A Clinical Study Investigating the Efficacy of an Occluding Dentifrice in Providing Relief From Dentinal Hypersensitivity
Phase: NA
Conditions: Dentin Sensitivity
Sponsor: GlaxoSmithKline

Copyright:  GlaxoSmithKline.  An unpublished work subject to trade secret 
protection.  This work contains confidential and proprietary information of 
GlaxoSmithKline and should not be copied, circulated, or distributed to persons not 
employed by GlaxoSmithKline unless specifically authorized.  Unauthorized 
disclosure of this work is expressly prohibited.
Clinical Protocol
207212
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 1 of 69

CONFIDENTIAL
SUMMARY INFORMATION
Title:
A Clinical Study Investigating the Efficacy of an 
Occluding Dentifrice in Providing Relief from Dentinal 
Hypersensitivity
Protocol Number:
207212
Sponsor:
GlaxoSmithKline Consumer Healthcare (GSKCH)St 
Georges Avenue, Weybridge, Surrey, KT13 0DE,
United Kingdom (UK)
Tel: 
Product Name:
Experimental Dentifrice containing 
 
stannous fluoride ( 
 fluoride)
Development Phase:
N/A
Expert Advice Outside of Normal 
Working Hours:
Tel: 
Key Protocol Authors:
PRIMARY CONTACT
Clinical Study Manager:
, PhD
GSK Consumer Healthcare
Route de l'Etraz, 1260, Ny
on, 
Switzerland
Tel 
Clinical Research
, MSc, CStat
, MSc, PhD
Biostatistician:
, BSc, MSc
Clinical Supplies:
, MSc
Principal Investigator:
Professor Nicola West, BDS, FDS, RCS, 
PhD, FDS
Study Site Name & Address:
Clinical Trials Unit (Periodontology) 
School of Oral and Dental Sciences
Bristol Dental School and Hospital
Lower Maudlin Street, Bristol
BS1 2LY, UK
Study Site Telephone Number:
Tel: 
Fax:
Study Examiner:
, BDS, MFDS RCPS
(Tactileassessments and Evaporative air 
assessments)
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 2 of 69
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
PPD
CCI
CCI

PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT PAGE
I confirm agreement to conduct the study in compliance with the protocol and 
any amendments and according to the current ICH GCP guidelines.
I acknowledge that I am responsible for overall study conduct. I agree to 
personally conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the 
conduct of the study are informed about their obligations. Mechanisms are in 
place to ensure site staff receives all appropriate information throughout the 
study.
I agree to conduct this study in full conformance with the laws and regulations 
of the country in which the research is conducted and the Declaration of 
Helsinki.
Investigator Name:
Prof Nicola West
Investigator Qualifications:
BDS, FDS, RCS, PhD, FDS
Investigator Signature:
Date of Signature/ Agreement:
DD/MMM/YYYY
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 3 of 69
PPD
PPD

Table of Content
PROCESS FOR AMENDING THE PROTOCOL..............................................8
PROTOCOL AMENDMENT PAGE...................................................................9
Brief Summary......................................................................................................12
Objectives and Endpoints......................................................................................12
Study Design..........................................................................................................12
Type and Planned Number of Subjects................................................................14
Diagnosis and Main Criteria for Inclusion...........................................................14
Product Information..............................................................................................15
Statistical Methods................................................................................................16
1. INTRODUCTION.............................................................................................17
2. OBJECTIVES AND ENDPOINTS...................................................................18
3. STUDY PLAN....................................................................................................19
3.1. Study Design..............................................................................................19
3.2. Subject Restrictions..................................................................................21
3.3. Type and Planned Number of Subjects....................................................22
3.4. Study Design and Dose Justification........................................................22
4. SELECTION OF STUDY POPULATION AND WITHDRAWAL CRITERIA
....................................................................................................................24
4.1. Inclusion Criteria......................................................................................24
4.2. Exclusion Criteria.....................................................................................26
4.3. Screening/ Baseline Failures.....................................................................28
4.4. Withdrawal/ Stopping Criteria.................................................................28
4.5. Subject Replacement.................................................................................29
4.6. Subject and Study Completion.................................................................29
5. PRODUCT INFORMATION...........................................................................29
5.1. Study Product............................................................................................29
5.2. Dose Schedule............................................................................................32
5.3. Dose Modification.....................................................................................32
5.4. Product Compliance..................................................................................32
5.5. Precautions................................................................................................32
5.6. Overdose....................................................................................................32
5.7. Rescue Therapy.........................................................................................33
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 4 of 69

5.8. Product Assignment..................................................................................33
5.8.1 Randomisation...................................................................................33
5.8.2 Blinding..............................................................................................34
5.8.3 Code Breaks.......................................................................................34
5.9. Packaging and Labelling...........................................................................34
5.9.1. Accountability of Product................................................................35
5.9.2. Storage of Product............................................................................35
6. STUDY ASSESSMENTS AND PROCEDURES..............................................36
6.1. Visit 1 -Screening Visit.............................................................................36
6.1.1. Informed Consent.............................................................................36
6.1.2. Demographics...................................................................................36
6.1.3. Medical History and Concomitant Medication...............................36
6.1.4. Oral Soft Tissue (OST) Examination...............................................37
6.1.5.  Oral Hard Tissue (OHT) Visual Examination...............................37
6.1.6. Eligible Tooth Assessment................................................................37
6.1.6.1.  Erosion, Abrasionand Recession (EAR) assessment..................37
6.1.6.2. Modified Gingival Index (MGI) Assessment................................38
6.1.6.3. Tooth Mobility Assessment...........................................................38
6.1.6.4. Qualifying Evaporative air Sensitivity..........................................38
6.1.7. Acclimatisation Product Supervised Brushing................................39
6.2. Visit 2 –Baseline (Pre-treatment).............................................................39
6.2.1. Oral Soft Tissue (OST) Examination...............................................39
6.2.2. Tactile Assessment (Yeaple probe)..................................................39
6.2.2.1 Subject Response............................................................................40
6.2.2.2 Calibration of the Yeaple Probe.....................................................40
6.2.3. Evaporative Air Sensitivity Assessment..........................................41
6.2.3.1. Schiff Sensitivity Scale...................................................................42
6.2.4. Selection of Two Test Teeth.............................................................42
6.2.5. Study treatment direct application..................................................42
6.3. Visit 2 (Post-treatment).............................................................................43
6.3.1. Oral Soft Tissue (OST) Examination...............................................43
6.3.2. Tactile Assessment (Yeaple probe)..................................................43
6.3.3. Evaporative Air Sensitivity Assessment..........................................43
6.3.3.1. Schiff Sensitivity Scale...................................................................43
6.4. Visit 3 (Day 3)............................................................................................43
6.4.1. Oral Soft Tissue (OST) Examination...............................................43
6.4.2. Tactile Assessment (Yeaple Probe)..................................................43
6.4.3. Evaporative Air Sensitivity Assessment..........................................44
6.4.3.1. Schiff Sensitivity Scale...................................................................44
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 5 of 69

