Conditions: Dentin Sensitivity
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 111
Healthy volunteers: yes

Brief summary:
The aim of this study is to confirm the clinical Dentin Hypersensitivity (DH) efficacy of a 0.454 percent (%) Stannous Fluoride (SnF2) toothpaste.

Detailed description:
This will be a single center, 8-week, randomized, controlled, examiner-blind, 2-treatment arm, parallel design, stratified (by maximum baseline Schiff sensitivity score of the two selected 'test teeth') clinical study to evaluate the anti-sensitivity efficacy of a 0.454% SnF2 toothpaste in a DH population. The clinical efficacy of the 0.454% SnF2 toothpaste (test toothpaste) will be compared with that of a reference toothpaste, a commercially available, regular fluoride toothpaste with no known anti-sensitivity properties (negative control). Sufficient participants will be screened to randomize approximately 110 participants to investigational product (approximately 55 per treatment group) and to ensure approximately 100 evaluable participants complete the entire study (approximately 50 per treatment group).

Arms:
arm 1: Participants will dose the toothbrush with a ribbon of toothpaste, across the full brush head and will brush the entire dentition thoroughly for at least 1-timed minute, twice daily (morning and evening), for approximately 56 days making sure to brush the sensitive areas of the two 'test teeth' carefully first. Participants who wish to rinse after brushing will be instructed to rinse with 10 milliliter (ml) water using graduated rinsing cup provided. arm 2: Participants will dose the toothbrush with a ribbon of toothpaste, across the full brush head and will brush the entire dentition thoroughly for at least 1-timed minute, twice daily (morning and evening) for approximately 56 days. Participants who wish to rinse after brushing will be instructed to rinse with 10 ml water using graduated rinsing cup provided.

Interventions: intervention 1: Stannous fluoride toothpaste intervention 2: Crest cavity protection toothpaste
Intervention descriptions: intervention 1: Toothpaste containing 0.454 % weight/weight (w/w) SnF2 intervention 2: Regular fluoride toothpaste containing 1100 parts per million (ppm) fluoride.

Protocol document:
Prot_000.pdf: 
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CLINICAL PROTOCOL
AN 8-WEEK, RANDOMIZED, CONTROLLED, EXAMINER-BLIND, 
CLINICAL STUDY TO EVALUATE THE EFFICACY OF A STANNOUS 
FLUORIDE TOOTHPASTE FOR THE RELIEF OF DENTIN 
HYPERSENSITIVITY IN A POPULATION OF DENTIN 
HYPERSENSITIVITY SUFFERERS
Protocol Number:
300103
Product Name:
0.454 percent (%) weight/weight (w/w) 
stannous fluoride (SnF2) toothpaste
United States (US) Investigational 
New Drug (IND) Number:
N/A
European Clinical Trials Database 
(EudraCT) Number:
N/A
Other Regulatory Agency 
Number:
N/A
Phase:
N/A
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available version
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Sponsor Information
Sponsor Name & Legal 
Registered Address
Haleon (UK) 
The Heights,
Building 5, First Floor,
Weybridge,
Surrey,
KT13 0NY,
United Kingdom (UK)
Sponsor Contact Details
Haleon
St Georges Avenue,
Weybridge,
Surrey,
KT13 0DE,
UK
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Document History
Document
Version
Summary of Changes 
Original Protocol
1.0
N/A
Protocol
2.0
Correction of an administrative error relating to the DHEQ 
endpoints and analysis.
Section 1.1. Synopsis, Objectives and Endpoints and Section 
3. Study Objectives and Endpoints: DHEQ-related endpoints.
Section 1 Impact on Everyday Life (Q1-3) corrected to Section 1 
Impact on Everyday Life (Q7-9).
12.3.2. Secondary Endpoint Analyses, DHEQ-48:
Section 1 - Impact on Everyday Life: Q1, Q2 & Q3 (separate 
scores) corrected to Section 1 - Impact on Everyday Life: Q7, Q8 
& Q9 (separate scores)
Amendments incorporate all revisions to date, including amendments made at the request of the 
country health authority, institutional review board (IRB), etc.  
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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, and applicable medical device regulations.
•
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 
receive 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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Table of Contents
Sponsor Information............................................................................................................2
Document History ...............................................................................................................3
Investigator Protocol Agreement Page................................................................................4
Table of Contents ................................................................................................................5
1
PROTOCOL SUMMARY ................................................................................................10
1.1
Synopsis.................................................................................................................10
1.2
Schedule of Activities............................................................................................14
2
INTRODUCTION.............................................................................................................18
2.1
Background and Rationale for Study.....................................................................19
2.2
Benefit/Risk Assessment .......................................................................................19
2.3
Mechanism of Action/Indication...........................................................................20
3
STUDY OBJECTIVES AND ENDPOINTS ....................................................................21
4
STUDY DESIGN ..............................................................................................................23
4.1
Overall Design.......................................................................................................23
4.2
Scientific Rationale for Study Design ...................................................................24
4.3
Justification for Dose.............................................................................................28
4.4
End of Study Definition.........................................................................................29
5
STUDY POPULATION....................................................................................................29
5.1
Type and Planned Number of Subjects .................................................................29
5.2
Inclusion Criteria ...................................................................................................29
5.3
Exclusion Criteria..................................................................................................30
5.4
Randomization Criteria..........................................................................................32
5.5
Lifestyle Considerations........................................................................................32
5.5.1
Oral Hygiene Restrictions.....................................................................33
5.5.2
Dietary and Alcohol Restrictions..........................................................33
5.5.3
Contraception........................................................................................33
5.6
Screen Failures.......................................................................................................33
5.7
Sponsor’s Qualified Medical Personnel ................................................................33
5.8
Rater/Clinical Assessor Qualifications..................................................................34
6
INVESTIGATIONAL/STUDY PRODUCTS...................................................................34
6.1
Study Product Supplies..........................................................................................34
6.1.1
Medical Devices....................................................................................36
6.1.2
Dosage Form and Packaging.................................................................36
6.1.3
Product Dispensing ...............................................................................36
6.2
Administration.......................................................................................................37
6.2.1
Medication/Dosing Errors.....................................................................37
6.2.2
Overdose ...............................................................................................38
6.3
Study Product Storage ...........................................................................................38
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6.4
Study Product Accountability................................................................................38
6.4.1
Destruction of Study Product Supplies .................................................39
6.5
Blinding and Allocation/Randomization ...............................................................39
6.6
Breaking the Blind.................................................................................................40
6.7
Compliance............................................................................................................41
6.8
Concomitant Medication/Treatment......................................................................41
7
DISCONTINUATION OF STUDY INTERVENTION AND SUBJECT 
DISCONTINUATION/WITHDRAWAL .........................................................................42
7.1
Subject Discontinuation/Withdrawal.....................................................................42
7.2
Lost to Follow Up..................................................................................................43
8
STUDY PROCEDURES...................................................................................................43
8.1
Visit 1 / Screening .................................................................................................43
8.1.2
Demographics .......................................................................................44
8.1.3
Review of Oral Care Products...............................................................44
8.1.4
Medical History and Prior Medications/Treatments.............................44
8.1.5
Clinical Examinations and Assessments...............................................44
8.1.6
Inclusion/Exclusion Criteria .................................................................45
8.1.7
Subject Eligibility .................................................................................45
8.2
Study Period ..........................................................................................................46
8.2.1
Visit 2 / Baseline (Day 0)......................................................................46
8.2.2
Visit 3 / Day 28 (± 2 days)....................................................................49
8.2.3
Visit 4 / Day 56 (± 3 days)....................................................................51
8.3
Study Conclusion...................................................................................................52
8.4
Follow-Up Contact ................................................................................................52
9
STUDY ASSESSMENTS.................................................................................................53
9.1
Screening Examinations/DH Assessments............................................................53
9.1.1
Erosion, Abrasion and Recession (EAR)..............................................53
9.1.2
Modified Gingival Index (MGI) ...........................................................53
9.1.3
Clinical Mobility...................................................................................54
9.1.4
Screening Tactile Sensitivity Assessment.............................................54
9.1.5
Screening Evaporative (Air) Sensitivity Assessment ...........................56
9.2
DH Efficacy Assessments......................................................................................56
9.2.1
Dentine Hypersensitivity Experience Questionnaire (DHEQ-48)........56
9.2.2
Tactile Sensitivity Assessments............................................................57
9.2.3
Evaporative (Air) Sensitivity Assessments...........................................58
9.2.4
Labelled Magnitude Scales (LMSs)......................................................58
9.3
Safety Assessments................................................................................................59
9.3.1
Oral Soft Tissue (OST) Examination....................................................59
9.3.2
Oral Hard Tissue (OHT) Examination..................................................59
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9.3.3
Pregnancy..............................................................................................59
9.3.4
Satisfaction with Treatment ..................................................................60
10 ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS .........................................60
10.1
Definition of an Adverse Event (AE)....................................................................60
10.2
Definition of a Serious Adverse Event (SAE).......................................................62
10.3
Time Period and Frequency for Collecting AE and SAE Information..................63
10.4
Reporting Procedures.............................................................................................63
10.4.1
Reporting an AE....................................................................................64
10.4.2
Reporting an SAE .................................................................................64
10.5
Evaluating AEs......................................................................................................65
10.5.1
Assessment of Intensity ........................................................................65
10.5.2
Assessment of Causality .......................................................................65
10.6
Follow-up of AEs and SAEs..................................................................................66
10.7
Withdrawal Due to an Adverse Event ...................................................................66
10.8
Regulatory Reporting Requirements for SAEs......................................................66
10.9
Pregnancy ..............................................................................................................67
10.9.1
Time Period for Collecting Pregnancy Information..............................67
10.9.2
Action to be Taken if Pregnancy Occurs ..............................................67
10.10 Medical Device Incidents ......................................................................................67
10.10.1
Definition of an Incident.......................................................................67
10.10.2
Reporting of Incidents and Malfunctions..............................................68
10.10.3
Follow-up of Medical Device Incidents................................................69
10.10.4
Regulatory Reporting Requirements for Medical Device Incidents.....69
11 DATA MANAGEMENT..................................................................................................69
11.1
Case Report Form..................................................................................................70
11.2
Data Handling........................................................................................................70
11.2.1
Data Queries..........................................................................................70
11.3
Processing Subject Reported Outcomes ................................................................71
12 STATISTICAL CONSIDERATIONS AND DATA ANALYSES ..................................71
12.1
Sample Size Determination ...................................................................................71
12.2
Populations for Analysis........................................................................................71
12.2.1
Definitions of Analysis Populations .....................................................71
12.2.2
Exclusions of Data from Analysis.........................................................72
12.3
Statistical Analyses................................................................................................72
12.3.1
Primary Endpoint Analysis ...................................................................73
12.3.2
Secondary Endpoint Analyses...............................................................73
12.3.3
Exploratory Analyses............................................................................75
12.3.4
Safety Analyses.....................................................................................76
12.3.5
Demographic and Baseline Characteristics...........................................77
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12.3.6
Study Product Compliance and Use of Other Therapies ......................77
12.3.7
Handling of Dropouts and Missing Data ..............................................77
12.3.8
Interim Analysis....................................................................................78
13 STUDY GOVERNANCE CONSIDERATIONS..............................................................78
13.1
Quality Control......................................................................................................78
13.2
Quality Assurance..................................................................................................78
13.3
Regulatory and Ethical Considerations .................................................................79
13.3.1
Institutional Review Board (IRB).........................................................79
13.3.2
Ethical Conduct of the Study ................................................................79
13.3.3
Subject Information and Consent..........................................................79
13.3.4
Subject Recruitment..............................................................................80
13.3.5
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP...............................................................................................80
13.4
Posting of Information on Publicly Available Clinical Trial Registers.................80
13.5
Provision of Study Results to Investigators...........................................................80
13.6
Records Retention..................................................................................................81
13.7
Conditions for Terminating the Study...................................................................81
14 REFERENCES..................................................................................................................82
15 APPENDICIES..................................................................................................................89
15.1
Abbreviations.........................................................................................................89
15.2
Dentine Hypersensitivity Experience Questionnaire (Example DHEQ-48) .........91
15.3
Labelled Magnitude Scales: Intensity, Duration, Tolerability & Description 
(Example LMSs)....................................................................................................98
15.4
LMS Training Exercise (Example)......................................................................100
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List of In-Text Tables
Table 1-1
Schedule of Activities ...........................................................................15
Table 6-1
Acclimatization/Investigational Toothpastes........................................34
Table 6-2
Sundry Items .........................................................................................35
Table 15-1
Abbreviations........................................................................................89
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1
PROTOCOL SUMMARY 
1.1
Synopsis
Summary Title:
Clinical study to evaluate the anti-sensitivity efficacy of a stannous fluoride toothpaste in a 
population of dentin hypersensitivity sufferers.
Background and Rationale for the Study:
Stannous fluoride (SnF2) has been incorporated into oral hygiene products indicated for the 
relief of dentin hypersensitivity (DH) since the 1990s; it provides relief from DH by the physical 
occlusion of dentin tubules through chemical precipitation of stannous oxides and hydroxides. 
Randomized controlled clinical trials (many of 8 weeks treatment duration) support the longer-
term anti-sensitivity efficacy of 0.454% SnF2-containing toothpastes with twice daily use. The 
aim of the current 8-week study is to confirm the clinical DH efficacy of a 0.454% SnF2
toothpaste. Changes to the formulation, compared to those previously investigated by the 
sponsor, include removal of the opacifier, addition of a blue pigment, introduction of a new 
flavor for improved in-use experience, and modification of the dental abrasive system for 
improved stain removal and enamel polishing benefits. None of these changes are expected to 
impact the occlusion mode of action (MoA) of SnF2 or the anti-sensitivity efficacy of a 0.454% 
SnF2 toothpaste. In addition to demonstrating the efficacy of the Test Toothpaste, this study 
will monitor the impact of daily use of a 0.454% SnF2 toothpaste on the number of ‘Sensitive 
Teeth’, and subject perception of product benefits.
DH will be assessed at Baseline, and after 4- and 8-weeks treatment. At each post-Baseline time 
point, the efficacy of the 0.454% SnF2 toothpaste will be compared with that of a regular 
fluoride toothpaste with no known anti-sensitivity efficacy (negative control).
Objectives and Endpoints:
Objectives
Endpoints
Efficacy
Primary
To demonstrate the clinical efficacy of a 
0.454% w/w SnF2 toothpaste in reducing DH 
to an evaporative (air) stimulus (as measured 
by Schiff sensitivity score), compared to a 
negative control toothpaste, after 8 weeks
twice daily use.
Change from Baseline in Schiff sensitivity 
score at Day 56 (Week 8).
Secondary
To demonstrate the clinical efficacy of a 
0.454% w/w SnF2 toothpaste in reducing DH
to a tactile stimulus (as measured by tactile 
threshold in grams [g]), compared to a 
negative control toothpaste, after 8 weeks
twice daily use.
Change from Baseline in tactile threshold 
(g) at Day 56 (Week 8).
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To demonstrate the clinical efficacy of a 
0.454% w/w SnF2 toothpaste in reducing DH 
to evaporative (air) and tactile stimuli (as 
measured by Schiff sensitivity score and
tactile threshold (g), respectively), compared 
to a negative control toothpaste, after 4 weeks
twice daily use.
Change from Baseline in Schiff sensitivity 
score at Day 28 (Week 4).
Change from Baseline in tactile threshold 
(g) at Day 28 (Week 4).
To describe subject-perceived changes in oral 
health-related quality of life (OHrQoL), as 
measured by the Dentin Hypersensitivity 
Experience Questionnaire (DHEQ-48), after 
4- and 8-weeks twice daily use of their 
assigned investigational toothpaste.
At Day 28 (Week 4) & Day 56 (Week 8):
Change from Baseline in DHEQ-48 
endpoints.
Section 1 
•
Impact on Everyday Life (Q7-9) 
Section 2 
•
Total Score (Q1-34) 
•
Individual Domain Scores
-
Restrictions (Q1-4) 
-
Adaptation (Q5-16)  
-
Social Impact (Q17-21)  
-
Emotional Impact (Q22-29)  
-
Identity (Q30-34)  
•
Global Oral Health Score (Q35) 
•
Effect on Life Overall Score (Q36-39)
Exploratory
To determine the number of ‘Sensitive Teeth’
(evaporative (air) sensitivity only) in the pool 
of ‘Eligible Teeth’ identified at Screening, at 
Screening, Baseline, and after 4 and 8 weeks 
twice daily use of assigned investigational
toothpaste.
At Screening, Baseline, Day 28 (Week 4) & 
Day 56 (Week 8):
Number of ‘Sensitive Teeth’ 
Defined as the number of ‘Eligible Teeth’ 
(identified at Screening) with a Schiff Sensitivity 
Score ≥2.
To investigate subject-perceived changes in 
DH to an evaporative (air) stimulus, as 
measured by Labelled Magnitude Scales 
(LMSs), after 4 and 8 weeks twice daily use
of their assigned investigational toothpaste.
At Day 28 (Week 4) & Day 56 (Week 8):
Change from Baseline in LMS endpoints.
•
Intensity
•
Duration
•
Tolerability
•
Description
To investigate the relationship between 
subject responses to the DHEQ-48 and the 
LMSs at Baseline, and after 4 and 8 weeks
twice daily use of assigned investigational
toothpaste.
At Baseline, Day 28 (Week 4) & Day 56 
(Week 8):
•
DHEQ-48 endpoints, as listed above.
•
LMS endpoints, as listed above.
To investigate the relationship between the 
Schiff sensitivity scale and the LMSs at 
Baseline, and after 4 and 8 weeks twice daily 
use of assigned investigational toothpaste.
At Baseline, Day 28 (Week 4) & Day 56 
(Week 8):
•
Mean Schiff sensitivity score of the two 
‘Test Teeth’.
•
LMS endpoints, as listed above.
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To investigate subject satisfaction with their 
assigned investigational toothpaste for the 
overall management of DH, as measured by a 
Numeric Rating Scale (NRS), after 8 weeks 
treatment.
At Day 56 (Week 8):
Satisfaction NRS score  
Safety
To monitor the safety and oral tolerability of 
the investigational toothpastes over 8 weeks
twice daily use.
Treatment emergent adverse events 
(TEAEs).
Study Design:
This will be a single center, 8-week, randomized, controlled, examiner-blind, 2-treatment arm, 
parallel design, stratified (by maximum Baseline Schiff sensitivity score of the two selected 
‘Test Teeth’) clinical study to evaluate the anti-sensitivity efficacy of a 0.454% SnF2 toothpaste
in a DH population. The clinical efficacy of the 0.454% SnF2 toothpaste (Test Toothpaste) will 
be compared with that of a Reference Toothpaste, a commercially available, regular fluoride 
toothpaste with no known anti-sensitivity properties (negative control).
At Screening (Visit 1), following provision of written informed consent, suitability to 
participate will be reviewed against the protocol inclusion/exclusion criteria. Eligible subjects 
will enter an acclimatization period (14-28 days) prior to Baseline assessments during which 
they will brush twice daily (morning and evening) with the acclimatization toothpaste (a 
different commercially available, regular fluoride toothpaste from the Reference Toothpaste).
At Baseline (Visit 2), eligibility to continue will be assessed. Subjects who demonstrate the 
required qualifying levels of DH at Screening (Visit 1) and Baseline (Visit 2) will be
randomized to study treatment and instructed to brush with their assigned investigational 
toothpaste twice daily (morning and evening) for the duration of the 8-week treatment period. 
DH will be assessed at Screening (Visit 1) and Baseline (Visit 2), and after 28- and 56-days 
treatment (Visits 3 and 4, respectively) using two independent clinical measures: (i) tactile 
threshold (g) following a tactile stimulus and (ii) Schiff sensitivity score following an 
evaporative (air) stimulus.
Oral health-related quality of life (OHRQoL) will be monitored over the treatment period using 
the Dentin Hypersensitivity Experience Questionnaire (DHEQ-48), completed by study 
subjects at Baseline (Visit 2), and after 28- and 56-days treatment (Visits 3 and 4, respectively). 
Subject-perceived DH will also be investigated across the 8-week treatment period using four 
Labelled Magnitude Scales (LMSs) to capture the Intensity, Duration, Tolerability and 
Description of their response to the evaporative (air) stimulus. At the final visit (Day 56), 
subjects will rate their level of satisfaction with their assigned investigational toothpaste for the 
overall management of their DH, using a Numeric Rating Scale (NRS).
Safety and oral tolerability of the investigational toothpastes will be monitored over the 8-week 
usage period by review of treatment emergent adverse events (TEAEs).
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Investigational Products:
Description
Test 
Toothpaste
Reference Toothpaste 
(Negative Control)
Name
0.454% w/w SnF2 toothpaste
Regular fluoride toothpaste
(Crest Cavity Protection*)
Master 
Formulation Code 
N/A
Fluoride Level
1100 parts per million (ppm) fluoride†
1100 ppm fluoride¥
Route of 
Administration
Topical Oral Use
Toothpaste Usage 
Instructions
Dose the toothbrush with a ribbon of toothpaste, across the full brush head.
Brush the entire dentition thoroughly 
for at least 1-timed minute, twice daily 
(morning & evening), making sure to 
brush the sensitive areas of the two 
'Test teeth' carefully first.
Brush the entire dentition 
thoroughly for at least 1-timed 
minute, twice daily (morning & 
evening).
Subjects who wish to rinse after brushing will be instructed to rinse with 10 
milliliter (ml) water using graduated rinsing cup provided.
* Commercially available daily use toothpaste, US market.  
† As SnF2
¥ As sodium fluoride (NaF)
Type and Planned Number of Subjects:
Male and female subjects aged 18-65 years (inclusive), in good general and oral health, with a 
minimum of 20 natural teeth, a self-reported history of tooth sensitivity and clinically confirmed 
DH will be enrolled. Qualifying subjects with at least two teeth with clinically confirmed DH, 
(tactile threshold ≤ 20g and Schiff sensitivity score ≥ 2 at both Screening and Baseline visits)
will be randomized to treatment.
Sufficient subjects will be screened and entered into the acclimatization period to randomize 
approximately 110 subjects to investigational product (approximately 55 per treatment group)
and so ensure approximately 100 evaluable subjects complete the entire study (approximately 
50 per treatment group), allowing for approximately 10% dropouts.
Statistical Analysis Summary:
A modified Intent-To-Treat (mITT) population (all randomized subjects who receive at least 
one dose of investigational product and complete at least one-post Baseline DH efficacy 
assessment) will be used for the efficacy analyses. Significance testing will be conducted at the 
two-sided 5% significance level.
Schiff sensitivity score and tactile threshold (g) will be derived as the mean score/value of the 
two ‘Test Teeth’ (selected at Baseline). Change from Baseline will be derived for each
individual tooth first before calculating mean change for the two ‘Test Teeth’.
The primary endpoint, change from Baseline in Schiff sensitivity score at Day 56, will be 
analyzed using a Mixed Model with Repeated Measures (MMRM) with investigational product, 
visit and [investigational product x visit] interaction as fixed effects, and Baseline Schiff 
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sensitivity score as covariate. Subject will be included as a repeated measure with unstructured 
covariance matrix. Kenward Rogers degrees of freedom approach will be applied. The 
difference between the least square mean changes from Baseline for the Test Toothpaste 
compared to Reference Toothpaste (negative control) at Day 56 from the MMRM will be 
presented, along with the two-sided p-value and 95% confidence intervals (CIs).
The key secondary endpoint, change from Baseline in tactile threshold (g) at Day 56, will be 
analysed using the same MMRM as the primary endpoint but with Baseline tactile threshold (g) 
as covariate. In addition, the maximum Baseline Schiff sensitivity score of the two ‘Test Teeth’
(2 or 3) will be fitted as a fixed effect. The difference between the least square mean changes 
from Baseline for the Test Toothpaste compared to Reference Toothpaste (negative control) at 
Day 56 from the MMRM will be presented, along with the two-sided p-value and 95% CIs. 
Summary statistics (mean, median, standard error (SE), standard deviation (SD), minimum, 
maximum) will be presented for each Schiff sensitivity score and tactile threshold (g) outcome 
variable at each assessment time point. Raw means (± SE) of Schiff sensitivity score and tactile 
threshold (g) at each assessment timepoint will be plotted by treatment group.
1.2
Schedule of Activities
The Schedule of Activities (Table 1-1) provides an overview of the subject visits, study 
procedures and assessments. The investigator may schedule additional (unplanned) visits to 
conduct additional evaluations or assessments required to protect the well-being of the subject.
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Table 1-1
Schedule of Activities
Procedure/Assessment
Study Visits
Visit 1
Screening
Visit 2
Day 0
Baseline
Visit 3
Day 28
(± 2 days) 
Visit 4
Day 56
(± 3 days)  
Informed Consent
X
Acclimatization Period (14-28 days)
Demographics
X
Review Subject’s Oral Care Products
X
Review Medical History & Current/Prior Concomitant Medication/Treatment 1
X
Review Changes in Health & Medications/Treatments 1
X
X
X
Return Acclimatization Toothpaste, Toothbrush & Diary 2
X
Return Investigational Toothpaste, Toothbrush & Diary 2
X
Compliance Checks 2
X
X
X
Subject-Completed DHEQ 3
X
X
X
Subject-Completed LMS Training Exercise
X
Oral Soft Tissue (OST) Examination
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 Clinical Assessment of Tactile Sensitivity 4
X
X
Qualifying Clinical Assessment of Evaporative (Air) Sensitivity (Schiff sensitivity score) 5
X
X
Subject-Perceived Evaporative (Air) Sensitivity (LMSs) 6
X
Clinical Assessment of Evaporative (Air) Sensitivity of the Remaining ‘Eligible Teeth’
Identified at Screening 5
X
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Procedure/Assessment
Study Visits
Visit 1
Screening
Visit 2
Day 0
Baseline
Visit 3
Day 28
(± 2 days) 
Visit 4
Day 56
(± 3 days)  
Clinical Examiner Selects Two ‘Test Teeth’ (Qualifying Subjects Only) 7
X
Review Inclusion/Exclusion Criteria 
X
X
Confirm Subject Eligibility/Qualification
X
X
Dispense Acclimatization Toothpaste, Toothbrush, Timer, Rinsing Cups & Diary
X
Supervised Brushing with Acclimatization Toothpaste 
X
Stratification/Randomization
X
Dispense Investigational Toothpaste, Toothbrush, Rinsing Cups & Diary
X
X8
Supervised Brushing with Investigational Toothpaste
X
Clinical Assessment of Tactile Sensitivity: Two ‘Test Teeth’ Only 4
X
X
Clinical Assessment of Evaporative (Air) Sensitivity (Schiff sensitivity score): Assess the 
Two ‘Test Teeth’ First, then the Remaining ‘Eligible Teeth’ Identified at Screening 5
X
X
Subject-Perceived Evaporative (Air) Sensitivity (LMSs): Two ‘Test Teeth’ Only 6
X
X
Supervised Brushing with Investigational Toothpaste
X
Satisfaction with Treatment: Subject-Completed NRS
X
Study Conclusion
X
Monitor Adverse Events (AEs) and Medical Device Incidents 9
X
X
X
X
FOOTNOTES: 
1.
Female subjects of child-bearing potential should be asked to confirm pregnancy status at each visit.
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2.
Subjects will be required to bring their study supplies (minus timer & rinsing cups) to every visit. 
Perform visual check of returned study supplies, review diary & evaluate compliance.
Visit 2: Check compliance with use of acclimatization toothpaste.
Visit 3 & Visit 4: Check compliance with use of investigational toothpaste.
Visits 2-4: Check compliance with Lifestyle Guidelines/Medication requirements. 
3.
DHEQ-48 must be completed prior to the OST examination and clinical assessments.
Visit 2: Complete all questions.
Visits 3 & 4: Complete Section 1, Questions 7-9 & Section 2, all questions.
4.
Tactile Threshold Assessments: Visits 1-2: Maximum force 20g (Screening and Baseline); Visits 3-7: Maximum force 80g.
5. Evaporative (air) sensitivity (Schiff sensitivity score) should be assessed after tactile sensitivity, ensure minimum 5-minute delay after the last tactile 
assessment before the first evaporative (air) assessment for tooth recovery. 
Visit 1 (Screening): Assess evaporative (air) sensitivity for all teeth with a Screening tactile threshold ≤ 20g.
Visit 2 (Baseline): First assess evaporative (air) sensitivity for all ‘Eligible Teeth’ identified at Screening with a Baseline tactile threshold of ≤20g, then
assess the remaining ‘Eligible Teeth’ (i.e., the remaining teeth from the pool of ‘Eligible Teeth’ identified at Screening, with a Baseline tactile 
threshold >20g).
Visit 3 (Day 28) & Visit 4 (Day 56): First assess evaporative (air) sensitivity for the two ‘Test Teeth’ first, then assess the remaining ‘Eligible Teeth’ 
identified at Screening (excluding the two ‘Test Teeth’).
‘Eligible Teeth’ = Teeth with no dentition exclusions which met EAR, MGI & mobility criteria, with Screening tactile threshold ≤ 20g & Screening Schiff sensitivity score ≥ 2.
6. Visit 2 (Baseline): Complete 4 LMSs (Intensity, Duration, Tolerability & Description) for each tooth with a Baseline Schiff sensitivity score ≥ 2 only, 
immediately after the Baseline Schiff sensitivity score has been recorded for that tooth.
Visit 3 (Day 28) & Visit 4 (Day 56): Complete 4 LMSs for each ‘Test Tooth’, immediately after its Schiff sensitivity score has been recorded.
7.
Selected ‘Test Teeth’ should be in different quadrants, with the requisite qualifying levels of DH at both Screening (Visit 1) and Baseline (Visit 2), i.e., tactile 
threshold ≤ 20 g and Schiff sensitivity score ≥ 2.
8.
Visit 3: Supply new diary only.
9.
AEs, and therefore all serious adverse events (SAEs) will be recorded from immediately after signing the informed consent form (ICF) until 5 days after the
last use of investigational toothpaste. Incidents will be recorded from first to last use of the medical device (the manual toothbrush used to apply the 
acclimatization and investigational toothpastes).
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2
INTRODUCTION
Dentin hypersensitivity (DH) is a common dental condition; prevalence is reported to range 
from 3% to 57% in the general population (Addy, 2002). It is typically associated with the 
enamel wear and/or gingival recession experienced in adulthood (both of which lead to 
exposure of the underlying dentin) (West, 2022) and has been described as a ‘short, sharp pain 
arising from exposed dentine in response to stimuli typically thermal, evaporative, tactile, 
osmotic or chemical and which cannot be ascribed to any other form of dental defect or disease’
(Addy, 1985; Canadian Advisory Board on Dentin Hypersensitivity, 2003). Clinically, the
primary diagnosis of tooth hypersensitivity is made when a patient complains of brief, well-
localized pain resulting from thermal (typically cold), tactile, or osmotic stimulation of exposed 
dentin in the absence of any other dental pathology (Addy, 2002).  
The most widely accepted theory to explain DH is the hydrodynamic theory, first described in 
the literature by Gysi (Gysi, 1900) and expanded on later by Brännström (Brännström, 1963). 
The hydrodynamic theory proposes that an external stimulus, such as a temperature (cold or
hot) or osmotic differential, or tactile pressure, applied to exposed dentin disrupts the movement 
of fluid within dentin tubules. This disruption is thought to stimulate mechanoreceptors 
associated with odontoblast processes and nerve fibers located near the cervical pulp-dentin 
complex, triggering the short, sharp pain characteristic of DH (Absi, 1987; Pashley, 1994). 
Other mechanisms for DH have been proposed, however only the hydrodynamic theory 
explains the paradoxical finding that the dentin-enamel junction is sensitive to external stimuli, 
even though the dentin itself appears not to be highly innervated (Dababneh, 1999). The theory 
is also consistent with the observation that treatment of hypersensitive dentin with agents that 
either occlude the exposed dentin tubules or reduce mechanoreceptor/nerve activity, results in 
a reduction in the discomfort or pain observed clinically (West, 2014). 
Twice daily use of an anti-hypersensitivity toothpaste is generally recommended as the first line 
treatment for DH; treatment modalities are based on either dentin tubule occlusion or intra-
dental nerve desensitization (Addy, 2002; Pereira, 2015). SnF2 is one of the most commonly 
employed tubule occluding agents used in Over-the-Counter (OTC) toothpastes and has been 
widely marketed as a tooth desensitizer in OTC daily use toothpastes (0.454% w/w SnF2) in the 
US for many years. The stannous (tin [II]) ion reacts with water and phosphate minerals found 
in the saliva and dentin tubule fluid to rapidly form insoluble deposits over the surface of the 
dentin (Makin, 2013; Miller, 1994). These deposits act as barriers to external stimuli for DH, 
physically blocking or narrowing the openings of exposed tubules, thereby reducing dentin fluid 
movement and decreasing the ability of the stimulus to activate the intra-dental nerves and 
evoke a pain response (Addy M, 2002; Burnett GR, 2013; Miller S, 1994; Parkinson, 2011).
The use of SnF2 as a therapeutic agent in oral care products dates back to the 1950s when it was 
first used as an anti-caries agent in dentifrices (Makin, 2013). Numerous clinical studies 
reported in the scientific literature since then have established the safety and clinical efficacy 
of SnF2, not only as an anti-caries active, but also as an anti-DH and anti-plaque/gingivitis agent.
Citizens Petitions were submitted by Procter & Gamble in 2006, and GlaxoSmithKline 
Consumer Healthcare (GSKCH now Haleon) in 2012, requesting the FDA to reopen the Oral 
Health Care Drug Products TFM administrative record and review new efficacy data supporting 
the reclassification of SnF2 (0.454% w/w) as a Category I safe and effective tooth sensitizer, in 
addition to its recognized anti-caries GRASE status. The outcome of the FDA review of these 
citizens petitions and the finalization of the Oral Health Care Drug Product monograph is 
pending.    
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2.1
Background and Rationale for Study
Stannous fluoride (SnF2) has been incorporated into oral hygiene products indicated for the 
relief of DH since the 1990s (Schiff, 2006); it provides relief from DH by the occlusion of the 
dentin tubules via the chemical precipitation of insoluble tin salts on to the surface of exposed 
dentin (Makin, 2013; Miller, 1994). Haleon (the sponsor of this study) has marketed 0.454% 
SnF2 toothpastes indicated for DH relief in the US since 2013.
Numerous clinical studies of 4-24 weeks treatment duration (typically 8 weeks) demonstrate 
the longitudinal anti-sensitivity efficacy of SnF2-containing formulations (e.g., Amini, 2019; 
Chaknis, 2011; Creeth, 2021; Day, 2010; Du, 2011; Gallob, 2017; Hazen, 1968; He, 2014[a];
He, 2019; Hines, 2019; Kim, 2021; Mason, 2019; Ni, 2010; Ni, 2011; Parkinson, 2013;
Parkinson, 2015[a]; Schiff, 2005; Schiff, 2006; Sharma, 2010; Vinaya, 2010). Reviews and 
pooled/meta-analyses of randomized controlled trials also report SnF2-containing toothpastes 
to be clinically effective in the treatment of DH (Badadhe, 2023; Bae, 2015; Creeth, 2019[a];
Creeth, 2019[b]; Exterkate 2022; Gerlach, 2017; Kanouté, 2022; Konradsson, 2020; Martins, 
2020; Martins, 2022; Marto, 2020; Pollard, 2023; West, 2015; West, 2019; West, 2021; Yang, 
2016). The longer-term clinical efficacy of the sponsor’s marketed 0.454% SnF2 toothpastes is 
supported by two 8-week DH studies (Parkinson, 2013; Parkinson, 2015[a]). 
