study and should subsequent amendments to the protocol requiring REC 
approval be made. 
The only circumstance in which an amendment may be initiated prior to REC approval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.  In 
that event, the investigator must notify the REC and GSK CH in writing immediately after 
the implementation. 
13.3.2 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol and legal and regulatory 
requirements, as well as the general principles set forth in the International Ethical 
Guidelines for Biomedical Research Involving Human Subjects (Council for International 
Organizations of Medical Sciences 2002), International Ethical Guidelines for Health-
Related Research Involving Humans (Council for International Organizations of Medical 
Sciences, 2016), guidelines for GCP (ICH 1996 and revision 2), and the Declaration of 
Helsinki (World Medical Association 2013).  
In addition, the study will be conducted in accordance with the protocol, the ICH guideline 
on GCP and applicable local regulatory requirements and laws. 
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 authorised parties, subject 
names, addresses and other identifiable data will be replaced by numerical codes based on 
a numbering system provided by GSK CH in order to de-identify study subjects.   
The study site will maintain a confidential list of subjects who participated in the study, 
linking each subject’s numerical code to their 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 the REC and investigator databases may be used as 
recruitment procedures.  Use of an REC approved, generic, pre-screening questionnaire to 
assess basic subject characteristics to determine general eligibility for this study is 
allowed.  This generic questionnaire may be used by the site as a phone script and/or to 
review internal databases to identify potential study subjects.   
GSK CH will have an opportunity to review and approve the content of any study 
recruitment materials directed to potential study subjects before such materials are used.  
13.3.5 
Reporting of Safety Issues and Serious Breaches of the Protocol or ICH 
GCP  
Within GSK CH a serious breach is defined as a breach likely to affect to a significant 
degree the safety and rights of a subject or the reliability and robustness of the data 
generated in GSK CH-sponsored human subject research studies.  
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In the event of any prohibition or restriction imposed (i.e., clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the study 
products, GSK CH should be informed immediately.  
In addition, the investigator will inform GSK CH immediately of any urgent safety 
measures taken by the investigator to protect the study subjects against any immediate 
hazard, and of any serious breaches of this protocol or of ICH GCP that the investigator 
becomes aware of. 
13.4 
Posting of Information on Publicly Available Clinical Trial 
Registers 
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins in accordance with applicable GSK CH 
processes. 
GSK intends to make anonymised subject-level data from this trial available to external 
researchers for scientific analyses or to conduct further research that can help advance 
medical science or improve patient care. This helps ensure the data provided by study 
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. 
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A manuscript will be progressed for publication in the scientific literature if the results 
provide important scientific or medical knowledge. 
13.6 
Records Retention 
Following closure of the study, the investigator must maintain all site study records (except 
for those required by local regulations to be maintained elsewhere) in a safe and secure 
location.   
The records (study/site master file) must be maintained to allow easy and timely retrieval 
when needed (e.g., for a GSK CH audit or regulatory inspection) and must be available for 
review in conjunction with assessment of the facility, supporting systems and relevant site 
staff. 
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 eCRFs 
or other documents submitted to GSK CH, subjects should not be identified by their names 
or initials, but by an identification code. The investigator should keep a separate log of 
subjects’ codes, names and addresses.  Documents not for submission to GSK CH (e.g., 
subjects’ written consent forms) should be maintained by the investigator in strict 
confidence. 
Records and documents, including signed ICF, pertaining to the conduct of this study must 
be retained by the investigator as per the signed contractual agreement, from the issue of 
the final Clinical Study Report (CSR) or equivalent summary, unless local regulations or 
institutional policies require a longer retention period. The minimum retention time will 
meet the strictest standard applicable to that site for the study, as dictated by any 
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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 REC, study product safety problems, or at the discretion of GSK 
CH.  In addition, GSK CH retains the right to discontinue development of the test product 
at any time.  
If the 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 eCRFs completed to the greatest extent possible. 
Where required by the applicable regulatory requirements, GSK CH should inform the 
regulatory authority and the investigator should promptly inform the REC and provide the 
REC a detailed written explanation of the termination or suspension.  
If the REC terminates or suspends its approval/favorable opinion of the study, 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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14 
REFERENCES 
Available upon request  
ICH Topic E6 (R2) Guideline for Good Clinical Practice, Nov 2016. 
[Addy M (2000)] Dentine hypersensitivity: definition, prevalence, distribution and 
aetiology. In  ADDY, M., EMBERY, G., EGAR, M. & ORCHARDSON, R. (eds.) 
Tooth wear and sensitivity. London: Martin Dunitz. 
[Addy M (2002)] Dentine hypersensitivity: new perspectives on an old problem. 
International Dental Journal; 52(S5P2): 367-75. 
[Addy M, Smith SR (2010)] Dentin hypersensitivity: an overview on which to base tubule 
occlusion as a management concept. J Clin Dent; 21(2): 25-30. 
[Ayad F, Berta R, De Vizio W, et al. (1994)] Comparative efficacy of two dentifrices 
containing 5% potassium nitrate on dentinal sensitivity: a twelve-week clinical 
study. J Clin Dent; 5 Spec No: 97-101. 
[Bae JH, Kim YK, Myung SK (2015)] Desensitizing toothpaste versus placebo for dentin 
hypersensitivity: a systematic review and meta-analysis. J Clin Periodontol; 42(2): 
131-41. 
[Baker SR, Gibson BJ, Sufi F, et al. (2014)] The Dentine Hypersensitivity Experience 
Questionnaire: a longitudinal validation study. J Clin Periodontol; 41(1): 52-9. 
[Bartold PM (2006)] Dentinal hypersensitivity: A review. Aust. Dent. J.; 51(3): 212-8. 
[Boiko OV, Baker SR, Gibson BJ, et al. (2010)] Construction and validation of the quality 
of life measure for dentine hypersensitivity (DHEQ). J Clin Periodontol; 37(11): 
973-80. 
[Brännström M (1963)] A hydrodynamic mechanism in the transmission of pain producing 
stimuli through the dentin. In  ANDERSON, D. J. (ed.) Sensory Mechanism in 
Dentin. Oxford: Pergammon Press. 
[Chaknis P, Panagakos FS, Devizio W, et al. (2011)] Assessment of hypersensitivity 
reduction of a dentifrice containing 0.3% triclosan, 2.0% PVM/MA copolymer, 
0.243% NaF and specially-designed silica as compared to a dentifrice containing 
0.454% stannous fluoride, sodium hexametaphosphate and zinc lactate and to a 
dentifrice containing 0.243% NaF on dentin hypersensitivity reduction: An 8-week 
study. American Journal of Dentistry; 24(Spec Iss A): 14A-20A. 
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Protocol Number: 218220 
 