6.4.4. Study Conclusion..............................................................................44
7. SAFETY ASSESSMENTS................................................................................44
7.1. Definitions of an Adverse Event and Serious Adverse Event..................44
7.1.1. Adverse Events.................................................................................44
7.1.2. Serious Adverse Events....................................................................45
7.2. Recording Adverse Events and Serious Adverse Events.........................46
7.3. Evaluating Adverse Events and Serious Adverse Events........................47
7.4. Reporting Adverse Events and Serious Adverse Events.........................48
7.5. Follow-up of Adverse Events and Serious Adverse Events.....................49
7.6. Definition of and Procedure for Reporting Medical Device Incidents....50
7.6.1. Definition of an Incident..................................................................50
7.6.2. Reporting of Incidents and Malfunctions........................................51
7.6.3. Follow-up of Incidents......................................................................52
7.7. Collection of Pregnancy Information.......................................................52
7.7.1. Time Period for Collecting of Pregnancy Information...................52
7.7.2. Action to be Taken if Pregnancy Occurs.........................................53
8. DATA MANAGEMENT...................................................................................53
8.1. Source Documents/ Data...........................................................................53
8.2. Electronic Case Report Form...................................................................54
8.3. Data Handling...........................................................................................54
8.3.1. Data Queries.....................................................................................55
8.4. Processing Patient Reported Outcomes...................................................55
9. STATISTICAL CONSIDERATIONS AND DATA ANALYSES....................55
9.1 Sample Size Determination........................................................................55
9.2. General Considerations............................................................................56
9.2.1. Definition of Analysis Populations...................................................56
9.2.2. Exclusion of Data from Analysis......................................................56
9.2.3. Criteria for Evaluation.....................................................................57
9.2.4. Criteria for Assessing Efficacy.........................................................57
9.2.5. Criteria for Assessing Tolerability...................................................57
9.2.6. Handling of Dropouts and Missing Data.........................................57
9.2.7. Other Issues......................................................................................57
9.3. Statistical Methods and Analytical Plan..................................................58
9.3.1. Demographic and Baseline Characteristics.....................................58
9.3.2. Primary Analysis..............................................................................58
9.3.2.1 Schiff Sensitivity Score following three days of treatment............58
9.3.3. Secondary Analyses..........................................................................59
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 6 of 69

9.3.3.1 Schiff Sensitivity Score following a single use...............................59
9.3.3.2 Tactile sensitivity followinga single use and 3 days treatment......59
9.3.4. Safety Analyses.................................................................................59
10. STUDY GOVERNANCE CONSIDERATIONS............................................59
10.1. Posting of Information on Publicly Available Clinical Trials Registers59
10.2. Regulatory and Ethical Considerations, Including the Informed Consent
...............................................................................................................60
10.3. Quality Control (Study Monitoring)......................................................60
10.4. Quality Assurance...................................................................................61
10.5. Conditions for Terminating the Study...................................................61
10.6. Records Retention...................................................................................62
10.7. Provision of Study Results to Investigators, posting of Information on 
Publicly Available Clinical Trials Registers and Publication.............63
11. REFERENCES................................................................................................63
12. APPENDICES..................................................................................................68
12.1. Appendix 1 -Abbreviations and Trademarks.......................................68
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 7 of 69

PROCESS FOR AMENDING THE PROTOCOL
Protocol modifications to ongoing studies which could potentially adversely affect the 
safety of subjects or which alter the scope of the investigation, the scientific quality of 
the study, the experimental design, dosages, duration of therapy, assessment 
variables, the number of subjects treated, or subject selection criteria are considered 
major/substantial amendments and must be made only after appropriate consultation 
between an appropriate representative of GSKCH and the investigator.
Details of amendments to the protocols should be recorded on the following page. 
Protocol modifications must be prepared by a representative of GSKCH.  All changes 
must be justified in the Reason for Amendment section of the following Protocol 
Amendment Page. Approval of amendments will be made by the original protocol 
signatories or their appropriate designees.
All major/substantial protocol modifications must be reviewed and approved by the 
appropriate IEC in accordance with local requirements, before the revised edition can 
be implemented. 
All non-substantial/ minor/ administrative amendments should be submitted to the 
IECas per country specific requirements. In some countries pre-approval of a minor 
amendment is not required and will just be held on file by the sponsor and 
investigator.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 8 of 69

PROTOCOL AMENDMENT PAGE
Details of all amendments should be recorded in the table below. Affected sections should be listed in the table; the actual 
amendment/ change should be made in the relevant section of the main protocol. 
To highlight the change, the following features will be used: 
To addtext: Use of CAPITAL LETTERS, BOLD AND UNDERLINE
To delete text: Use of Strikethrough e.g. strikethrough
Amendment 
No. & New 
Protocol 
Version No.
Type of Amendment
Reason for Amendment
Other 
Documents 
Requiring 
Amendment
Section(s) Amended 
PI Amendment 
Agreement
Signature & 
Date
Amendment 
No.:
Non-Substantial/Minor    
Informed 
Consent   
Yes No
Safety 
Statement     
Yes No
CRF                       
Yes 
No
Signature:
Protocol 
Version 
No.:
Substantial/ Major           
Date:
Amendment 
No.:
Non-Substantial/Minor    
Informed 
Consent   
Yes No
Safety 
Statement     
Yes No
CRF                       
Yes No
Signature:
Protocol 
Version 
No.:
Substantial/ Major           
Date:
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6