The aim of this 8-week clinical study is to confirm the longitudinal anti-sensitivity efficacy of 
a 0.454% SnF2 toothpaste. Changes to the formulation, compared to those previously 
investigated, include removal of the opacifier, addition of a blue pigment, a new flavor for 
improved in-use experience, and modification of the dental abrasive system for improved stain 
removal and enamel polishing benefits. None of these changes are expected to impact the MoA
of SnF2 (dentin tubule occlusion) or the anti-sensitivity efficacy of a 0.454% SnF2 toothpaste. 
Clinical DH assessments will be completed at Baseline, and after 28- and 56-days treatment. At 
each post-Baseline assessment time point, the efficacy of the 0.454% SnF2 toothpaste will be 
compared with that of a regular fluoride toothpaste with no known anti-sensitivity efficacy 
(negative control).
2.2
Benefit/Risk Assessment 
SnF2 has been included as a therapeutic agent (anti-caries) in daily use toothpastes since the 
1950s (Makin, 2013). Numerous clinical studies reported in the scientific literature since then 
have established the safety and clinical efficacy of SnF2, not only for anti-caries, but also for 
anti-hypersensitivity and anti-plaque/anti-gingivitis indications. 
SnF2 is included in the investigational toothpaste at 0.454% w/w to provide relief from the pain 
and discomfort of DH. The formulation contains only ingredients with a history of safe use in 
oral healthcare products and is designed for daily use by DH sufferers. Complete safety 
information for this 0.454% SnF2 toothpaste can be found in the single reference safety 
document for this product, which for this study is the Investigator’s Brochure (IB).
Numerous clinical studies support the longer-term clinical efficacy and safety of 0.454% SnF2
toothpastes in reducing the pain and discomfort associated with DH following exposure to a 
range of accepted stimuli (thermal and tactile (Holland, 1997)), see Section 2.1. In these studies, 
0.454% SnF2 toothpastes were applied twice daily by toothbrushing for 4 to 24 weeks (typically 
8 weeks) and were well tolerated.
Review of the sponsor’s interventional clinical studies involving 0.454% SnF2 toothpastes has 
not identified any significant safety issues. As per the sponsor's Global Data Sheet (GDS) for 
0.454% SnF2 toothpaste, which is continuously maintained by the ongoing post-marketing 
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surveillance activities, the frequency of adverse reactions is rare or very rare. The sponsor 
considers the overall benefit-risk profile of 0.454% SnF2 toothpaste to be favorable when used 
as directed in its intended target treatment population.
The Acclimatization and Reference Toothpastes will be daily use, regular fluoride toothpastes
(two different products); each will be commercially available in the US. The ingredients listed 
on both commercial packs have a history of safe use in oral healthcare products. The usage 
instructions given to study subjects will be consistent with the instructions on the commercial 
packs. No specific clinical benefits, risks or adverse effects are anticipated from their use in this 
study.
The manual toothbrush (Oral B Sensi-Soft toothbrush) to be used to apply the study toothpastes
by toothbrushing is a medical device in the US. Device usage instructions will be consistent 
with its commercial pack instructions. No specific clinical benefits, risks or adverse device 
effects are anticipated from its use in this clinical study.
Based on currently available data, the investigational and acclimatization toothpastes, and the 
manual toothbrush (medical device) to be used to apply them, are considered safe for use under 
the conditions of the proposed clinical study.
2.3
Mechanism of Action/Indication
Dentin tubule occluding agents, such as stannous salts, are understood to act by physically 
blocking or narrowing the exposed ends of dentin tubules, thereby reducing dentinal fluid 
movement in response to an external stimulus for DH and decreasing the effect of that stimulus
(Makin, 2013). 
•
In the presence of water (saliva) and saliva-derived ions, stannous (Sn [II]) ions rapidly 
oxidize to stannic (Sn [IV]) ions and hydrolyze to form insoluble tin compounds 
(hydroxides, oxides, phosphates and fluorophosphates) (Makin, 2013). 
•
The chemical precipitation of insoluble tin salts onto the surface of exposed dentin and 
within exposed dentin tubules serves to occlude patent dentin tubules (Burnett, 2013;
Earl, 2013), thereby providing relief from DH. 
•
Sn [II] ions have been shown in vitro to form insoluble precipitates on the dentin surface 
and within exposed dentin tubules (Ellingsen, 1987; Miller, 1994; Parkinson, 2011; Shi,
2012; White, 2007; Zsiska, 2012).
The smear layer is an amorphous deposit of organic (hydroxyapatite) and inorganic (e.g., from
toothpastes/toothbrushing or dental treatments such as prophylaxis) matter which covers the 
surface of exposed dentin and provides a degree of natural occlusion of patent dentin tubules. 
The smear layer is vulnerable to acid challenge (e.g., from dietary acids). Stannous ions are 
known to protect the smear layer from acid dissolution by interacting with hydroxyapatite to 
precipitate acid-resistant layers of stannous oxide, hydroxide, phosphate or fluorophosphate 
(Burnett, 2013). 
To maximise delivery of bioavailable stannous (tin [II]) ions to the oral cavity, SnF2 toothpastes
are often ‘stabilized’ by reducing the pH of the formulation, by the addition of complexing 
agents, and/or by developing low water content/anhydrous formulations. The investigational 
0.454% SnF2 toothpaste is an anhydrous formulation.
The longitudinal exposure of radicular or coronal primary dentin (due to enamel erosion, enamel 
abrasion and/or gum recession) results in the synthesis of tertiary or reparative dentin; the 
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primary purpose of reparative dentin is to protect the pulp tissue where the tooth’s normal 
protective tissues (enamel and gum) have been irreversibly lost (Linde, 1993). The reparative 
process can be initiated in response to the effect of external stimuli at the dentin surface, as 
experienced by DH sufferers (Cox, 1992; D’Souza, 1995; Magloire, 1992; Mjor, 2002). The 
occluding layer formed over the dentin surface, and within dentin tubules, with daily use of a 
0.454% SnF2 toothpaste functions in a similar way to this natural repair process. It too is
reparative in nature, acting to protect the dentin and the underlying pulp tissue from external 
pain-inducing stimuli where enamel and/or gingival tissue has been lost.
3
STUDY OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Efficacy
Primary
To demonstrate the clinical efficacy of a 
0.454% w/w SnF2 toothpaste in reducing DH 
to an evaporative (air) stimulus (as measured 
by Schiff sensitivity score), compared to a 
negative control toothpaste, after 8 weeks
twice daily use.
Change from Baseline in Schiff sensitivity 
score at Day 56 (Week 8).
Secondary
To demonstrate the clinical efficacy of a 
0.454% w/w SnF2 toothpaste in reducing DH
to a tactile stimulus (as measured by tactile 
threshold in grams [g]), compared to a 
negative control toothpaste, after 8 weeks
twice daily use.
Change from Baseline in tactile threshold 
(g) at Day 56 (Week 8).
To demonstrate the clinical efficacy of a 
0.454% w/w SnF2 toothpaste in reducing DH 
to evaporative (air) and tactile stimuli (as 
measured by Schiff sensitivity score and
tactile threshold (g), respectively), compared 
to a negative control toothpaste, after 4 weeks
twice daily use.
Change from Baseline in Schiff sensitivity 
score at Day 28 (Week 4).
Change from Baseline in tactile threshold 
(g) at Day 28 (Week 4).
To describe subject-perceived changes in oral 
health-related quality of life (OHrQoL), as 
measured by the Dentin Hypersensitivity 
Experience Questionnaire (DHEQ-48), after 
4- and 8-weeks twice daily use of their 
assigned investigational toothpaste.
At Day 28 (Week 4) & Day 56 (Week 8):
Change from Baseline in DHEQ-48 
endpoints.
Section 1 
•
Impact on Everyday Life (Q7-9) 
Section 2 
•
Total Score (Q1-34) 
•
Individual Domain Scores
-
Restrictions (Q1-4) 
-
Adaptation (Q5-16)  
-
Social Impact (Q17-21)  
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-
Emotional Impact (Q22-29)  
-
Identity (Q30-34)  
•
Global Oral Health Score (Q35) 
•
Effect on Life Overall Score (Q36-39)
Exploratory
To determine the number of ‘Sensitive Teeth’ 
(evaporative (air) sensitivity only) in the pool 
of ‘Eligible Teeth’ identified at Screening, at 
Screening, Baseline, and after 4 and 8 weeks 
twice daily use of assigned investigational
toothpaste.
At Screening, Baseline, Day 28 (Week 4) & 
Day 56 (Week 8):
Number of ‘Sensitive Teeth’ 
Defined as the number of ‘Eligible Teeth’ 
(identified at Screening) with a Schiff Sensitivity 
Score ≥2.
To investigate subject-perceived changes in 
DH to an evaporative (air) stimulus, as 
measured by Labelled Magnitude Scales 
(LMSs), after 4 and 8 weeks twice daily use
of their assigned investigational toothpaste.
At Day 28 (Week 4) & Day 56 (Week 8):
Change from Baseline in LMS endpoints.
•
Intensity
•
Duration
•
Tolerability
•
Description
To investigate the relationship between 
subject responses to the DHEQ-48 and the 
LMSs at Baseline and after 4 and 8 weeks
twice daily use of assigned investigational
toothpaste.
At Baseline, Day 28 (Week 4) & Day 56 
(Week 8):
•
DHEQ-48 endpoints, as listed above.
•
LMS endpoints, as listed above.
To investigate the relationship between the 
Schiff sensitivity scale and the LMSs at 
Baseline, and after 4 and 8 weeks twice daily 
use of assigned investigational toothpaste.
At Baseline, Day 28 (Week 4) & Day 56 
(Week 8):
•
Mean Schiff sensitivity score of the two 
‘Test Teeth’.
•
LMS endpoints, as listed above.
To investigate subject satisfaction with their 
assigned investigational toothpaste for the 
overall management of DH, as measured by a 
Numeric Rating Scale (NRS), after 8 weeks 
treatment.
At Day 56 (Week 8):
Satisfaction NRS score  
Safety
To monitor the safety and oral tolerability of 
the investigational toothpastes over 8 weeks
twice daily use.
Treatment emergent adverse events 
(TEAEs).
This study will be considered successful if the 0.454% SnF2 toothpaste demonstrates 
statistically significant, superior anti-hypersensitivity efficacy, compared to the negative control
toothpaste, as measured by Schiff sensitivity score at Day 56 (Week 8).
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4
STUDY DESIGN 
4.1
Overall Design
This will be a single center, 8-week, randomized, controlled, examiner-blind, 2-treatment arm, 
parallel group, stratified study in healthy subjects with DH. Subjects who meet the required 
study criteria at Screening and Baseline will be randomized to one of two study treatments: 
0.454% SnF2 toothpaste (Test Toothpaste) or a regular fluoride toothpaste (Reference
Toothpaste)
Two independent stimulus-based clinical measures will be employed to assess the efficacy of 
the investigational toothpastes. 
•
A tactile stimulus will be administered using a constant pressure probe - Yeaple Probe 
(Polson, 1980); subject response to the stimulus determines the tactile threshold in 
grams (g). 
•
An evaporative (air) stimulus (i.e., a thermal stimulus) will be administered using a 
dental air syringe; subject response to the stimulus will be examiner-evaluated using the 
Schiff sensitivity scale (Schiff, 1994).
DH will be assessed at Screening, Day 0 (Baseline), Day 28 (Week 4) and Day 56 (Week 8).
On completion of the Baseline assessments, the clinical examiner will select two ‘Test Teeth’ 
for assessment of tactile and evaporative (air) sensitivity at all subsequent visits. To qualify for 
selection as a ‘Test Tooth’, the tooth must meet the protocol-specific inclusion/exclusion 
criteria (Section 5.2 Inclusion Criteria 6 & 7; Section 5.3 Exclusion Criterion 26), specifically 
tactile threshold ≤ 20g and Schiff sensitivity score ≥ 2 at both Screening and Baseline visits.
In addition, the number of ‘Sensitive Teeth’ will be determined at each study visit (Schiff 
sensitivity score ≥2) as described in Sections 8.1.5, 8.2.1.5, 8.2.2.5 and 8.2.3.5.
Approximately 110 qualifying subjects will be stratified according to the maximum Baseline 
Schiff sensitivity score of their two ‘Test Teeth’ and randomized to treatment (approximately 
55 subjects per treatment group). Randomized subjects will be instructed to brush twice daily 
(morning and evening) with their assigned investigational toothpaste for the next 56 days 
(8 weeks) and record each brushing in the diary provided. First use will be performed under 
supervision at the investigator site; to facilitate compliance an additional supervised on-site 
brushing will be completed at the end of Visit 3.
Changes in OHRQoL will be monitored over the treatment period using the validated Dentin 
Hypersensitivity Experience Questionnaire (DHEQ-48). The DHEQ-48 will be completed by 
study subjects at Baseline, and after 28- and 56-days treatment. Subject-perceived DH will also 
be investigated for the two selected ‘Test Teeth’ using Labelled Magnitude Scales (LMSs).
Subjects will complete four LMSs to capture the Intensity, Duration, Tolerability and 
Description of their response to the evaporative (air) stimulus administered at Baseline, Day 28 
and Day 56. At the final visit (Day 56), after all clinical procedures have been completed, 
subjects will rate their level of satisfaction with their assigned investigational toothpaste for the 
overall management of DH using a NRS. 
To standardize oral hygiene practice in the study population prior to treatment and to help 
minimize the potential impact of ‘placebo’/‘no treatment’ effects, eligible subjects will 
complete an acclimatization period (14-28 days duration) between the Screening and Baseline 
visits during which they will brush twice daily (morning and evening) with a regular fluoride 
toothpaste (a different commercially available product from the Reference Toothpaste). First 
use of acclimatization toothpaste will be performed under supervision at the investigator site.
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Safety and oral tolerability of the investigational toothpastes will be monitored over the 
treatment period by review of TEAEs.
4.2
Scientific Rationale for Study Design
The randomized, controlled, examiner-blind, parallel group design selected for this DH study
follows published guidance for the design and conduct of studies investigating the clinical 
efficacy of anti-sensitivity products (Holland, 1997). In line with these same recommendations, 
two independent, controllable DH stimuli (tactile and thermal) will be employed to assess the 
performance of the 0.454% SnF2 toothpaste, with the least severe stimulus (tactile) applied first
(Holland, 1997). To avoid inter-examiner variability, the same clinical examiner will administer
a given stimulus (tactile and/or evaporative (air)) and assess its associated DH measure (tactile 
threshold (g) or Schiff sensitivity score) throughout the study. 
DH will be clinically assessed at Screening and Baseline (pre-treatment) to determine suitability
to participate and confirm subject qualification, and again after 28- and 56-days treatment to 
evaluate the efficacy of the Test Toothpaste with twice-daily use. At all post-Baseline time 
points, the anti-sensitivity efficacy of the Test Toothpaste will be compared with that of a
Reference Toothpaste - a conventional, daily use fluoride toothpaste with no known anti-
sensitivity efficacy (i.e., a non-desensitising toothpaste will act as the negative control).
Qualifying subjects will be randomized to one of the two investigational treatments using a 1:1 
allocation ratio. 
•
Day 56 has been selected as the primary time point to confirm the anti-sensitivity
efficacy of the investigational 0.454% SnF2 toothpaste; 56-day (8-week) study duration 
is accepted as appropriate to evaluate the long-term efficacy of most anti-sensitivity 
products (Holland, 1997).
•
Evaporative (air) is a thermal stimulus representative of the impact of chilled foods and 
drinks, or an intake of cold air, on sensitive teeth. ‘Cold’ is reported to be the most 
common stimuli for DH pain (Fischer, 1992; Flynn, 1985; Gillam, 2002). Thus, change 
from Baseline in Schiff sensitivity score at Day 56 has been selected as the primary 
endpoint, with study success defined as statistically significant, superior anti-
hypersensitivity efficacy for the 0.454% SnF2 toothpaste, vs. negative control, as 
measured by Schiff sensitivity score at Day 56 (Week 8).
On completion of the Baseline assessments, the clinical examiner will select two ‘Test Teeth’
from those that qualify at both Screening (Visit 1) and Baseline (Visit 2) for assessment of 
tactile and evaporative (air) sensitivity at all subsequent visits. Qualifying subjects will be 
stratified according to the maximum Schiff sensitivity score of their two selected ‘Test Teeth’
to ensure treatment groups are balanced for DH severity. Repeated stimulation of multiple 
sensitive teeth may alter the pain response as testing continues around the mouth; the 
anticipation of pain or discomfort with protracted testing, along with the discomfort of having 
to keep the mouth open for an extended period of time, may also affect subject perception of 
pain (Holland, 1997). Thus, the selection of two representative ‘Test Teeth’ to evaluate changes 
in DH with treatment is common practice in DH efficacy studies. To be representative of 
different areas of the mouth, with independent innervation, the ‘Test Teeth’ should be non-
adjacent and in different quadrants.
The number of teeth sensitive to an evaporative (air) stimulus in the pool of ‘Eligible Teeth’ 
identified at Screening will be monitored across the study period. The evaporative (air) 
sensitivity of all ‘Eligible Teeth’ identified at Screening (i.e., teeth with no dentition exclusions 
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which meet the EAR, MGI and mobility inclusion criteria, and have a Screening tactile 
threshold ≤ 20g and a Screening Schiff sensitivity score ≥ 2) will be assessed at Baseline, and 
after 28- and 56-days treatment. For this purpose, a ‘Sensitive Tooth’ will be defined as having 
a marked response to the evaporative (air) stimulus (Schiff sensitivity score ≥2). 
To help minimize exposure to environmental triggers for sensitivity prior to clinical DH
assessment, subjects will be instructed to refrain from oral hygiene, chewing gum, eating and 
drinking for a period of time prior to their arrival at the investigator site.
Clinical trials evaluating pain-related endpoints can be prone to ‘placebo effects’ (Addy, 1985; 
West, 1997); such effects are frequently observed in DH studies. A study conducted to evaluate 
the natural history of the DH condition also highlighted the existence of a ‘no treatment’ effect,
characterized by an improvement in sensitivity simply as a result of study participation (Leight, 
2008). To help minimize the potential impact of such effects, an acclimatization period (14-28 
days duration) will precede the Baseline visit. During this period, study subjects will brush 
twice daily with the regular fluoride toothpaste and toothbrush provided (in place of their own
oral hygiene products) and record each brushing occasion in a diary. The acclimatization period 
will also serve to standardize oral hygiene practice across the study population and familiarize
participants with several important study procedures (e.g., toothpaste dosage, timed brushings,
diary completion) prior to treatment. 
DH is an episodic condition; symptoms are known to vary spontaneously (West, 2008, West, 
2013). Baseline clinical values that would support enrolment may represent random highs that 
could be followed by regression to the mean, leaving the subject or selected test tooth without 
the condition under investigation (i.e., DH) during the treatment period. To help minimize the 
potential for this to occur in the current study, randomized subjects will be required to 
demonstrate consistency in response to both DH stimuli at both the Screening and Baseline 
visits. Qualifying subjects will have a minimum of two qualifying teeth with a tactile threshold 
≤ 20g and a Schiff sensitivity score ≥ 2 at both Screening and Baseline. In line with published 
guidelines for the design and conduct of studies investigating the clinical efficacy of anti-
sensitivity products, inconsistent responders will be excluded (Holland, 1997).
The etiology of DH requires tooth wear (loss of enamel) and/or gingival recession (with loss of 
cementum) to expose the underlying dentin (Addy, 1987). In the absence of an underlying 
condition or pathology, these processes are slow and progressive, leading to dentin exposure in 
early adulthood; thus, DH is rarely seen in children (West, 2022). While the age range over
which an individual can experience DH is wide (early teens to 70s), peak incidence is known 
to occur between the ages of 20-40 years and decline thereafter (Bartold, 2006; Dababneh, 1999; 
Fischer, 1992; Flynn, 1985; West, 2014). The fall in prevalence observed in later decades 
reflects age-related changes in the dentin and pulp of the tooth which act to reduce both dentin 
permeability and the tooth’s response to external triggers of DH (Seltzer, 1975; Splieth, 2013). 
Dental pain experienced by older members of the population is less likely to be diagnosed as
DH (Rees, 2000), thus an age range of 18-65 years has been selected for this study to target 
individuals with tooth sensitivity due to DH.
Currently, there is no published evidence to indicate that gender, race or ethnicity impacts the 
pathophysiology of DH. Thus, the investigator site will make every effort to enroll subjects 
representative of the adult population who would benefit from use of an anti-sensitivity 
toothpaste. The study population will comprise male and female subjects and the protocol 
inclusion/exclusion criteria will not unnecessarily preclude any subject from participation. To 
further increase the diversity of enrolled subjects: (i) the investigator site will be encouraged to 
employ a range of advertising methods (e.g., posters in local community centers, retail outlets 
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and healthcare facilities, local radio, social media) to maximize their ability to reach a diverse 
population within their geographic location; (ii) wherever possible, the investigator site will 
ensure accessibility to clinical areas for subjects with mobility issues; (iii) flexibility will be 
added to Visit 3 and Visit 4 timings to facilitate subject attendance at site (Day 28 ± 2 days; 
Day 56 ± 3 days); (iv) study payment will appropriately compensate potential subjects for the 
anticipated costs of participation (e.g., travel to the investigator site for scheduled visits) to 
ensure financial considerations do not impede participation.
Female subjects who are pregnant (or intending to become pregnant during the study) or breast-
feeding will be excluded from participation in the study. The study toothpastes are not contra-
indicated for pregnancy or breastfeeding (their use would not be expected to cause harm to the 
mother, the foetus or a baby), however, pregnant and lactating females will be excluded due to 
the increased prevalence/severity of gingivitis and periodontal disease reported during 
pregnancy and breastfeeding which, together with the increased amounts of calculus and plaque 
observed on the teeth during pregnancy, could affect DH assessment (Aghazadeh, 2019; 
Samant, 1976).
Potential study subjects will be asked to bring their current oral hygiene products to Screening 
(Visit 1) where they will be checked for presence of known anti-sensitivity ingredients. 
Individuals already using anti-sensitivity product(s) as part of their normal oral hygiene routine 
will be excluded. If they are using such products and continuing to experience DH, they would
be unlikely to respond to further use of anti-sensitivity toothpaste in this study and will be 
advised to seek help from their dental healthcare provider.
‘Patient-reported outcomes’ (PROs) can provide valuable information about the effect of a 
condition, and its treatment, on day-to-day life from the perspective of the person suffering with 
the condition. The inclusion of well-defined, reliable ‘PROs’ in clinical studies is increasingly 
encouraged to ensure the impact of treatment on quality of life and subject-reported symptoms
is assessed alongside conventional clinical outcomes. Indeed, published guidelines for the 
design and conduct of studies investigating the clinical efficacy of anti-sensitivity products
(Holland, 1997), recommend that treatment evaluations include subject-assessment of overall 
change to every day triggers for DH. Three ‘PRO’ measures will be included in this study: 
(i) the Dentine Hypersensitivity Experience Questionnaire (DHEQ); (ii) a series of Labelled 
Magnitude Scales (LMSs); (iii) a Treatment Satisfaction NRS. Given study participants will not 
be patients, for the purposes of this study, these measures will be described as ‘subject-reported 
outcomes’.
The DHEQ and the LMSs were developed with DH sufferers and can be used to assess the 
impact of DH on daily life, to measure DH pain and/or assess subject response to DH treatment.
Study subjects will complete a DHEQ-48 (Appendix 15.2) at Baseline (Visit 1), and after 28-
and 56-days treatment (Visits 6 and 7), prior to any clinical examinations or assessments. 
•
The DHEQ is a validated, condition-specific measure of OHRQoL used to investigate 
the impacts of tooth sensitivity on everyday life. It was developed by the sponsor in 
collaboration with Sheffield University through a robust theoretical framework, (Baker, 
2014; Boiko, 2010; Robinson, 2014) and has shown reliability and validity in both a 
general population (Porritt, 2016) and in clinical studies (Boiko 2010; Gibson, 2015).
It has been validated as both long- and short-form versions (DHEQ-48 and DHEQ-15),
comprising 48 (Baker, 2014; Boiko, 2010) and 15 (Machuca, 2014) questions, 
respectively, and has been translated into multiple languages (e.g., Chinese, Turkish, 
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Portuguese), confirming its global relevance (Başaran, 2018; Douglas-De-Oliveira;
2018; He, 2015[a]; He, 2015[b]). 
Study subjects will complete four LMSs (Appendix 15.3) relating to condition-specific 
characteristics of the DH pain response (intensity, duration, tolerability and description) at 
Baseline (for each tooth which qualifies for evaporative (air) assessment), and after 28- and 56-
days treatment (for the two selected ‘Test Teeth’ only). LMSs will be completed shortly after 
the evaporative (air) stimulus has been administered, and after the clinical examiner has 
recorded their Schiff sensitivity score. To avoid bias, the examiner and the subject will have no 
visibility of their respective ‘scores’. 
•
Visual Analogue Scales (VASs) with two anchor points at 0 millimeters (mm) and 100 
mm (typically labelled ‘no pain’ and ‘worst imaginable pain’) are frequently employed 
in the clinical study of pain. While are effective for measuring change in high intensity 
pain (e.g., post-operative pain Gagliese, 2005), they can be less useful for low-level, 
episodic pain, such as that associated with DH. The LMSs to be used in this study were 
developed by the sponsor in collaboration with the University of Washington (Seattle, 
US), specifically to discriminate between different levels of DH pain, and have been 
piloted, validated, and utilized in observational and interventional clinical DH studies 
(Cunha-Cruz, 2013; Heaton, 2013; Mason, 2017; Mason, 2019). Recurring, consistent
descriptors of DH pain (from the mildest to the most severe) were identified during
focus groups with clinically confirmed DH sufferers. Psychophysical procedures 
(magnitude estimation and cross-modality magnitude matching) were then applied to 
align these condition-specific descriptors along VASs at distances reflecting the 
psychological distances between the descriptive terms. 
To investigate satisfaction with their assigned investigational toothpaste for the overall 
management of DH, subjects will be asked to complete a NRS (an 11-point ordinal scale) at the 
end of the treatment period. They will record the numeric value (from 0 to 10) that best describes 
their level of satisfaction and describe why they gave the product that rating (free text).
Per International Conference on Harmonization (ICH) GCP guidance (ICH E6 (R2) Good 
Clinical Practice), for a study to be classified as double blind, the subjects, investigator(s) and 
staff involved in the treatment or clinical evaluation of subjects should be unaware of treatment 
received; this includes staff involved in the determination of subject eligibility, evaluation of
endpoints (clinical examiners), or assessments of protocol compliance (e.g., monitors, data 
analysts). In summary, neither the subject nor the researchers should know if the subject has 
been assigned to Test or Reference treatment. In addition, the products under test should have 
the same appearance, smell and taste (i.e., study arms should not be distinguishable from each 
other). Given this will not be possible for the investigational products evaluated in this study 
(an experimental toothpaste and commercially available regular fluoride toothpaste), the study 
is described as ‘examiner blind’. However, given design of the study and the procedures in 
place at the investigator site to maintain the blind during study conduct, it is highly unlikely 
that the subjects, investigator, clinical examiner(s) or any member of the site staff involved in 
efficacy and safety assessments will be aware of treatment allocation.
•
In this parallel-design study, study subjects will see and use only one of the two 
investigational toothpastes for the duration of the treatment period. They will be 
instructed not to discuss the appearance, usage or perceived performance of their 
assigned investigational toothpaste with the clinical examiner(s), with staff involved in 
clinical assessments or with other study subjects. 
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•
Both investigational products are blue toothpastes. They will be provided to the 
investigator site overwrapped in white vinyl to mask their identity, and to obscure any 
branding on the Reference Toothpaste, with a study label affixed.
•
The investigational toothpastes will be supplied in cartons, each carton will contain 4
over-wrapped tubes of toothpaste. The carton and its 4 tubes will be labelled with the 
same unique randomization number. Subjects will be centrally randomized to treatment
in order of qualification using an Interactive Response Technology (IRT); product codes 
will not be used.
•
The clinical examiner(s) and site staff involved in efficacy and safety assessments will 
not be permitted in any area where the investigational toothpastes or diaries are stored, 
dispensed or in use.
•
Site staff involved in the dispensing of investigational toothpastes, providing brushing 
and diary completion instruction, supervision of on-site brushings, treatment 
compliance checks and product accountability will not be involved in clinical efficacy 
and safety assessments and will work in a separate area from the clinical examiner(s) 
and site staff involved in efficacy and safety assessments.
•
Subjects will be instructed not to remove their assigned investigational toothpaste or 
diary from the opaque carrier bag provided outside of the dispensing/supervised 
brushing room, while at the investigator site.
•
Where certain staff will be unblinded to carry out their responsibilities (e.g., staff
involved in SAE reporting, monitors), the investigator and sponsor are required to put
adequate procedures in place to prevent inappropriate dissemination of treatment 
identification.
4.3
Justification for Dose
The investigational products are toothpastes; they are intended for topical oral use and will be 
applied by toothbrushing using a manual toothbrush.
In line with widely recommended oral hygiene practice and typical consumer habit, qualifying 
subjects will be instructed to brush twice daily (morning and evening) with their assigned 
investigational toothpaste, covering the toothbrush head with full ribbon of toothpaste 
(approximately 1.5g) on each brushing occasion. 
•
Subjects randomized to Test Toothpaste will be instructed to brush their entire dentition 
thoroughly for at least 1-timed minute, making sure to brush the sensitive areas of their 
two 'Test teeth' carefully first.
•
Subjects randomized to Reference Toothpaste will be instructed to brush their entire 
dentition thoroughly for at least 1-timed minute.
Usage instructions are consistent with the proposed labelling for the Test Toothpaste and with 
the commercial pack instructions of the Reference Toothpaste. At least 1-minute brushing is in 
line with the brushing times specified in similar DH efficacy studies (Docimo, 2009; Hall, 2017; 
He, 2014[b]); Parkinson, 2013; Parkinson, 2015[a]). 
After 8 weeks (i.e., 56 ± 3 days) twice daily usage, each subject should complete between 106-
118 brushings.
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4.4
End of Study Definition
A subject will be considered to have completed the study if they have completed all phases of 
the study, including the last visit or the last scheduled procedure shown in the Schedule of 
Activities (Table 1-1). The end of this study is defined as the date of the last scheduled 
procedure for the last subject, as described in the Schedule of Activities (Table 1-1).
5
STUDY POPULATION
5.1
Type and Planned Number of Subjects
The study will be conducted in male and female subjects in good general/oral health, with pre-
existing self-reported tooth sensitivity, and at least two sensitive teeth (with clinically confirmed 
DH) that meet study eligibility criteria at both Screening (Visit 1) and Baseline (Visit 2). 
Sufficient subjects will be screened and entered into the acclimatization phase to ensure 
approximately 110 subjects are randomized to investigational product (approximately 55
subjects per treatment group) and approximately 100 subjects complete the study 
(approximately 50 subjects per treatment group), allowing for 10% dropouts. Subjects will be 
recruited primarily from the investigator site database.
For this study, an enrolled subject is defined as a subject who has agreed to participate in the 
study following completion of the informed consent process and successfully met the study 
eligibility criteria to proceed beyond the screening visit.
The investigator site will make every effort to enroll subjects representative of the adult 
population who would benefit from use of an anti-sensitivity toothpaste; the rationale for study 
population selection is provided in the Scientific Rationale for Study Design (Section 4.2).
A clinical study can only fulfill its objectives if appropriate subjects are enrolled. The following 
eligibility criteria have been designed to select subjects for whom participation in the study is 
considered appropriate while not unnecessarily precluding any subject from study participation. 
All relevant medical and non-medical conditions should be taken into consideration when 
deciding whether or not a subject is suitable. Eligibility to participate will be reviewed and 
documented by the investigator (or medically qualified designee) before each subject is 
included in the study.
5.2
Inclusion Criteria
Each individual subject must meet all the following inclusion criteria to be eligible to participate
in the study.
1. Subject provision of signed and dated informed consent before any study procedures are 
performed.
2. Subject is male or female.
3. Subject is 18 to 65 years of age, inclusive, at the time of signing the informed consent.
4. Subject is willing and able to comply with the study visit schedule, product usage 
instructions, lifestyle restrictions and other study procedures.
5. Subject is 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 self-
reported medical history, or upon oral examination, that would impact their safety or
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wellbeing, or the outcomes of the study, if they were to participate in the study, or affect 
their ability to understand and follow study requirements.
6. SCREENING (Visit 1)
Subject must have:
a) History of tooth sensitivity lasting more than six months but not more than 10 years
(self-reported).
b) Good general oral health, with a minimum of 20 natural teeth.
c) Minimum of 2 accessible, non-adjacent teeth (incisors, canines, premolars), in different 
quadrants, which meet all of the following criteria:
•
Exposed dentin due to facial/cervical erosion, abrasion or gingival recession (EAR).
•
MGI = 0 directly adjacent to the exposed dentin (i.e., the test area only) (Lobene, 
1986).
•
Clinical mobility = 0 (Laster, 1975).  
•
Clinically confirmed DH to both tactile and evaporative (air) stimuli:
-
Qualifying tactile threshold ≤ 20g
-
Qualifying Schiff sensitivity score ≥ 2.
7. BASELINE (Visit 2, Pre-Treatment)
Subject must have a minimum of two, non-adjacent accessible teeth (incisors, canines, 
premolars), in different quadrants, with clinically confirmed DH to both tactile and 
evaporative (air) stimuli at both Screening (Visit 1) and Baseline (Visit 2).
•
Qualifying tactile threshold ≤ 20g at Screening & Baseline
•
Qualifying Schiff sensitivity score ≥ 2 at Screening & Baseline
The clinical examiner will select two ‘Test Teeth’ from those which meet the tactile 
threshold and Schiff sensitivity score inclusion criteria at both Screening and Baseline.
Notes: All teeth with clinically confirmed, qualifying levels of DH at Screening (i.e., a 
Screening tactile threshold ≤ 20 g and a Screening Schiff sensitivity score ≥ 2) will be 
assessed for tactile sensitivity at Baseline. Teeth with a Baseline tactile threshold ≤ 20g will 
then be assessed for Baseline evaporative (air) sensitivity.
5.3
Exclusion Criteria
An individual who meets any of the following exclusion criteria will be excluded from 
participation in the study.
1. Subject is an employee of the investigator site directly involved in the conduct of the study,
or an employee of the investigator site otherwise supervised by the investigator, or a 
member of their immediate family.
2. Subject is an employee of the sponsor directly involved in the conduct of the study or a 
member of their immediate family.
3. Female subject who is pregnant or intending to become pregnant during the study (self-
reported).
4. Female subject who is breastfeeding (self-reported).
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5. Subject with known or suspected intolerance or hypersensitivity to the study products, any 
of their stated ingredients or closely related compounds (self-reported). 
6. Subject with a recent history (within the last year) of alcohol or other substance abuse (self-
reported).
7. Subject is participating in or has participated in other studies (including non-medicinal 
studies) involving investigational product(s) within 30 days of Screening (Visit 1) or plans 
to participate in other studies (including non-medicinal studies) during this study.
8. Subject has participated in a tooth sensitivity study within 8 weeks of Screening (Visit 1).
9. Subject is currently using an oral care product indicated for DH relief or care of sensitive 
teeth or has used an anti-sensitivity product within 8 weeks of Screening (Visit 1)
Subjects will be required to bring their current oral care products to Screening (Visit 1) for 
staff to verify the absence of known anti-sensitivity ingredients and sensitivity-related claims
on the product packaging/label text.