 
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[Dababneh RH, Khouri AT, Addy M (1999)] Dentine hypersensitivity - an enigma? A 
review of terminology, mechanisms, aetiology and management. Br Dent J; 
187(11): 606-11; discussion 3. 
[Drisko HC (2002)] Dentine hypersensitivity – dental hygiene and periodontal 
considerations. International Dental Journal; 53(5): 385-93. 
[Favaro Zeola L, Soares PV, Cunha-Cruz J (2019)] Prevalence of dentin hypersensitivity: 
Systematic review and meta-analysis. J Dent; 81: 1-6. 
[Gillam DG (1996)] Efficacy of a potassium nitrate mouthwash in alleviating cervical 
dentine sensitivity (CDS). Journal of Clinical Periodontology; 23(11): 993-7. 
[Gillam DG, Bulman JS, Jackson RJ, et al. (1996)] Efficacy of a potassium nitrate 
mouthwash in alleviating cervical dentine sensitivity (CDS). J Clin Periodontol; 
23(11): 993-7. 
[GSKCH Clinical Study 209723 (2020)] Randomized controlled examiner-blind phase II 
exploratory clinical study to characterise the efficacy profile of an experimental 
dual active combination dentifrice for the relief of dentin hypersensitivity, in 
subjects with clinically diagnosed dentin hypersensitivity,  
[Hatcher RA, Nelson AL 2007] Contraceptive technology. Ardent Media. 
[Hawker GA, Mian S, Kendzerska T, et al. (2011)] Measures of adult pain: Visual Analog 
Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill 
Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), 
Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), 
and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis 
Care Res (Hoboken); 63 Suppl 11: S240-52. 
[Irwin CR, McCusker P (1997)] Prevalence of dentine hypersensitivity in a general dental 
population. Journal of the Irish Dental Association; 43(1): 7-9. 
[Jeandot J, Fricain JC, Nadal J (2007)] Efficacite des Dentifrices au KCL et au KNO3 sur 
la Sensibilite Dentinaire. Clinic; 28: 379-84. 
[Kakar A, Kakar K (2013)] Measurement of dentin hypersensitivity with the Jay 
Sensitivity Sensor Probe and the Yeaple probe to compare relief from dentin 
hypersensitivity by dentifrices. Am J Dent; 26 Spec No B: 21B-8B. 
[Laster L, Laudenbach KW, Stoller NH (1975)] An evaluation of clinical tooth mobility 
measurements. J Periodontol; 46(10): 603-7. 
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Clinical Protocol 
 