SCHEDULE OF EVENTS
Procedure/ Assessment
Visit 1
Acclimatisation Period (minimum 4 weeks –maximum 8weeks)
Visit 2
Visit 3
Screening
Day 0
Baseline   
(Pre-
Treatment)
Day 0
Post-
Treatment
Day 3
Informed consent
X
Demographics and Medical History
X
Current / Concomitant medication 
X
X
X
Inclusion / Exclusion Criteria
X
X1
Subject Eligibility
X
X
X
Continuation Criteria
X
X
Oral Soft Tissue (OST) Examination 
X
X 
X 
X
Oral Hard Tissue Examination 
including Eligible Teeth Assessments 
(Dentition Exclusions, EAR, MGI, 
Tooth Mobility) 
X
Qualifying Evaporative Air 
Sensitivity Assessment (Y/N)
X
Dispense Acclimatisation 
Toothpaste, Toothbrush, Timer 
X
Supervised Brushing with 
Acclimatisation Toothpaste
X
Return Acclimatisation Toothpaste, 
Toothbrush
X
Compliance Check
X2
X7
Tactile Sensitivity Assessment     
(Yeaple Probe) 
X3
Evaporative Air Sensitivity 
Assessments (Schiff sensitivity 
score) 
X4
Selection of two ‘Test Teeth’
X5
Stratification/Randomisation 
X
Dispense Study Supplies
X6
Supervised direct application of 
allocated dentifrice (Test Teeth Only)
X8
Tactile and Evaporative Air 
Assessments9(Test Teeth only)
X
X
Supervised Brushing
X10
Return Study Supplies
X
Adverse Events / Incidents11
X
X 
X 
X
Study Conclusion
X
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 10 of 69

1. Inclusion criteria 5d
2. Subject asked to confirm that they have brushed with the acclimatisationproduct as directed during the 
acclimatisation period. 
3. To be performed pre treatment on all teeth that meet the dentition exclusions, EAR, MGI and tooth mobility criteria 
at Screeninguntil the examiner selects 2 teeth meet the study criteria, at which point no further teeth will be tested.  
Maximum force to be tested will be 20g.
4. To be performed pre-treatment on teeth that meet tactile threshold inclusion criterion (<=20g) at Baseline and 
should follow the tactile assessment with a minimum of 5 mins between the last tactile assessment and the first 
evaporative air assessment to allow the teeth recovery time.
5. Tactile assessment tobe performed, on the two selected test teeth only.  Maximum force to be tested will be 80g.  
Evaporative air assessment should follow the tactile assessment with a minimum of 5 mins between the last tactile 
assessment and the first evaporative air assessment to allow the teeth recovery time.
6. Experimental dentifrice, control dentifrice, toothbrush, product usage instructions, and diary. Timer dispensed in 
Visit 1 will be kept and re used. 
7. Based on subject completed diary card
8. To be performed after stratification and randomisation
9. Tactile assessment to be performed, on the two selected test teeth only.  Maximum force to be tested will be 80g.  
Evaporative air assessment should follow the tactile assessment with a minimum of 5 mins between the last tactile 
assessment and the first evaporative air assessment to allow the teeth recovery time.
10. Supervised whole mouth brushing before leaving the site (after all clinical assessments have been performed)
11. Incidents captured from Visit 2. 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 11 of 69

PROTOCOL SYNOPSIS FOR STUDY 207212
Brief Summary
This single centre study will be used to investigate theefficacy of an experimental 
stannous fluoride containing dentifrice in relieving dentinal hypersensitivity (DH) 
after short term usecompared with a standard fluoride dentifrice. 
The study will beconducted in subjects in good general health, with pre-existing self-
reported and clinically diagnosed tooth sensitivity atscreening.
Objectivesand Endpoints
Objectives
Endpoints
Primary
To investigate the ability of an 
experimental  
 stannous fluoride 
dentifrice to provide relief from DH, as 
elicited by an evaporative (air) stimulus 
(Schiff sensitivity scale) after3 days use.
Change from baseline in Schiff 
sensitivity score after 3 days use.
Secondary
To investigate the ability of an 
experimental  
 stannous fluoride 
dentifrice to provide relief from DH, as 
elicited by a tactile stimulus (Yeaple 
probe) after3 days use.
Change from baseline in a tactile 
threshold after 3 days use.
To investigate the ability of a 
 
stannous fluoride dentifrice to provide 
relief from DH, as elicited by an 
evaporative (air) stimulus (Schiff 
sensitivity scale) and a tactile stimulus 
(Yeaple probe) aftera single use (60 
second direct applicationon selected 
teeth)
Change from baselinein Schiff 
sensitivity score after a single 60 second 
direct application.
Change from baseline in tactilethreshold 
after a single 60 seconds direct 
application.
Study Design
Overall Design
This will be a single centre, three day, randomised, examiner blind, two treatment 
arm, parallel design, stratified (by maximum baseline Schiff sensitivity score of the 
two selected test teeth), controlled study, in subjects with at least two sensitive teeth 
that meet all the criteria at the screening and baseline (pre-treatment) visits.  DHwill 
be assessed at baseline (pre-treatment), post-treatment and after 3 days twice daily 
brushing.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 12 of 69
CCI
CCI
CCI