10. Subject takes daily doses of medications/treatments which, in the opinion of the investigator 
or medically qualified designee, could interfere with their perception of tooth sensitivity 
(e.g., analgesics, anticonvulsants, antihistamines that cause marked or moderate sedation, 
sedatives, tranquilizers, antidepressants, mood-altering and anti-inflammatory drugs).
11. SCREENING (Visit 1)
Subject has taken antibiotics in the 2 weeks prior to Screening (Visit 1).
12. BASELINE (Visit 2, Pre-Treatment)
Subject has taken antibiotics in the 2 weeks prior to Baseline (Visit 2), i.e., during the 
acclimatization period.
13. Subject takes daily doses of a medication which, in the opinion of the investigator or 
medically qualified designee, is causing xerostomia.
14. Subject requires antibiotic prophylaxis for dental procedures.
15. Subject has had professional tooth de-sensitising treatment within 8 weeks of Screening 
(Visit 1).
16. Subject has had a tooth bleaching procedure within 8 weeks of Screening (Visit 1).
17. Subject has had dental prophylaxis within 4 weeks of Screening (Visit 1).
18. Subject has had treatment for periodontal disease (including surgery) within 12 months of 
Screening (Visit 1).
19. Subject has had scaling or root planning within 3 months of Screening (Visit 1).
20. Subject with gross periodontal disease.
21. Subject with a tongue or lip piercing.
22. Subject with evidence of gross intra-oral neglect or the need for extensive dental therapy.
23. Subject with a fixed or removable partial prosthesis which, in the opinion of the investigator
or dentally qualified designee, could impact study outcomes.
24. Subject with multiple dental implants which, in the opinion of the investigator or dentally
qualified designee, could impact study outcomes.
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25. Subject with fixed or removable orthodontic braces/bands or a fixed orthodontic retainer.
26. SPECIFIC DENTITION EXCLUSIONS FOR ‘TEST TEETH’:
a) Tooth with evidence of current/recent caries
b) Tooth with (self-reported) treatment for decay within 12 months of Screening (Visit 1).
c) Tooth with exposed dentin and deep, defective or facial restorations.
d) Tooth with a full crown or veneer.
e) Tooth adjacent to a bridge abutment or crown which, in the opinion of the investigator
or dentally qualified designee, could impact study outcomes.
f)
Sensitive tooth with contributing etiologies other than EAR to exposed dentin.
g) Sensitive tooth not expected to benefit from use of an anti-sensitivity toothpaste, in the 
opinion of the investigator or dentally qualified designee.
27. Subject who, in the opinion of the investigator or designee, is unable to provide appropriate
responses to the LMS training questions (Appendix 15.4). 
28. Subject has previously been enrolled in this study.
29. Subject who, in the opinion of the investigator or medically qualified designee, should not 
participate in the study.
5.4
Randomization Criteria
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria. Each eligible subject will be stratified by the maximum Baseline Schiff sensitivity score 
of their two selected ‘Test Teeth’. The stratification factor will give rise to two strata.
•
Stratum 1: Maximum Schiff sensitivity score = 2.
•
Stratum 2: Maximum Schiff sensitivity score = 3.
5.5
Lifestyle Considerations
The investigator site may contact subjects to remind them of an approaching scheduled visit 
and any applicable lifestyle restrictions.
If, in the opinion of the investigator or medically qualified designee, a subject has not complied 
with a lifestyle restriction (oral hygiene, dietary or alcohol-related) prior to a study visit, every 
effort will be made to re-appoint them within the permitted visit tolerances, as defined in the 
Schedule of Activities (Table 1-1)). The reason for re-appointment will be documented in the 
electronic case report form (eCRF).
If re-appointment is not possible, the following visit specific actions should be taken.
•
Baseline (Visit 2): the subject will be withdrawn from the study (Section 7.1). No 
clinical assessments will be performed. The subject may be replaced.
•
Day 28 (Visit 3): the subject will continue in the study. No clinical assessments will be 
performed.
•
Day 56 (Visit 4): 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: From Screening (Visit 1) to the Subject’s Last Visit
•
Subjects should not use any other oral care products (e.g., toothpastes, toothbrushes, 
oral rinses, tongue cleaners, whitening/bleaching products, inter-dental cleaning 
products) than those provided during the study.
Note: Use of dental floss is permitted to remove impacted food only. 
•
Subjects should not use any other 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: From Baseline (Visit 2) to the Subject’s Last Visit
•
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 the Subject’s Last Visit
•
Subjects must not eat or drink for at least 2 hours before a clinical assessment visit.
Note: Small sips of room-temperature water are permitted to take medications or to 
relieve a dry mouth up to 1 hour before their appointment time
•
Subjects should refrain from excessive alcohol consumption for 24 hours before a 
clinical assessment visit.
5.5.3
Contraception
The study toothpastes are not contra-indicated for pregnancy or breastfeeding (their use would 
not be expected to cause harm to the mother, the foetus or a baby) and there will be no pregnancy 
warnings on the labelling of any of the study products. Thus, study-specific contraceptive 
requirements are not deemed necessary for study subjects (female or male). 
5.6
Screen Failures
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not subsequently randomized. To ensure transparent reporting of screen failure subjects, a 
minimal set of screen failure information will include demography, screen failure reason (e.g.,
withdrawal of consent), eligibility criteria, any protocol deviations and any AEs, as applicable. 
Individuals who do not meet the criteria for participation in this study (screen failure) will not 
be re-screened.
5.7
Sponsor’s Qualified Medical Personnel
Contact information for the sponsor's appropriately qualified and experienced medical/dental 
personnel or Clinical Research Scientist (CRS) for this study is documented in the Study 
Contact List located in the investigator site file held at the investigator site.
The contact number is only to be used by investigator staff seeking advice on medical/dental 
questions or problems in the event that the established communication pathways between the 
investigator site and the sponsor’s 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 qualified and experienced investigator site or sponsor 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 investigator site, and contact details in the event that the 
investigator site cannot be reached to provide advice on a medical question or problem 
identified by a healthcare professional other than the investigator.
5.8
Rater/Clinical Assessor Qualifications 
The examiner responsible for the clinical efficacy measures will be a qualified dental hygienist
trained in the clinical assessment of DH (tactile and/or evaporative (air) sensitivity). 
The oral (OST and OHT) examinations will be completed by a qualified dentist, or a dental 
hygienist, as needed.  
6
INVESTIGATIONAL/STUDY PRODUCTS
For the purposes of this study, per ICH guidelines and sponsor 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 subject according to the study protocol. This 
includes a product with a marketing authorization when used or assembled (formulated or 
packaged) in a way different from the approved form, or when used for an unapproved 
indication, or when used to gain further information about an approved use. 
6.1
Study Product Supplies
Each subject will receive sufficient tubes of the acclimatization toothpaste and their assigned 
investigational toothpaste to cover usage during the acclimatization and treatment periods, 
respectively. The following study products (acclimatization and investigational toothpastes) 
will be supplied by the sponsor’s Clinical Supplies department (Table 6-1).
The toothpaste usage instructions are consistent with the proposed labelling for the Test 
Toothpaste, when marketed, and with the commercial pack instructions for the Reference and 
Acclimatization Toothpastes.
Table 6-1
Acclimatization/Investigational Toothpastes
Description
Acclimatization
Toothpaste
Test 
Toothpaste
Reference Toothpaste 
(Negative Control)
Product Name
Regular fluoride 
toothpaste
(Colgate Cavity 
Protection*)
0.454 % w/w SnF2
toothpaste
Regular fluoride 
toothpaste
(Crest Cavity Protection*)
Fluoride Level
1000 ppm fluoride†
1100 ppm fluoride¥
1100 ppm fluoride≠
Master 
Formulation Code 
N/A
N/A
Dispensing Details
One carton containing 
2 tubes of toothpaste at 
Screening (Visit 1)
One carton containing 4 over-wrapped tubes of 
toothpaste at Baseline (Visit 2)
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Route of 
Administration
Topical Oral Use
Toothpaste Usage 
Instructions
Dose the toothbrush with a ribbon of toothpaste, across the full brush head.
Start the timer (pre-set for 1-minute). 
Brush the entire 
dentition thoroughly 
for at least 1-timed 
minute, twice daily 
(morning & evening).
Brush the entire 
dentition thoroughly for 
at least 1-timed minute, 
twice daily (morning & 
evening), making sure to 
brush the sensitive areas 
of the two 'Test teeth' 
carefully first.
Brush the entire 
dentition thoroughly 
for at least 1-timed 
minute, twice daily 
(morning & evening).
Subjects who wish to rinse after brushing will be instructed to rinse with 
10 ml water using graduated rinsing cup provided.
Duration of 
Treatment
Approximately 8 weeks (56 ± 3 days)
Return 
Requirements
All used/unused tubes to be returned to the sponsor
* Commercially available daily use, regular fluoride toothpaste, US market.  
† As sodium monofluorophosphate   ¥ As SnF2    ≠As NaF  
Sufficient supplies of the following sundry items (Table 6-2) will be supplied to complete the 
study by the sponsor’s Clinical Supplies department (to be dispensed by site staff, as required).
Table 6-2
Sundry Items
Item
Pack Design
Dispensing Details
Return/Disposal Details
Used Samples
Unused 
Samples
Oral B Sensi-Soft
(US market)
Manual, flat trim, 
medium toothbrushes
One toothbrush in 
its commercial 
pack 
Screening (Visit 1): 
One toothbrush
Baseline (Visit 2): 
One toothbrush
Destroy at site 
using site disposal 
procedures.
Return to 
sponsor
Countdown 
Timers
One timer in its 
commercial pack 
Screening (Visit 1): 
One timer
Subject to keep or 
destroy at site 
using site disposal 
procedures.
Graduated 
Rinsing Cups
N/A
Screening (Visit 1): 
4 cups
Baseline (Visit 2): 
8 cups
Subject to keep or 
destroy at site 
using site disposal 
procedures.
Opaque Carrier 
Bags
N/A
Screening (Visit 1): 
One bag
Baseline (Visit 2): 
One bag
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Detailed instructions for the return of study products and sundry supplies for accountability 
checks and subsequent destruction will be provided by the sponsor at Site Initiation and prior 
to study close out.
6.1.1
Medical Devices
The medical device provided by the sponsor for use in this study is the manual toothbrush (Oral 
B Sensi-Soft toothbrush, US market) to be used to apply the study products by twice daily 
toothbrushing. The device will be supplied to study subjects in its commercial pack; usage 
instructions will be consistent with the commercial pack instructions.
Device deficiencies, (including malfunction, use error and inadequate labelling) will be 
documented and reported by the investigator throughout the study and appropriately managed 
by the sponsor (see Section 10.10). The device does not include any medicinal, human or animal 
or biologically active materials. 
6.1.2
Dosage Form and Packaging
The study products are toothpastes. They are intended for topical oral use and will be applied 
using a manual toothbrush. 
The investigational toothpastes will be provided to the investigator site in laminate tubes, 
overwrapped in white vinyl (to mask their identity, and to obscure any branding, images and 
text on the commercial pack of the Reference Toothpaste) with a study label affixed. The 
acclimatization toothpaste will be supplied in its commercial pack, without overwrapping, 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 sponsor’s Clinical Supplies 
department. Each study label will contain (but not be limited to) the protocol number and 
storage requirements.
Care should be taken to ensure all supplied study product is maintained in good condition.  It is 
important that all product labels remain intact and legible for the duration of the study. Subjects 
should be instructed to not remove or deface any part of the study label.
Study products will be received at site by members of the investigator team responsible for 
product administration. These individuals will not be involved in any safety or efficacy 
assessments or any other aspect of the study that could be influenced by knowledge of the 
investigational toothpaste a subject has been assigned to.
Study products supplied are for use in this clinical study only and should not be used for any 
other purpose.
6.1.3
Product Dispensing 
Subjects will be assigned to investigational toothpaste in accordance with the randomization 
schedule generated by a sponsor-approved vendor, prior to the start of the study, using validated 
software.
The product dispensing area(s) will be separate from the clinical examination area(s). 
Investigational toothpastes will be dispensed to the subject, per protocol, in blinded fashion by 
trained study personnel. These staff members will not be involved in any safety or clinical 
efficacy assessments or any other aspect of the study that could be influenced by knowing which 
product a subject has been assigned to. An additional member of the dispensing staff will verify 
the dispensing procedure has been completed correctly for each subject. 
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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 eCRF.
6.2
Administration
Only subjects enrolled in the study may receive study products and only authorized site staff 
may supply and administer study products. All study interventions must be stored in a secure, 
environmentally controlled, and monitored (manual or automated) area in accordance with the 
product label storage conditions with access limited to the authorized site staff only.
Subjects will self-administer the acclimatization toothpaste (from Visit 1 to Visit 2) and their 
assigned investigational toothpaste (from Visit 2 to Visit 4) according to the usage instructions 
provided by the dispensing staff at the investigator site and as described in their diary. Subjects 
will be instructed to record each brushing with study product in their diary. 
To help ensure subjects fully understand the amount of toothpaste to use, the brushing 
instructions and how to complete the diary: 
•
Screening (Visit 1): Staff will demonstrate dispensing a full ribbon of toothpaste along 
the length of the toothbrush head to each enrolled subject and supervise their first timed 
brushing with the acclimatization toothpaste and diary completion at the end of the visit, 
after all clinical assessments have been completed. 
•
Baseline (Visit 2): Staff will supervise the dispensing of a full ribbon of toothpaste by 
each randomized subject and supervise the first timed brushing with their assigned 
investigational toothpaste and diary completion. Staff will show each subject 
randomized to Test Toothpaste the location of their ‘Test Teeth’ and confirm the subject 
can correctly locate the two ‘Test Teeth’ themselves, prior to starting their on-site timed 
brushing.
•
Day 28 (Visit 3): Staff will supervise each subject brushing with their assigned 
investigational toothpaste and completing their diary at the end of the visit, after all 
clinical assessments have been completed. Staff will check that subjects randomized to 
Test Toothpaste can correctly identify their ‘Test Teeth’ prior to starting their on-site 
timed brushing. If a subject cannot correctly identify their two ‘Test Teeth’, they will 
be re-instructed in their location and a deviation will be recorded.
On-site administration of study products will be recorded in the dispensing log and the eCRF.
6.2.1
Medication/Dosing Errors
In this study, dosing errors may result from the administration or use of the wrong study product,
by the wrong subject, at the wrong time, in the wrong way. Such dosing errors should be 
captured in the eCRF.
Dosing errors are reportable irrespective of the presence of an associated AE, including:
•
Dosing errors involving subject exposure to any of the study products.
•
Potential dosing errors or uses outside of what is foreseen in the protocol that do or do 
not involve the participating subject.
If a dosing error is accompanied by an AE, as determined by the investigator or medically 
qualified designee, the dosing error and any associated AEs are to be recorded in the eCRF. 
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6.2.2
Overdose
An overdose is a deliberate or inadvertent administration of a study product at an amount higher 
than specified in the protocol. Overdose is not likely to occur in this study.
Overdose per se is not an AE. However, any clinical sequelae of an overdose should be reported 
as an AE (or serious adverse event (SAE), as appropriate) per protocol following 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 that 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 the required storage conditions, in accordance with applicable 
regulatory requirements and the product label.  
Investigator site systems must be capable of measuring and documenting (e.g., via a log), as a 
minimum, daily minimum and maximum temperatures for all study product storage locations 
(including frozen, refrigerated, and/or room-temperature products).  This should be captured 
from the time of first product receipt throughout the study.  For continuous monitoring systems, 
a log or site procedure that ensures active daily evaluation for excursions should be in place.  
The operation of temperature-monitoring devices and temperature-controlled storage units
(e.g., refrigerators) should be regularly inspected to ensure they are 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 investigator site 
should actively pursue options for returning the study product to the storage conditions 
described on its label as soon as possible.  Excursions from 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 study product (or products) must be quarantined 
and not used until the sponsor provides documentation of permission to use. Use of any of the 
affected study 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 study 
products, in accordance with the label requirements. 
6.4
Study Product Accountability
Study products are supplied for use in this clinical study only and should not be used for any 
other purpose. The investigator is responsible for study product accountability, reconciliation, 
and record maintenance. 
Study products must be received by designated personnel at the investigator site, handled and 
stored safely and properly, and kept in a secured location to which only authorized staff have 
access. Upon receipt, each study product should be stored in accordance with the instructions 
specified on the product label. 
Study products will be dispensed to enrolled/randomized subjects only, in accordance with the 
protocol, by authorized site staff. Subjects will return all used/unused tubes of acclimatization 
toothpaste to the investigator site at their Baseline visit (Visit 2). Subjects will bring all
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used/unused tubes of their assigned investigational toothpaste to each of their scheduled visits 
to the investigator site (per Schedule of Activities, Table 1-1) and return all used/unused study 
product to the investigator site at study conclusion. Returned study products should not be re-
dispensed to any subject.
The investigator site must maintain adequate records (e.g., product accountability forms) 
documenting the receipt, use, loss, return or other disposition of all study product and supplies. 
Accountability records must be available for inspection by the study monitor during the study. 
Product accountability will be monitored during investigator site visits and on the completion 
of the study, as required by the study monitoring plan. 
6.4.1
Destruction of Study Product Supplies 
At the end of the study, the investigator or an appropriate designee and the sponsor’s
representative (study monitor) will inventory all used and unused study products and the study 
product accountability record for returned study products will be completed. 
All study product (used and unused) for this clinical study will be returned to the sponsor or 
designated vendor for destruction using the return instructions provided by the sponsor’s 
Clinical Supplies Department. 
Unused sundry items will be returned to the sponsor; used items will be disposed of at the 
investigator site as described in Section 6.1 (Table 6.2). Documented approval for disposal of 
used sundry items must be received from the sponsor’s Clinical Supplies Department prior to 
destruction.
Detailed instructions for the return of study products and the destruction of sundry items, will 
be provided by the sponsor prior to the study close out visit.
6.5
Blinding and Allocation/Randomization
Qualifying subjects will be centrally randomized to one of two investigational toothpastes using 
an Interactive Response Technology (IRT). Before the study is initiated, training, login 
information and directions for the IRT will be provided to the investigator site. Investigational 
toothpaste will be dispensed according to the instruction received through the IRT at the 
Baseline visit (Visit 2). Returned study products should not be re-dispensed to any subject.
Only subjects who meet the study selection criteria will be randomized to treatment. Qualifying 
subjects will be stratified by the maximum Baseline Schiff sensitivity score of their two selected 
‘Test Teeth’; this stratification factor will give rise to two strata.
•
Stratum 1: Maximum Schiff sensitivity score = 2.
•
Stratum 2: Maximum Schiff sensitivity score = 3.
This study is described as examiner-blind (the clinical examiner(s) will be blinded to treatment
received). However, study subjects, investigator site staff involved in safety or efficacy 
assessments, study statistician(s), data management staff, other employees of the Sponsor 
(including the CRS) and vendors acting on behalf of the sponsor who may influence study 
outcomes will also be blinded to treatment allocation. Monitors and the sponsor’s Clinical Study 
Manager (CSM) cannot be fully blinded as they may observe subjects brushing with their 
allocated treatment while at the investigator site.
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As described in Section 4.2, to maintain the blind throughout the study:
•
Study subjects will see and use only one of the two investigational toothpastes for the 
duration of the treatment period. They will be instructed not to discuss the appearance, 
usage or perceived performance of their assigned investigational toothpaste with the 
clinical examiner(s), with staff involved in clinical assessments or with other study 
subjects. 
•
The investigational toothpastes will be provided to the investigator site overwrapped in 
white vinyl to mask their identity, and to obscure any branding on the Reference 
Toothpaste, with a study label affixed.
•
The investigational toothpastes will be supplied in cartons; each carton will contain 4 
over-wrapped tubes of toothpaste. The carton and its 4 tubes will be labelled with the 
same unique randomization number. Subjects will be centrally randomized to treatment
in order of qualification using an IRT; product codes will not be used.
•
The clinical examiner(s) and site staff involved in efficacy and safety assessments will 
not be permitted in any area where the investigational toothpastes or diaries are stored, 
dispensed or in use.
•
Site staff involved in the dispensing of investigational toothpastes, providing brushing 
and diary completion instruction, supervision of on-site brushings, treatment 
compliance checks and product accountability will not be involved in clinical efficacy 
and safety assessments and will work in a separate area from the clinical examiner(s) 
and investigator staff involved in efficacy and safety assessments.
•
Subjects will be instructed not to remove their assigned investigational toothpaste or 
diary from the opaque carrier bag provided outside of the dispensing/supervised
brushing room, while at the investigator site.
•
Where certain staff will be unblinded to carry out their responsibilities (e.g., staff
involved in SAE reporting, monitors), the investigator and sponsor are required to put
adequate procedures in place to prevent inappropriate dissemination of treatment 
identification.
6.6
Breaking the Blind
At study initiation, the investigator site will be instructed on the method for breaking the blind; 
this will be an electronic process.
The electronic system will be programmed with blind-breaking instructions. In case of an 
emergency, the investigator has sole responsibility for determining if the unblinding of the
subject’s treatment assignment is warranted. Subject safety must always be the first 
consideration in making such a determination. If the investigator decides that unblinding is 
warranted, they should make every effort to contact the sponsor prior to unblinding the subject’s 
treatment assignment unless this would delay emergency treatment of the subject.
Once treatment assignment is unblinded, the sponsor must be notified within 24 hours of
breaking the blind. The date and reason for breaking the blind must be recorded in source 
documentation and the eCRF, as applicable. The investigator site may also be required be 
required to inform the IRB if the blind is broken. 
Any AE associated with breaking the blind must be recorded and reported per protocol. 
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6.7
Compliance
Diaries will be supplied to promote compliance and to capture details of study product use 
throughout the study period. Each subject will be provided with three diaries, one at Screening 
(Visit 1), one at Baseline (Visit 2) and one at Day 28 (Visit 3), to record each brushing with the 
acclimatization and investigational toothpastes. The diaries will also provide product usage 
instructions for the subject to refer to throughout their participation in the study.
•
Subjects will be instructed to note any missed/additional brushings and the reasons for 
missed/additional brushings in the diary.
•
Subjects will also be instructed to record additional information in the diary such as 
changes in health, oral problems, changes in medications/treatments, new medications/
treatments and any issues with the toothpaste they are using in the diary. 
Subjects will be instructed to bring their completed diary to each scheduled study visit. 
Completed diaries will be reviewed by investigator staff at the start of each study visit (to 
maintain the blind, staff performing diary reviews should not be involved in any safety or 
efficacy assessments). Any missed or additional brushings will be recorded in the eCRF as 
protocol deviations and subjects will be re-instructed in correct product usage requirements and 
diary completion, as needed.
Information recorded in the diary relating to changes in health, medications and treatments will
be reviewed by the investigator, or medically qualified designee, with the subject and 
transcribed into the eCRF, as appropriate (e.g., as an AE). Information related to product use or 
issues should also transcribed into the eCRF, as needed, taking care to maintain the blind.
Subjects will be instructed to bring all tubes of study product (used and unused) and their
toothbrush to each scheduled study visit. Study staff will perform a visual check of product 
usage and toothbrush condition. Any suspected over or under use will be documented in the 
eCRF and the subject will be re-instructed in the correct usage requirements. 
To confirm the subject understands the usage instructions provided at Screening (Visit 1) and 
Baseline (Visit 2), their first use of study product (acclimatization toothpaste and investigational
toothpaste, respectively) will be supervised on-site. To facilitate compliance, a further 
supervised brushing will be completed on-site at the end of Visit 3 (Day 28). Subjects deemed 
non-compliant with any aspect of the usage requirements or diary completion will be re-
instructed in correct procedure. Any deviation from protocol requirements will be recorded in 
the eCRF.
6.8
Concomitant Medication/Treatment
Any medications, treatments or vaccines (including over-the-counter or prescription medicines, 
vitamins and/or herbal supplements) taken or received during the study, from the signing of
informed consent, must be recorded in the eCRF with indication, reason for use, unit dose, daily 
dose and start/stop dates of administration. Subjects will be questioned about changes in their 
medications/treatments at the start of each study visit.
Medications and treatments taken or received in the 30 days prior to signing the informed 
consent will be documented as prior medication/treatment. Medications and treatments taken 
or received after signing the informed consent will be documented as concomitant 
medication/treatments. 
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For the Duration of the Study: Screening (Visit 1) to the Subject’s Last Study Visit 
•
Subjects should delay any non-emergency, elective dental treatments until after study 
completion (including dental prophylaxis). 
•
Should an enrolled/randomized subject start a course of treatment which includes daily, 
regular or intermittent use of any medication, details of that treatment will be recorded 
in the eCRF. The investigator or their medically qualified designee will decide if the 
subject should continue in 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 the subject’s perception of pain (e.g., 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. The medication and 
any associated AE should be recorded in the eCRF.
If re-appointment is not possible, the following visit specific actions should be taken:
-
Screening (Visit 1): The subject will be withdrawn from the study. No tooth 
sensitivity assessments will be performed. The subject may be replaced.
-
Baseline (Visit 2): The subject will be withdrawn from the study. No tooth 
sensitivity assessments will be performed. The subject will not be replaced. 
-
Day 28 (Visit 3) & Day 56 (Visit 4): The subject 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 investigational product for the duration of this study.
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 
from the study at any time at the discretion of the investigator or the sponsor for safety or
behavioral reasons, or due to the inability of the subject to comply with the protocol-required 
schedule of study visits or procedures.  
The following circumstances will require discontinuation of study product and/or premature 
subject withdrawal.
•
Protocol violation that could impact the subject’s safety
•
Withdrawal of informed consent
•
Subject lost to follow-up 
•
Unblinding of the subject 
•
Pregnancy
If a subject is discontinued or prematurely withdraws from the study, the reason(s) for 
discontinuation or withdrawal, and the associated date, must be documented in the eCRF. 
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7.2
Lost to Follow Up
If a subject fails to return to the investigator site for a required study visit, the investigator staff
must attempt to contact the subject, reschedule the missed visit as soon as possible, 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 attend scheduled visits 
and cannot be contacted by the study staff. Before the subject is deemed lost to follow up, the 
investigator or designee must make every effort to regain contact with them (where possible
three telephone calls and, if necessary, a certified letter to the subject’s last known mailing 
address or equivalent local methods). Each contact attempt should be documented. If contact is 
made, the investigator or designee should inquire about the reason for their withdrawal, request 
that the subject return all products provided and, if appropriate, request that the subject return 
for a final visit and follow-up any unresolved AEs. Final safety assessments may be carried out 
when the subject returns to the investigator site, at the investigator’s discretion, which may 
include 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. This will be documented in the eCRF. Lack of completion of 
all or any of the early termination procedures will not be viewed as protocol deviations provided
subject safety was preserved.
If the subject withdraws from the study and withdraws consent for disclosure of future 
information, no further evaluations should be performed, and no additional data should be 
collected.  The sponsor may retain and continue to use any data collected before the withdrawal 
of consent.
8
STUDY PROCEDURES
This section lists the procedures to be completed at each scheduled study visit.  The timing of 
each procedure is listed in the Schedule of Activities (Table 1-1). Adherence to the study design 
requirements, including all procedures is essential and required for study conduct.
8.1
Visit 1 / Screening
Screening procedures will be conducted by the investigator, the clinical examiner(s) or suitably 
qualified/experienced and trained designees, 14-28 days prior to the Baseline visit (Visit 2).
Where practically feasible, they should be completed in the order listed below. Data collected 
will be recorded in the eCRF.
8.1.1.1
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. 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.  Subjects will be provided 
with an ingredients list for the products to be used in the study 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 
investigator or designee will also sign and date each copy of the ICF, after the subject has 
signed, to confirm that the consent process was completed correctly. The subject will retain one 
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copy and the other will be kept at the investigator site. The time of consent will also be captured 
on the ICF; AEs will be captured from this point. The date and time of consent will be recorded 
in the eCRF. Appropriate forms for documenting informed consent will be provided by the 
investigator or by the sponsor.
If new information becomes available during the conduct of the study that might affect subject 
willingness to participate in the study, each ongoing subject should receive a verbal explanation 
and written summary of the new information and be re-consented into the study. Each subject 
will be provided with a copy of their signed/dated amended ICF. Date of re-consent will be 
recorded in the eCRF.
After signing the ICF, each subject will undergo a series of screening procedures and clinical 
assessments to confirm that they meet the protocol required inclusion criteria and none of the 
exclusion criteria. 
8.1.2
Demographics
The following demographic information will be recorded in the eCRF: year of birth, gender, 
race and ethnicity.
8.1.3
Review of Oral Care Products
Subjects will be required to bring their current oral care products to Screening (Visit 1) for 
investigator staff to confirm the absence of known anti-sensitivity ingredients and sensitivity-
related claims on the product packaging/label text. Subjects who are currently using anti-
sensitivity oral care product(s) will be excluded.
Subjects will also be asked about the oral care products they have been using in the last 8 weeks; 
those who report using anti-sensitivity product(s) in the 8 weeks prior to Screening will be 
excluded.
8.1.4
Medical History and Prior Medications/Treatments
The following will be documented in the eCRF:
•
Details of relevant medical history and recent surgery (within the last year), including 
allergies and drug sensitivities.
•
Female subjects: pregnancy status (self-reported).
•
Prior medications/treatments, including prescription and non-prescription drugs, dietary 
supplements and herbal remedies, taken in the 30 days prior to Screening.
8.1.5
Clinical Examinations and Assessments
In preparation for LMS completion at Visits 2-4, each subject will complete the LMS Training 
Exercise (source), see Appendix 15.4 (training exercise responses will not be transcribed in to 
the eCRF). Any subject who, in the opinion of the investigator or designee, is unable to provide 
appropriate responses to the LMS training questions, will be excluded from participation in the 
study (Section 5.3 Exclusion Criterion 27).
The following clinical examinations and DH assessments will be completed as described in 
Study Assessments (Section 9) and the findings recorded in the eCRF. To facilitate subject flow, 
source documents can be used to record clinical data for later transcription into the eCRF. 
Transcription into the eCRF must be completed within 5 days of recording the data for each 
subject.
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•
Oral soft tissue (OST) examination
•
Oral hard tissue (OHT) examination 
•
Clinical assessment of incisors, canines and pre-molars for dentition exclusions, erosion 
abrasion and attrition (EAR), Modified Gingival Index (MGI), adjacent to the test area 
only, and clinical mobility to identify appropriate teeth for DH assessment.
•
Clinical assessment of tactile sensitivity (tactile threshold (g); maximum force 20g):
Assess all teeth with no dentition exclusions (Section 5.3 Exclusion Criterion 26) which
meet EAR, MGI and tooth mobility requirements (Section 5.2 Inclusion Criteria 6(c)).
Ensure at least a 5-minute break between completing the tactile assessments and 
starting the evaporative (air) assessments.
•
Clinical assessment of evaporative (air) sensitivity (Schiff sensitivity score):
Assess each tooth with a Screening tactile threshold of ≤ 20g.
Subjects must have a minimum of two ‘Eligible Teeth’ in different quadrants to continue
in the study (Section 5.2 Inclusion Criterion 6c); ‘Eligible Teeth’ must have a Screening 
tactile threshold ≤ 20g and a Screening Schiff sensitivity score ≥ 2
Subjects with fewer than two ‘Eligible Teeth’ will be discontinued.
8.1.6
Inclusion/Exclusion Criteria
Information relating to inclusion/exclusion criteria will be completed in the eCRF.
8.1.7
Subject Eligibility
The investigator or medically qualified designee will review the medical history, prior 
medications/treatments, clinical examination/assessment data and the inclusion/exclusion 
criteria for each subject to determine their eligibility to participate in the study. The eligibility
decision will be documented in the eCRF.
If confirmed as eligible to participate, the subject will be considered enrolled in the study.
To prepare for study participation, enrolled subjects will be instructed in the Lifestyle 
Guidelines (Section 5.5) and Concomitant Medications/Treatments (Section 6.8) requirements 
of the study (as already detailed in the ICF and described during the consent process). 
Adherence to the requirements of the study protocol is essential for successful study conduct.
8.1.7.1
Supervised Brushing with Acclimatization Toothpaste
Enrolled subjects will be provided with the acclimatization toothpaste, a toothbrush, a timer, 
rinsing cups and a diary to use during the acclimatization period. 
Dispensing staff will describe the toothpaste usage instructions to the subject, demonstrate 
covering the full brush head with a ribbon of toothpaste and how to use the timer. Staff will 
then supervise the subject carrying out their first timed brushing with the acclimatization 
toothpaste and recording first use in their diary. Any deviation from the product usage 
instructions will be captured as a protocol deviation in the eCRF and the subject will be re-
instructed in the correct directions for use. Dispensing of the acclimatization toothpaste and 
completion of the supervised first brushing will be documented in the eCRF. 
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Spontaneously reported AEs and any AEs elicited by asking the subject to respond to non-
leading questions (such as ‘how do you feel?’) on completion of the supervised brushing will 
be recorded in the eCRF.
Dispensing staff will remind subjects to note any changes in their health, medications or 
treatments in the diary (or report such changes to the investigator staff between visits using the 
contact numbers provided or inform staff at their next visit, if preferred) and to bring their 
acclimatization toothpaste, toothbrush and completed diary to their next study visit.
8.2
Study Period
8.2.1
Visit 2 / Baseline (Day 0)
The following procedures and assessments will be completed by the investigator, the clinical 
examiner(s) or a suitably qualified/experienced and trained designee. Where practically 
feasible, the procedures and assessments should be completed in the order listed below. All data 
collected will be recorded in the eCRF.
8.2.1.1
Compliance Checks
Dispensing staff will complete visual checks of the returned acclimatization toothpaste and the 
toothbrush and review the completed diary to assess compliance.
Suspected over or under use and the number of missed or additional brushings will be recorded 
in the eCRF. Any deviation from the required usage instructions will be captured as a protocol 
deviation in the eCRF and subjects will be re-instructed in the correct usage.
Do not return the acclimatization toothpaste, toothbrush or completed diary to the subject.
8.2.1.2
Changes in Medical History and Concomitant Medications/Treatments
Investigator staff will ask subjects if there have been any changes in their health, concomitant 
medications and non-drug treatments; female subjects of child-bearing potential will self-report 
pregnancy status. All changes will be documented in the eCRF. 
Spontaneously reported AEs and any AEs elicited during questioning about changes in health 
or by asking subjects to respond to non-leading questions (such as ‘how do you feel?’) will 
recorded in the eCRF. AEs and/or changes in medications/treatments identified during review 
of the diary will be recorded in the eCRF.
8.2.1.3
Subject Adherence and Continuance
Investigator staff will question subjects about adherence to the requirements of the protocol; 
any deviations from study requirements will be recorded in the eCRF. Subject continuance will 
be confirmed.
8.2.1.4
Subject-Reported Outcomes
Prior to commencing the OST examination and DH assessments, each subject will 
independently (without supervision) complete a hard copy of the DHEQ-48 (source), Sections 
1 and 2 (i.e., all questions in both sections), see Appendix 15.2. Subject responses will be 
transcribed in to the eCRF.
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8.2.1.5
Clinical Examinations and Assessments
The following clinical examination and DH assessments will be completed as described in 
Study Assessments (Section 9). To facilitate subject flow, source documents can be used to 
record clinical data for later transcription into the eCRF.
•
OST examination
•
Clinical assessment of tactile sensitivity (tactile threshold (g); maximum force 20g):
Assess each ‘eligible tooth’ identified at Screening (Screening tactile threshold of ≤ 20g 
and a Screening Schiff sensitivity score ≥ 2).