 
Protocol Number: 218220 
 
 
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May not be used, divulged, published or otherwise disclosed without the consent of 
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[Lobene RR (1986)] A clinical study of the anticalculus effect of a dentifrice containing 
soluble pyrophosphate and sodium fluoride. Clin Prev Dent; 8(3): 5-7. 
[Lobene RR, Weatherford T, Ross NM, et al. (1986)] A modified gingival index for use in 
clinical trials. Clin Prev Dent; 8(1): 3-6. 
[Machuca C, Baker SR, Sufi F, et al. (2014)] Derivation of a short form of the Dentine 
Hypersensitivity Experience Questionnaire. J Clin Periodontol; 41(1): 46-51. 
[Nagata T, Ishida H, Shinohara H, et al. (1994)] Clinical evaluation of a potassium nitrate 
dentifrice for the treatment of dentinal hypersensitivity. J Clin Periodontol; 21(3): 
217-21. 
[Orchardson R, Collins WJ (1987)] Clinical features of hypersensitive teeth. British dental 
journal; 162(7): 253-6. 
[Parkinson C, Constantin P, Goyal C, et al. (2017)] An exploratory clinical trial to evaluate 
the efficacy of an experimental dentifrice formulation in the relief of dentine 
hypersensitivity. Journal of Dentistry; 56: 39-44. 
[Polson AM, Caton JG, Yeaple RN, et al. (1980)] Histological determination of probe tip 
penetration into gingival sulcus of humans using an electronic pressure-sensitive 
probe. J Clin Periodontol; 7(6): 479-88. 
[Rocha MOC, Cruz A, Santos DO, et al. (2020)] Sensitivity and specificity of assessment 
scales of dentin hypersensitivity - an accuracy study. Braz Oral Res; 34: e043. 
[Schiff T, Dotson M, Cohen S, et al. (1994)] Efficacy of a dentifrice containing potassium 
nitrate, soluble pyrophosphate, PVM/MA copolymer, and sodium fluoride on 
dentinal hypersensitivity: A twelve-week clinical study. Journal of Clinical 
Dentistry; 5(SPEC. ISS.): 87-92. 
[Schiff T, Zhang YP, DeVizio W, et al. (2000)] A randomized clinical trial of the 
desensitizing efficacy of three dentifrices. Compend Contin Educ Dent Suppl; (27): 
4-10; quiz 28. 
[Silverman G (1985)] The sensitivity-reducing effect of brushing with a potassium nitrate-
sodium monofluorophosphate dentifrice. Compend Contin Educ Dent; 6(2): 131-
3, 6. 
[Splieth CH, Tachou A (2013)] Epidemiology of dentin hypersensitivity. Clin Oral 
Investig; 17 Suppl 1: S3-8. 
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Protocol Number: 218220 
 
 
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[Wara‐aswapati N, Krongnawakul D, Jiraviboon D, et al. (2005)] The effect of a new 
toothpaste containing potassium nitrate and triclosan on gingival health, plaque 
formation and dentine hypersensitivity. Journal of Clinical Periodontology; 32(1): 
53-8. 
[West N, Seong J, Davies M (2014)] Dentine hypersensitivity. Monogr Oral Sci; 25: 108-
22. 
[West NX (2006)] Dentine hypersensitivity. Monographs in oral science; 20: 173-89. 
[West NX, Addy M, Jackson RJ, et al. (1997)] Dentine hypersensitivity and the placebo 
response. A comparison of the effect of strontium acetate, potassium nitrate and 
fluoride toothpastes. J Clin Periodontol; 24(4): 209-15. 
 
15 
APPENDICIES 
15.1 
ABBREVIATIONS 
 
The following is a list of abbreviations that may be used in the protocol. 
Table 15-1 
Abbreviations 
 
Abbreviation 
Term 
AE 
Adverse event 
ANCOVA 
Analysis of covariance 
BDR 
Blinded data review 
DH 
Dentin Hypersensitivity 
DHEQ 
Dentin Hypersensitivity Experience Questionnaire 
EAR  
Erosion, Abrasion, Recession 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Capture 
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Protocol Number: 218220 
 
 
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Abbreviation 
Term 
EudraCT 
European Clinical Trials Database 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GSK CH 
GlaxoSmithKline Consumer Healthcare 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
KNO3 
Potassium Nitrate 
MFC 
Manufacturing formulation code 
MGI 
Modified gingival index 
mITT 
Modified Intent-to-Treat 
N/A 
Not applicable 
OHT 
Oral hard tissue 
OST 
Oral soft tissue 
PI 
Principal investigator 
PI 
Personal information 
POP 
Proof of Principle 
PVM/MA 
methyl vinyl ether/maleic anhydride co-polymer 
RAP 
Reporting and analysis plan 
REC 
Research ethics committee 
SAE 
serious adverse event 
SD 
Standard deviation 
SE 
Standard error 
SRSD 
Single reference study document 
SS 
Safety statement 
UPT 
Urine Pregnancy Test 
 
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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’. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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The following questions are about your sensitive teeth, and the impact it has on your everyday life. 
 
 
 
 
 
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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 
 
 
 
 
 
 
 
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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. 
 
 
 
 
 
 
 
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. 
 
 
 
 
 
 
 
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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. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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