Visit 1 -Screening Visit
The following assessments will be conducted:
Written informed consent.
Inclusion/exclusion criteria
Review of the oral care products the subject is currently usingto confirm they do 
not contain any ingredients intended for treating sensitive teeth. 
Demographics, current/concomitant medications and medical history.
Oral examination including an oral soft tissue (OST) and oral hard tissue (OHT) 
examinations and assessments to determine eligible teethOral Hard Tissue 
Examination including Eligible Teeth Assessments (Dentition Exclusions, EAR, 
MGI, Tooth Mobility). 
Qualifying evaporative air sensitivity.
Confirmation of subject eligibility.
Dispensation of acclimatisationtoothpaste, toothbrushand timer.
Supervised brushing with acclimatisation toothpaste.
Adverse Events (AEs) and incidents will be documented from completion of the 
supervised brushing with acclimatisation toothpaste.
Visit 2 -Baseline Visit(Pre-treatment)
The following assessments will beconducted:
Review of current/concomitant medications, AEs. 
Return of acclimatisation toothpasteandtoothbrush. 
Compliance check of acclimatisation product usage during acclimatisation 
period.
Confirmation of subject eligibility and continuance. 
OST examination.
Tactile sensitivity assessment of eligible teeth.
Evaporative air sensitivity assessment of eligible teeth which meet the tactile 
sensitivityentry criterion.
Inclusion criteria 5d. 
Selection of two test teeth.
Stratification and Randomisation.
Dispensation of study toothpaste and toothbrush with usage instructions and 
diary.
Supervised direct application using finger with allocated study treatment(test 
teeth only)
Adverse events and Incidents.
Visit 2 –Post-treatment
The following assessments will be conducted:
Review of AEs and incidents. 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 13 of 69

OST examination.
Tactile sensitivity assessment of the two selected test teeth.
Evaporative air sensitivity assessment of the two selected test teeth.
Supervised brushing (whole mouth) with allocated study treatment before leaving 
site after all clinical assessments performed.
Visit 3 –Day 3
The following procedures will be conducted:
Review of current/concomitant medications, AEs and incidents. 
Subject adherence
Return of study supplies (toothpaste, toothbrush) and diary
. 
Review of completed diary to determine usage compliance.
OSTexamination.
Tactile sensitivity assessment of the two selected testteeth.
Evaporative air sensitivity assessment of the two selected test teeth.
Subjects will be reminded to report AEs and incidents for 5 days after last 
treatment. 
Study conclusion.
Type and Planned Number of Subjects
A sufficient number of subjects will be screened in order that approximately 210
subjects enter the acclimatisation phase so that approximately 190 subjects 
(approximately 95 per treatment arm) are randomised. This should ensure 
approximately 184 subjects (approximately 92 per treatment arm) complete the study.
Diagnosis and Main Criteria for Inclusion
Subjects aged 18-65 years of age, with a minimum of 20 natural teeth and in good 
general health who suffer from tooth sensitivity.  At Screening, subjects must have a 
minimum of twoaccessible non adjacent teeth (incisors, canines, or pre-molars) with 
signs of erosion or abrasion or facial/cervical gingival recession (EAR), with a
modified gingival index (MGI) =0 adjacent to the test areaand aclinical mobility of 
≤1, and with signs of sensitivity measured by qualifying evaporative air assessment. 
At Baseline subjects must have a minimum of two, non-adjacent accessible teeth 
(incisors, canines or pre-molars), with signs of sensitivity, measured by qualifying 
tactile stimulus (Yeaple ≤ 20g) and evaporative air assessment (Schiff Sensitivity 
Score ≥ 2).
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 14 of 69

Product Information
Test dentifrice
Control dentifrice
Treatment 
Description
Experimental dentifrice 
containing  
 
stannous fluoride
(
 fluoride)
Dentifrice containing  
 sodium 
monofluorophosphate 
(
 fluoride)
MFC or Commercial 
product
Colgate Cavity Protection 
(USAMarketed Product)
Route of 
administration
Topical oral use
Supervised direct 
application time 
(Test Teeth only)
60 seconds
60 seconds
Supervised direct 
application (Test 
Teeth only) dosing 
instructions 
Subjects will directly apply (under supervision) a pea-
sized dose to each of the two qualifying teeth using their 
washed, clean finger by direct application and gently 
rubbing into the tooth’s cervical margin for the allocated 
time.  
No rinsing will be permitted.
Supervised brushing 
(Visit 2) 
Before leaving the site 
(after all the clinical 
assessments have been 
completed), subjects will 
dose a dry toothbrush with 
a full strip of toothpaste.
Subjects will then brush 
each of the two selected 
sensitive test teeth first, 
followed by the whole 
mouth thoroughly for at 
least 1 minute.
Subjects will be permitted 
to rinse with 5ml tap 
water (kept at room 
temperature) for a 
maximum 5 timed 
seconds.
Before leaving the site (after 
all the clinical assessments 
have been completed), 
subjects will  dose a dry 
toothbrush with a full strip of 
toothpaste
Subjects will brush their 
whole mouth thoroughly for at 
least 1minute under.
Subjects will be permitted to 
rinse with 5ml tap water (kept 
at room temperature) for a 
maximum 5 timed seconds.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 15 of 69
CCI
CCI
CCI
CCI
CCI

Home use 
instructions
Twice daily 
(morning/ evening)
Subjects will be instructed 
to dose a dry toothbrush 
with a full strip of 
toothpaste.    
Subjects will then brush 
each of the two selected 
sensitive test teeth first, 
followed by the whole 
mouth thoroughly for at 
least 1 minute.  
Subjects will be permitted 
to rinse with tap water.
Subjects will be instructed to 
dose a dry toothbrush with a 
full strip of toothpaste.    
Subjects will then brush the 
whole mouth thoroughly for at 
least 1 minute. 
Subjects will be permitted to 
rinse with tap water.
Statistical Methods
Change from baseline (pre-treatment) to post-treatment time point (single use and 
after 3 days use) in Schiff sensitivity score will be analysed usingan analysis of 
covariance (ANCOVA) model.The model will include treatment and baseline Schiff 
Sensitivity Score as a covariate.
Change from baseline (pre-treatment) to post-treatment time point (single use and 
after 3 days use) in tactile score will be analysed using ANCOVAwith treatment and 
baseline Schiff stratification as factors and thebaselinetactile score as a covariate.
Adverse events (AEs), incidents, and OSTabnormalities will be listed by treatment.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 16 of 69