Ensure at least a 5-minute break between completing the tactile sensitivity assessments 
and starting the evaporative (air) sensitivity assessments.
•
Clinical assessment of evaporative (air) sensitivity (Schiff sensitivity score):
-
First assess each tooth with a Baseline tactile threshold of ≤ 20g.
-
Subject will complete the four LMSs (Intensity, Duration, Tolerability &
Description) for each tooth with a Baseline Schiff sensitivity score ≥ 2 immediately 
after the Schiff sensitivity score for that tooth is recorded.
-
When Schiff sensitivity scores have been recorded, and LMSs completed, for all 
teeth with a Baseline tactile threshold of ≤ 20g, then assess Schiff sensitivity score 
for any remaining ‘Eligible Teeth’ identified at Screening (i.e., the ‘Eligible Teeth’ 
with a Baseline tactile threshold >20g).
‘Eligible Teeth’ = Teeth with no dentition exclusions which met EAR, MGI and mobility inclusion 
criteria, with a Screening tactile threshold ≤ 20g and a Screening Schiff sensitivity score ≥ 2.
Note: LMSs should not be completed for the remaining ‘Eligible Teeth’.
Subjects must have at least two ‘qualifying teeth’, in different quadrants, with a tactile 
threshold ≤ 20g and a Schiff sensitivity score ≥ 2 at both Screening and Baseline to
continue in the study Section 5.2 Inclusion Criterion 7.
Subjects with fewer than two ‘qualifying teeth’ will be discontinued.
Transcription of data from source documents into the eCRF must be completed within 5 days 
of recording the data for each subject.
8.2.1.6
Selection of Test Teeth
The clinical examiner responsible for evaporative (air) assessments will select two ‘Test Teeth’ 
for assessment of both tactile and evaporative (air) sensitivity at all subsequent study visits. 
‘Test Teeth’ should only be selected from teeth which met the EAR, MGI and tooth mobility 
requirements and had no dentition exclusions at Screening, with the required qualifying levels 
of DH at both Screening (Visit 1) and Baseline (Visit 2):
•
Tactile threshold ≤ 20g at Screening and Baseline.
•
Schiff sensitivity score ≥ 2 at Screening and Baseline.
To be representative of different areas of the mouth with independent innervation, ‘Test Teeth’ 
should be non-adjacent and in different quadrants. The identity of the two ‘Test Teeth’ will be 
recorded in the eCRF.
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8.2.1.7
Subject Eligibility
The investigator, or medically qualified designee, will review the inclusion/exclusion criteria 
and verify the presence of two qualifying ‘Test Teeth’ which meet all study criteria before 
confirming each subject’s suitability to continue in the study; the eligibility decision will be 
documented in the eCRF.
8.2.1.8
Stratification and Randomization
Each qualifying subject will be stratified to one of two strata as described in Section 6.5 and 
randomized to treatment. Subject stratum will be entered directly into the eCRF. 
Each subject will be assigned a randomization number from their designated stratum in 
ascending numerical order, and as each subject is determined to be fully eligible. The 
randomized toothpaste code will be entered directly into the eCRF.
8.2.1.9
Supervised Brushing with Investigational Toothpaste
Randomized subjects will be provided with their allocated investigational toothpaste, a new
toothbrush, additional rinsing cups and a new diary.
Dispensing staff will describe the toothpaste usage instructions to each subject, reminding them 
to cover the full brush head with a ribbon of toothpaste and use the timer each time they brush. 
•
Subjects randomized to the Test Toothpaste will be shown the location of their two ‘Test 
Teeth’ within the mouth (using a tooth diagram/model and a mirror, as needed).
They will be then instructed to start their timer (pre-set for 1-minute) and brush their 
entire dentition thoroughly for at least 1-timed minute, making sure to brush the 
sensitive areas of their two selected 'Test teeth' carefully first. 
•
Subjects randomized to the Reference Toothpaste will be instructed to start their timer 
(pre-set for 1-minute) and brush their entire dentition thoroughly for at least 1-timed 
minute. 
Dispensing staff will supervise each subject carrying out the first brushing with their allocated 
investigational toothpaste and recording the first use in their diary. Any deviation from the 
required product usage instructions will be captured as a protocol deviation in the eCRF and the 
subject will be re-instructed in the correct directions for use.
Dispensing of the investigational toothpaste and completion of the supervised first brushing 
will be documented in the eCRF. 
Spontaneously reported AEs and any AEs elicited by asking the subject to respond to non-
leading questions (such as ‘how do you feel?’) on completion of the supervised brushing will 
be recorded in the eCRF.
Dispensing staff will remind subjects to note any changes in their health, medications or 
treatments in the diary (or report such changes to the investigator staff between visits using the 
contact numbers provided or inform staff at their next visit, if preferred) and to bring their 
investigational toothpaste, toothbrush and completed dairy to their next study visit.
Randomized subjects will also be re-instructed in the Lifestyle Guidelines (Section 5.5) and 
Concomitant Medications/Treatments (Section 6.8) requirements of the study. 
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8.2.2
Visit 3 / Day 28 (± 2 days)
The following procedures and assessments will be completed by the investigator, the clinical 
examiner(s) or a suitably qualified/experienced and trained designee. Where practically 
feasible, the procedures and assessments should be completed in the order listed below. All data 
collected will be recorded in the eCRF.
8.2.2.1
Compliance Checks
Dispensing staff will complete visual checks of the returned investigational toothpaste and
toothbrush and review the completed diary to assess compliance.
Suspected over or under use and the number of missed or additional brushings will be recorded 
in the eCRF. Any deviation from the required usage instructions will be captured as protocol 
deviations in the eCRF and subjects will be re-instructed in the correct usage.
Return the investigational toothpaste and toothbrush to the subject. Retain the completed 
diary.
8.2.2.2
Changes in Medical History and Concomitant Medications/Treatments
Investigator staff will ask subjects if there have been any changes in their health, concomitant 
medications and non-drug treatments; female subjects of child-bearing potential will self-report 
pregnancy status. All changes will be documented in the eCRF. 
Spontaneously reported AEs and any AEs elicited during questioning about changes in health 
or by asking subjects to respond to non-leading questions (such as ‘how do you feel?’) will 
recorded in the eCRF.
AEs and/or changes in medications/treatments identified during review of the diary will be 
recorded in the eCRF.
8.2.2.3
Subject Adherence and Continuance
Investigator staff will question subjects about adherence to the requirements of the protocol; 
any deviations from study requirements will be recorded in the eCRF. Subject continuance will 
be confirmed.
8.2.2.4
Subject-Reported Outcomes
Prior to commencing the clinical examinations and DH assessments, each subject will 
independently (without supervision) complete a hard copy of the DHEQ-48 (source), Section 1 
Questions 7-9 only and Section 2 all questions (see Appendix 15.2). Subject responses will be 
later transcribed into the eCRF.
8.2.2.5
Clinical Examinations and Assessments
The following clinical examination and DH assessments will be completed as described in 
Study Assessments (Section 9). To facilitate subject flow, source documents can be used to 
record clinical data for later transcription into the eCRF.
•
OST examination
•
Clinical assessment of tactile sensitivity (tactile threshold (g); maximum force 80g):
Assess the two ‘Test Teeth’ only.
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Ensure at least a 5-minute break between completing the tactile sensitivity assessments 
and starting the evaporative (air) sensitivity assessments.
•
Clinical assessment of evaporative (air) sensitivity (Schiff sensitivity score):
-
First assess the two ‘Test Teeth’.
-
Subject will complete the four LMSs (Intensity, Duration, Tolerability &
Description) for each ‘Test Tooth’ immediately after the Schiff sensitivity score 
for that tooth is recorded.
-
When Schiff sensitivity scores have been recorded, and LMSs completed, for both 
‘Test Teeth’, then assess Schiff sensitivity score for any remaining ‘Eligible Teeth’, 
as identified at Screening (do not re-assess the two ‘Test Teeth’).
‘Eligible Teeth’ = Teeth with no dentition exclusions which met EAR, MGI and mobility inclusion 
criteria, with a Screening tactile threshold ≤ 20g and a Screening Schiff sensitivity score ≥ 2.
Note: LMSs should not be completed for the remaining ‘Eligible Teeth’.
Transcription of data from source documents into the eCRF must be completed within 5 days 
of recording the data for each subject.
8.2.2.6
Supervised Brushing with Investigational Toothpaste
Dispensing staff will visually check the condition of the subject’s toothbrush. If it is damaged, 
a new toothbrush should be provided; supply of a replacement toothbrush will be documented 
in the eCRF. Each subject will be provided with a new diary.
Dispensing staff will re-describe the toothpaste usage instructions to each subject (reminding 
them to cover the full brush head with a ribbon of toothpaste and use the timer each time they 
brush) and then supervise each subject completing an on-site brushing with their allocated 
investigational toothpaste and recording this use in their diary. 
Dispensing staff will ask subjects randomized to the Test Toothpaste to indicate the location of 
their two ‘Test Teeth’ in the mouth (before they start brushing) and confirm the subject brushes
these teeth first, prior to brushing their entire dentition.
Any deviation from the required product usage instructions will be captured as a protocol 
deviation in the eCRF and the subject will be re-instructed in the correct directions for use.
Completion of each supervised on-site brushing will be documented in the eCRF. 
Spontaneously reported AEs and any AEs elicited by asking the subject to respond to non-
leading questions (such as ‘how do you feel?’) on completion of the supervised brushing will 
be recorded in the eCRF.
Dispensing staff will remind subjects to note any changes in their health, medications or 
treatments in the diary (or report such changes to the investigator staff between visits using the 
contact numbers provided or inform staff at their next visit, if preferred) and to bring their 
investigational toothpaste, toothbrush and completed diary to their next study visit.
Randomized subjects will also be re-instructed in the Lifestyle Guidelines (Section 5.5) and 
Concomitant Medications/Treatments (Section 6.8) requirements of the study. 
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8.2.3
Visit 4 / Day 56 (± 3 days)
The following procedures and assessments will be completed by the investigator, the clinical 
examiner(s) or a suitably qualified/experienced and trained designee. Where practically 
feasible, the procedures and assessments should be completed in the order listed below. All data 
collected will be recorded in the eCRF.
8.2.3.1
Compliance Checks
Dispensing staff will complete visual checks of the returned investigational toothpaste and 
toothbrush and review the completed diary to assess compliance. Suspected over or under use 
and the number of missed or additional brushings will be recorded in the eCRF. Any deviation 
from the required usage instructions will be captured as protocol deviations in the eCRF. 
Do not return the investigational toothpaste, toothbrush or completed diary to the subject.
8.2.3.2
Changes in Medical History and Concomitant Medications/Treatments
Investigator staff will ask subjects if there have been any changes in their health, concomitant 
medications and non-drug treatments; female subjects of child-bearing potential will self-report 
pregnancy status. All changes will be documented in the eCRF. 
Spontaneously reported AEs and any AEs elicited during questioning about changes in health 
or by asking subjects to respond to non-leading questions (such as ‘how do you feel?’) will 
recorded in the eCRF.
AEs and/or changes in medications/treatments identified during review of the diary will be 
recorded in the eCRF.
8.2.3.3
Subject Adherence and Continuance
Investigator staff will question subjects about adherence to the requirements of the protocol; 
any deviations from study requirements will be recorded in the eCRF.
8.2.3.4
Subject-Reported Outcomes
Prior to commencing the OST/OHT examinations and DH assessments, each subject will 
independently (without supervision) complete a hard copy of the DHEQ-48 (source), Section 1 
Questions 7-9 only, and Section 2 all questions (see Appendix 15.2). Subject responses will be 
later transcribed into the eCRF.
8.2.3.5
Clinical Examinations and Assessments
The following clinical examinations and DH assessments will be completed as described in 
Study Assessments (Section 9). To facilitate subject flow, source documents can be used to 
record clinical data for later transcription into the eCRF.
•
OST examination
•
OHT examination
•
Clinical assessment of tactile sensitivity (tactile threshold (g); maximum force 80g):
Assess the two ‘Test Teeth’ only.
Ensure at least a 5-minute break between completing the tactile sensitivity assessments 
and starting the evaporative (air) sensitivity assessments.
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•
Clinical assessment of evaporative (air) sensitivity (Schiff sensitivity score):
-
First assess the two ‘Test Teeth’.
-
Subject will complete the four LMSs (Intensity, Duration, Tolerability &
Description) for each ‘Test Tooth’ immediately after the Schiff sensitivity score 
for that tooth is recorded.
-
When Schiff sensitivity scores have been recorded, and LMSs completed, for both 
‘Test Teeth’, then assess Schiff sensitivity score for any remaining ‘Eligible Teeth’, 
as identified at Screening (do not re-assess the two ‘Test Teeth’).
‘Eligible Teeth’ = Teeth with no dentition exclusions which met EAR, MGI and mobility inclusion 
criteria, with a Screening tactile threshold ≤ 20g and a Screening Schiff sensitivity score ≥ 2.
Note: LMSs should not be completed for the remaining ‘Eligible Teeth’.
After the clinical examinations/assessments have been completed, subjects will complete a 
Satisfaction with Treatment NRS and describe (free text) why they gave their rating (Section 
9.3.4).
Transcription of data from source documents into the eCRF must be completed within 5 days 
of recording the data for each subject.
8.3
Study Conclusion
The Study Conclusion page of the eCRF will be completed for all subjects whether or not they 
complete all study procedures (i.e., even if they are discontinued early at any point during the 
study). If the subject is discontinued early, the primary reason for withdrawal should be 
recorded on the Study Conclusion page. For subjects who attend all scheduled study visits, the 
Study Conclusion page of the eCRF will be completed at Visit 4.
Investigator staff will instruct each subject to inform the site if they experience any change in 
health, medications or treatments in the 5 days following their last use of study product.
If a subject has any clinically significant, study-related abnormalities or AEs at the end of the 
study, the sponsor’s medical monitor (or designated representative) should be notified. The 
subject may be asked to return to the investigator site for a follow-up visit to ensure any issue 
is resolved or deemed not clinically significant. 
8.4
Follow-Up Contact
The investigator site may contact a subject to follow up an AE post-study completion or 
withdrawal and, in some circumstances, may request they return to the site for additional follow-
up visits (final safety assessments). At the discretion of the investigator or medically qualified 
designee, additional oral examinations may be carried out at such visits.
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9
STUDY ASSESSMENTS
Every effort should be made to ensure study-required examinations and assessments are 
completed as described and scheduled in this protocol.  However, it is anticipated that from 
time to time there may be circumstances, outside the control of the investigator that make it 
unfeasible to complete an examination or 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 
examination or assessment cannot be performed, the investigator or designee will document the 
reason for the missed procedure as a protocol deviation and any corrective and preventative 
actions they have taken to ensure the required procedures are adhered to as soon as possible. 
The sponsor should be informed of any missed examinations or assessments in a timely manner.
9.1
Screening Examinations/DH Assessments
Screening examinations and assessments will be performed by appropriately trained and 
experienced clinical examiners/staff at the times and in the order defined in the Study 
Procedures section of this protocol (Section 9).
The eligibility of each tooth will be assessed against the protocol inclusion/exclusion criteria 
(Sections 5.2 and 5.3) and recorded in the eCRF. If, in the opinion of the clinical examiner, the
value/score for a particular tooth/area of gingiva lies between two values/descriptions, a 
conservative approach should be adopted, and the more conservative value/score recorded. The 
same approach should be applied throughout the study to ensure consistency of assessment at 
all timepoints. 
9.1.1
Erosion, Abrasion and Recession (EAR) 
The facial surfaces of all incisor, canine and pre-molar teeth (Figure 9-1) 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 facial/cervical EAR (Addy, 2000).
Figure 9-1
Dental Nomenclature (Dempsey, 2001)
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 (Figure 9-1) exhibiting none of the dentition 
exclusions and presenting with facial/cervical EAR. MGI should be scored for the facial gingiva 
directly adjacent to the area of exposed dentin (i.e., the test area only). 
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‘Eligible Teeth’ will have a MGI of zero (0) directly adjacent to the area of exposed dentin.
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, oedema, and/or hypertrophy of the marginal 
or papillary gingival unit.
4
Severe inflammation; marked redness, oedema and/or hypertrophy of the marginal or 
papillary gingival unit, spontaneous bleeding, congestion, or ulceration.
9.1.3
Clinical Mobility 
Clinical mobility will be assessed for incisor, canine and pre-molar teeth (Figure 9-1) exhibiting 
none of the dentition exclusions, with facial/cervical EAR and a MGI = 0 adjacent to the test 
area only, using a modification of the Miller Index (Laster, 1975).
‘Eligible Teeth’ will have clinical mobility = 0.
Score
Description
0
No movement or mobility of the crown of the tooth < 0.2mm in a horizontal direction
1
Mobility of the crown of the tooth 0.2 - 1mm in a horizontal direction
2
Mobility of the crown of the tooth exceeding 1mm in a horizontal direction
3
Mobility of the crown of the tooth in a vertical direction as well.
9.1.4
Screening Tactile Sensitivity Assessment
The tactile sensitivity of incisor, canine and pre-molar teeth (Figure 9-1) exhibiting none of the 
dentition exclusions, and meeting the EAR, MGI and clinical mobility criteria, will be assessed 
using a constant pressure probe (Yeaple probe (Polson, 1980)). The probe tip will be placed 
perpendicular to the facial surface of the tooth and drawn slowly across the exposed dentin to 
ensure application of the stimulus across the potentially ‘sensitive’ area. 
After each application of the tactile stimulus, the subject will be asked to indicate whether they 
experienced any pain or discomfort. The examiner will tell the subject to only respond ‘yes’ if 
they feel PAIN or DISCOMFORT when the probe is applied to their tooth. ‘Yes’ and ‘no’ are 
the only acceptable answers. The subject may respond ‘yes’ if they feel pressure. The examiner 
will remind them, if needed, that they will feel pressure each time the probe is in contact with 
the tooth but they should only respond ‘yes’ if they feel pain or discomfort. 
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The gram setting which elicits two consecutive ‘yes’ responses will be recorded as the tactile 
threshold (g) for that tooth. At Screening, the upper force setting will be 20g. 
•
To be deemed ‘eligible’ for Baseline DH assessment, a tooth must have a Screening 
tactile threshold ≤ 20g. 
•
If no sensitivity is observed at the upper force setting, Screening tactile threshold 
will be recorded as > 20g 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 a 
response (‘yes’ or ‘no’). If their uncertainty continues, this should be recorded in the source 
document. If the subject continues to be unsure, or the examiner is unsure of the reliability of 
their response, the examiner may opt to re-probe at the same force setting (indicated to the 
scribe by a non-verbal signal, e.g., a hand gesture) or move to the next force setting (10g 
increase). If the examiner considers the subject’s ‘yes’ response may be between gram settings, 
a conservative approach should always be adopted, and the lower (more ‘severe’) tactile 
threshold (g) recorded.
The examiner will generally make the force setting adjustments (this can also be done by an 
assistant or the scribe); the scribe will record the micro-amperage setting and subject’s 
responses in the source document.
Calibration of the Yeaple Probe: 
The Yeaple probe will be calibrated by an appropriately trained member of the investigator staff 
(typically the clinical examiner, their assistant or 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 
be used 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 mean of the three used for that day’s settings. The settings will be 
recorded on the Yeaple probe calibration record (along with 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
Screening Evaporative (Air) Sensitivity Assessment
Evaporative (air) sensitivity will be assessed on the facial surfaces of incisor, canine and pre-
molar teeth (Figure 9-1) which exhibit none of the dentition exclusions, meet the EAR, MGI, 
clinical mobility criteria and have a Screening tactile threshold ≤20g. Evaporative (air) 
assessments will start a minimum of 5 minutes after the tactile assessments have completed
(tooth recovery time). 
The assessment will be made by directing a 1-second application of air from a standard dental 
syringe held perpendicular to the tooth surface, approximately 1-2 mm coronal to the gingival 
margin, and from a distance of approximately 1 cm. The dental examiner will take appropriate 
measures to isolate the tooth surface to prevent stimulation of adjacent teeth or surrounding soft 
tissue.
Subject response to the stimulus will be evaluated using the Schiff sensitivity scale (Schiff, 
1994). This is an examiner-based index, scored immediately following administration of the 
evaporative (air) stimulus. The scale focuses on a combination of specific, observable, physical, 
behavioral and verbal responses from the subject, which may facilitate discrimination. 
Score
Description
0
Subject does not respond to air stimulation
1
Subject responds to air stimulus but does not request discontinuation of stimulus
2
Subject responds to air stimulus and requests discontinuation or moves from stimulus
3
Subject responds to stimulus, considers stimulus to be painful, and requests 
discontinuation of the stimulus
•
To be deemed ‘eligible’ for Baseline DH assessments, a tooth must have a Screening 
tactile threshold ≤ 20g and a Screening Schiff sensitivity score ≥ 2. 
•
Teeth with a Screening Schiff sensitivity score < 2 will be disqualified from further 
testing.
9.2
DH Efficacy Assessments
The following DH efficacy assessments will be performed by appropriately trained and 
experienced clinical examiners/staff, at the times and in the order defined in the Study 
Procedures section of this protocol (Section 8).
If, in the opinion of the clinical examiner, the value/score for a particular tooth is between two 
values/descriptions, a conservative approach should be adopted, and the more conservative 
value/score recorded. The same approach should be applied throughout the study to ensure 
consistency of assessment at all timepoints. 
9.2.1
Dentine Hypersensitivity Experience Questionnaire (DHEQ-48)
The DHEQ-48 is a condition-specific measure of OHrQoL in relation to DH (Boiko, 2010) that 
has been previously validated in longitudinal studies and shown to be responsive to treatment 
(Baker, 2014). The DHEQ total score can be broken down into 5 separate ‘domain’ scores to 
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provide a more granular understanding of the specific areas of improvement subjects experience 
in their OHrQOL.
•
Restrictions: Derived from participant responses to Section 2, Q1-4 (‘the ways in which 
any sensations in your teeth affect you in your daily life’).
•
Adaptation: Derived from participant responses to Section 2, Q5-16 (‘the ways in 
which the sensations in your teeth have forced you to change things in your daily life’; 
‘things you do in your daily life to avoid experiencing the sensations in your teeth’).
•
Social Impact: Derived from participant responses to Section 2, Q17-21 (‘the way the 
sensations affect you when you are with other people or in certain situations’). 
•
Emotional Impact: Derived from participant responses to Section 2, Q22-29 (‘the way 
the sensations in your teeth make you feel’). 
•
Identity: Derived from participant responses to Section 2, Q30-34 (‘what the sensations 
in your teeth mean for you’). 
The DHEQ also provides specific information on how much the sensations in the participant’s 
teeth affect their life overall: 
•
Global Oral Health: Derived from participant response to Section 2, Q35 (‘rate the 
health of your mouth, teeth and gums’). 
•
Effect on Life Overall: Derived from participant responses to Section 2, Q36-39
(impact of DH on overall QoL).
Subjects will independently (unsupervised) complete a hard copy of the DHEQ-48 (Appendix 
15.2) at Baseline (Visit 2), Day 28 (Visit 3) and Day 56 (Visit 4), prior to any clinical 
examinations and assessments.
•
Baseline: Complete Section 1 and Section 2 (i.e., all questions in both sections).
•
Day 28 & Day 56: Complete Section 1 Questions 7-9 only, and Section 2 all questions. 
9.2.2
Tactile Sensitivity Assessments
Tactile sensitivity will be assessed at Baseline (Visit 2), Day 28 (Visit 3) and Day 56 (Visit 4). 
The tactile stimulus will be administered, and subject response recorded, as described in Section 
9.1.4. The gram setting which elicits two consecutive ‘yes’ responses will be recorded as the 
tactile threshold (g).
•
Baseline: Assess the tactile sensitivity of all teeth which exhibit none of the dentition 
exclusions and meet the EAR, MGI and clinical mobility criteria, with a Screening 
tactile threshold of ≤ 20g and a Screening Schiff sensitivity score ≥ 2 (i.e., the ‘eligible 
teeth’ identified at Screening). 
The upper force setting will be 20g; if no sensitivity is found at the upper setting, record 
tactile threshold as > 20g.
•
Day 28 & Day 56: Assess the tactile sensitivity of the two ‘Test Teeth’ only (i.e., the 
two teeth selected by the clinical examiner at Baseline, as described in Section 8.2.1.5).
The upper force setting will be 80g; if no sensitivity is found at the upper setting, record 
tactile threshold as > 80g.
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9.2.3
Evaporative (Air) Sensitivity Assessments
Evaporative (air) sensitivity will be assessed at Baseline (Visit 2), Day 28 (Visit 3) and Day 56 
(Visit 4). The evaporative (air) stimulus will be administered, and subject response recorded
(Schiff Sensitivity Score), as described in Section 9.1.5. Evaporative (air) assessments will start
a minimum of 5 minutes after the tactile assessments have completed (tooth recovery time).
•
Baseline:
-
First assess evaporative (air) sensitivity for all ‘Eligible Teeth’ identified at 
Screening with a Baseline tactile threshold of ≤ 20g.
-
Then assess evaporative (air) sensitivity for the remaining ‘Eligible Teeth’
identified at Screening with a Baseline tactile threshold of > 20g.
•
Days 28 & 56:
-
First assess evaporative (air) sensitivity for the two ‘Test Teeth’ (i.e., the two teeth 
selected by the clinical examiner at Baseline, as described in Section 8.2.1.5).
-
Then assess evaporative (air) sensitivity for all remaining ‘Eligible Teeth’
identified at Screening. Do not re-assess the two ‘Test Teeth’.
‘Eligible Teeth’ = Teeth with no dentition exclusions which meet EAR, MGI and mobility inclusion criteria, 
and have a Screening tactile threshold ≤ 20g and a Screening Schiff sensitivity score ≥ 2.
Score
Description
0
Subject does not respond to air stimulation
1
Subject responds to air stimulus but does not request discontinuation of stimulus
2
Subject responds to air stimulus and requests discontinuation or moves from stimulus
3
Subject responds to stimulus, considers stimulus to be painful, and requests 
discontinuation of the stimulus
9.2.4
Labelled Magnitude Scales (LMSs)
Subjects will rate the (i) intensity, (ii) duration and (iii) tolerability of their response to the
evaporative (air) stimulus and (iv) describe their response, using four 100-millimetre (mm) 
LMSs (Appendix 15.3), at Baseline (Visit 2), Day 28 (Visit 3) and Day 56 (Visit 4). 
LMSs should be completed immediately after the clinical examiner has recorded the Schiff 
sensitivity score for a given tooth. To avoid bias, the subject should be unaware of the 
examiner’s score and the clinical examiner should not have visibility of the subject’s LMS 
responses.
•
Baseline: Complete four LMSs for each tooth with a Baseline tactile threshold of ≤ 20g
and a Baseline Schiff sensitivity score ≥ 2.
•
Days 28 & 56: Complete four LMSs for each ‘Test Tooth’ (i.e., the two teeth selected 
by the clinical examiner at Baseline, as described in Section 8.2.1.5).
Study staff will measure the distance to the subject’s mark (‘X’) from left to right along the 100 
mm line and record this value (in mm) in the eCRF for each LMS completed.
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Note: Subjects will complete the LMS training exercise (Appendix 15.4) at Screening (Visit 1),
before their clinical examinations/DH assessments. Any subject who, in the opinion of the 
investigator or designee, is unable to provide appropriate responses to the LMS training 
questions, will be excluded from participation in the study (Section 5.3 Exclusion Criterion 27). 
9.3
Safety Assessments
The following safety assessments will be performed by appropriately trained clinical examiners, 
at the times and in the order defined in the Study Procedures section of this protocol (Section 8).  
9.3.1
Oral Soft Tissue (OST) Examination
The OST examination will be accomplished by direct visual observation and palpation, using 
retraction aids as appropriate, and will include examination of the labial mucosa (including 
lips), buccal mucosa, 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’; 
details of any abnormalities will be documented in the eCRF. Any observation that changes 
from ‘normal’ to ‘abnormal’, or worsens, from the OST examination completed at Screening
will be recorded as an AE.
9.3.2
Oral Hard Tissue (OHT) Examination
The OHT examination will be accomplished by direct visual observation, using retraction aids 
as appropriate, and will identify enamel irregularities, tooth fractures, grossly carious 
lesions/gross decay, defective/faulty restorations (both direct and indirect restorations,
including fixed/ removable prostheses), non-carious tooth surface loss (abrasion, attrition, 
abfraction and erosion), any other hard tissue irregularities (e.g., hypo- and hyper-
mineralization, decalcification) and significant tooth staining. 
Observations will be listed as ‘absent’ or ‘present’; conditions noted as ‘present’ will be 
described in the eCRF. Any observation that changes from ‘absent’ to ‘present’ or worsens from 
the OHT examination completed at Screening will be recorded as an AE.
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, along with 
evidence of gross intra-oral neglect or the need for extensive dental therapy.
The OHT examination will also be used to assess the subject’s dentition against the general and 
specific dentition exclusions described in Section 5.3 (Exclusion Criteria 22, 23, 24, 25, 26a-g).
9.3.3
Pregnancy 
This clinical study will utilize toothpastes classified as OTC monograph drugs in the US. 
However, none of the study toothpastes are contra-indicated for pregnancy or breastfeeding 
(their use would not be expected to cause harm to the mother, the foetus or a baby); the US 
commercial products (the Acclimatization and Reference Toothpastes) do not carry pregnancy 
warnings on the labelling (e.g., instructions to speak to a doctor before use if pregnant); the Test 
Toothpaste will not carry a pregnancy warning when marketed in the US. Thus, pregnancy 
testing of female subjects is not required prior to their enrolment.
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Female subjects will provide verbal confirmation of pregnancy status at Screening (Visit 1) and 
at each subsequent study visit; this will be recorded in the eCRF. They will be instructed to 
inform the investigator staff immediately should they find out they are pregnant at any point 
during the study.
Female subjects who are pregnant or intending to become pregnant during the study (self-
reported) will be excluded (the rationale for exclusion is provided in Section 4.2).
9.3.4
Satisfaction with Treatment
At the end of the study (Visit 4), subjects will be asked to rate their level of satisfaction with 
their allocated investigational toothpaste using a Numeric Rating Scale (NRS). 
The NRS is an 11-point ordinal scale used to assess the subject’s satisfaction with the product’s 
overall management of their DH. The scale ranges from 0 (completely dissatisfied) to 10 
(completely satisfied), with higher scores indicative of greater satisfaction (van Berckel, 2017): 
see example below. 
Subjects will be asked to record the numeric value on the segmented scale that best describes 
their level of satisfaction after 8 weeks twice daily use and indicate why they selected a 
particular score in answer to the question ‘Please give more details on why you are satisfied or 
dissatisfied with the product’ (free text response).
Example NRS - Not to Scale
10
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS
The investigator and their medically qualified designees are responsible for detecting, 
documenting and reporting events that meet the definition of an AE or SAE and remain 
responsible for following up AEs that are serious, considered related to study product, a study 
procedure or study participation, or that caused the subject to discontinue use of study product 
or study participation.
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 an acclimatization product (or medical device), 
whether or not considered related to the study product, including an acclimatization product (or 
medical device).
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Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a study product including an acclimatization product (or medical device).
Events Meeting the AE Definition:  
•
Any abnormal laboratory test results (hematology, clinical chemistry or urinalysis) or 
other safety assessments (e.g., electrocardiogram, radiological scans, vital sign 
measurements), including those that worsen from Baseline, considered clinically 
significant in the medical and scientific judgment of the investigator (i.e., not related to 
progression of underlying disease).
Note: Any OST observation that changes from ‘normal’ to ‘abnormal’, or worsens, from the OST 
examination completed at Screening should be recorded as an AE’ irrespective of clinical significance.
•
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
•
New conditions detected or diagnosed after study product administration even though it 
may have been present before the start of the study.
•
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
•
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study product 
or a concomitant medication. Overdose per se will not be reported as an AE/SAE unless 
it is an intentional overdose taken with possible suicidal/self-harming intent. Such 
overdoses should be reported regardless of sequelae.
•
‘Lack of efficacy’ or ‘failure of expected pharmacological action’ per se will not be 
reported as an AE. Such instances will be captured in the efficacy assessments. 
However, the signs, symptoms and/or clinical sequelae resulting from lack of efficacy 
will be reported as an 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. 
•
A medical or surgical procedure (e.g., endoscopy, appendectomy) is not an AE. The 
condition that leads to the procedure is an AE (e.g., appendicitis).
•
Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
•
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
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10.2
Definition of a Serious Adverse Event (SAE)
A serious adverse event (SAE) is a particular category of AE where the adverse outcome is 
serious. If an event is not an AE per definition above, then it cannot be an SAE, even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
A serious adverse event is any untoward medical occurrence at any dose that:
•
Results in death
•
Is life-threatening
-
The term 'life-threatening' in the definition of 'serious' refers to an event in which 
the subject was at risk of death at the time of the event. It does not refer to an event, 
which hypothetically might have caused death, if it were more severe.
•
Requires inpatient hospitalization or prolongation of existing hospitalization
-
In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications
that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
‘hospitalization’ occurred, or was necessary, the AE should be considered serious.
-
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from Baseline is not considered an AE.
•
Results in persistent or significant disability/incapacity
-
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.
-
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
•
Results in congenital anomaly/birth defect
•
Other situations:
-
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the subject or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization, or development of drug 
dependency or drug abuse.
Note: Classification of an AE as ‘serious’ is based on the outcome of the event and is a factor 
in determining reporting requirements.
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10.3
Time Period and Frequency for Collecting AE and SAE 
Information
All AEs, and therefore all SAEs, will be collected from immediately after a subject provides 
consent to participate in the study by the completion (signature) of the ICF until 5 days 
following the last administration of study product (or the last study 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.
Details recorded by the subject in a diary or similar document that meet the definition of an AE 
must be discussed with the subjects and transcribed into 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 updated SAE data to 
the sponsor within 24 hours of it being available.
The investigator and their medically qualified designees are not obligated to actively seek AEs 
or SAEs after the conclusion of study participation. However, if the investigator or their 
medically qualified designee learns of an SAE, including a death, at any time after a subject has 
been discharged from the study, and they consider the event to be reasonably related to study 
product or study participation, they must promptly notify the sponsor.
10.4
Reporting Procedures
The investigator and their medically qualified designees are responsible for detecting, 
documenting and reporting events that meet the definition of an AE and remain responsible for 
following up AEs that are serious, considered related to study product, a study procedure or 
study participation, or that caused the subject to discontinue use of study product or study 
participation.
The investigator and their medically qualified designees are to report all AEs directly observed 
at study visits and all AEs spontaneously reported by study subjects. 
Study subjects will be questioned about AEs. 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.
AEs spontaneously reported by study subjects and those elicited by asking subjects to respond 
to non-leading questions (such as ‘how do you feel?’) will be assessed, recorded in the eCRF
and reported, as appropriate.
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 their medically qualified 
designee to review all documentation (e.g., hospital progress notes, laboratory and diagnostics 
reports) related to the event. The investigator or study staff will then record all relevant 
information relating to the event in the AE section of the eCRF. In addition, all details relating 
to an SAE will be recorded on the paper SAE form provided.
It is not acceptable for the investigator or their medically qualified designee to send photocopies 
of a subject’s medical records to the sponsor in lieu of completion of the AE section of the 
eCRF/paper SAE form. There may be instances when copies of medical records for certain 
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cases are requested by the sponsor.  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 the sponsor.
The investigator or their medically qualified designee will attempt to establish a diagnosis based 
on signs, symptoms and/or other clinical information related to the event. The diagnosis will be 
the documented as the AE/SAE, where known, and not the individual signs/symptoms (e.g.,
upper respiratory tract infection or seasonal allergy, not ‘runny nose’).