1. INTRODUCTION
Dentinal hypersensitivity (DH) is described by Addy et al as ‘pain derived from 
exposed dentine in response to chemical, thermal, tactile, or osmotic stimuli which 
can’t be explained as arising from any other dental defect or pathology’ [Addy 1985].  
The definition was later revised to replace the word ‘pathology’ with ‘disease’ to 
avoid confusion with pain origins from other dental conditions [Canadian Advisory 
Board, 2003].  DH originates from aetiologic factors such as gingival recession, 
erosion and/or abrasion that result in loss of enamel or cementum and exposure of 
underlying dentine with patent dentinal tubules[Orchardson, 1987].  Brännström’s 
hydrodynamic theory of DH hypothesises movement of the fluid within the dentine 
tubules when an externalstimulus is applied to the dentine, which in turn stimulates 
nerve processes in the pulpal area of the dentine and produces pain impulse 
transmission [Brannstrom, 1964].
Currently there are two approaches to the management of DH.
Nerve depolarisation 
Dentinal tubule occlusion.
Nerve depolarising agents, such as potassium nitrate, generally require a period of use 
(for example, 14 to 28 days) before their benefit is established.  The delivery of 
potassium ions to the dentine-pulp junction (odontoblastic layer) via dentinal tubules 
is believed to result in depolarisation of the afferent nerve membrane thereby 
blocking the pain response[Orchardson, 1975].  Tubule occluding agents such as 
strontium salts, stannous salts, bioglasses or silicas serve to physically seal or block 
the dentine tubules and thereby reduce the effect of external stimuli.  
Stannous fluoride has been incorporated into oral hygiene products indicated for the 
reduction of DH since the 1960s [Schiff, 2006]. Its long-term efficacy has been 
reported in a number of published studies with treatment periods of 2-8 weeks 
[Schiff, 2000a, 2000b, 2005, 2006; Sharma, 2010; Chaknis, 2011; Du, 2011; Ni, 
2011; Parkinson, 2013], with somestudies also reporting short term efficacy [He, 
2011b; Sharma, 2011].Morerecently, studies have also demonstrated relief of DH 
following a single treatment with an occlusion technology dentifrice at the start of a 
period of twice daily brushing. The single treatment involves direct application of a 
dentifrice to the sensitive dentine, either by massaging the sensitive tooth with 
dentifriceor by focusedtoothbrushing of thesensitive teeth prior to brushing the 
whole mouth. The direct application approach has been shown to be effective for two 
occlusion technologies to date (strontium acetate and arginine) [Ayad, 2009; Nathoo, 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 17 of 69

2009; Schiff, 2009; Fu, 2010; Mason, 2010]and focussed toothbrushing for stannous 
fluoride dentifrices[GSKCH Study RH01324; He, 2011a; Sharma, 2011].
GSK consumer healthcare (GSKCH) has conducted several short term studies with 
stannous fluoride dentifrices looking at DH relief with up to 14 days treatment 
[GSKCH Study RH01324; GSKCH Study RH01327; GSKCH Study Z7871335]. 
Stannous fluoride dentifrices were applied using the ‘focusedbrushing’ application 
which involved brushing the sensitive teeth prior to brushing the whole mouth.
The current study will investigate the ability of an experimental 
 
stannous fluoride dentifrice in providing relief from DH after 3 days twice daily use, 
and after an initial direct application to the cervical margin.  
2. OBJECTIVESAND ENDPOINTS
Objectives
Endpoints
Primary
To investigate the ability of an 
experimental  
 stannous fluoride 
dentifrice to provide relief from DH, as 
elicited by an evaporative (air) stimulus 
(Schiff sensitivity scale) after3 days use.
Change from baseline in Schiff 
sensitivity score after 3 days use.
Secondary
To investigate the ability of an 
experimental  
 stannous fluoride 
dentifrice to provide relief from DH, as 
elicited by a tactile stimulus (Yeaple 
probe) after3 days use.
Change from baseline in a tactile 
threshold after 3 days use.
To investigate the ability of a  
 
stannous fluoride dentifrice to provide 
relief from DH, as elicited by an 
evaporative (air) stimulus (Schiff 
sensitivity scale) and a tactile stimulus 
(Yeaple probe) aftera singleuse (60 
second direct applicationon selected 
teeth).
Change from baseline in Schiff 
sensitivity score after a single 60 second 
direct application.
Change from baseline in tactile threshold 
after a single 60 seconddirect
application.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 18 of 69
CCI
CCI
CCI
CCI

3. STUDY PLAN
3.1. Study Design
Overall Design
This will be a single centre, three day, randomised, examiner blind, two treatment 
arm, parallel design, stratified (by maximum baseline Schiff sensitivity score of the 
two selected test teeth), controlled study, in subjects with at least two sensitive teeth 
that meet all the criteria at the screeningand baseline (pre-treatment) visits.  DHwill 
be assessed at baseline (pre-treatment), post-treatment and after 3 days twice daily 
brushing.
At the Screening visit, subjects will give their written informed consent to participate 
in the study.  Demography, medical history and concomitant medications will be
recorded, followed by an oral examination.  This will include an oral soft tissue 
(OST) and oral hard tissue (OHT) examination, dentition exclusions, assessment of 
erosion, abrasion, recession (EAR), gingival status, tooth mobility and subject 
response toa qualifying air sensitivity assessment(Y/N).  Eligible subjects will be 
supplied with a standard fluoride dentifrice to use twice daily (morning and evening) 
during the acclimatisationperiod between the Screening and Baseline (pre-treatment).  
First use of the acclimatisation dentifrice will be carried out under supervision at the 
study site.
At the Baseline visit (pre-treatment),eligibility to continue will be assessed.    
Subjects will undergo anOST examination, followed by tooth sensitivity assessments 
(to a tactile stimulus [Yeaple probe, maximum 20g pressure],andan evaporative air 
stimulus [with Schiff Sensitivity Scale]),and a review of the inclusion/exclusion 
criteria. Eligible subjects will be stratified according to their maximum baseline 
Schiff sensitivity scoreof the two selected teeth (2 / 3) and then randomised to 
treatment. 
At Visit 2, randomised subjects will directly apply assigned treatment to the two 
selected teeth (under supervision) as per the instructions provided.  Following direct 
application of the assigned treatment (and within 5 minutes of it), tooth sensitivity of 
the two test teeth will be assessed to a tactile and evaporative air stimuli. Before 
leaving the site (after all the clinical assessments have been completed), subjects will 
brush their whole mouth for at least one minute under supervision.  Subjects will 
brush at least once on the day of baseline (first brushing will be supervised at site). 
Subjects will return to the study site on day 3 (Visit 3) after six brushings.  Every 
effort will be made to ensure similar appointment times are kept for subjects at Visit 3 
as per Visit 2.  Subjects will undergo an OST examination, followed by tooth 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 19 of 69

sensitivityassessments (to a tactile stimulus [Yeaple probe, maximum 80g pressure], 
and an evaporative air stimulus [with Schiff Sensitivity Scale]).  Following reviewof 
AEs and incidents subjects will be exited from the study.
Visit 1 -Screening Visit
The following assessments will be conducted:
Written informed consent.
Inclusion/exclusion criteria
Review of the oral care products the subject is currently usingto confirm they do 
not contain any ingredients intended for treating sensitive teeth. 
Demographics, current/concomitant medications and medical history.
Oral examination including an oral soft tissue (OST) and oral hard tissue (OHT) 
examinations,including eligible teeth assessments (Dentition Exclusions, EAR, 
MGI, Tooth Mobility). 
Qualifying evaporative air sensitivity.
Confirmation of subject eligibility.
Dispensation of acclimatisationtoothpaste, toothbrush, and timer.
Supervised brushing with acclimatisation toothpaste.
Adverse Events (AEs) and incidents will be documented from completion of the 
supervised brushing with acclimatisation toothpaste.
Visit 2 -Baseline (Pre-treatment)
The following assessments will beconducted:
Review of current/concomitant medications, AEs. 
Return of acclimatisation toothpasteandtoothbrush. 
Compliance check of acclimatisation product usage during acclimatisation 
period.
OST examination.
Tactile sensitivity assessment of eligible teeth.
Evaporative air sensitivity assessment of eligible teeth which meet the tactile 
sensitivity entry criterion.
Inclusion criteria 5d. 
Selection of two test teeth.
Stratification and Randomisation.
Dispensation of study toothpaste with usage instructions and diary.
Supervised direct application using finger with allocated study treatment(test 
teeth only).
Adverse events and Incidents.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 20 of 69

Visit 2 –Post-treatment
The following assessments will be conducted:
Review of AEs and incidents. 
OST examination.
Tactile sensitivity assessment of the two selected test teeth.
Evaporative air sensitivity assessment of the two selected test teeth.
Supervised brushing with allocated study treatment.
Visit 3 –Day3
The following procedures will be conducted:
Review of current/concomitant medications, AEs and incidents. 
Subject adherence
Return of study supplies (toothpaste, toothbrush) and diary
. 
Review of completed diary to determine usage compliance.
OSTexamination.
Tactile sensitivity assessment of the two selected test teeth.
Evaporative air sensitivity assessment of the two selected test teeth.
Subjects will be reminded to report AEs and incidents for 5 days after last 
treatment. 
Study conclusion.
3.2. Subject Restrictions
Lifestyle/ Dietary
For the duration of the study (Screening –last visit):
Eligible subjects will be asked to stop using their regular oral care products from 
Screening for the duration of the study. 
Subjects will not be permitted to use any oral care products (e.g.  mouthwashes, 
tongue cleaners, whitening/bleaching products) otherthan those provided to 
them.
Subjects will not be permitted to use any dental products, including home 
remedies, intended for treating sensitive teeth. 
Subjects will not be permitted to chew gum.
Subjects will not be permitted to floss, except to remove impacted food
Prior to study visits (Baseline -Day 3):
Subjects will be asked to refrain from all oral hygiene procedures for at least 8 
hours, and from eating and drinking for at least 4 hours in order to standardise 
oral hygiene practices.  Within 4 hours of a visit (but not within one hour of the 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 21 of 69

visit), small sips of room-temperature water will be permitted to take medications 
and relieve thirst if necessary
Subjects will be requested to refrain from excessive alcohol consumption for 24 
hours prior to the Baseline and all subsequent visits. If, in the opinion of the 
Investigator, the subject has consumed an excessive amount of alcohol prior to a 
visit, the visit may be rescheduled.  If this is not possible, the subject should be 
treated as per section 4.4.
Medications and Treatments
For the duration of the study (Screening –last visit):
If concomitant medications and traditional herbal ingredients/treatments are used 
during the study, their identity, as well as their dosage and frequency, start and 
stop dates must be recorded in the CRF.
Should a subject take an analgesic within 8 hours of a scheduled visit, every effort 
will be made to reappoint them to the next day. If this is not possible, the subject 
should be treated as per section 4.4.
Subjects who enter the study will be requested to delay having any non -
emergency, elective dental treatment until after study completion (including dental 
prophylaxis).
3.3. Type and Planned Number of Subjects
A sufficient number of subjects will be screened in order that approximately 210 
subjects enter the acclimatisation phase so that approximately 190 subjects 
(approximately 95 per treatment arm) are randomised. This should ensure 
approximately 184 subjects (approximately 92 per treatment arm) complete the study.
Subjects will be recruited by the clinical site, primarily from their volunteer database.  
Subjects may also be recruited via posters or by word of mouth.
3.4. Study Design and Dose Justification
A randomized, single-blind(examiner blind), parallel group design is a recognized 
approach for providing evidence of the clinical effectiveness of atreatment forthe 
reduction of DH[Holland, 1997].  
In line with published recommendations [Holland, 1997], two independent stimulus-
based efficacy measures will be employed (tactile and evaporative air sensitivity). To 
avoid inter-examiner variation, a single examiner will be responsible for the conduct 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 22 of 69