10.4.1
Reporting an AE
AEs will be reported by the investigator, their medically qualified designee or site staff in the 
AE section of the eCRF.  The paper form used for collection of SAE information is not the same 
as the AE section of the eCRF. AEs/SAEs should be reported using concise medical 
terminology. Where the same data are collected, the AE section of the eCRF and the SAE form 
must be completed in a consistent manner (e.g., the same AE term should be used for both).  
10.4.2
Reporting an SAE
In addition to recording the details of each SAE in the AE section of the eCRF, an SAE form 
should be completed, as fully as possible. Hard copies of the ‘paper’ SAE form will be provided 
in the investigator site file. Original, completed SAE forms will be retained in the investigator 
site file.
It is essential to record the following information for each SAE: 
•
Protocol and subject identifiers
•
Subject demography
•
Description of event with diagnosis, if available
•
Investigator opinion of relationship to study product (or study procedure)
•
Criterion for seriousness.
The following are desirable and are of particular relevance for investigator and sponsor
assessment of the SAE report:
•
Date of onset of SAE 
•
Date SAE stopped, if relevant
•
Study product start date
•
Study product end date, if relevant
•
Action taken in relation to study product
•
Outcome, if known
The SAE form, completed as fully as possible, must be scanned and e-mailed to the sponsor’s 
Case Management Group mailbox 
, with the appropriate 
sponsor Study Manager in copy, with the study number and subject number in the subject line 
of the email immediately after site staff learn of the event, and under no circumstances
should this exceed 24 hours. The investigator will submit any updated SAE data to the sponsor, 
immediately it becomes available, and under no circumstance should this exceed 24 hours 
of it being available. 
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The initial report will be followed up with more information as relevant, or as requested by the
sponsor’s Study Manager. The sponsor’s Study Manager will be responsible for forwarding the 
SAE form to other sponsor personnel as appropriate.
10.5
Evaluating AEs 
10.5.1
Assessment of Intensity
The investigator or their 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 assessed as ‘severe’ should not be confused with an SAE. ‘Severe’ is a category 
utilized for rating the intensity of an event. Both non-serious AEs and SAEs can be assessed as 
severe, e.g., a headache may be severe (significantly interferes with the subject's usual function) 
but would not be classified as serious unless it met one of the criteria for SAEs listed in Section 
10.2. An event is defined as ‘serious’ when it meets at least one of the pre-defined outcomes
described in the definition of an SAE (Section 10.2), not when it is rated as ‘severe’.
10.5.2
Assessment of Causality
For each AE (non-serious and serious), the investigator or their medically qualified designee
must provide an assessment of causality in the AE section of the eCRF and on the SAE form 
(as appropriate, subject to classification of the AE). Causality is one of the criteria used to
determine regulatory reporting requirements. 
A ‘reasonable possibility’ of a relationship conveys 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 in the AE/SAE
report.
The investigator or their medically qualified designee will use clinical judgment to determine 
causality and will also consult the Investigator Brochure (IB), Safety Statement and/or Product 
Information, as appropriate, when making their assessment. Alternative causes, such as 
underlying disease(s), concomitant therapy, other risk factors and the temporal relationship of 
the event to study product use will be considered and investigated.
Where applicable, the investigator or their medically qualified designee must document in the 
medical notes they have reviewed the AE/SAE and provided an assessment of causality.
There may be situations, when an SAE has occurred, where the investigator or their medically 
qualified designee has minimal information to include in the initial SAE report. However, it is 
very important that the investigator or their medically qualified designee always makes
an assessment of causality for every event prior to initial transmission of the SAE data to
the sponsor. The investigator may change their opinion of causality, in light of follow-up 
information, and send an SAE follow-up report with an updated causality assessment. 
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10.6
Follow-up of AEs and SAEs
After the initial AE/SAE report, the investigator or their medically qualified designee is required 
to proactively follow up with each subject and provide further information on the subject’s 
condition, as available.
All AEs (non-serious and serious) should be followed until resolution, until the condition 
stabilizes, until the event is otherwise explained or until the subject is lost to follow-up.  
The investigator or their medically qualified designee is obligated to perform or arrange for the 
conduct of supplemental measurements and/or evaluations as may be indicated (or as requested 
by the sponsor) to elucidate as fully as possible the nature and/or causality of the AE/SAE.
These may include additional laboratory tests or investigations, histopathological examinations, 
or consultation with other healthcare professionals.
New or updated information will be recorded in the AE section of the eCRF and on the SAE 
form (as appropriate, subject to classification of the AE). The investigator or their medically 
qualified designee will submit any updated SAE data to the sponsor within 24 hours of receipt 
of the information.
The investigator and their medically qualified designees are not obligated to actively seek AEs 
or SAEs after the conclusion of study participation. However, if the investigator or their 
medically qualified designee learns of an SAE, including a death, at any time after a subject has 
been discharged from the study, and they consider the event to be reasonably related to study 
product or study participation, they must promptly notify the sponsor by emailing the 
information 
to 
the 
sponsor’s 
Case 
Management 
Group
mailbox 
, with the appropriate sponsor Study Manager in copy.
The investigator or their medically qualified designee will submit any updated SAE data to the 
sponsor within the designated reporting time frames.
10.7
Withdrawal Due to an Adverse Event 
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, according 
to the definition of an AE provided (Section 10.1) and recorded in the AE section of the eCRF. 
When a subject withdraws due to an SAE, the SAE must be reported in accordance with the 
reporting requirements defined in this protocol.
10.8
Regulatory Reporting Requirements for SAEs
The sponsor has a legal responsibility to notify, as appropriate, the local regulatory authority 
and other regulatory authorities about the safety of a product under clinical investigation.  
Prompt notification of SAEs by the investigator to the sponsor is essential so that legal 
obligations and ethical responsibilities towards the safety of subjects are met.
The sponsor will comply with country specific regulatory requirements relating to safety 
reporting to the regulatory authority, the IRB and the investigator.
The investigator and the sponsor will comply with local medical device reporting requirements.
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and sponsor policy, and forwarded to the 
investigator, as appropriate.
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If the investigator receives an investigator safety report describing a SAE or other specific safety 
information (e.g., a summary or listing of SAEs) from the sponsor, they will review it, file it
with other safety information (e.g., the IB) in the investigator site file and notify the IRB, 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 is 
participating in the study from the date/time of signing the informed consent until 5 days after
the last administration of study product.
10.9.2
Action to be Taken if Pregnancy Occurs
The investigator or their medically qualified designee will record pregnancy information on the 
appropriate form scan and e-mail it to the Case Management Group mailbox 
, with the appropriate sponsor Study Manager in copy. 
Original completed pregnancy information forms will be retained in the investigator site file. 
The female 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 pregnancy) will be forwarded by the investigator or their medically qualified 
designee
to 
the 
sponsor’s 
Case 
Management 
Group 
mailbox 
, with the appropriate sponsor Study Manager in copy. 
Generally, follow-up will be for no longer than 6 to 8 weeks following the estimated delivery 
date. Termination of 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 be withdrawn.   
10.10
Medical Device Incidents
A medical device is being provided by the sponsor for use in this study; the medical device in 
this study is the manual toothbrush (Oral B Sensi-Soft, US market) used to apply the study 
toothpastes.
The investigator and the sponsor will comply with local medical device reporting requirements.
10.10.1
Definition of an Incident
A medical device incident is any malfunction or deterioration in the characteristics and/or 
performance of a device as well as any inadequacy in the labeling or the instructions for use 
which, directly or indirectly, might lead to or might have led to the death of a subject/user/other 
person or to a serious deterioration in their state of health.
Not all incidents lead to death or serious deterioration in health. The non-occurrence of such a 
result might have been due to other fortunate circumstances or to the intervention of healthcare 
personnel.
It is sufficient that an incident associated with a device happened and the incident was such 
that, if it occurred again, might lead to death or a serious deterioration in health.
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A serious deterioration in state of health can include any of the following:
•
Life-threatening illness
•
Permanent impairment of body function or permanent damage to body structure
•
Condition necessitating medical or surgical intervention to prevent one of the above 
•
Fetal distress, fetal death, or any congenital abnormality or birth defects
Examples of incidents:
•
A subject, user, caregiver, or healthcare professional is injured as a result of a medical 
device failure or its misuse.
•
A subject’s study treatment is interrupted or compromised by a medical device failure.
•
A misdiagnosis due to medical device failure leads to inappropriate treatment.
•
A subject’s health deteriorates due to medical device failure.
10.10.2
Reporting of Incidents and Malfunctions
All incidents must be reported to the sponsor immediately the investigator or their medically 
qualified designee becomes aware of the situation, and under no circumstance should this 
exceed 24 hours of the investigator or designee becoming aware of the situation.
Any medical device incident occurring during the study will be documented in the subject's 
medical records, if in accordance with the investigator's normal clinical practice, and on the 
appropriate Incident Report Form.  In addition, for incidents fulfilling the definition of an AE 
(non-serious and serious), the AE section of the eCRF/SAE form will be completed and reported 
as per the AE/SAE reporting sections above.
The Incident Report Form will be completed as thoroughly as possible and signed by the 
investigator before transmittal to the sponsor.  It is very important that the investigator describes 
any corrective or remedial actions taken to prevent recurrence of the incident.
The completed Incident Report Form should be scanned and emailed to the sponsor’s Case 
Management Group mailbox 
), with the appropriate sponsor
Study Manager in copy, with the study number and subject number in the subject line of the 
email immediately after site staff learn of the event and under no circumstances should this 
exceed 24 hours after site staff learn of the event. If there is an SAE, the completed SAE form
should be sent together with the Incident Report Form. The copy of the SAE report sent with 
this Incident Report Form does not replace the procedure for reporting an SAE.  The original 
completed Incident Report Form will be retained in the investigator site file. 
The initial medical device incident report will be followed up with more information as relevant, 
or as requested by the sponsor’s study manager.
The investigator will follow the following directions regarding the reporting of a device failure 
(malfunction):
•
Notify the sponsor immediately (as described above).
•
Schedule the subject to return to site promptly to return the failed device.
•
Record any incidents in the eCRF and on the Incident Report Form (as described above).
•
For any incident/malfunction occurring with a medical device (including those that are 
part of combination products) supplied by the sponsor, return the failed device to the 
sponsor as soon as possible, including documentation of the details of the failure.
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•
For any incident/malfunction occurring with a medical device (including those that are 
part of combination products) supplied by the investigator site, report the incident to the 
device manufacturer and follow the manufacturer instructions for the return of the failed 
device (whilst keeping the sponsor informed).
10.10.3
Follow-up of Medical Device Incidents
Medical device incidents involving an AE will be followed and reported in the same manner as 
other AEs. This applies to all subjects, including those who discontinue study product or are 
withdrawn from the study.
The investigator is responsible for ensuring that follow-up includes any supplemental 
investigations as indicated to elucidate the nature and/or causality of the incident.
New or updated information will be recorded on the originally completed Incident Report form,
with all changes signed and dated by the investigator.
10.10.4
Regulatory Reporting Requirements for Medical Device Incidents
To fulfill regulatory reporting obligations worldwide, the investigator is responsible for the 
detection and documentation of events meeting the definitions of incident or malfunction that 
occur during all periods of the study in which a medical device is used. 
The investigator will promptly report all incidents occurring with any medical device provided 
for use in the study in order for the sponsor to fulfill the legal responsibility to notify appropriate 
regulatory authorities and other entities about certain safety information relating to medical 
devices being used in clinical studies.
The investigator will comply with applicable local regulatory requirements relating to the 
reporting of incidents to the IRB.
11
DATA MANAGEMENT
As used in this protocol, the term CRF refers to either a paper form or an electronic data record 
or both, depending on the data collection method. For this study, subject data will be entered 
into an electronic CRF (eCRF), using a validated system. Data relating to SAEs, pregnancy and 
incidents will also be collected on paper forms.
Subjects will complete paper copies of the DHEQ-48 (source), the LMSs (source) and the 
Treatment Satisfaction NRS (source); to facilitate subject flow, paper forms (source) may also 
be used to record clinical data for later transcription into the eCRF. Transcription of 
DHEQ/LMS/NRS responses and clinical data into the eCRF must be completed within 5 days 
of the data being recorded. The eCRF and the subject-completed diary can be used as a source 
document at the discretion of Data Management.
The source documents that contain source data recorded in the eCRF should be specified. 
The investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the eCRF.
Each subject will be assigned and identified by a unique Screening Subject Number. Any 
reference made to an individual subject within the study must be done using their unique 
Screening Subject Number.
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11.1
Case Report Form
A CRF is a printed, optical or electronic document designed to record protocol-required 
information to be reported to the sponsor on each study subject.
For each subject who gives informed consent, the CRF must be completed and signed by the 
investigator (or authorized designee) to certify that the data are complete and correct.  The 
investigator must maintain accurate documentation (source data) to support the information 
entered in the CRF.
Management of clinical data will be performed in accordance with Third Party BDM Vendor 
applicable standards and data cleaning procedures, with oversight by the sponsor to ensure data
integrity (e.g., to remove errors and inconsistencies in the data). 
To protect the privacy of study subjects, no Personal Information (PI), including subject name, 
initials and birth date, is to be recorded in the CRF or as part of query text.
All CRF pages should be completed during a subject assessment when the CRF is the designated 
source.  Data recorded elsewhere should be transcribed from the source document into the CRF 
within 5 days of the data being recorded.  
The sponsor will obtain and retain all CRFs and associated study data, as applicable, on
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. 
Changes and corrections to data will be performed in the Electronic Data Capture (EDC) System
which will include a rationale for the change or correction. The EDC system has an audit trail 
to provide a complete record of the changes and corrections endorsed by the investigator.
AEs will be coded using Medical Dictionary for Regulatory Activities (MedDRA), and 
concomitant medication terms (if applicable) using an internal validated medication dictionary
(WHO Drug).  
11.2.1
Data Queries
Programmed edit checks will be generated automatically as the data are being entered into the 
system. Reports and listings on the CRF data will also be run, in addition to the queries already 
programmed and generated by the system, to raise manual queries as needed for investigator 
site clarification or correction. The Clinical Dictionary Development and Management Group 
will raise queries as needed on safety data to code the terms (AEs and Drugs or concomitant 
medication) appropriately. 
The study monitor will perform ongoing review of the CRFs, in accordance with the monitoring 
plan, to confirm that data entered into the CRF by authorized investigator 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.
Queries generated in the EDC System will automatically be sent to the investigator site, 
enabling errors to be addressed in parallel with Data Management review. The study monitor 
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will also run reports and listings on the CRFs to raise manual queries, as needed, for investigator 
site clarification or correction.
11.3
Processing Subject Reported Outcomes
Subject reported outcomes will be recorded in paper-based diaries and in questionnaires 
(DHEQ-48, LMSs and NRS) for later transcription into the eCRF.
Source documents recording subject-reported outcomes will be reviewed by the investigator 
staff and the study monitor to ensure the data, and any potential AEs or concomitant medications 
reported in these documents, are accurately transcribed into the eCRF.
Subject reported outcomes classed as source data will be retained by the investigator; 
true/certified copies may be sent to the sponsor or a third-party vendor, as required. To protect 
subject privacy, no PI (including subject name, initials or birth date) is to be recorded in any 
subject reported outcome source document that will be forwarded to the sponsor or a third-party 
vendor.
12
STATISTICAL CONSIDERATIONS AND DATA ANALYSES
12.1
Sample Size Determination
Sufficient subjects will be screened and entered into the acclimatization period to randomize 
approximately 110 subjects to investigational product (approximately 55 subjects per treatment 
group) to ensure approximately 100 complete the study (approximately 50 subjects per 
treatment group), allowing for approximately 10% dropouts.
The study will be sufficiently powered to demonstrate statistical superiority of the Test 
Toothpaste compared to the Reference Toothpaste (negative control) for the change from 
Baseline in the Schiff sensitivity score (primary objective) and tactile threshold (key secondary 
objective) after 56 days (8 weeks) treatment. A sample size of 50 evaluable subjects per 
treatment group will provide at least 90% power to detect a mean difference of 0.4 units (SD = 
0.6) in change from Baseline in Schiff sensitivity score after 56 days treatment, using a 2-tailed 
2-sample t-test with a 5% significance level. The sample size calculation was performed using 
PASS software version 23.0.1.
The dropout rate and SD estimates are based on the results of DH efficacy studies of similar 
design and duration evaluating 0.454% SnF2 toothpastes (Clinical Studies 205794, 208153 and
216954: sponsor data held on file, available on request). 
12.2
Populations for Analysis
12.2.1
Definitions of Analysis Populations
The Safety population will comprise all randomized subjects who receive at least one dose of 
investigational product. Summaries and analyses of this population will be based on the 
investigational product the subject received.
The primary population for the assessment of efficacy will be a modified intention-to-treat 
(mITT) population. The mITT population will comprise all randomized subjects who receive at 
least one dose of investigational product and complete at least one-post Baseline DH efficacy 
assessment. This population will be based on the investigational product the subject was 
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randomized to. All subjects who receive a randomization number will be considered
randomized.
The Per-Protocol (PP) population will comprise all subjects in the mITT population who have 
at least one DH efficacy assessment considered to be unaffected by protocol deviations.
12.2.2
Exclusions of Data from Analysis
Exclusion of data from any of the planned analyses will be agreed during Blinded Data Review 
(BDR), prior to database lock. The reason(s) for exclusion of a subject from an analysis 
population or specific data from an analysis will be documented and, if applicable, listed in the 
Clinical Study Report (CSR).
A PP analysis will be performed for the primary endpoint if ≥ 10% subjects in the mITT 
population are excluded from the PP population. Efficacy data determined to have been 
potentially impacted by a protocol deviation will be excluded from the PP analysis. The 
decisions as to whether or not a protocol deviation impacts efficacy data and whether to perform 
a PP analysis will be made during BDR, prior to database lock.
12.3
Statistical Analyses
This is a summary of the planned statistical analyses; the detail of the proposed statistical 
analyses will be documented in the Statistical Analysis Plan (SAP), to be written following 
finalization of the protocol and prior to study unblinding.
The mITT population will be used for all efficacy analyses.
All p-values presented will be two-sided and assessed at the 5% significance level. A sequential 
testing strategy will be used to adjust for the comparisons between the Test and Reference 
Toothpastes in change from Baseline in Schiff sensitivity score and tactile threshold (g) at each 
assessment time point.
At each time point, change from Baseline in tactile threshold (g) will only be assessed for 
confirmatory evidence if the change from Baseline in Schiff sensitivity score achieves a 
statistically significant greater reduction for the Test Toothpaste compared to the Reference 
Toothpaste (negative control). This strategy will begin at Day 56, then move to Day 28, only 
moving to the earlier time point for confirmatory evidence if the Day 56 time point achieves
statistically significant greater reductions for the Test Toothpaste compared to the Reference 
Toothpaste (negative control) for both Schiff sensitivity score and tactile threshold (g). There 
will be no further adjustments for multiplicity for the other secondary endpoints (DHEQ-48).
Summary statistics (mean, median, SE, SD, minimum, maximum) will be presented for each
Schiff sensitivity score and tactile threshold (g) outcome variable at each assessment time point. 
Raw means (± SE) of Schiff sensitivity score and tactile threshold (g) at each assessment 
timepoint will be plotted by treatment group.
The results from each Mixed Model with Repeated Measures (MMRM) will be tabulated, 
presenting the following information, in addition to the results specified for the primary and 
secondary analyses below: least square mean change from Baseline for each investigational 
product at Days 28 and 56 (based on the observed stratification margins for those MMRM with 
a term for randomized strata) and used to test for any change from Baseline, with two-sided p-
values and 95% CIs.
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12.3.1
Primary Endpoint Analysis
The primary endpoint of this study is the change from Baseline in Schiff sensitivity score at 
Day 56 (Week 8); the primary hypothesis test will be the comparison between the Test 
Toothpaste and the Reference Toothpaste (negative control) in the mITT population.
Schiff sensitivity score will be derived as the mean score for the two ‘Test Teeth’ (selected at 
Baseline). Change from Baseline will be derived for each individual tooth first before 
calculating mean change for the two ‘Test Teeth’ where change from Baseline in Schiff 
sensitivity score at Day X is defined as [(Schiff sensitivity score at Day X) minus (Baseline 
Schiff sensitivity score)].
Change from Baseline in Schiff sensitivity score at Day 56 will be analysed using a Mixed 
Model with Repeated Measures (MMRM) with investigational
product, visit and 
[investigational product x visit] interaction as fixed effects, and Baseline Schiff sensitivity score 
as a covariate. Subject will be included as a repeated measure with unstructured covariance 
matrix. Kenward Rogers degrees of freedom approach will be applied (Kenward, 1997). The 
difference between the least square mean changes from Baseline for the Test Toothpaste 
compared to Reference Toothpaste (negative control) at Day 56 from the MMRM will be 
presented, along with the two-sided p-value and 95% CIs.
The assumptions of normality and homogeneity of variance in the MMRM will be investigated. 
In case of violation of these assumptions, a suitable non-parametric test (adjusted for the 
randomization stratification) will be performed to assess the change from Baseline comparison 
(Test Toothpaste vs. Reference Toothpaste at Day 56); the results will be provided to support 
the MMRM results.
12.3.2
Secondary Endpoint Analyses
Tactile Threshold at Day 56:
Tactile threshold (g) will be derived as the mean value for the two ‘Test Teeth’ (selected at 
Baseline). Change from Baseline will be derived for each individual tooth first before 
calculating mean change for the two ‘Test Teeth’ where change from Baseline in tactile 
threshold (g) at Day X is defined as [(tactile threshold at Day X) minus (Baseline tactile 
threshold)].
This key secondary endpoint, change from Baseline in tactile threshold (g) at Day 56, will be 
analysed using the same MMRM as the primary endpoint but with Baseline tactile threshold (g)
as a covariate (rather than Baseline Schiff sensitivity score). In addition, the maximum Baseline 
Schiff sensitivity score of the two ‘Test Teeth’ (2 or 3) will be fitted as a fixed effect. The 
difference between the least square mean changes from Baseline for the Test Toothpaste 
compared to Reference Toothpaste (negative control) at Day 56 from the MMRM will be 
presented, along with the two-sided p-value and 95% CIs. 
Tactile Threshold/Schiff Sensitivity Score at Day 28:
The other secondary endpoints:
•
Change from Baseline in Schiff sensitivity score at Day 28
•
Change from Baseline in tactile threshold (g) at Day 28
will be analysed using the same MMRM models described above for Schiff sensitivity score 
and tactile threshold (g), respectively. Differences between the least square mean changes from 
Baseline in Schiff sensitivity score and tactile threshold (g) will be presented for the Test 
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Toothpaste compared to Reference Toothpaste (negative control) at Day 28 from their 
respective MMRMs, along with two-sided p-values and 95% CIs.
The assumptions of normality and homogeneity of variance in each MMRM will be 
investigated. In case of violation of these assumptions, a suitable non-parametric test (adjusted 
for the randomization stratification value) will be performed to assess change from Baseline
comparisons (Test Toothpaste vs. Reference Toothpaste at Day 56 and Day 28, as appropriate); 
the results will be provided to support the MMRM results. 
DHEQ-48:
Change from Baseline will be calculated at Day 28 and Day 56 for all DHEQ endpoints.
•
Section 1 
-
Impact on Everyday Life: Q7, Q8 & Q9 (separate scores)
•
Section 2
-
DHEQ Total Score (sum of Q1-34)
-
DHEQ Restrictions Domain score (sum of Q1-4)
-
DHEQ Adaptation Domain score (sum of Q5-16) 
-
DHEQ Social Impact Domain score (sum of Q17-21)
-
DHEQ Emotional Impact Domain score (sum of Q22-29)
-
DHEQ Identity Domain score (sum of Q30-34)
-
DHEQ Global Oral Health (Q35)
-
DHEQ Effect on Life Overall (sum of Q36-Q39)
Change from Baseline will be calculated at the subject-level first then mean change from 
Baseline will be calculated for each DHEQ endpoint across all subjects. 
Change from Baseline for each DHEQ endpoint listed above will be analyzed using a MMRM 
with time point and maximum Baseline Schiff sensitivity score of the two ‘Test Teeth’ (2 or 3) 
as fixed effects, and the respective Baseline DHEQ score as covariate. Subject will be included 
as a repeated measure with unstructured covariance matrix. Kenward-Rogers degrees of 
freedom will be applied. The estimates of the adjusted mean (SE) change from Baseline will be 
presented along with 95% CIs for each treatment group.
For each DHEQ endpoint listed above, and each individual DHEQ question, the value at each 
timepoint (Baseline, Day 28 and Day 56) and the corresponding change from Baseline will be 
summarized descriptively for each treatment group. Raw means (± SE) for each DHEQ 
endpoint, and the individual DHEQ questions, at each assessment timepoint will be plotted by 
treatment group.
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12.3.3
Exploratory Analyses
Number of ‘Sensitive Teeth’:
The number of teeth sensitive to an evaporative (air) stimulus in the pool of ‘Eligible Teeth’ 
identified at Screening will be monitored across the study period. For this purpose, a ‘Sensitive 
Tooth’ will be defined as having a Schiff sensitivity score ≥2. 
‘Eligible Teeth’ = Teeth with no dentition exclusions which meet EAR, MGI and mobility inclusion criteria, and 
have a Screening tactile threshold ≤ 20g and a Screening Schiff sensitivity score ≥ 2.
The number of ‘Sensitive Teeth’ (i.e., the number of ‘Eligible Teeth’ with Schiff sensitivity 
score ≥ 2) will be calculated at Screening, Baseline, Day 28 and Day 56.
•
At Screening, the number of ‘Sensitive Teeth’ will be equal to the number of ‘Eligible 
Teeth’ (as described in Section 8.1.5).
‘Eligible Teeth’ = Teeth with Screening tactile threshold ≤ 20g and Screening Schiff sensitivity 
score ≥2.
•
At Baseline, Day 28 and Day 56, all ‘Eligible Teeth’ will be tested for evaporative (air) 
sensitivity. The number of ‘Sensitive Teeth’ will be the number of ‘Eligible Teeth’ with 
a Schiff sensitivity score ≥ 2 at that visit.
Summary statistics (mean, median, SE, SD, minimum, maximum) will be presented at each 
assessment timepoint for each treatment group. For each subject, the Schiff sensitivity score of 
each ‘eligible tooth’ at each timepoint will be listed by treatment group. Mean (± SE) number 
of ‘Sensitive Teeth’ will be plotted by treatment group
Labelled Magnitude Scales (LMSs):
Change from Baseline will be calculated at Day 28 and Day 56 for each LMS endpoint.
•
Intensity
•
Duration
•
Tolerability
•
Description
LMS data will be analysed for the two ‘Test Teeth’ only. Change from Baseline will be derived 
for each ‘Test Tooth’ first before calculating mean change for the two ‘Test Teeth’ for each 
subject.
Change from Baseline for each LMS endpoint listed above will be analyzed using a MMRM 
with time point and maximum Baseline Schiff sensitivity score of the two test teeth (2 or 3) as 
fixed effects, the respective Baseline LMS value as a covariate and subject as a repeated 
measure with unstructured covariance matrix. Kenward-Rogers degrees of freedom will be 
applied. The estimates of the adjusted mean (SE) change from Baseline will be presented along 
with 95% CIs for each treatment group.
For each LMS endpoint listed above, the value (in mm) at each timepoint (Baseline, Day 28 
and Day 56) and the corresponding change from Baseline (in mm) will be summarized 
descriptively for each treatment group. Raw means (± SE) for each LMS endpoint, at each 
assessment timepoint, will be plotted by treatment group.
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DHEQ-48 and Labelled Magnitude Scales (LMSs) Relationship:
The relationship between subject responses to the DHEQ-48 and the four LMSs will be 
investigated. For each DHEQ domain (Restrictions, Adaptation, Social Impact, Emotional 
Impact, Identity), each LMS endpoint (Intensity, Duration, Tolerability, Description) will be 
plotted against domain score at each assessment timepoint (Baseline, 28 and 56 days). A matrix 
of correlation plots will be presented for each domain. Spearman’s correlation coefficient will 
be calculated along with the associated p-value and presented with its respective correlation 
plot.
Schiff Sensitivity Score and Labelled Magnitude Scales (LMSs) Relationship:
The relationship between Schiff sensitivity score and the four LMSs will be investigated. Schiff 
sensitivity score (mean score of the two ‘Test Teeth’) and the four LMS endpoints (Intensity, 
Duration, Tolerability, Description) will be plotted at each assessment timepoint (Baseline, 28 
and 56 days) in a matrix of correlation plots. Spearman’s correlation coefficient will be 
calculated along with the associated p-value and presented with its respective correlation plot.
Satisfaction with Treatment NRS
A summary of the number of subjects reporting at each level of the NRS and the cumulative 
number of subjects reporting at each level or higher at Day 56 (Week 8) will be presented, and 
the NRS score at Day 56 (Week 8) will be summarized descriptively, by treatment group.
Subject free text comments will be listed by treatment group.
12.3.4
Safety Analyses
Safety analyses will be performed on the Safety population, according to investigational product 
received. AEs will be regarded as ‘treatment emergent’ if they occur on or after the first use of 
investigational product at Baseline (Visit 2). In the event of a missing start date, an AE will be 
assumed to be ‘treatment emergent’ unless the end date is prior to starting treatment. In case of 
misallocation, compared to the randomization schedule, TEAEs will be associated with the 
most recent study investigational received.
Each AE will be categorized as oral or non-oral by the investigator or medically qualified 
designee. All will be reviewed by the CRS and coded using the MedDRA prior to database lock 
and unblinding. 
A listing of all AEs will be presented for all subjects in the Safety population with the following 
AE summaries (number of distinct AEs and frequency/proportion of subjects affected) 
presented by treatment group and overall: 
•
TEAEs
•
TEAEs by System Organ Class (SOC) and Preferred Term (PT) 
•
TEAEs by Oral/Non-Oral and PT 
•
Treatment emergent treatment related AEs by Oral/Non-Oral and PT
•
Treatment emergent treatment related serious AEs by SOC and PT
Separate listings will be presented for:
•
Deaths, SAEs and any AEs leading to product or study discontinuation.
•
OST findings (with a summary of abnormalities by visit)
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•
OHT findings (with a summary of changes by visit)
•
Exposure to study product (Section 12.3.6.1.)
Medical device incidents will be listed; if there are no incidents, a null listing will be produced.
While no specific risks or anticipated adverse device effects are expected from use of the 
medical device (manual toothbrush) provided, any medical device incidents reported during the 
conduct of this study will be assessed to evaluate the safety of the device.
12.3.5
Demographic and Baseline Characteristics
Demographic and Baseline characteristics will be summarized by treatment group for the Safety 
and mITT populations (and for the PP population, if a PP analysis is performed) using 
descriptive statistics.
Categorical variables (such as sex, race, ethnicity and Baseline Schiff sensitivity score 
stratification value) will be summarized by the number and percentage of subjects with each 
relevant characteristic in each treatment group. Continuous variables such as (age) will be 
summarized by mean, SD, median, minimum and maximum values in each treatment group.
12.3.6
Study Product Compliance and Use of Other Therapies
12.3.6.1 Study Product Compliance
Compliance with investigational product use (number of brushings) will be listed and 
summarized for the mITT population at each visit, and cumulatively for the entire treatment 
period (for most subjects this will be approximately 8 weeks) by treatment group. 
Number of expected brushings = 
2 × Number of days between Visit 2 and Visit X
Number of actual brushings      = 
(Number of expected brushings) – (Number of missed
brushings) + (Number of additional brushings)
% Compliance at ‘Visit X’ = 
(Number of actual brushings prior to Visit X)     x 100
(Number of expected brushings prior to Visit X)
12.3.6.2 Prior and Concomitant Medications
Prior medications/non-drug therapies and concomitant medications/significant non-drug 
therapies taken during the study will be listed for the Safety population.
12.3.7
Handling of Dropouts and Missing Data 
MMRM analyses account for missing data using ‘a missing at random’ assumption, i.e., there 
is a systematic relationship between the propensity for missing values and the observed data, 
but not the missing data. 
Under such assumptions, MMRM is shown to provide unbiased estimates of the treatment effect 
whilst analysis of only complete cases using analysis of covariance (ANCOVA) is biased 
(Ashbeck, 2016; Baron, 2008). 
Such complete case analysis requires a ‘missing completely at random’ assumption to remain 
unbiased and this is unlikely to hold, i.e., the fact that the data are missing is independent of the 
observed and unobserved data.
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Using an MMRM, it will therefore be assumed that a subject with missing data at one post-
Baseline assessment visit would have obtained a similar efficacy result at that visit compared 
to a subject using the same investigational product with similar non-missing results at other 
timepoints (Baseline and the other post-Baseline assessment visits). 
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 sponsor procedures, the sponsor
or designee (i.e., third-party vendor) monitors will contact the investigator site prior to the start 
of the study to review the protocol, study requirements and site responsibilities to satisfy 
regulatory, ethical and sponsor requirements with the study staff.
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.
The sponsor or designee will monitor the study and site activity to verify that:
•
Data are authentic, accurate, and complete.
•
The safety and rights of subjects are being protected.
•
The study is conducted in accordance with the currently approved protocol, any other 
study agreements, GCP and all applicable regulatory requirements.
The extent and nature of monitoring will be described in a written monitoring plan held on file 
by the sponsor. 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, the sponsor may 
conduct a quality assurance assessment and/or audit of the investigator site records; 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 must agree to grant advisors, 
auditors and inspectors 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 the sponsor or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with the 
sponsor or its agents to prepare the investigator site for the inspection and will allow the sponsor
or its agent, whenever feasible, to be present during the inspection. The investigator will 
promptly supply copies of the inspection findings to the sponsor or its agent. Before response 
submission to the regulatory authority, the investigator will provide the sponsor or its agents 
with opportunity to review and comment on responses to any such findings. 
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The sponsor will be available to help the investigator prepare for an inspection.
13.3
Regulatory and Ethical Considerations
13.3.1
Institutional Review Board (IRB)
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, the ICF, the IB and/or safety statement (including any updates), and other 
relevant documents (e.g., recruitment advertisements, diaries), as applicable, from the IRB.  All 
correspondence with the IRB should be retained in the investigator site file. Copies of IRB 
approvals should be forwarded to the sponsor prior to the initiation of the study, and 
subsequently for any protocol amendments.
The only circumstance in which an amendment may be initiated prior to IRB approval is where 
the change is necessary to eliminate apparent immediate hazards to the subjects.  In that event, 
the investigator must notify the IRB and the sponsor in writing immediately after 
implementation.
13.3.2
Ethical Conduct of the Study
The study will be conducted in accordance with the protocol and applicable local regulatory 
requirements and laws, 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 Topic E6 (R2) Guideline for Good Clinical Practice, Nov 
2016), and the Declaration of Helsinki (World Medical Association, 64th General Assembly, 
Fortaleza 2013). In addition, the study will be conducted in accordance with applicable medical 
device regulations.
13.3.3
Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names or 
other identifiable data in any reports, publications, or other disclosures, except where required 
by laws.
When study data are compiled for transfer to the sponsor and other authorized parties, subject 
names, addresses and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by the sponsor in order to de-identify study subjects. Use of subject 
initials should be avoided.  
The investigator 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, the 
sponsor will maintain high standards of confidentiality and protection of subjects’ personal data 
consistent with applicable privacy laws.
Informed consent documents must be in compliance with ICH GCP, local regulatory 
requirements (including applicable local medical device regulations) and legal requirements
(including applicable privacy laws). All documents used during the informed consent process 
must be reviewed and approved by the sponsor, approved by the IRB before use, and available 
for inspection.