of a given clinical measure of DH for the duration of the entire study for all study 
subjects. 
A tactile stimulus will be administered using a constant pressure probe (Yeaple Probe
[Polson, 1980]).  Response to this stimulus will be evaluated as:
Tactile Threshold: The constant pressure probe allows the examiner to vary 
the force applied to the dentine surface from 10 g to an upper threshold of 80 
g in increments of 10 g.  The tactile threshold is the maximum pressure 
applied without the subject reporting pain or discomfort.  The greater the 
tactile threshold, the less sensitive the tooth.
An evaporative air stimulus will be administered using a dental air syringe.  Response 
to this stimulus will be evaluated using:
Schiff Sensitivity Scale[Schiff, 1994]:This is an examiner assessment of the 
subject’s response to an evaporative air stimulus.  It is scored immediately 
following the stimulus and focuses on a combination of specific, observable, 
physical, behavioural and verbal responses from the subject as a result of the 
stimulation of exposed dentine, rather than solely an oral request from the 
subject to discontinue stimulation and may facilitate discrimination.
Clinical trials evaluating clinical end points relating to pain can be prone to ‘placebo 
effects’ [Addy, 1985; West, 1997].   Sucheffects are frequently observed in dentine 
hypersensitivity studies.   A study conducted to evaluate the natural history of the 
dentine hypersensitivity condition highlighted the existence of a ‘no treatment’ effect 
characterized by an improvement in sensitivity simply as a function of clinical study 
participation [Leight, 2008].   To help minimize the potentialimpact of such 
‘placebo’ and ‘no treatment’ effects, an acclimatisation period will be included in this 
study from Screening, ahead of theVisit 2 assessments and randomisation.   During 
this period subjects will be provided with a toothbrush and a marketed, standard 
fluoride toothpasteto use in place of their regular oral hygiene products.  Use of the 
acclimatisation toothpaste will also help provide a standardized oral hygiene regimen
prior to Visit 2.Subjects will brush twice daily, in line with recommended oral 
hygiene practice,and typical consumer habit, during this period.
The selection of two ‘test teeth’to evaluate changes in DH is common practice in 
sensitivity studies [Docimo, 2009].  
Other causes of dental pain can present with the same symptoms as DH, for example 
cracked tooth syndrome, fractured restorations, chipped tooth, dental caries, post-
restorative sensitivity and teeth in acute hyperfunction [Dababneh, 1999].  While the 
age range over which an individual can experience DH is wide (from early teens to 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 23 of 69

70s) [Fischer, 1992], peak incidence is known to occur between the ages of 20-40 
years [Graf, 1977; Flynn, 1985].The fall in prevalence observed in later decades 
reflects age related changes in the dentine and pulp of the tooth which act to reduce 
dentine permeability and the tooth’s response to the external triggers of DH[Seltzer, 
1975; Pashley, 2008]. Given that the dental pain experienced by older members of the 
population is less likely to be diagnosed as DH[Rees, 2000], the age range of 18-65 
selected for this study targets individuals suffering from tooth sensitivitywhich is 
most likely due to DH. This will facilitate recruitment and minimize inconvenience to 
older participants who are more likely to be rejected at screening. 
A dose of twice daily brushing has been selected to be in line with dental professional 
recommendation, and is standard practice inclinical studies to evaluate DHefficacy.
Dose for the direct application has been selected to be in line with similar published 
methodologies [Ayad, 2009].   
4. SELECTION OF STUDY POPULATION AND WITHDRAWAL 
CRITERIA
Specific information regarding warnings, precautions, contraindications, adverse 
events, and other pertinent information on the GSK investigational product or other 
study treatment that may impact subjecteligibility is provided in theSafety Statement
Deviations from inclusion andexclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is 
essential.
4.1. Inclusion Criteria
A subject will be eligible for inclusion in this study only if all of the following criteria 
apply:
1. CONSENT
Demonstrates understanding of the study procedures, restrictions and willingness to 
participate as evidenced by voluntary written informed consent and has received a 
signed and dated copy of the informed consent form. 
2. AGE
Aged 18-65years inclusive
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 24 of 69

3. COMPLIANCE
Understands and iswilling, able and likely to comply with all study procedures and 
restrictions.
4. GENERAL HEALTH
Good general and mental health with, in the opinion of the investigator or medically 
qualified designee:
a) No clinically significant and relevant abnormalities of medical history or oral 
examination.
b) Absenceof any condition that would impact on the subject’s safety or wellbeing or 
affect the individual’s ability to understand and follow study procedures and 
requirements.
5. DENTAL HEALTH
AtVisit 1 (Screening):
a) Self-reported history of dentinal hypersensitivity (DH) lasting more than six
months but not more than 10 years.
b) Minimum of 20 natural teeth.
c) Minimum of 2accessible non-adjacentnaturalteeth(incisors, canines, pre-
molars), preferably in different quadrants, that meet all of the following criteria:
- Signs of facial/cervical gingival recession and/or signs of erosion or abrasion 
(EAR).
- Tooth with MGI score =0adjacent to the test area (exposed dentine) only 
[Lobene, 1986]and a clinical mobility of ≤1
- Tooth with signs of sensitivity measured by qualifying evaporative air 
assessment (Y/N response) 
At Visit 2, Baseline (Pre-treatment):
d) Minimum of two, non-adjacent accessible teeth (incisors, canines, pre-molars), 
that meet all of the following criteria:
- Tooth with signs of sensitivity, measured by qualifying tactile stimulus 
(Yeaple ≤ 20g) and evaporative air assessment (Schiff sensitivity score ≥ 2) 
Note: Teeth which meet the EAR, MGI and mobility inclusion criteria and none of 
the dentition exclusion criteria at Screening should be assessed by tactile stimulus 
at Visit 2. Those teeth which meet the required tactile threshold (Yeaple ≤ 20g) 
should then be assessed by evaporative air stimulus.When twoteeth that meet the 
study criteria are identified, no further testing is necessary.The examiner will select 
two Test Teethfrom those which meet boththe tactile threshold and Schiff sensitivity 
score criteria.  
Test Teethshould not be adjacent to each other and preferably in different quadrants.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 25 of 69