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The investigator must ensure that each study subject is fully informed about the nature and 
objectives of the study, and possible risks associated with participation. Informed consent 
documents should be comprehensive, concise, clear, relevant and understandable to a layperson.
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subject before any study-specific activity is performed.  The investigator will 
retain the original of each subject's informed consent signed document(s).
13.3.4
Subject Recruitment 
Advertising materials approved by the IRB and the investigator’s database may be used to 
recruit study subjects.  Use of an IRB approved pre-screening questionnaire to assess general 
suitability (basic subject characteristics) for the study is permitted. This generic questionnaire 
may be used as a phone script and/or to review internal databases to identify potential subjects.  
The sponsor will have an opportunity to review and approve the content of any recruitment 
materials before such materials are submitted for IRB review and used to identify potential 
study subjects. 
13.3.5
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP 
Within the sponsor, 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 Haleon-
sponsored human subject research studies. 
In the event of any prohibition or restriction imposed (i.e., clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational 
product(s), the sponsor should be informed immediately. 
In addition, the investigator will inform the sponsor 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 sponsor processes.
To help ensure the data provided by study participants are used to maximum effect in the 
creation of knowledge and understanding, the sponsor intends to make anonymized subject-
level data from this study available to external researchers for scientific analyses or to conduct 
further research that could help advance medical science or improve patient care. 
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 CSR. 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 sponsor site or other mutually agreeable location.
The sponsor will also provide the investigator with a full summary of the study results. The 
investigator is encouraged to share the summary results with the study subjects, as appropriate.
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A manuscript will be progressed for publication in the scientific literature if the results provide 
important scientific or medical knowledge. The procedures and timing for public disclosure of 
the results summary and for the development of a manuscript for publication will be in 
accordance with country specific regulatory requirements for disclosure and sponsor policy.
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.  
Records (investigator site file) must be maintained in such a way to allow easy and timely 
retrieval when needed (e.g., for sponsor audit or regulatory inspection) and must be available 
for review in conjunction with assessment of the facility, supporting systems and relevant 
investigator 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, are a true and accurate copy of the original and meet 
accessibility and retrieval standards, including re-generation of 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 the subject’s anonymity will be maintained. In CRFs or other 
documents submitted to the sponsor, 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 the sponsor (e.g., subject signed consent 
forms) should be maintained by the investigator in strict confidence.
Records and documents, including signed ICFs, 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 
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 
investigator site for this study, as dictated by any institutional requirements or local laws or 
regulations, sponsor standards/procedures, and/or institutional requirements.  
No study document should be destroyed without a prior written agreement between the sponsor
and the investigator. The investigator must notify the sponsor 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 
investigator site.
13.7
Conditions for Terminating the Study 
Premature termination of this study may occur because of a regulatory authority decision, a 
change in IRB opinion, study product safety problems, or at the discretion of the sponsor. In 
addition, the sponsor retains the right to discontinue development of the investigational product
at any time. 
If a study is prematurely terminated, the sponsor 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 the sponsor, all study materials 
must be collected and all CRFs completed to the greatest extent possible. Where required by 
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the applicable regulatory requirements, the sponsor should inform the regulatory authority(ies) 
and the investigator should promptly inform the IRB and provide the IRB a detailed written 
explanation for the termination or suspension. 
If the IRB terminates or suspends its approval/favorable opinion of the study, the investigator 
should promptly notify the sponsor and provide the sponsor with a detailed written explanation 
for the termination or suspension.
Upon completion or premature discontinuation of the study, the sponsor’s monitor will conduct 
site closure activities with the investigator and site staff, as appropriate, in accordance with 
applicable regulations, including GCP and sponsor Standard Operating Procedures.
14
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[Pereira JC, de Carvalho Sales-Peres SH, Francisconi-dos-Rios LF, et al. (2015)] Current and 
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Dentifrice (Abstract #1354). AADR Annual Meeting 2012 Tampa, Florida.
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[West N, Addy M, Jackson R, et al. (1997)] Dentine hypersensitivity and the placebo response: 
A comparison of the effect of strontium acetate, potassium nitrate and fluoride toothpastes. J
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professionally and self‐administered agents. J Clin Periodontol 2015; 42: S256-S302.
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sensitivity: meta-analysis (Abstract #2323). IADR 2019 Vancouver, Canada.
[West NX, He T, Zou Y, et al. (2021)] Bioavailable gluconate chelated stannous fluoride 
toothpaste meta-analyses: Effects on dentine hypersensitivity and enamel erosion. J Dent 2021; 
105: 103566.
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children. Available on request.
[White DJ, Lawless M, Fatade A, et al. (2007)] Stannous fluoride/sodium hexametaphosphate 
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toothpaste for patients with dentine hypersensitivity: a meta-analysis. West China J Stomatol; 
34(2): 150-155.
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dentifrices. J Dent Res; 91: 744.
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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
BDR
Blinded Data Review
CI
Confidence Interval
CRF
Case Report Form
CRS
Clinical Research Scientist
CSM
Clinical Study Manager
CSR
Clinical Study Report
DH
Dentin Hypersensitivity
DHEQ
Dentin Hypersensitivity Experience Questionnaire
EAR
Erosion/Abrasion/Attrition
eCRF
Electronic Case Report Form
EDC
Electronic Data Capture
EudraCT
European Clinical Trials Database
FDA
Food and Drug Administration (United States)
g
Gram
GCP
Good Clinical Practice
GDS
Global Data Sheet
GRASE
Generally Recognized as Safe and Effective
GSKCH
GlaxoSmithKline Consumer Healthcare
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Conference on Harmonisation
IND
Investigational New Drug 
IRB
Institutional Review Board
IRT
Interactive Response Technology
LMS
Labelled Magnitude Scale
LSLV
Last Subject Last Visit 
MedDRA
Medical Dictionary for Regulatory Activities
MGI
Modified Gingival Index
mITT
Modified Intention-to-Treat
ml
Milliliter
mm
Millimeter
MMRM
Mixed Model with Repeated Measures
MoA
Mode of Action
N/A
Not Applicable
NRS
Numeric Rating Scale
OHrQoL
Oral Health-Related Quality of Life
OHT
Oral Hard Tissue
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Abbreviation
Term
OST
Oral Soft Tissue
OTC
Over-the-Counter
PI
Personal Information
PP
Per Protocol
ppm
Parts per Million
PRO
Patient-Reported Outcome
PT 
Preferred Term
Q
Question
QC
Quality Control
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SD
Standard Deviation
SE
Standard Error
SnF2
Stannous Fluoride
SOC
System Organ Class
SOP
Standard Operating Procedure
TEAE
Treatment Emergent Adverse Event
US
United States
VAS
Visual Analogue Scale
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15.2
Dentine Hypersensitivity Experience Questionnaire (Example 
DHEQ-48)
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 month 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) There have been times when I 
can’t finish my meal because of 
the sensations. 
3) It takes a long time to finish 
some foods and drinks because of 
sensations in my teeth. 
4) There have been times when I 
have had problems eating ice 
cream because of these 
sensations. 
The following questions are about the ways in which the sensations in your teeth have 
forced you to change things in your daily life. Thinking about yourself over the last month
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) 
5) I have to change the way I eat 
or drink certain things. 
6) I have to be careful how I 
breathe on a cold day. 
7) I have to leave some cold 
foods or drinks to warm up 
before I can have them. 
8) I have to cool some foods or 
drinks down before I can have 
them. 
9) I have to cut up some fruits 
before being able to eat them. 
10) I have to wear a scarf over 
my mouth on cold days. 
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The following questions are about the things you do in your daily life to avoid experiencing 
the sensations in your teeth. Thinking about yourself over the last month 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) 
11) I have avoided very cold 
drinks or foods. 
12) I have avoided very hot 
drinks or foods. 
13) When eating some foods I 
have made sure they don’t 
touch certain teeth. 
14) I have changed the way I 
brush my teeth. 
15) When eating some foods I 
have made sure I bite in small 
pieces. 
16) There are other foods I 
have avoided. 
The following questions are about the way the sensations affect you when you are with other 
people or in certain situations. Thinking about yourself over the last month 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) 
17) Because of the sensations I 
take longer than others to finish 
a meal. 
18) I have to be careful what I 
eat when I am with others 
because of the sensations in 
my teeth. 
19) I hide the way I am eating 
when I am with others because 
of the sensations in my teeth. 
20) I am unable to fully take 
part in conversations because 
of the sensations in my teeth. 
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21) 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. 
The following questions are about the way the sensations in your teeth make you feel.
Thinking about yourself over the last month 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)
22) I’ve been frustrated because I 
can’t find anything that deals with 
the sensations I have in my teeth. 
23) I’ve been anxious that 
something I eat or drink might 
cause sensations in my teeth. 
24) The sensations in my teeth 
have been irritating. 
25) I have been annoyed with 
myself because I did something 
that I knew caused these 
sensations. 
26) I felt guilty because I might 
have contributed to the sensations 
I am having with my teeth. 
27) The sensations in my teeth 
have been annoying. 
28) The sensations in my teeth 
have been embarrassing. 
29) I have been anxious because 
of the sensations in my teeth. 
The following questions are about what the sensations in your teeth mean for you. Thinking 
about yourself over the last month 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) 
30) I find it difficult to accept 
that I am a person who has 
these sensations in my teeth. 
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31) Having these sensations in 
my teeth makes me feel 
different from others. 
32) Having these sensations in 
my teeth makes me feel old. 
33) Having these sensations in 
my teeth makes me feel 
damaged. 
34) Having these sensations in 
my teeth makes me feels as 
though I am unhealthy. 
The last five questions ask about how much the sensations in your teeth affect your life 
overall. 
Excellent 
(1) 
Very
good 
(2) 
Good  
(3) 
Fair 
(4) 
Poor 
(5) 
Very poor 
(6) 
35) Overall how would you rate the 
health of your mouth, teeth and gums?
Very Much
(4)
Quite a bit
(3)
Somewhat
(2)
A little
(1)
Not at all
(0)
36) Overall how much do the sensations in 
your teeth bother you?
37) Overall, how much do the things you 
do to manage the sensations bother you?
38) Overall, how much do the sensations 
in your teeth affect your quality of life?
39) Overall, how much do the things you 
do to manage the sensations in your teeth 
affect your quality of life?
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15.3
Labelled Magnitude Scales: Intensity, Duration, Tolerability & 
Description (Example LMSs)
NOT TO SCALE
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NOT TO SCALE
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15.4
LMS Training Exercise (Example)
STUDY STAFF INSTRUCTIONS 
Subjects will be given a hard copy of the instructions for completing the LMSs; the investigator
(or designee) should read the ‘Subject Instructions’ aloud while the subject reads along. 
Subjects should be encouraged to ask questions if they are unsure about anything they read.
The subject will then complete the LMS training exercise, and the investigator (or designee)
will determine whether the subject understands how to use the LMS based on their training 
exercise responses and the guidance below. 
Interpretation of the Line Scale Training Exercise 
The objective of the training exercise is NOT to determine whether the subject can provide 
specific ‘correct’ answers but to determine if they understand the concept of LMS completion. 
The following general assessment criteria are suggested.
•
Is the subject placing their marks only on the verbal descriptors? If so, remind them they 
should use the entire scale, including areas of the line between descriptors. 
•
Is the subject placing their marks in the same place on all four LMSs. If so, explain 
again that each LMS measures a different aspect of their response (intensity, duration, 
their ability to tolerate it, and how they would describe it) and this likely produce marks 
in different places on each scale. 
•
The subject should indicate their response by marking an ‘X’ on the LMS. If they are 
circling descriptors or making unclear marks, remind them of the correct way to record 
their response. 
If the subject appears unable to complete the LMSs (intensity, duration, tolerability and 
description) with appropriate responses, the investigator (or designee) should talk through their
grading of the first two scenarios. If the marks are generally correctly ordered but far from their 
likely true positions, ask the subject to verbalize why they placed the marks where they did. 
However, the investigator/ designee should be careful not to pressure the subject to change their 
responses. Start with an item the subject rated ‘well’, ask about that, then continue by asking 
about an item where they did less well. 
If the investigator (or designee) deems a subject unable to provide appropriate responses to the 
LMS training questions, it is unlikely they will provide reliable LMS responses following 
application of the evaporative (air) stimulus. The subject should be withdrawn.
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SUBJECT INSTRUCTIONS 
The purpose of this training exercise is to introduce you to four different line scales you will be 
asked to use during the study. Each one has different words positioned along the line that can 
be used to rate the feelings or sensations people can experience in their mouths.
There are no right or wrong answers. 
Read the description of each example sensation or feeling carefully, then try to remember or 
imagine what each one feels like. If you haven’t experienced exactly what is described, try to 
think of something similar. As you think about the example, think about the word on the line 
that best describes what that sensation feels like. You can ‘fine tune’ your rating to best reflect 
that experience by marking the line between that word and the words next to it, up or down the 
scale. 
INDICATE HOW YOU WOULD RATE THE FEELING DESCRIBED BY PLACING AN 
‘X’ ON THE LINE. 
YOU CAN PLACE YOUR MARK ANYWHERE ALONG THE LINE, EXACTLY ON A 
DESCRIPTIVE WORD OR BETWEEN WORDS. 
Please turn to the next page for the first example in this exercise. 
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Let’s start with this example. 
The touch of a pill on your tongue. 
Have you ever experienced this feeling or sensation before? Yes / No (Please circle one)
First please rate the INTENSITY of this feeling or sensation. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words. 
NOT TO SCALE 
Please turn to the next page. 
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Still thinking about the touch of a pill on your tongue, please rate the DURATION of this 
feeling or sensation. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words.
NOT TO SCALE 
Please turn to the next page. 
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Clinical Protocol
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Still thinking about the touch of a pill on your tongue, please rate how much you are able to 
TOLERATE with this feeling or sensation. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words. 
NOT TO SCALE 
Please turn to the next page. 
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Finally, still thinking about the touch of a pill on your tongue, please give a rating that 
DESCRIBES the kind of feeling or sensation this is. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words. 
NOT TO SCALE 
Please turn to the next page. 
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Clinical Protocol
Protocol Number: 300103
Property of Haleon- Confidential
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Let’s try this example. 
The pain from biting your tongue. 
Have you ever experienced this feeling or sensation before? Yes / No (Please circle one)
First please rate the INTENSITY of this feeling or sensation. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words. 
NOT TO SCALE 
Please turn to the next page. 
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Clinical Protocol
Protocol Number: 300103
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Clinical Protocol Template v10.0
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Still thinking about the pain from biting your tongue, please rate the DURATION of this 
feeling or sensation. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words.
NOT TO SCALE 
Please turn to the next page. 
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Clinical Protocol
Protocol Number: 300103
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Clinical Protocol Template v10.0
Page 108 of 113
Still thinking about the pain from biting your tongue, please rate how much you are able to 
TOLERATE with this feeling or sensation. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words.
NOT TO SCALE 
Please turn to the next page. 
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Clinical Protocol
Protocol Number: 300103
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Clinical Protocol Template v10.0
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Finally, still thinking about the pain from biting your tongue, please give a rating that 
DESCRIBES the kind of feeling or sensation this is. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words. 
NOT TO SCALE 
Please turn to the next page. 
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Clinical Protocol
Protocol Number: 300103
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Let’s try one last example. 
The pain of a persistent toothache. 
Have you ever experienced this feeling or sensation before? Yes / No (Please circle one)
First please rate the INTENSITY of this feeling or sensation. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words. 
NOT TO SCALE 
Please turn to the next page. 
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Clinical Protocol
Protocol Number: 300103
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Clinical Protocol Template v10.0
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Still thinking about the pain of a persistent toothache, please rate the DURATION of this 
feeling or sensation. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words. 
NOT TO SCALE 
Please turn to the next page. 
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Protocol Number: 300103
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Clinical Protocol Template v10.0
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Still thinking about the pain of a persistent toothache, please rate how much you are able to 
TOLERATE with this feeling or sensation. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words. 
NOT TO SCALE 
Please turn to the next page. 
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Haleon
Clinical Protocol
Protocol Number: 300103
Property of Haleon- Confidential
May not be used, divulged, published or otherwise disclosed without the consent of Haleon
Clinical Protocol Template v10.0
Page 113 of 113
Finally, still thinking about the pain of a persistent toothache, please give a rating that 
DESCRIBES the kind of feeling or sensation this is. 
Mark the scale below with an ‘X’ to indicate the best description of that feeling or sensation. 
Remember, you can mark anywhere on the line, including between the descriptive words. 
NOT TO SCALE 
You have finished the training exercise and are now ready to take part in the main part 
of the study. 
If you have any questions about this training, please ask the member of staff training you.
If you feel that you understand how to use these scales, please tell the member of staff too. 
Thank you for your time!
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SAP_001.pdf: 
0.454 percent weight/weight Stannous Fluoride Toothpaste
300103
Property of Haleon
Confidential
May not be used, divulged, published, or otherwise disclosed
without the consent of Haleon
Statistical Analysis Plan Template v6.0
Page 1 of 48
STATISTICAL ANALYSIS PLAN 
AN 8-WEEK, RANDOMIZED, CONTROLLED, EXAMINER-BLIND, 
CLINICAL STUDY TO EVALUATE THE EFFICACY OF A STANNOUS 
FLUORIDE TOOTHPASTE FOR THE RELIEF OF DENTIN 
HYPERSENSITIVITY IN A POPULATION OF DENTIN 
HYPERSENSITIVITY SUFFERERS
Protocol Number:
300103
Phase:
N/A
This document contains confidentiality statements that are not relevant 
for this publicly available version
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Document History
Document
Version Date
Summary of Changes (New analysis or 
Change in planned analysis)
Original Analysis Plan
03-May-2024
Not applicable (N/A)
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Table of contents
Document History ...............................................................................................................2
Table of contents .................................................................................................................3
List of Tables.......................................................................................................................4
List of Figures......................................................................................................................4
Abbreviations..............................................................................................................................5
1
Summary of Key Protocol Information...............................................................................6
1.1
Study Design............................................................................................................7
1.2
Study Objectives....................................................................................................11
1.3
Study Products.......................................................................................................12
1.4
Sample Size Calculation........................................................................................13
2
Planned Analyses...............................................................................................................14
2.1
Interim Analysis.....................................................................................................14
2.2
Final Analyses .......................................................................................................14
3
Considerations for Data Analyses and Data Handling Conventions.................................14
3.1
Baseline Definition ................................................................................................14
3.2
Subgroups/Stratifications.......................................................................................15
3.3
Centers Pools .........................................................................................................15
3.4
Timepoints and Visit Windows .............................................................................15
4
Data Analysis.....................................................................................................................15
4.1
Populations for Analysis........................................................................................15
4.1.1
Subject Disposition ...............................................................................15
4.1.2
Protocol Deviations...............................................................................16
4.1.3
Analysis Populations.............................................................................17
4.2
Subject Demographics and Other Baseline Characteristics...................................18
4.2.1
Demographic and Baseline Characteristics...........................................18
4.2.2
General Medical History.......................................................................18
4.3
Treatments (Study Product, Rescue Medication, other Concomitant 
Therapies, Compliance).........................................................................................18
4.3.1
Study Product Compliance and Exposure.............................................18
4.3.2
Prior and Concomitant Medication .......................................................19
4.4
Analysis of Efficacy ..............................................................................................19
4.4.1
Primary Efficacy Endpoint....................................................................20
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4.4.2
Secondary Efficacy Endpoints..............................................................21
4.4.3
Exploratory Efficacy Variables.............................................................26
4.4.4
Handling of Missing Values/Censoring/Discontinuations....................29
4.5
Analysis of Safety..................................................................................................29
4.5.1
Adverse Events and Serious Adverse Events........................................29
4.5.2
Other Safety Variables ..........................................................................30
4.6
Analysis of Other Variables...................................................................................31
4.6.1
DHEQ-48 and LMSs Relationship........................................................31
4.6.2
Schiff Sensitivity Score and LMSs Relationship..................................31
5
Changes to the Protocol Defined Statistical Analysis Plan...............................................32
Appendix 1: List of Data Displays ....................................................................................33
List of Tables
Table 1-1
Schedule of Activities .............................................................................8
Table 1-2
Study Objectives and Endpoints ...........................................................11
Table 1-3
Acclimatization/Investigational Toothpastes........................................13
List of Figures
Figure 4-1
Numerical Rating Scale (0 to 10)..........................................................28
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Abbreviations
Abbreviation
Term
AE
Adverse Events 
BDRM
Blinded Data Review Meeting
CIs
Confidence Intervals 
CRF
Case Report Form
DH
Dentin Hypersensitivity
DHEQ
Dentin Hypersensitivity Experience Questionnaire
EAR
Erosion/Abrasion/ Recession 
eCRF
Electronic Case Report Form
ICF
Informed Consent Form
LSM
Labelled Magnitude Scale
MedDRA
Medical Dictionary for Regulatory Activities
mITT
Modified Intent-To-Treat 
MMRM 
Mixed Model with Repeated Measures
N/A
Not Applicable
NRS
Numeric Rating Scale 
OHRQoL
Oral health-related quality of life 
OHT
Oral Hard Tissue 
OST
Oral Soft Tissue 
PP
Per-Protocol
PT
Preferred Term
SAE
Serious Adverse Events 
SAP
Statistical Analysis Plan
SD 
Standard Deviation
SE
Standard Error 
SnF2
Stannous Fluoride
SOC
System Organ Class
TEAEs
Treatment Emergent Adverse Events 
WHODD
World Health Organization Drug Dictionary 
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The purpose of this Statistical Analysis Plan (SAP) is to describe the planned analyses and 
outputs to be included in the Clinical Study Report for Protocol 300103 (version 2.0, dated 
07-Feb-2024).
1
Summary of Key Protocol Information
The purpose of this trial is to evaluate the anti-sensitivity efficacy of a stannous fluoride 
toothpaste in a population of Dentin Hypersensitivity (DH) sufferers. The clinical efficacy of 
the 0.454% Stannous Fluoride (SnF2) toothpaste will be compared with that of a regular fluoride 
toothpaste with no known anti-sensitivity efficacy (negative control). The study will follow a 
single center, 8-week, randomized, controlled, examiner-blind, 2-treatment arm, parallel 
design, stratified (by maximum Baseline Schiff sensitivity score of the two selected ‘Test 
Teeth’) clinical study to evaluate the anti-sensitivity efficacy of a 0.454% SnF2 toothpaste in a 
DH population. The clinical efficacy of the 0.454% SnF2 toothpaste (Test Toothpaste) will be 
compared with that of a Reference Toothpaste, a commercially available, regular fluoride 
toothpaste with no known anti-sensitivity properties (negative control). 
At Screening (Visit 1), following provision of written Informed Consent Form (ICF), suitability 
to participate will be reviewed against the protocol inclusion/exclusion criteria. Eligible 
subjects will enter an acclimatization period (14-28 days) prior to Baseline assessments during 
which they will brush twice daily (morning and evening) with the acclimatization toothpaste (a 
different commercially available, regular fluoride toothpaste from the Reference Toothpaste). 
At Baseline (Visit 2), eligibility to continue will be assessed. Subjects who demonstrate the 
required qualifying levels of DH at Screening (Visit 1) and Baseline (Visit 2) will be 
randomized to study treatment and instructed to brush with their assigned investigational 
toothpaste twice daily (morning and evening) for the duration of the 8-week treatment period. 
DH will be assessed at Screening (Visit 1) and Baseline (Visit 2), and after 28- and 56-days 
treatment (Visits 3 and 4, respectively) using two independent clinical measures: (i) tactile 
threshold (g) following a tactile stimulus and (ii) Schiff sensitivity score following an 
evaporative (air) stimulus. 
Oral health-related quality of life (OHRQoL) will be monitored over the treatment period using 
the Dentin Hypersensitivity Experience Questionnaire (DHEQ-48), completed by study 
subjects at Baseline (Visit 2), and after 28- and 56-days treatment (Visits 3 and 4, respectively). 
Subject-perceived DH will also be investigated across the 8-week treatment period using four 
Labelled Magnitude Scales (LMSs) to capture the Intensity, Duration, Tolerability and 
Description of their response to the evaporative (air) stimulus. At the final visit (Day 56), 
subjects will rate their level of satisfaction with their assigned investigational toothpaste for the 
overall management of their DH, using a Numeric Rating Scale (NRS). 
Safety and oral tolerability of the investigational toothpastes will be monitored over the 8-week 
usage period by review of treatment emergent adverse events (TEAEs).
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1.1
Study Design
This will be a single center, 8-week, randomized, controlled, examiner-blind, 2-treatment arm, 
parallel group, stratified study in healthy subjects with DH. Subjects who meet the required 
study criteria at Screening and Baseline will be randomized to one of two study treatments: 
0.454% SnF2 toothpaste (Test Toothpaste) or a regular fluoride toothpaste (Reference 
Toothpaste) 
Two independent stimulus-based clinical measures will be employed to assess the efficacy of 
the investigational toothpastes. 
•
A tactile stimulus will be administered using a constant pressure probe - Yeaple Probe 
(Polson, 1980); subject response to the stimulus determines the tactile threshold in grams 
(g). 
•
An evaporative (air) stimulus (i.e., a thermal stimulus) will be administered using a dental 
air syringe; subject response to the stimulus will be examiner-evaluated using the Schiff 
sensitivity scale (Schiff, 1994).
DH will be assessed at Screening, Day 0 (Baseline), Day 28 (Week 4) and Day 56 (Week 8). 
On completion of the Baseline assessments, the clinical examiner will select two ‘Test Teeth’ 
for assessment of tactile and evaporative (air) sensitivity at all subsequent visits. To qualify for 
selection as a ‘Test Tooth’, the tooth must meet the protocol-specific inclusion/exclusion 
criteria (Section 5.2 Inclusion Criteria 6 & 7; Section 5.3 Exclusion Criterion 26 of protocol), 
specifically tactile threshold ≤ 20g and Schiff sensitivity score ≥ 2 at both Screening and 
Baseline visits. In addition, the number of ‘Sensitive Teeth’ will be determined at each study 
visit (Schiff sensitivity score ≥ 2) as described in Sections 8.1.5, 8.2.1.5, 8.2.2.5 and 8.2.3.5 of 
the protocol. 
Approximately 110 qualifying subjects will be stratified according to the maximum Baseline 
Schiff sensitivity score of their two ‘Test Teeth’ and randomized to treatment (approximately 
55 subjects per treatment group). Randomized subjects will be instructed to brush twice daily 
(morning and evening) with their assigned investigational toothpaste for the next 56 days (8 
weeks) and record each brushing in the diary provided. First use will be performed under 
supervision at the investigator site; to facilitate compliance an additional supervised on-site 
brushing will be completed at the end of Visit 3. 
Changes in OHRQoL will be monitored over the treatment period using the validated DHEQ-
48. The DHEQ-48 will be completed by study subjects at Baseline, and after 28- and 56-days 
treatment. Subject-perceived DH will also be investigated for the two selected ‘Test Teeth’ 
using LMSs. Subjects will complete four LMSs to capture the Intensity, Duration, Tolerability 
and Description of their response to the evaporative (air) stimulus administered at Baseline, 
Day 28 and Day 56. At the final visit (Day 56), after all clinical procedures have been 
completed, subjects will rate their level of satisfaction with their assigned investigational 
toothpaste for the overall management of DH using an NRS. 
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To standardize oral hygiene practice in the study population prior to treatment and to help 
minimize the potential impact of ‘placebo’/‘no treatment’ effects, eligible subjects will 
complete an acclimatization period (14-28 days duration) between the Screening and Baseline 
visits during which they will brush twice daily (morning and evening) with a regular fluoride 
toothpaste (a different commercially available product from the Reference Toothpaste). First 
use of acclimatization toothpaste will be performed under supervision at the investigator site.
Safety and oral tolerability of the investigational toothpastes will be monitored over the 
treatment period by review of TEAEs.
Table 1-1 presents the schedule of activities. 
Table 1-1
Schedule of Activities
Procedure/Assessment
Study Visits
Visit 1
Screening
Visit 2
Day 0
Baseline
Visit 3
Day 28
(± 2 
days)
Visit 4
Day 
56 (± 
3 
days)
Informed consent
x
Acclimatization Period (14-28 days)
Demographics
x
Review Subject’s Oral Care Products
x
Review Medical History & Current/Prior 
Concomitant Medication/Treatment1
x
Review Changes in Health & 
Medications/Treatments1
x
x
x
Return Acclimatization Toothpaste, Toothbrush & 
Diary2
x
Return Investigational Toothpaste, Toothbrush & 
Diary2
x
Compliance Checks2
x
x
x
Subject-Completed DHEQ3
x
x
x
Subject-Completed LMS Training Exercise 
x
Oral Soft Tissue (OST) Examination
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 Clinical Assessment of Tactile 
Sensitivity4
x
x
Qualifying Clinical Assessment of Evaporative 
(Air) Sensitivity (Schiff sensitivity score)5
x
x
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Procedure/Assessment
Study Visits
Visit 1
Screening
Visit 2
Day 0
Baseline
Visit 3
Day 28
(± 2 
days)
Visit 4
Day 
56 (± 
3 
days)
Subject-Perceived Evaporative (Air) Sensitivity 
(LMSs)6
x
Clinical Assessment of Evaporative (Air) 
Sensitivity of the Remaining ‘Eligible Teeth’ 
Identified at Screening5
x
Clinical Examiner Selects Two ‘Test Teeth’ 
(Qualifying Subjects Only)7
x
Review Inclusion/Exclusion Criteria
x
x
Confirm Subject Eligibility/Qualification
x
x
Dispense Acclimatization Toothpaste, 
Toothbrush, Timer, Rinsing Cups & Diary
x
Supervised Brushing with Acclimatization 
Toothpaste
x
Stratification/Randomization
x
Dispense Investigational Toothpaste, 
Toothbrush, Rinsing Cups & Diary
x
x8
Supervised Brushing with Investigational 
Toothpaste
x
Clinical Assessment of Tactile Sensitivity: Two 
‘Test Teeth’ only4
x
x
Clinical Assessment of Evaporative (Air) 
Sensitivity (Schiff sensitivity score): 
Assess the Two ‘Test Teeth’ First, then the 
Remaining ‘Eligible Teeth’ Identified at 
Screening5
x
x
Subject-Perceived Evaporative (Air) Sensitivity 
(LMSs): Two ‘Test Teeth’ Only6
x
x
Supervised Brushing with Investigational 
Toothpaste
x
Satisfaction with Treatment: Subject-Completed 
NRS
x
Study Conclusion
x
Monitor Adverse Events (AEs) and Medical 
Device Incidents9
x
x
x
x
AE: Adverse Event; DHEQ: Dentin Hypersensitivity Experience Questionnaire; EAR: Erosion/Abrasion/ 
Recession; LMS: Labelled Magnitude Scales; MGI: Modified Gingival Index; OHT: Oral Hard Tissue; 
OST: Oral Soft Tissue.
Footnotes:
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1. Female subjects of child-bearing potential should be asked to confirm pregnancy status at each 
    visit.
2. Subjects will be required to bring their study supplies (minus timer & rinsing cups) to every visit. 
    Perform visual check of returned study supplies, review diary & evaluate compliance. 
    Visit 2: Check compliance with use of acclimatization toothpaste. 
    Visit 3 & Visit 4: Check compliance with use of investigational toothpaste. 
    Visits 2-4: Check compliance with Lifestyle Guidelines/Medication requirements. 
3. DHEQ-48 must be completed prior to the OST examination and clinical assessments. 
    Visit 2: Complete all questions. 
    Visits 3 & 4: Complete Section 1, Questions 7-9 & Section 2, all questions. 
4. Tactile Threshold Assessments: Visits 1-2: Maximum force 20g (Screening and Baseline); 
    Visits 3-7: Maximum force 80g. 
5. Evaporative (air) sensitivity (Schiff sensitivity score) should be assessed after tactile sensitivity,   
    ensure minimum 5-minute delay after the last tactile assessment before the first evaporative (air)   
    assessment for tooth recovery. 
    Visit 1 (Screening): Assess evaporative (air) sensitivity for all teeth with a Screening tactile   
    threshold ≤ 20g. 
    Visit 2 (Baseline): First assess evaporative (air) sensitivity for all ‘Eligible Teeth’ identified at   
    Screening with a Baseline tactile threshold of ≤ 20g, then assess the remaining ‘Eligible Teeth’ (i.e.,   
    the remaining teeth from the pool of ‘Eligible Teeth’ identified at Screening, with a Baseline tactile 
    threshold >20g). 
    Visit 3 (Day 28) & Visit 4 (Day 56): First assess evaporative (air) sensitivity for the two ‘Test Teeth’   
    first, then assess the remaining ‘Eligible Teeth’ identified at Screening (excluding the two ‘Test   
    Teeth’). ‘Eligible Teeth’ = Teeth with no dentition exclusions which met EAR, MGI & mobility criteria,   
    with Screening tactile threshold ≤ 20g & Screening Schiff sensitivity score ≥ 2. 
6. Visit 2 (Baseline): Complete 4 LMSs (Intensity, Duration, Tolerability & Description) for each tooth 
   with a Baseline Schiff sensitivity score ≥ 2 only, immediately after the Baseline Schiff sensitivity 
   score has been recorded for that tooth. 
   Visit 3 (Day 28) & Visit 4 (Day 56): Complete 4 LMSs for each ‘Test Tooth’, immediately after its   
   Schiff sensitivity score has been recorded. 
7. Selected ‘Test Teeth’ should be in different quadrants, with the requisite qualifying levels of DH at    
    both Screening (Visit 1) and Baseline (Visit 2), i.e., tactile threshold ≤ 20 g and Schiff sensitivity   
    score ≥ 2. 
8. Visit 3: Supply new diary only. 
9. AEs, and therefore all serious adverse events (SAEs) will be recorded from immediately after ICF   
   until 5 days after the last use of investigational toothpaste. Incidents will be recorded from first to last   
   use of the medical device (the manual toothbrush used to apply the acclimatization and   
    investigational toothpastes).
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1.2
Study Objectives
Study objectives and endpoints are defined in Table 1-2:
Table 1-2
Study Objectives and Endpoints
Objectives
Endpoints
Efficacy
Primary 
To demonstrate the clinical efficacy of a 
0.454% w/w SnF2 toothpaste in reducing DH 
to an evaporative (air) stimulus (as measured 
by Schiff sensitivity score), compared to a 
negative control toothpaste, after 8 weeks 
twice daily use.
Change from Baseline in Schiff sensitivity score 
at Day 56 (Week 8).
Secondary 
To demonstrate the clinical efficacy of a 
0.454% w/w SnF2 toothpaste in reducing DH 
to a tactile stimulus (as measured by tactile 
threshold in grams [g]), compared to a 
negative control toothpaste, after 8 weeks 
twice daily use. 
Change from Baseline in tactile threshold (g) at 
Day 56 (Week 8).
To demonstrate the clinical efficacy of a 
0.454% w/w SnF2 toothpaste in reducing DH 
to evaporative (air) and tactile stimuli (as 
measured by Schiff sensitivity score and 
tactile threshold (g), respectively), compared 
to a negative control toothpaste, after 4 
weeks twice daily use. 
Change from Baseline in Schiff sensitivity score 
at Day 28 (Week 4). 
Change from Baseline in tactile threshold (g) at 
Day 28 (Week 4). 
To describe subject-perceived changes in 
oral health-related quality of life (OHrQoL), 
as measured by the Dentin Hypersensitivity 
Experience Questionnaire (DHEQ-48), after 
4- and 8-weeks twice daily use of their 
assigned investigational toothpaste.
At Day 28 (Week 4) & Day 56 (Week 8): 
Change from Baseline in DHEQ-48 endpoints. 
Section 1 
•
Impact on Everyday Life (Q7-9) 
Section 2 
•
Total Score (Q1-34) 
•
Individual Domain Scores
o
Restrictions (Q1-4)
o
Adaptation (Q5-16) 
o
Social Impact (Q17-21) 
o
Emotional Impact (Q22-29) 
o
Identity (Q30-34) 
•
Global Oral Health Score (Q35) 
•
Effect on Life Overall Score (Q36-39) 
Exploratory 
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Objectives
Endpoints
Efficacy
To determine the number of ‘Sensitive Teeth’ 
(evaporative (air) sensitivity only) in the pool 
of ‘Eligible Teeth’ identified at Screening, 
Baseline, and after 4 and 8 weeks twice daily 
use of assigned investigational toothpaste.
At Screening, Baseline, Day 28 (Week 4) & Day 
56 (Week 8): 
Number of ‘Sensitive Teeth’ 
Defined as the number of ‘Eligible Teeth’ (identified at 
Screening) with a Schiff Sensitivity Score ≥ 2. 
To investigate subject-perceived changes in 
DH to an evaporative (air) stimulus, as 
measured by Labelled Magnitude Scales 
(LMSs), after 4 and 8 weeks twice daily use 
of their assigned investigational toothpaste. 
At Day 28 (Week 4) & Day 56 (Week 8): 
Change from Baseline in LMS endpoints. 
•
Intensity 
•
Duration 
•
Tolerability 
•
Description 
To investigate the relationship between 
subject responses to the DHEQ-48 and the 
LMSs at Baseline, and after 4 and 8 weeks 
twice daily use of assigned investigational 
toothpaste. 
At Baseline, Day 28 (Week 4) & Day 56 (Week 
8): 
DHEQ-48 endpoints, as listed above. 
LMS endpoints, as listed above. 
To investigate the relationship between the 
Schiff sensitivity scale and the LMSs at 
Baseline, and after 4 and 8 weeks twice daily 
use of assigned investigational toothpaste. 
At Baseline, Day 28 (Week 4) & Day 56 (Week 
8): 
Mean Schiff sensitivity score of the two ‘Test 
Teeth’. 
LMS endpoints, as listed above. 
To investigate subject satisfaction with their 
assigned investigational toothpaste for the 
overall management of DH, as measured by 
a Numeric Rating Scale (NRS), after 8 weeks 
treatment. 
At Day 56 (Week 8): 
Satisfaction NRS score
Safety
To monitor the safety and oral tolerability of 
the investigational toothpastes over 8 weeks 
twice daily use. 
Treatment emergent adverse events (TEAEs). 
This study will be considered successful if the 0.454% SnF2 toothpaste demonstrates 
statistically significant, superior anti-hypersensitivity efficacy, compared to the negative control 
toothpaste, as measured by Schiff sensitivity score at Day 56 (Week 8). 
1.3
Study Products
Table 1-3 presents the study products.
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Table 1-3
Acclimatization/Investigational Toothpastes
Description
Acclimatization 
Toothpaste
Test Toothpaste
Reference 
Toothpaste (Negative 
Control)
Product Name
Regular fluoride 
toothpaste
(Colgate Cavity 
Protection1)
0.454 % w/w SnF2 
toothpaste
Regular fluoride 
toothpaste
(Crest Cavity 
Protection1)
Fluoride Level
1000 ppm fluoride2
1100 ppm fluoride3
1100 ppm fluoride4
Master Formulation 
Code (MFC)
N/A
N/A
Dispensing Details
One carton containing 
2 tubes of toothpaste 
at Screening (Visit 1)
One carton containing 4 over-wrapped tubes of 
toothpaste at Baseline (Visit 2)
Route of 
Administration
Topical Oral Use
Toothpaste
Usage
Instructions
Dose the toothbrush with a ribbon of toothpaste, across the full brush 
head.
Start the timer (pre-set for 1-minute).
Brush the entire
dentition thoroughly 
for at least 1-timed 
minute, twice daily 
(morning & evening).
Brush the entire 
dentition thoroughly for 
at least 1-timed minute, 
twice daily (morning & 
evening), making sure 
to brush the sensitive 
areas of the two 'Test 
teeth' carefully first.
Brush the entire
dentition thoroughly
for at least 1-timed
minute, twice daily
(morning & evening).
Subjects who wish to rinse after brushing will be instructed to rinse with 10 
ml water using graduated rinsing cup provided.
Duration of 
Treatment
Approximately 8 weeks (56 ± 3 days)
Return Requirements
All used/unused tubes to be returned to the sponsor.
N/A: Not Applicable
1.
Commercially available daily use, regular fluoride toothpaste, US market.
2.
As sodium monofluorophosphate
3.
As SnF2
4.
As NaF
1.4
Sample Size Calculation
Sufficient subjects will be screened and entered into the acclimatization period to randomize 
approximately 110 subjects to investigational product (approximately 55 subjects per treatment 
group) to ensure approximately 100 complete the study (approximately 50 subjects per 
treatment group), allowing for approximately 10% dropouts. 
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The study will be sufficiently powered to demonstrate statistical superiority of the Test 
Toothpaste compared to the Reference Toothpaste (negative control) for the change from 
Baseline in the Schiff sensitivity score (primary objective) and tactile threshold (key secondary 
objective) after 56 days (8 weeks) treatment. A sample size of 50 evaluable subjects per 
treatment group will provide at least 90% power to detect a mean difference of 0.4 units (SD = 
0.6) in change from Baseline in Schiff sensitivity score after 56 days treatment, using a 2-tailed 
2-sample t-test with a 5% significance level. The sample size calculation was performed using 
PASS software version 23.0.1. 
The dropout rate and SD estimates are based on the results of DH efficacy studies of similar 
design and duration evaluating 0.454% SnF2 toothpastes (Clinical Studies 205794, 208153 and 
216954: sponsor data held on file, available on request).
2
Planned Analyses
2.1
Interim Analysis
No interim analysis is planned.
2.2
Final Analyses
The final planned primary analyses will be performed after the completion of the following 
sequential steps:
•
All subjects have completed the study as defined in the protocol.
•
All required database cleaning activities including any external data reconciliation 
have been completed and database has been locked.
•
All criteria for unblinding the randomization codes have been met and the 
randomization codes have been distributed.
3
Considerations for Data Analyses and Data Handling 
Conventions
3.1
Baseline Definition
For all endpoints, the baseline value will be the Day 0 (Visit 2) pre-treatment assessment with 
a non-missing value.
Unless otherwise stated, if baseline data is missing no derivation will be performed and the 
baseline value will be set to missing.
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3.2
Subgroups/Stratifications
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria. Each eligible subject will be stratified by the maximum Baseline Schiff sensitivity score 
of their two selected ‘Test Teeth’. The stratification factor will give rise to two strata.
•
Stratum 1: Maximum Schiff sensitivity score = 2.
•
Stratum 2: Maximum Schiff sensitivity score = 3.
In the event of mis-stratification, the correct strata according to CRF information will be used 
in the analysis i.e. derived stratification variable from ADSL will be used for analysis.
3.3
Centers Pools
Since this is single center study, pooling of centres is not applicable.
3.4
Timepoints and Visit Windows
The timepoints and visits for this study are defined in the Table 1-1 “Schedule of Activities”. 
Any deviation from the study schedule may be reviewed on case-by-case basis at the Blinded 
Data Review Meeting (BDRM) to determine whether the data should be excluded from the Per-
Protocol (PP) analyses.
4
Data Analysis
Data analysis will be performed by 
 with oversight from Haleon. The statistical 
analysis software used will be SAS version 9.4 or higher.
Prior to database closure a BDRM will be conducted in which various aspects of the trial will 
be discussed and agreed.
Except as described below, all listings will be produced for all randomized subjects.
4.1
Populations for Analysis
4.1.1
Subject Disposition
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not subsequently randomized. An enrolled subject is a subject who has signed informed consent 
and is eligible to proceed beyond the screening visit.
The number of subjects screened, enrolled, and randomized subjects will be presented in 
Table 14.1.1.
The number and percentage of screen failure subjects (subjects not randomized) with reasons 
why subjects are not randomized will be displayed. Percentages for screen failure subjects will 
be based on the total number of subjects screened.
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The number and percentage of randomized subjects who complete and discontinue the study, 
broken down by reason for discontinuation, by study product and overall will also be displayed. 
The percentages will be based on the number of subjects randomized.
Table 14.1.1 will also present the number and percentage of subjects in each of the defined 
analysis populations (as defined in Section 4.1.3) by study product and overall. Percentages will 
be based on the number of subjects randomized.
Subject disposition including demographic data (age, sex, race, and ethnicity), screening date, 
study product start date and time, subject status (completer, Yes/No), study completion
/withdrawal date, duration (in days) in the study (defined as [(date of completion or withdrawal 
– start date of study product) + 1], and the primary reason for withdrawal will be listed (Listing 
16.2.1.1) by study product.
Subject disposition information will be listed for non-randomized subjects (Listing 16.2.1.2), 
displaying subject number, demographic information (age, sex, race and ethnicity), screening 
date, reason for screen failure and any further details of reason for screen.
4.1.2
Protocol Deviations
Protocol deviations will be tracked by the study team throughout the conduct of the study. Data 
will be reviewed prior to unblinding and closure of the database to ensure all important 
deviations are captured and categorised. Subjects with important protocol deviations liable to 
influence the efficacy outcomes will have affected data excluded from the PP analyses. Subjects 
may also be identified as having important protocol deviations not leading to exclusion of data
from the PP analyses.
Important deviations of the protocol procedures may include, but will not necessarily be limited 
to the following:
•
Consent procedures
•
Inclusion/Exclusion criteria
•
Concomitant medication/therapy
•
Study procedures
•
Randomization procedures
•
Study drug dosing/study product administration/study product compliance Visit 
schedule/interval
•
Other
The specific details of the important protocol deviations will be listed in Protocol Deviation 
Management Plan and assessment process will be specified in the Blind Data Review Plan and 
subjects with important protocol deviations will be identified at the BDRM.
The number and percentage of subjects with at least one important protocol deviation, subjects 
with important protocol deviations not leading to exclusion from PP population with reasons 
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for deviations and subjects with important protocol deviations leading to exclusion from the PP
population with reasons for deviations will be presented by study product and overall, for all 
randomized subjects (Table 14.1.2) and listed in Listing 16.2.2.1.
All protocol deviations collected on the protocol deviation case report form page will be listed 
in Listing 16.2.2.2. The listing will present date of deviation, type of deviation, and deviation 
description.
4.1.3
Analysis Populations
Three analysis populations are defined.
Population
Definition / Criteria
Analyses Evaluated
Safety
Comprise of all randomized subjects who receives
at least one dose of study product. Any subject 
who receives a randomization number will be 
considered to have been randomized.
This population will be based on the treatment the 
subject actually received.
•
Safety
Modified Intent-
To-Treat (mITT)
Comprise all randomized subjects who complete 
at least one dose of study product and complete
at least one post-baseline DH efficacy 
assessment.
Any subject who receives a randomization 
number will be considered to have been 
randomized.
This population will be based on the study product 
to which the subject was randomized.
•
Demographic
•
Baseline 
Characteristics
•
Efficacy Analysis
Per-Protocol
Comprise all subjects in the mITT population who 
have at least one DH efficacy assessment 
considered to be unaffected by protocol 
deviations.
Protocol deviations that would exclude subjects 
from the PP population are defined in Section 
4.1.2 (Protocol Deviations).
This population will be based on the study product 
to which the subject was randomized.
•
Efficacy Analysis
NOTES :
Please refer to Appendix 1: List of Data Displays which details the population to be used for each 
displays being generated.
The numbers of subjects included in each of the analysis populations will be summarized (Table 
14.1.1). Subjects excluded from any of the analysis populations will be listed in Listing 16.2.3.1, 
with the reason for exclusion.
The primary population for assessment of efficacy will be the mITT Population. A PP analysis 
will be performed on the DH endpoints if at least 10% of the mITT subjects are excluded from 
the PP Population. Efficacy data determined to have been potentially impacted by a protocol 
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deviation will be excluded from the PP analysis. A decision on whether a protocol deviation 
impacts efficacy data and whether to perform a PP analysis will be made prior to study 
unblinding (release of the randomization codes).
4.2
Subject Demographics and Other Baseline Characteristics
4.2.1
Demographic and Baseline Characteristics
Descriptive statistics (number of subjects [n], mean, standard deviation [SD], median, 
minimum, and maximum for continuous variables and frequency count [n] and percentage [%] 
of subjects for categorical variables) will be presented for demographic characteristics by study 
product and overall. These variables include age, sex, race, ethnicity, and stratification group
and will be presented for the Safety population (Table 14.1.3.1) and the mITT population (Table 
14.1.3.2).
Demographic information will be listed (Listing 16.2.4.1) for all randomized subjects.
4.2.2
General Medical History
Medical and surgical history (in the last year) including allergies or drug sensitivity will be 
listed in Listing 16.2.4.2, with start date and end date or ongoing at the start of study product.
4.3
Treatments (Study Product, Rescue Medication, other Concomitant 
Therapies, Compliance)
Randomization details will be listed, including the randomization number, stratification group, 
the planned study product, the actual study product the subject was randomized to and the 
randomization date (Listing 16.1.7.1) for all randomized subjects.
The study product kit allocations will be listed (Listing 16.1.7.2), including kit number and 
study product information.
4.3.1
Study Product Compliance and Exposure
Compliance data will be summarized for the mITT population and will be assessed by number 
of brushings.
Number of actual brushings, brushing compliance (%), number of missed brushings, number of 
additional brushings will be summarized using descriptive statistics by cumulative visit and by 
study product (Table 14.2.1).
Number of actual brushings is defined as: [(date of Visit x– date of Visit 2) multiplied by 2 –
number of missing brushings + number of additional brushings], where x = 3 and 4, 
respectively.
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Brushing compliance (%) is defined as: [100 × (Number of actual brushings / Expected number 
of brushings)], where expected number of brushings is defined as: [(date of Visit x – date of 
Visit 2) multiplied by 2].
Study product compliance (number of actual brushings / brushing compliance [%] / number of 
missed brushings / numbers of additional brushings) will be listed in Listing 16.2.5.1 for all 
randomized subjects by study product.
Supervised study product application (subject number, completion status, date of visit and time 
of the supervised procedure) will be listed (Listing 16.2.5.2) for all subjects in safety population.
4.3.2
Prior and Concomitant Medication
Prior medications/treatments, including prescription and non-prescription drugs, dietary 
supplements and herbal remedies, taken in the last 30 days and prior to signing the informed 
consent form, will be documented in the CRF. The prior and concomitant medications will be 
coded using a validated medication dictionary, World Health Organization Drug Dictionary 
(WHODD).
Prior medications and prior non-drug treatments will be listed by subject, with drug name, 
WHODD Drug Synonym, reason for medication, route, dose, frequency, start date, start day 
relative to the study product start date, end date and end day relative to the study product start 
date (Listing 16.2.4.3) for all safety subjects. Prior medications are defined as those which 
stopped before the first use of the study product.
Concomitant medications and significant non-drug therapies taken during treatment will be 
listed similarly (Listing 16.2.4.4) for all safety subjects with either ongoing or end date 
displayed. Concomitant medications are defined as medications that started or stopped on or 
after the first use of the study product or are ongoing.
Unknown dates will not be imputed. However, if the start or stop date is unknown, then it will 
be assumed to be concomitant medication unless the partial start date or stop date indicates 
differently.
4.4
Analysis of Efficacy
The primary population for assessment of efficacy will be the mITT Population.
All p-values presented will be two-sided and assessed at the 5% significance level. A sequential 
testing strategy will be used to adjust for the comparisons between the Test and Reference 
Toothpastes in change from Baseline in Schiff sensitivity score and tactile threshold (g) at each 
assessment time point. 
At each time point, change from Baseline in tactile threshold (g) will only be assessed for 
confirmatory evidence if the change from Baseline in Schiff sensitivity score achieves a 
statistically significant greater reduction for the Test Toothpaste compared to the Reference 
Toothpaste (negative control). This strategy will begin at Day 56, then move to Day 28, only 
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moving to the earlier time point for confirmatory evidence if the Day 56 time point achieves 
statistically significant greater reductions for the Test Toothpaste compared to the Reference 
Toothpaste (negative control) for both Schiff sensitivity score and tactile threshold (g). There 
will be no further adjustments for multiplicity for the other secondary endpoints (DHEQ-48).
The results from each Mixed Model with Repeated Measures (MMRM) will be tabulated, 
presenting the following information, in addition to the results specified for the primary and 
secondary analyses below: least square mean change from Baseline for each investigational 
product at Days 28 and 56 (based on the observed stratification margins for those MMRM with 
a term for randomized strata) and used to test for any change from Baseline, with two-sided p-
values and 95% CIs.
4.4.1
Primary Efficacy Endpoint
4.4.1.1
Change from Baseline in Schiff Sensitivity Score at Day 56
The primary efficacy variable is the change from Baseline in Schiff sensitivity score at Day 56.
Schiff sensitivity score will be derived as the mean score for the two ‘Test Teeth’ (selected at 
Baseline). Change from Baseline will be derived for each individual tooth first before 
calculating mean change for the two ‘Test Teeth’ where change from Baseline in Schiff 
sensitivity score at Day x is defined as [(Schiff sensitivity score at Day x) minus (Baseline Schiff 
sensitivity score)].
Descriptive statistics (n, mean, SD, standard error [SE], median, minimum, and maximum) will 
be presented for Schiff sensitivity score calculated as the average score of the two test teeth at 
each assessment time point in Table 14.2.2.1.1 for all subjects in mITT population by study 
product. Raw means (± SE) of the Schiff sensitivity score at each time point will be plotted by 
study product in Figure 14.2.2.1.1 for all subjects in mITT population. 
Individual Schiff sensitivity score data will be listed for each subject by visit and study product 
group in Listing 16.2.6.1 and Listing 16.2.6.2, for Screening and Baseline, and separately for 
two test teeth respectively, for all randomized subjects. 
4.4.1.2
Statistical Hypothesis, Model, and Method of Analysis
The following null and alternative hypotheses will be evaluated:
•
H0: There is no difference in change from baseline in Schiff sensitivity score in the Test 
Toothpaste compared to Reference Toothpaste
•
H1: There is a difference in change from baseline in Schiff sensitivity score in the Test 
Toothpaste compared to Reference Toothpaste
Change from Baseline in Schiff sensitivity score at Day 56 will be analysed using a MMRM 
with study product, visit and [study product x visit] interaction as fixed effects, and Baseline 
Schiff sensitivity score as a covariate. Note that since the Baseline Schiff sensitivity score will 
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be included as a covariate, the Baseline Schiff stratification value will not be included in the 
model. Subject will be included as a repeated measure with unstructured covariance matrix. 
Kenward-Roger’s degrees of freedom approach will be applied (Kenward, 1997). The 
difference between the least square mean changes from Baseline for the Test Toothpaste 
compared to Reference Toothpaste (negative control) at Day 56 from the MMRM will be 
presented, along with the two-sided p-value and 95% CIs. In the event that the model does not 
converge on the unstructured covariance matrix, an appropriate alternative will be considered.
Using the above model, the adjusted mean change from baseline in the Schiff sensitivity score 
will be reported by study product along with 95% confidence intervals (CIs) and p-values
testing for a non-zero change from baseline and will be provided in Table 14.2.2.2.1. Also, 
mean differences between Test Toothpaste compared to the Reference Toothpaste in the change 
from baseline in Schiff sensitivity score at Day 56 will be presented along with 95% CIs and p-
values in the same Table 14.2.2.2.1.
The assumptions of normality and homogeneity of variance in the MMRM will be investigated. 
In case of violation of these assumptions, a suitable non-parametric test (Van Elteren Test, 
adjusted for the randomization stratification, Maximum Baseline Schiff Sensitivity Score) will 
be performed to assess the change from Baseline comparison (Test Toothpaste vs. Reference 
Toothpaste at Day 56); the results will be provided to support the MMRM results.
4.4.1.3
Supportive Analyses
If there is at least 10% difference in the overall number of subjects between PP and mITT 
Populations, a summary and statistical analysis of the Schiff sensitivity score will be presented 
for the PP Population in Table 14.2.2.1.2 and Table 14.2.2.2.2, respectively. In addition, Schiff 
sensitivity score (Figure 14.2.2.1.2) at each time point will be plotted by study product in for 
all subjects in PP Population.
A decision on whether a PP analysis will be performed will be made prior to study unblinding 
(release of the randomization codes).
4.4.2
Secondary Efficacy Endpoints
4.4.2.1
Change from Baseline in Tactile Threshold (g) at Day 56
The key secondary variable is the change from Baseline in tactile threshold (g) at Day 56.
Tactile threshold (g) will be derived as the mean value for the two ‘Test Teeth’ (selected at 
Baseline). Change from Baseline will be derived for each individual tooth first before 
calculating mean change for the two ‘Test Teeth’ where change from Baseline in tactile 
threshold (g) at Day x is defined as [(tactile threshold at Day x) minus (Baseline tactile 
threshold)].
Descriptive statistics (n, mean, SD, SE, median, minimum, and maximum) will be presented 
for Tactile threshold (g) calculated as the average score of the two test teeth at each assessment 
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time point in Table 14.2.3.1.1 for all subjects in mITT population by study product. Raw means 
(± SE) of the Tactile threshold (g) of the two test teeth at each time point will be plotted by 
study product in Figure 14.2.2.2.1 for all subjects in mITT population.
Individual Tactile threshold (g) data will be listed for each subject by visit and study product 
group in Listing 16.2.6.3 and Listing 16.2.6.4, for Screening and Baseline, and separately for 
two test teeth respectively, for all randomized subjects.
4.4.2.1.1 Statistical Hypothesis, Model and Method of Analysis
The following null and alternative hypotheses will be evaluated:
•
H0: There is no difference in change from baseline in tactile threshold (g) in the Test 
Toothpaste compared to Reference Toothpaste
•
H1: There is a difference in change from baseline in tactile threshold (g) in the Test 
Toothpaste compared to Reference Toothpaste
Key secondary endpoint, change from Baseline in tactile threshold (g) at Day 56, will be 
analysed using the same MMRM method detailed in Section 4.4.1.2 but with Baseline tactile 
threshold (g) as a covariate (rather than Baseline Schiff sensitivity score). In addition, the 
maximum Baseline Schiff sensitivity score of the two ‘Test Teeth’ (2 or 3) will be fitted as a 
fixed effect. The results will be presented in Table 14.2.3.2.1.
4.4.2.1.2 Supportive Analyses
A PP analysis will be performed on the change from baseline in tactile threshold (g) as detailed 
in Section 4.4.1.3 and the same MMRM model will be used as detailed in Section 4.4.2.1.1.
The results will be presented in Table 14.2.3.1.2 and Table 14.2.3.2.2 respectively for summary 
table and analysis table. Also, Figure 14.2.2.2.2 will be generated for all subjects in PP
population.
4.4.2.2
Change from Baseline in Schiff Sensitivity Score at Day 28
The other secondary efficacy endpoint will be the Change from Baseline in Schiff Sensitivity 
Score at Day 28.
The summary results for this endpoint will be obtained as detailed in Section 4.4.1.1. The results 
will be presented in Table 14.2.2.1.1.
4.4.2.2.1 Statistical Hypothesis, Model and Method of Analysis
The analysis is same as primary endpoint and the details will be obtained from Section 4.4.1.2.
Also, the results will be presented in Table 14.2.2.2.1 and Figure 14.2.2.1.1.
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4.4.2.2.2 Supportive Analyses
A PP analysis will be performed on the change from baseline in Schiff sensitivity score as 
detailed in Section 4.4.1.3 and the same MMRM model will be used as detailed in Section 
4.4.1.2. The results will be presented in Table 14.2.2.1.2 and Table 14.2.2.2.2 respectively for 
summary table and analysis table. Also, Figure 14.2.2.1.2 will be generated for all subjects in 
PP population.
4.4.2.3
Change from Baseline in Tactile Threshold (g) at Day 28
The other secondary efficacy endpoint will be the Change from Baseline in tactile threshold (g)
at Day 28.
The summary results for this endpoint will be obtained as detailed in Section 4.4.2.1. The results 
will be presented in Table 14.2.3.1.1 and Figure 14.2.2.2.1.
4.4.2.3.1 Statistical Hypothesis, Model and Method of Analysis
The analysis is same as the key secondary endpoint and the details will be obtained from the 
MMRM detailed in Section 4.4.2.1.1. Also, the results will be presented in Table 14.2.3.2.1.
4.4.2.3.2 Supportive Analyses
A PP analysis will be performed on the change from baseline in tactile threshold (g) as detailed 
in Section 4.4.2.1.2. The results will be presented in Table 14.2.3.1.2 and Table 14.2.3.2.2
respectively for summary table and analysis table. Also, Figure 14.2.2.2.2 will be generated for 
all subjects in PP population.
4.4.2.4
Change from Baseline in DHEQ-48 endpoints at Day 56 and Day 28
DHEQ-48:
The DHEQ-48 is a condition-specific measure of OHrQoL in relation to DH (Boiko, 2010) that 
has been previously validated in longitudinal studies and shown to be responsive to treatment 
(Baker, 2014). The DHEQ total score can be broken down into 5 separate ‘domain’ scores to 
provide a more granular understanding of the specific areas of improvement subjects experience 
in their OHrQOL.
•
Restrictions: Derived from participant responses to Section 2, Q1-ϰ;‘the ways in which 
any sensations in your teeth affect you in your daily life’).
•
Adaptation: Derived from participant responses to Section 2, Q5-1ϲ(‘the ways in which 
the sensations in your teeth have forced you to change things in your daily life’; ‘things 
you do in your daily life to avoid experiencing the sensations in your teeth’Ϳ͘
•
Social Impact: Derived from participant responses to Section 2, Q17-21 (‘the way the 
sensations affect you when you are with other people or in certain situations’).
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•
Emotional Impact: Derived from participant responses to Section 2, Q22-29 (‘the way 
the sensations in your teeth make you feel’).
•
Identity: Derived from participant responses to Section 2, Q30-34 (‘what the sensations in 
your teeth mean for you’).
The DHEQ also provides specific information on how much the sensations in the participant’s 
teeth affect their life overall:
•
Global Oral Health: Derived from participant response to Section 2, Q35 (‘rate the 
health of your mouth, teeth and gums’).
•
Effect on Life Overall: Derived from participant responses to Section 2, Q36-39 (impact 
of DH on overall quality of life).
The other secondary efficacy endpoints will be the change from baseline in DHEQ-48 endpoints 
(as described below) at respective visits for each study product.
Change from Baseline will be calculated at Day 28 and Day 56 for all DHEQ endpoints.
Section 1
1. Impact on Everyday Life: Q7, Q8 & Q9 (separate scores)
Section 2
1. DHEQ Total Score (sum of Q1-34)
2. DHEQ Restrictions Domain score (sum of Q1-4)
3. DHEQ Adaptation Domain score (sum of Q5-16)
4. DHEQ Social Impact Domain score (sum of Q17-21)
5. DHEQ Emotional Impact Domain score (sum of Q22-29)
6. DHEQ Identity Domain score (sum of Q30-34)
7. DHEQ Global Oral Health score (Q35)
8. DHEQ Effect on Life Overall score (sum of Q36-Q39)
Change from Baseline will be calculated at the subject-level first then mean change from 
Baseline will be calculated for each DHEQ endpoint (mentioned above) across all subjects.
Descriptive statistics (n, mean, SD, SE, median, minimum, and maximum) will be presented 
for each DHEQ-48 endpoint (mentioned above) at each assessment time point in 
Table 14.2.4.1.1 and 14.2.5.1-8.1.1, for Section 1 and Section 2 respectively and for all subjects 
in mITT population by study product. Raw means (± SE) for each DHEQ endpoint, and the 
individual DHEQ questions, at each assessment will be plotted by study product in 
Figure 14.2.2.11.1 and Figure 14.2.2.3-10.1, for Section 1 and Section 2 respectively and for 
all subjects in mITT population.
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Individual DHEQ endpoint data for each endpoint (mentioned above) will be listed for each 
subject by visit and study product group in Listing 16.2.6.5, 16.2.6.6.1-7, for Section 1 and 
Section 2 respectively, for all randomized subjects.
4.4.2.4.1 Statistical Hypothesis, Model and Method of Analysis
The following null and alternative hypotheses will be evaluated:
•
H0: There is no difference between baseline and post-baseline (Day 28, Day 56) DHEQ 
scores in the test toothpaste compared to the reference toothpaste
•
H1: There is a difference between baseline and post-baseline (Day 28, Day 56) DHEQ 
scores in the test toothpaste compared to the reference toothpaste
Change from Baseline for each DHEQ endpoint listed above will be analyzed using a MMRM 
with visit and stratification [maximum Baseline Schiff sensitivity score of the two ‘Test Teeth’ 
(2 or 3)] as fixed effects, and the respective Baseline DHEQ score as a covariate. Subject will 
be included as a repeated measure with unstructured covariance matrix. Kenward-Roger’s 
degrees of freedom will be applied. The estimates of the adjusted mean (SE) change from 
Baseline will be presented along with 95% CIs for each treatment group. In the event that the 
model does not converge on the unstructured covariance matrix, then an appropriate alternative 
will be considered.
Using the above model, the adjusted mean change from baseline in each DHEQ endpoint listed 
above will be reported by study product group along with 95% CIs and p-values testing for a 
non-zero change from baseline will be provided in Table 14.2.4.2.1 and 14.2.5.1-8.2.1, for 
Section 1 and Section 2 respectively.
The assumptions of normality and homogeneity of variance in the MMRM will be investigated. 
In case of violation of these assumptions, a suitable non-parametric test (Wilcoxon Signed Rank 
Test) will be performed to assess the change from Baseline comparison (Post-Baseline vs. 
Baseline); the results will be provided to support the MMRM results.
4.4.2.4.2 Supportive Analyses
If there is at least 10% difference in the overall number of subjects between PP and mITT 
Populations, a summary and statistical analysis of each of the DHEQ-48 Score endpoint will be 
presented for the PP Population in (Table 14.2.4.1.2 and 14.2.5.1-8.1.2 for Section 1 and Section 
2 respectively) and (Table 14.2.4.2.2 and 14.2.5.1-8.2.2 for Section 1 and Section 2 
respectively), respectively for summary table and analysis table. In addition, DHEQ-48 score 
(Figure 14.2.2.11.2 and Figure 14.2.2.3-10.2 for Section 1 and Section 2 respectively) for each 
mentioned endpoint at each time point will be plotted by study product in for all subjects in PP 
Population.
A decision on whether a PP analysis will be performed will be made prior to study unblinding 
(release of the randomization codes).
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4.4.3
Exploratory Efficacy Variables
4.4.3.1
Number of Sensitive Teeth
The number of teeth sensitive to an evaporative (air) stimulus in the pool of ‘Eligible Teeth’ 
identified at Screening will be monitored across the study period. For this purpose, a ‘Sensitive 
Tooth’ will be defined as having a Schiff sensitivity score ≥ 2. 
‘Eligible Teeth’ = Teeth with no dentition exclusions which meet EAR, MGI and mobility 
inclusion criteria, and have a Screening tactile threshold ≤ 20g and a Screening Schiff sensitivity 
score ≥ 2. 
The number of ‘Sensitive Teeth’ (i.e., the number of ‘Eligible Teeth’ with Schiff sensitivity 
score ≥ 2) will be calculated at Screening, Baseline, Day 28 and Day 56. 
•
At Screening, the number of ‘Sensitive Teeth’ will be equal to the number of ‘Eligible 
Teeth’. Eligible Teeth’ = Teeth with Screening tactile threshold ≤ 20g and Screening 
Schiff sensitivity score ≥2. 
•
At Baseline, Day 28 and Day 56, all ‘Eligible Teeth’ will be tested for evaporative (air) 
sensitivity. The number of ‘Sensitive Teeth’ will be the number of ‘Eligible Teeth’ with a 
Schiff sensitivity score ≥ 2 at that visit.
Descriptive statistics (n, mean, SD, SE, median, minimum, and maximum) will be presented 
for Number of Sensitive Teeth at each assessment time point in Table 14.2.5.9.1 for all subjects 
in mITT population by study product. Raw means (± SE) of Number of Sensitive Teeth at each 
time point will be plotted by study product in Figure 14.2.4.1 for all subjects in mITT 
population.
Individual Schiff sensitivity Score (of each eligible tooth) data will be listed for each subject by 
visit and study product group in Listing 16.2.6.7, for all randomized subjects.
No formal statistical analysis is planned.
4.4.3.2
Labelled Magnitude Scale (LMSs)
Subjects will rate Intensity, Duration, Tolerability of their response to the evaporative (air) 
stimulus and Describe their response, using four 100-millimetre (mm) LMSs, at Baseline, Day 
28 and Day 56. 
LMSs should be completed immediately after the clinical examiner has recorded the Schiff 
sensitivity score for a given tooth. To avoid bias, the subject should be unaware of the 
examiner’s score and the clinical examiner should not have visibility of the subject’s LMS 
responses. 
Baseline: Complete four LMSs for each tooth with a Baseline tactile threshold of ≤ 20g and a 
Baseline Schiff sensitivity score ≥ 2. 
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Days 28 & 56: Complete four LMSs for each ‘Test Tooth’ (i.e., the two teeth selected by the 
clinical examiner at Baseline). 
Study staff will measure the distance to the subject’s mark (‘X’) from left to right along the 100 
mm line and record this value (in mm) in the eCRF for each LMS completed.
4.4.3.2.1 Change from Baseline in LMS endpoints at Day 28 and Day 56
The key exploratory variable is the change from Baseline in LMSs at Day 28 and Day 56 for 
each of the below LMS endpoints:
•
Intensity 
•
Duration 
•
Tolerability 
•
Description 
LMS data will be analysed for the two ‘Test Teeth’ only. Change from Baseline will be derived 
for each ‘Test Tooth’ first before calculating mean change for the two ‘Test Teeth’ for each 
subject.
Descriptive statistics (n, mean, SD, SE, median, minimum, and maximum) will be presented 
for each of LMS endpoints calculated individually (in mm) as the average score of the two test 
teeth at each assessment time point in Table 14.2.5.10.1-4.1 for all subjects in mITT population 
by study product. Raw means (± SE) for each of LMS endpoints at each time point will be 
plotted by study product in Figure 14.2.5.1-4 for all subjects in mITT population.
Individual LMS endpoints data will be listed for each subject by visit and study product group 
in Listing 16.2.6.8 for each visit, and separately for two test teeth respectively, for all 
randomized subjects.
4.4.3.2.2 Statistical Hypothesis, Model and Method of Analysis
The following null and alternative hypotheses will be evaluated:
•
H0: There is no difference between baseline and post-baseline (Day 28, Day 56) LMS 
scores in the test toothpaste compared to the reference toothpaste
•
H1: There is a difference between baseline and post-baseline (Day 28, Day 56) LMS 
scores in the test toothpaste compared to the reference toothpaste
Change from Baseline for each LMS endpoint listed above will be analyzed using a MMRM 
with visit and stratification [maximum Baseline Schiff sensitivity score of the two ‘Test Teeth’ 
(2 or 3)] as fixed effects, and the respective Baseline LMS score as a covariate. Subject will be 
included as a repeated measure with unstructured covariance matrix. Kenward-Roger’s degrees 
of freedom will be applied. The estimates of the adjusted mean (SE) change from Baseline will 
be presented along with 95% CIs for each treatment group. In the event that the model does not 
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converge on the unstructured covariance matrix, then an appropriate alternative will be 
considered.
Using the above model, the adjusted mean change from baseline in each LMS endpoint listed 
above will be reported by study product group along with 95% confidence intervals (CIs) and 
p-values testing for a non-zero change from baseline will be provided in Table 14.2.5.10.1-4.2.
The assumptions of normality and homogeneity of variance in the MMRM will be investigated. 
In case of violation of these assumptions, a suitable non-parametric test (Wilcoxon Signed Rank 
Test) will be performed to assess the change from Baseline comparison (Post-Baseline vs. 
Baseline); the results will be provided to support the MMRM results.
4.4.3.3
Satisfaction with Treatment using NRS
At the end of the study (Visit 4), subjects will be asked to rate their level of satisfaction with 
their allocated study product using NRS. The NRS is an 11-point ordinal scale used to assess 
the subject’s satisfaction with the product’s overall management of their DH. The scale ranges 
from 0 (completely dissatisfied) to 10 (completely satisfied), with higher scores indicative of 
greater satisfaction (van Berckel, 2017):
see example below. Subjects will be asked to record the numeric value on the segmented scale 
that best describes their level of satisfaction after 8 weeks twice daily use and indicate why they 
selected a particular score in answer to the question ‘Please give more details on why you are 
satisfied or dissatisfied with the product’ (free text response).
Figure 4-1
Numerical Rating Scale (0 to 10)
4.4.3.3.1 Satisfaction NRS Score
Descriptive statistics (n, mean, SD, SE, median, minimum, and maximum) will be presented 
for NRS Score at Day 56 in Table 14.2.5.12.2 for all subjects in mITT population by study 
product.
Also, summary of the number of subjects (%) reporting at each level of the NRS and the 
cumulative number of subjects (%) reporting at each level or higher at Day 56 will be presented
in Table 14.2.5.12.1 by study product.
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Individual NRS Score data will be listed for each subject for Day 56 by study product group in 
Listing 16.2.6.9, for all randomized subjects.
4.4.3.3.2 Statistical Hypothesis, Model and Method of Analysis
No formal statistical analysis is planned for assessment of NRS endpoint.
4.4.4
Handling of Missing Values/Censoring/Discontinuations
Missing data will not be replaced or imputed. Subjects who withdraw from the study 
prematurely will be included in the statistical analyses up to the point of discontinuation.
The use of MMRM analyses account for missing data assuming a missing at random 
assumption, i.e., there is a systematic relationship between the propensity of missing values and 
the observed data, but not the missing data.
It is therefore assumed that a subject with missing data at one post-Baseline assessment visit 
would have obtained a similar efficacy result at that visit compared to a subject using the same 
study product with similar non-missing results at other timepoints (Baseline and the other post-
Baseline assessment visits). Sensitivity analyses may be added to the SAP prior to unblinding 
in case of high drop-out rates and/or exclusion from PP analyses.
4.5
Analysis of Safety
The safety profile of the study products will be assessed with respect to AEs or incidents and
OST/OHT abnormalities in oral health study.
4.5.1
Adverse Events and Serious Adverse Events
All AEs will be reviewed by the Clinical Research Scientist or Designee prior to database lock 
and will be coded to a system organ class (SOC) and preferred term (PT) using the Medical 
Dictionary for Regulatory Activities (MedDRA).
AEs will be classified as oral and non-oral on the AE page of eCRF.
Treatment emergent adverse events (TEAEs) are defined as new AEs that occur on or after the 
first study product use (if this date is missing a suitable alternative will be used e.g., date of 
randomization). AEs with an onset date/time prior to the first study product use will be 
considered as non-treatment emergent.
The following summary tables and listings will be presented by study product on Safety 
population.
•
Table of TEAEs by SOC and PT (Table 14.3.1.1).
•
Table of TEAEs by Oral/Non-Oral and PT (Table 14.3.1.2)
•
Table of treatment related TEAEs by SOC and PT (Table 14.3.1.3)
•
Table of treatment related TEAEs by Oral/Non-Oral and PT (Table 14.3.1.4)
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•
Table of non-serious TEAEs by SOC and PT (Table 14.3.1.5) [only produced if there are 
more than 5 SAEs]
•
Table of serious TEAEs by SOC and PT (Table 14.3.1.6) [only produced if there are more 
than 5 SAEs
•
Listing of all AEs (Listing 16.2.7.1)
•
Listing of deaths (Listing 14.3.2.1)
•
Listing of non-fatal SAEs (Listing 14.3.2.2)
•
Listing of TEAEs leading to study or product discontinuation (Listing 14.3.2.3)
•
Listing of TEAEs classified as Oral (Listing 14.3.2.4)
In the event that there is nothing to report, a null table or listing will be produced.
All incidents will be listed in Listing 16.2.7.2 for all randomized population. In the event that 
there is nothing to report, a null listing will be produced.
4.5.2
Other Safety Variables
Other safety variables are listed below:
•
OST examination
•
OHT examination
4.5.2.1
OST Examination
This procedure will be conducted by a qualified, experienced clinical examiner. The OST 
examination will be accomplished by direct visual observation and palpation, using retraction 
aids as appropriate, and will include examination of the labial mucosa (including lips), buccal 
mucosa, 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’; details of any 
abnormalities will be documented in the eCRF.
Any observation that changes from ‘normal’ to ‘abnormal’, or worsens, from the OST 
examination completed at Screening will be recorded as an AE.
OST will be summarized (number and percentages of subjects with abnormalities, without 
abnormalities, or OST not examined) by visit and study product in Table 14.3.4.1 for all subjects 
in Safety Population. OST examination will be listed (Listing 16.2.8.1) for Safety Population.
4.5.2.2
OHT Examination
This procedure should be conducted by a qualified, experienced clinical examiner. The OHT 
examination will be accomplished by direct visual observation, using retraction aids as 
appropriate, and will identify enamel irregularities, tooth fractures, grossly carious lesions/gross 
decay, defective/faulty restorations (both direct and indirect restorations, including fixed/ 
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removable prostheses), non-carious tooth surface loss (abrasion, attrition, abfraction and 
erosion), any other hard tissue irregularities (e.g., hypo-
and hypermineralization, 
decalcification) and significant tooth staining. Observations will be listed as ‘absent’ or 
‘present’; conditions noted as ‘present’ will be described in the eCRF.
Any observation that changes from ‘absent’ to ‘present’ or worsens from the OHT examination 
completed at Screening will be recorded as an AE. 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, along with evidence of gross intra-oral neglect or the 
need for extensive dental therapy.
OHT examination will be listed (Listing 16.2.8.2) for safety population.
4.6
Analysis of Other Variables
4.6.1
DHEQ-48 and LMSs Relationship
The relationship between subject responses to the DHEQ-48 and the four LMSs will be 
investigated. For each DHEQ domain (Restrictions, Adaptation, Social Impact, Emotional 
Impact, Identity), each LMS endpoint (Intensity, Duration, Tolerability, Description) will be 
plotted against domain score at each assessment timepoint (Baseline, 28 and 56 days). A matrix 
of correlation plots will be presented for each domain in Figure 14.2.6.1. Spearman’s correlation 
coefficient will be calculated along with the associated p-value and presented with its respective 
correlation plot (Figure 14.2.6.1) for mITT population. Also, for each DHEQ domain 
(Restrictions, Adaptation, Social Impact, Emotional Impact, Identity) and each LMS endpoint 
(Intensity, Duration, Tolerability, Description), Spearman’s correlation coefficient will be 
calculated along with the associated p-value and presented at each assessment timepoint 
(Baseline, 28 and 56 days) in Table 14.2.5.11.1 for all subjects in the mITT Population.
4.6.2
Schiff Sensitivity Score and LMSs Relationship
The relationship between Schiff sensitivity score and the four LMSs will be investigated. Schiff 
sensitivity score (mean score of the two ‘Test Teeth’) and the four LMS endpoints (Intensity, 
Duration, Tolerability, Description) will be plotted at each assessment timepoint (Baseline, 28 
and 56 days) in a matrix of correlation plots (Figure 14.2.6.2) for mITT population. Spearman’s 
correlation coefficient will be calculated along with the associated p-value and presented with 
its respective correlation plot (Figure 14.2.6.2). Also, for Schiff sensitivity score and each LMS 
endpoint (Intensity, Duration, Tolerability, Description), Spearman’s correlation coefficient 
will be calculated along with the associated p-value and presented at each assessment timepoint 
(Baseline, 28 and 56 days) in Table 14.2.5.11.2 for all subjects in the mITT Population.
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5
Changes to the Protocol Defined Statistical Analysis Plan
There were no changes to the originally planned statistical analysis specified from the protocol 
version 2.0 (Dated: 07-Feb-2024).
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Appendix 1: List of Data Displays
CSR Section
TLF
Number
Title
Population
Template
Topline
14.1 Demographic Data Summary Tables and Figures
Table
14.1.1
Subject Disposition
All Screened 
Subjects
14.1.1
Yes
Table
14.1.2
Incidence of Important Protocol Deviations
All Randomized 
Subjects
14.1.2
Table
14.1.3.1
Demographic and Baseline Characteristics
Safety Population 
14.1.3.1
Table
14.1.3.2
Demographic and Baseline Characteristics
mITT Population
14.1.3.1
Yes
14.2 Efficacy Data Summary Tables and Figures
Table
14.2.1
Summary of Brushing Compliance
mITT Population
14.2.1
Table
14.2.2.1.1
Summary of Schiff Sensitivity Score of the Two Test 
Teeth
mITT Population
14.2.2.1.1
Yes
Table
14.2.2.1.2
Summary of Schiff Sensitivity Score of the Two Test 
Teeth
PP Population
14.2.2.1.1
Table
14.2.2.2.1
Statistical Analysis of Change from Baseline in Schiff 
Sensitivity Score of the Two Test Teeth Over Time
mITT Population
14.2.2.2.1
Yes
Table
14.2.2.2.2
Statistical Analysis of Change from Baseline in Schiff 
Sensitivity Score of the Two Test Teeth Over Time
PP Population
14.2.2.2.1
Table
14.2.3.1.1
Summary of Tactile Threshold (g) of the Two Test Teeth
mITT Population
14.2.3.1.1
Yes
Table
14.2.3.1.2
Summary of Tactile Threshold (g) of the Two Test Teeth
PP Population
14.2.3.1.1
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CSR Section
TLF
Number
Title
Population
Template
Topline
Table
14.2.3.2.1
Statistical Analysis of Change from Baseline in Tactile 
Threshold (g) of the Two Test Teeth Over Time
mITT Population
14.2.3.2.1
Yes
Table
14.2.3.2.2
Statistical Analysis of Change from Baseline in Tactile 
Threshold (g) of the Two Test Teeth Over Time
PP Population
14.2.3.2.1
Table
14.2.4.1.1
Summary of DHEQ (Section 1 Impact of Everyday Life, 
Q7 to Q9)
mITT Population
14.2.4.1.1
Table
14.2.4.1.2
Summary of DHEQ (Section 1 Impact of Everyday Life, 
Q7 to Q9)
PP Population
14.2.4.1.1
Table
14.2.4.2.1
Statistical Analysis of Change from Baseline in DHEQ 
(Section 1 Impact of Everyday Life, Q7 to Q9)
mITT Population
14.2.4.2.1
Table
14.2.4.2.2
Statistical Analysis of Change from Baseline in DHEQ 
(Section 1 Impact of Everyday Life, Q7 to Q9)
PP Population
14.2.4.2.1
Table
14.2.5.1.1.1
Summary of DHEQ (Section 2, Q1 to Q34) Total Score
mITT Population
14.2.5.1.1.1
Table
14.2.5.1.1.2
Summary of DHEQ (Section 2, Q1 to Q34) Total Score
PP Population
14.2.5.1.1.1
Table
14.2.5.1.2.1
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q1 to Q34) Total Score Over Time
mITT Population
14.2.5.1.2.1
Table
14.2.5.1.2.2
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q1 to Q34) Total Score Over Time
PP Population
14.2.5.1.2.1
Table
14.2.5.2.1.1
Summary of DHEQ (Section 2, Q1 to Q4) Restriction 
Domain Total Score
mITT Population
14.2.5.2.1.1
Table
14.2.5.2.1.2
Summary of DHEQ (Section 2, Q1 to Q4) Restriction 
Domain Total Score
PP Population
14.2.5.2.1.1
Table
14.2.5.2.2.1
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q1 to Q4) Restriction Domain Total Score
mITT Population
14.2.5.2.2.1
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CSR Section
TLF
Number
Title
Population
Template
Topline
Table
14.2.5.2.2.2
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q1 to Q4) Restriction Domain Total Score
PP Population
14.2.5.2.2.1
Table
14.2.5.3.1.1
Summary of DHEQ (Section 2, Q5 to Q16) Adaptation 
Domain Total Score
mITT Population
14.2.5.3.1.1
Table
14.2.5.3.1.2
Summary of DHEQ (Section 2, Q5 to Q16) Adaptation 
Domain Total Score
PP Population
14.2.5.3.1.1
Table
14.2.5.3.2.1
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q5 to Q16) Adaptation Domain Total Score
mITT Population
14.2.5.3.2.1
Table
14.2.5.3.2.2
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q5 to Q16) Adaptation Domain Total Score
PP Population
14.2.5.3.2.1
Table
14.2.5.4.1.1
Summary of DHEQ (Section 2, Q17 to Q21) Social 
Impact Domain Total Score
mITT Population
14.2.5.4.1.1
Table
14.2.5.4.1.2
Summary of DHEQ (Section 2, Q17 to Q21) Social 
Impact Domain Total Score
PP Population
14.2.5.4.1.1
Table
14.2.5.4.2.1
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q17 to Q21) Social Impact Domain Total 
Score
mITT Population
14.2.5.4.2.1
Table
14.2.5.4.2.2
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q17 to Q21) Social Impact Domain Total 
Score
PP Population
14.2.5.4.2.1
Table
14.2.5.5.1.1
Summary of DHEQ (Section 2, Q22 to Q29) Emotional 
Impact Domain Total Score
mITT Population
14.2.5.5.1.1
Table
14.2.5.5.1.2
Summary of DHEQ (Section 2, Q22 to Q29) Emotional 
Impact Domain Total Score
PP Population
14.2.5.5.1.1
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CSR Section
TLF
Number
Title
Population
Template
Topline
Table
14.2.5.5.2.1
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q22 to Q29) Emotional Impact Domain Total 
Score
mITT Population
14.2.5.5.2.1
Table
14.2.5.5.2.2
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q22 to Q29) Emotional Impact Domain Total 
Score
PP Population
14.2.5.5.2.1
Table
14.2.5.6.1.1
Summary of DHEQ (Section 2, Q30 to Q34) Identity 
Domain Total Score
mITT Population
14.2.5.6.1.1
Table
14.2.5.6.1.2
Summary of DHEQ (Section 2, Q30 to Q34) Identity 
Domain Total Score
PP Population
14.2.5.6.1.1
Table
14.2.5.6.2.1
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q30 to Q34) Identity Domain Total Score
mITT Population
14.2.5.6.2.1
Table
14.2.5.6.2.2
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q30 to Q34) Identity Domain Total Score
PP Population
14.2.5.6.2.1
Table
14.2.5.7.1.1
Summary of DHEQ (Section 2 Global Oral Health Score, 
Q35)
mITT Population
14.2.5.7.1.1
Table
14.2.5.7.1.2
Summary of DHEQ (Section 2 Global Oral Health Score, 
Q35)
PP Population
14.2.5.7.1.1
Table
14.2.5.7.2.1
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2 Global Oral Health Score, Q35)
mITT Population
14.2.5.7.2.1
Table
14.2.5.7.2.2
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2 Global Oral Health Score, Q35)
PP Population
14.2.5.7.2.1
Table
14.2.5.8.1.1
Summary of DHEQ (Section 2, Q36 to Q39) Effect on 
Life Overall score
mITT Population
14.2.5.8.1.1
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TLF
Number
Title
Population
Template
Topline
Table
14.2.5.8.1.2
Summary of DHEQ (Section 2, Q36 to Q39) Effect on 
Life Overall score
PP Population
14.2.5.8.1.1
Table
14.2.5.8.2.1
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q36 to Q39) Effect on Life Overall score
mITT Population
14.2.5.8.2.1
Table
14.2.5.8.2.2
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q36 to Q39) Effect on Life Overall score
PP Population
14.2.5.8.2.1
Table
14.2.5.9.1
Summary of Number of Sensitive Teeth
mITT Population
14.2.5.9.1
Table
14.2.5.10.1.1
Summary of Labelled Magnitude Scale – Intensity (in 
mm)
mITT Population
14.2.5.10.1.1
Table
14.2.5.10.1.2
Statistical Analysis of Change from Baseline in Labelled 
Magnitude Scale – Intensity (in mm)
mITT Population
14.2.5.10.1.2
Table
14.2.5.10.2.1
Summary of Labelled Magnitude Scale - Duration (in 
mm)
mITT Population
14.2.5.10.1.1
Table
14.2.5.10.2.2
Statistical Analysis of Change from Baseline in Labelled 
Magnitude Scale - Duration (in mm)
mITT Population
14.2.5.10.2.2
Table
14.2.5.10.3.1
Summary of Labelled Magnitude Scale - Tolerability (in 
mm)
mITT Population
14.2.5.10.1.1
Table
14.2.5.10.3.2
Statistical Analysis of Change from Baseline in Labelled 
Magnitude Scale - Tolerability (in mm)
mITT Population
14.2.5.10.3.2
Table
14.2.5.10.4.1
Summary of Labelled Magnitude Scale - Description (in 
mm)
mITT Population
14.2.5.10.1.1
Table
14.2.5.10.4.2
Statistical Analysis of Change from Baseline in Labelled 
Magnitude Scale - Description (in mm)
mITT Population
14.2.5.10.4.2
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CSR Section
TLF
Number
Title
Population
Template
Topline
Table
14.2.5.11.1
Spearman's Correlation between DHEQ-48 Domains 
and LMS Endpoints
mITT Population
14.2.5.11.1
Table
14.2.5.11.2
Spearman's Correlation between Schiff Sensitivity Score 
and LMS Endpoints
mITT Population
14.2.5.11.2
Table
14.2.5.12.1
Summary of Satisfaction (%) with Treatment Numerical 
Rating Score (NRS)
mITT Population
14.2.5.12.1
Table
14.2.5.12.2
Summary of Satisfaction with Treatment Numerical 
Rating Score (NRS)
mITT Population
14.2.5.12.2
Figure
14.2.2.1.1
Mean (±SE) Schiff Sensitivity Score of the Two Test 
Teeth Over Time by Study Product
mITT Population
14.2.2.1.1
Figure
14.2.2.1.2
Mean (±SE) Schiff Sensitivity Score of the Two Test 
Teeth Over Time by Study Product
PP Population
14.2.2.1.1
Figure
14.2.2.2.1
Mean (±SE) Tactile Threshold (g) of the Two Test Teeth 
Over Time by Study Product
mITT Population
14.2.2.2.1
Figure
14.2.2.2.2
Mean (±SE) Tactile Threshold (g) of the Two Test Teeth 
Over Time by Study Product
PP Population
14.2.2.2.1
Figure
14.2.2.3.1
Mean (±SE) DHEQ (Section 2, Q1 to Q34) Total Score 
Over Time by Study Product
mITT Population
14.2.2.3.1
Figure
14.2.2.3.2
Mean (±SE) DHEQ (Section 2, Q1 to Q34) Total Score 
Over Time by Study Product
PP Population
14.2.2.3.1
Figure
14.2.2.4.1
Mean (±SE) DHEQ (Section 2, Q1 to Q4) Restriction 
Domain Total Score Over Time by Study Product
mITT Population
14.2.2.4.1
Figure
14.2.2.4.2
Mean (±SE) DHEQ (Section 2, Q1 to Q4) Restriction 
Domain Total Score Over Time by Study Product
PP Population
14.2.2.4.1
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CSR Section
TLF
Number
Title
Population
Template
Topline
Figure
14.2.2.5.1
Mean (±SE) DHEQ (Section 2, Q5 to Q16) Adaptation 
Domain Total Score Over Time by Study Product
mITT Population
14.2.2.5.1
Figure
14.2.2.5.2
Mean (±SE) DHEQ (Section 2, Q5 to Q16) Adaptation 
Domain Total Score Over Time by Study Product
PP Population
14.2.2.5.1
Figure
14.2.2.6.1
Mean (±SE) DHEQ (Section 2, Q17 to Q21) Social 
Impact Domain Total Score Over Time by Study Product
mITT Population
14.2.2.6.1
Figure
14.2.2.6.2
Mean (±SE) DHEQ (Section 2, Q17 to Q21) Social 
Impact Domain Total Score Over Time by Study Product
PP Population
14.2.2.6.1
Figure
14.2.2.7.1
Mean (±SE) DHEQ (Section 2, Q22 to Q29) Emotional 
Impact Domain Total Score Over Time by Study Product
mITT Population
14.2.2.7.1
Figure
14.2.2.7.2
Mean (±SE) DHEQ (Section 2, Q22 to Q29) Emotional 
Impact Domain Total Score Over Time by Study Product
PP Population
14.2.2.7.1
Figure
14.2.2.8.1
Mean (±SE) DHEQ (Section 2, Q30 to Q34) Identity 
Domain Total Score Over Time by Study Product
mITT Population
14.2.2.8.1
Figure
14.2.2.8.2
Mean (±SE) DHEQ (Section 2, Q30 to Q34) Identity 
Domain Total Score Over Time by Study Product
PP Population
14.2.2.8.1
Figure
14.2.2.9.1
Mean (±SE) DHEQ (Section 2 Global Oral Health Score, 
Q35) Over Time by Study Product
mITT Population
14.2.2.9.1
Figure
14.2.2.9.2
Mean (±SE) DHEQ (Section 2 Global Oral Health Score, 
Q35) Over Time by Study Product
PP Population
14.2.2.9.1
Figure
14.2.2.10.1
Mean (±SE) DHEQ (Section 2, Q36 to Q39) Effect on 
Life Overall score Over Time by Study Product
mITT Population
14.2.2.10.1
Figure
14.2.2.10.2
Mean (±SE) DHEQ (Section 2, Q36 to Q39) Effect on 
Life Overall score Over Time by Study Product
PP Population
14.2.2.10.1
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CSR Section
TLF
Number
Title
Population
Template
Topline
Figure
14.2.2.11.1
Mean (±SE) DHEQ (Section 1, Q7 to Q9) score Over 
Time by Question, Study Product
mITT Population
14.2.2.11.1
Figure
14.2.2.11.2
Mean (±SE) DHEQ (Section 1, Q7 to Q9) score Over 
Time by Question, Study Product
PP Population
14.2.2.11.1
Figure
14.2.4.1
Mean (±SE) Number of Sensitive Teeth Over Time by 
Study Product
mITT Population
14.2.4.1
Figure
14.2.5.1
Mean (±SE) Labelled Magnitude Scale - Intensity (in 
mm) Over Time by Study Product
mITT Population
14.2.5.1
Figure
14.2.5.2
Mean (±SE) Labelled Magnitude Scale - Duration (in 
mm) Over Time by Study Product
mITT Population
14.2.5.1
Figure
14.2.5.3
Mean (±SE) Labelled Magnitude Scale - Tolerability (in 
mm) Over Time by Study Product
mITT Population
14.2.5.1
Figure
14.2.5.4
Mean (±SE) Labelled Magnitude Scale - Description (in 
mm) Over Time by Study Product
mITT Population
14.2.5.1
Figure
14.2.6.1
Correlation Plot for DHEQ-48 Domains and LMS 
Endpoints
mITT Population
14.2.6.1
Figure
14.2.6.2
Correlation Plot for Schiff Sensitivity Score and LMS 
Endpoints
mITT Population
14.2.6.2
14.3 Safety Data Summary Tables and Figures
14.3.1 Displays of Adverse Events 
Table
14.3.1.1
Treatment Emergent Adverse Events by System Organ 
Class and Preferred Term
Safety Population
14.3.1.1
Yes
Table
14.3.1.2
Treatment Emergent Adverse Events by Oral/Non-Oral 
and Preferred Term
Safety Population
14.3.1.2
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CSR Section
TLF
Number
Title
Population
Template
Topline
Table
14.3.1.3
Treatment Related Treatment Emergent Adverse Events 
by System Organ Class and Preferred Term
Safety Population
14.3.1.1
Table
14.3.1.4
Treatment Related Treatment Emergent Adverse Events 
by Oral/Non-Oral and Preferred Term
Safety Population
14.3.1.2
Table
14.3.1.5
Non-Serious Treatment Emergent Adverse Events by 
System Organ Class and Preferred Term
Safety Population
14.3.1.1
Table
14.3.1.6
Serious Treatment Emergent Adverse Events by System 
Organ Class and Preferred Term
Safety Population
14.3.1.1
14.3.2 Listings of Deaths, Other Serious and Significant Adverse Events
Listing
14.3.2.1
Death
Safety Population
16.2.7.1
Listing
14.3.2.2
Non-fatal Serious Adverse Events
Safety Population
16.2.7.1
Listing
14.3.2.3
Treatment Emergent Adverse Events leading to Study or 
Product Discontinuation
Safety Population
16.2.7.1
Listing
14.3.2.4
Treatment Emergent Adverse Events Classified as Oral
Safety Population
16.2.7.1
14.3.3 Narratives of Deaths, Other Serious and Certain Other Significant Adverse Events
14.3.4 Other Observations Related to Safety and Abnormal Laboratory Values 
Table
14.3.4.1
Summary of Oral Soft Tissue Examination
Safety Population
ϭϰ͘ϯ͘ϰ͘ϭ
APPENDIX
16.1.6 Listing of Subjects Receiving Test Drug(s)/Investigational Product(s) from Specific Batches, where more than one batch was used
NA
16.1.7 Randomization Scheme and Codes (Subject identification and treatment assigned)
Listing
16.1.7.1
Randomization Information
All Randomized 
Subjects
16.1.7.1
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TLF
Number
Title
Population
Template
Topline
Listing
16.1.7.2
Kit List Allocation
All Randomized 
Subjects
16.1.7.2
16.1.9 Documentation of Statistical Methods
Raw Output
16.1.9.1
Statistical Analysis of Change from Baseline in Schiff 
Sensitivity Score of the Two Test Teeth Over Time 
(Reference Table 14.2.2.2.1)
mITT Population
NA
Yes
Raw Output
16.1.9.2
Statistical Analysis of Change from Baseline in Schiff 
Sensitivity Score of the Two Test Teeth Over Time 
(Reference Table 14.2.2.2.2)
PP Population
NA
Raw Output
16.1.9.3
Statistical Analysis of Change from Baseline in Tactile 
Threshold (g) of the Two Test Teeth Over Time 
(Reference Table 14.2.3.2.1)
mITT Population
NA
Yes
Raw Output
16.1.9.4
Statistical Analysis of Change from Baseline in Tactile 
Threshold (g) of the Two Test Teeth Over Time 
(Reference Table 14.2.3.2.2)
PP Population
NA
Raw Output
16.1.9.5
Statistical Analysis of Change from Baseline in DHEQ 
(Section 1 Impact of Everyday Life, Q7 to Q9) 
(Reference Table 14.2.4.2.1)
mITT Population
NA
Raw Output
16.1.9.6
Statistical Analysis of Change from Baseline in DHEQ 
(Section 1 Impact of Everyday Life, Q7 to Q9) 
(Reference Table 14.2.4.2.2)
PP Population
NA
Raw Output
16.1.9.7
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q1 to Q34) Total Score Over Time 
(Reference Table 14.2.5.1.2.1)
mITT Population
NA
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CSR Section
TLF
Number
Title
Population
Template
Topline
Raw Output
16.1.9.8
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q1 to Q34) Total Score Over Time 
(Reference Table 14.2.5.1.2.2)
PP Population
NA
Raw Output
16.1.9.9
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q1 to Q4) Restriction Domain Total Score 
(Reference Table 14.2.5.2.2.1)
mITT Population
NA
Raw Output
16.1.9.10
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q1 to Q4) Restriction Domain Total Score 
(Reference Table 14.2.5.2.2.2)
PP Population
NA
Raw Output
16.1.9.11
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q5 to Q16) Adaptation Domain Total Score 
(Reference Table 14.2.5.3.2.1)
mITT Population
NA
Raw Output
16.1.9.12
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q5 to Q16) Adaptation Domain Total Score 
(Reference Table 14.2.5.3.2.2)
PP Population
NA
Raw Output
16.1.9.13
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q17 to Q21) Social Impact Domain Total 
Score (Reference Table 14.2.5.4.2.1)
mITT Population
NA
Raw Output
16.1.9.14
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q17 to Q21) Social Impact Domain Total 
Score (Reference Table 14.2.5.4.2.2)
PP Population
NA
Raw Output
16.1.9.15
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q22 to Q29) Emotional Impact Domain Total 
Score (Reference Table 14.2.5.5.2.1)
mITT Population
NA
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CSR Section
TLF
Number
Title
Population
Template
Topline
Raw Output
16.1.9.16
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q22 to Q29) Emotional Impact Domain Total 
Score (Reference Table 14.2.5.5.2.2)
PP Population
NA
Raw Output
16.1.9.17
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q30 to Q34) Identity Domain Total Score 
(Reference Table 14.2.5.6.2.1)
mITT Population
NA
Raw Output
16.1.9.18
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q30 to Q34) Identity Domain Total Score 
(Reference Table 14.2.5.6.2.2)
PP Population
NA
Raw Output
16.1.9.19
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2 Global Oral Health Score, Q35) (Reference 
Table 14.2.5.7.2.1)
mITT Population
NA
Raw Output
16.1.9.20
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2 Global Oral Health Score, Q35) (Reference 
Table 14.2.5.7.2.2)
PP Population
NA
Raw Output
16.1.9.21
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q36 to Q39) Effect on Life Overall score 
(Reference Table 14.2.5.8.2.1)
mITT Population
NA
Raw Output
16.1.9.22
Statistical Analysis of Change from Baseline in DHEQ 
(Section 2, Q36 to Q39) Effect on Life Overall score 
(Reference Table 14.2.5.8.2.2)
PP Population
NA
Raw Output
16.1.9.23
Statistical Analysis of Change from Baseline in Labelled 
Magnitude Scale - Intensity (Reference Table 
14.2.5.10.1.2)
mITT Population
NA
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CSR Section
TLF
Number
Title
Population
Template
Topline
Raw Output
16.1.9.24
Statistical Analysis of Change from Baseline in Labelled 
Magnitude Scale - Duration (Reference Table 
14.2.5.10.2.2)
mITT Population
NA
Raw Output
16.1.9.25
Statistical Analysis of Change from Baseline in Labelled 
Magnitude Scale - Tolerability (Reference Table 
14.2.5.10.3.2)
mITT Population
NA
Raw Output
16.1.9.26
Statistical Analysis of Change from Baseline in Labelled 
Magnitude Scale - Description (Reference Table 
14.2.5.10.4.2)
mITT Population
NA
16.2 Subject Data Listings
16.2.1 Discontinued Subjects
Listing
16.2.1.1
Subject Disposition
All randomized 
subjects
16.2.1.1
Listing
16.2.1.2
Subject Disposition
Non-randomized 
subjects
16.2.1.2
16.2.2 Protocol Deviations
Listing
16.2.2.1
Important Protocol Deviations
All randomized 
subjects
16.2.2.1
Listing
16.2.2.2
All Protocol Deviations 
All randomized 
subjects
16.2.2.2
16.2.3 Patients Excluded from the Efficacy Analysis 
Listing
16.2.3.1
Exclusions from Analysis Populations
All randomized 
subjects
16.2.3.1
16.2.4 Demographic Data 
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TLF
Number
Title
Population
Template
Topline
Listing
16.2.4.1
Demographic and Baseline Characteristics
All randomized 
subjects
16.2.4.1
Listing
16.2.4.2
Medical History and Current Medical Conditions 
All randomized 
subjects
16.2.4.2
Listing
16.2.4.3
Prior medications
Safety Population
16.2.4.3
Listing
16.2.4.4
Concomitant medications and significant non-drug 
therapies
Safety Population
16.2.4.4
16.2.5 Compliance and/or Drug Concentration Data (if available)
Listing
16.2.5.1
Brushing Compliance
All randomized 
subjects
16.2.5.1
Listing
16.2.5.2
Supervised Brushing
Safety Population
16.2.5.2
16.2.6 Individual Efficacy Response Data
Listing
16.2.6.1
Individual Efficacy Data for Schiff Sensitivity Score 
(Screening and Baseline)
All Randomized 
Subjects
16.2.6.1
Listing
16.2.6.2
Individual Efficacy Data for Schiff Sensitivity Score of the 
Two Test Teeth
All Randomized 
Subjects
16.2.6.2
Listing
16.2.6.3
Individual Efficacy Data for Tactile Threshold (g) at 
Screening and Baseline
All Randomized 
Subjects
16.2.6.3
Listing
16.2.6.4
Individual Efficacy Data for Tactile Threshold (g) of the 
Two Test Teeth
All Randomized 
Subjects
16.2.6.4
Listing
16.2.6.5
Individual Efficacy Data for DHEQ Section 1
All Randomized 
Subjects
16.2.6.5
Listing
16.2.6.6.1
Individual Efficacy Data for DHEQ Section 2 
(Restrictions Domain)
All Randomized 
Subjects
16.2.6.6.1
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TLF
Number
Title
Population
Template
Topline
Listing
16.2.6.6.2
Individual Efficacy Data for DHEQ Section 2 
(Adaptations Domain)
All Randomized 
Subjects
16.2.6.6.2
Listing
16.2.6.6.3
Individual Efficacy Data for DHEQ Section 2 (Social 
Impact Domain)
All Randomized 
Subjects
16.2.6.6.3
Listing
16.2.6.6.4
Individual Efficacy Data for DHEQ Section 2 (Emotional 
Impact Domain)
All Randomized 
Subjects
16.2.6.6.4
Listing
16.2.6.6.5
Individual Efficacy Data for DHEQ Section 2 (Identity 
Domain)
All Randomized 
Subjects
16.2.6.6.5
Listing
16.2.6.6.6
Individual Efficacy Data for DHEQ Section 2 (Total 
Score, Q1 to Q34)
All Randomized 
Subjects
16.2.6.6.6
Listing
16.2.6.6.7
Individual Efficacy Data for DHEQ Section 2 (Q35 to 
Q39)
All Randomized 
Subjects
16.2.6.6.7
Listing
16.2.6.7
Individual Efficacy Data for Number of Sensitive Teeth
All Randomized 
Subjects
16.2.6.7
Listing
16.2.6.8
Individual Efficacy Data for Labelled Magnitude Scale of 
the two test teeth (in mm)
All Randomized 
Subjects
16.2.6.8
Listing
16.2.6.9
Individual Efficacy Data for Numerical Rating Scale at 
Day 56
All Randomized 
Subjects
16.2.6.9
16.2.7 Adverse Event Listings 
Listing
16.2.7.1
All Adverse Events
Safety Population
16.2.7.1
Yes
Listing
16.2.7.2
Incidents
Safety Population
16.2.7.2
16.2.8 Other Listings and Listing of Laboratory Measurements, when required by regulatory authorities (if applicable) 
Listing
16.2.8.1
Oral Soft Tissue examination
Safety Population
16.2.8.1
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TLF
Number
Title
Population
Template
Topline
Listing
16.2.8.2
Oral Hard Tissue examination
Safety Population
16.2.8.2
16.4 Individual Subject Data Listings
NA
CCI