4.2. ExclusionCriteria
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply:
1. PREGNANCY
A womanwho isknown to be pregnant or who isintending to become pregnant over 
the duration of the study. 
2. BREAST-FEEDING
A woman who isbreast-feeding
3. ALLERGY/ INTOLERANCE
Known or suspected intolerance or hypersensitivity to the study materials (or closely 
related compounds) or any of their stated ingredients.
4. CLINICAL STUDY/ EXPERMENTAL PRODUCT
a) Participation in another clinical study (including cosmetic studies) or receipt of 
an investigational drug within 30 days of the screening visit.
b) Previous participation in this study.
c) Participation in study 205084
5. SUBSTANCE ABUSE
Recent history (within the last year) of alcohol or other substance abuse.
6. PERSONNEL
An employee of the sponsor or the study site or members of their immediate family
The site for this protocol is the Clinical trials Unit in the Bristol Dental School and 
Hospital. Employees of the Bristol Dental School and Hospital not associated with 
the Clinical Trials unit are eligible to participate.
7. DISEASE
a) Presence of chronic debilitating disease which, in the opinion of the investigator, 
could affect study outcomes.
b) Any condition which, in the opinion of the investigator, causes xerostomia.
8. GENERAL DENTITION EXCLUSIONS
a) Dental prophylaxis within 4 weeks of Screening.
b) Tongue or lip piercing.
c) Gross periodontal disease, treatment of periodontal disease (including surgery) 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 26 of 69

within 12 months of Screening, scaling or root planning within 3 months of 
Screening.
d) Vital teeth bleaching within 8 weeks of Screening.
e) Desensitizing treatment within 8 weeks of Screening (professional sensitivity 
treatments and non-dentifrice sensitivity treatments).
9. SPECIFIC DENTITION EXCLUSIONS FOR TEST TEETH
a) Tooth with evidence of current or recent caries, or reported treatment of decay 
within 12 months of Screening.
b) Tooth with exposed dentine but with deep, defective or facial restorations, teeth 
used as abutments for fixed or removable partial dentures,dental implants,teeth 
with full crowns or veneers, orthodontic bands or cracked enamel.  Sensitive 
teeth with contributing aetiologies other than erosion, abrasion or recession of 
exposed dentine.
c) Sensitive tooth not expected to respond to treatment with an over-the-counter 
dentifrice in the opinion of the investigator
10. PRODUCT USE
Use of an oral care product indicated for the relief of dentine hypersensitivity within 8 
weeks of screening (subjects will be required to bring their current oral care products 
to the site in order to verify the absence of known anti-sensitivity ingredients).
11. CONCOMITANT MEDICATION
a)Daily doses of medication/treatments which, in the opinion of the investigator, 
could interfere with the perception of pain.  Examples of such medications 
include analgesics, anticonvulsants, antihistamines that cause marked or 
moderate sedation, sedatives, tranquilisers, anti-depressants, mood-altering and 
anti-inflammatory drugs.
b)Currently taking antibiotics or has taken antibiotics within 2 weeks of Baseline.
c)Daily dose of a medication which, in the opinion of the investigator, is causing 
xerostomia.
12. OTHER
Any subject who, in the judgment of the investigator, should not participate in the 
study.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 27 of 69

4.3. Screening/ Baseline Failures
Screen failures are defined as subjects who consent to participate in the study but are 
never subsequently randomized.  In order to ensure transparent reporting of screen 
failure subjects, a minimal set of screen failure information is required including 
Demography, Screen Failure details, Eligibility Criteria, and any Serious Adverse 
Events. Re-screening of subjects will not be allowed in this study.
4.4. Withdrawal/ Stopping Criteria
A subject may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioural or 
administrative reasons. Where applicable, if a subject withdraws or is withdrawn 
from the study, all human biological samples collected before they left will be 
analyzed and reported unless the subject requests otherwise. A subject may request 
for their human biological samples to be destroyed. In these cases, the investigator 
must document this in the site study records and the samples should not be used for 
any further research.
If the reason for removal of a subject from the study is an AE or an abnormal 
laboratory test result, the principal specific event or test will be recorded on the 
electronic case report form (CRF).  If a subject is withdrawn from the study because 
of a product limiting AE, thorough efforts should be clearly made to document the 
outcome. Any AEs ongoing at the final visit will be followed up until resolved, the 
condition stabilizes, is otherwise explained, or the subject is lost to follow-up.
Should a subject take an analgesic medication within 8 hours of a treatment visit, or 
should any other factor, in the opinion of the investigator, be thought to affect study 
outcomes (e.g. excessive alcohol consumption), every attempt will be made to 
reschedule the subject. If they cannot be reappointed they will be withdrawn from the 
study. 
The following actions must be taken in relation to a subject who fails to attend the 
clinic for a required study visit:
The site must attempt to contact the subject and re-schedule the missed visit as 
soon as possible. 
The site must counsel the subject on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the subject wishes to 
and/or should continue in the study. 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 28 of 69

In cases where the subject is deemed ‘lost to follow up’, the investigator or 
designee must make every effort to regain contact with the subject (where 
possible, at least2 telephone calls). The contact attempt should be 
documented in the subject’s record. 
Should the subject continue to be unreachable, only thenwill he/she be 
considered to have withdrawn from the study with a primary reason of “Lost 
to Follow-up”.
4.5. Subject Replacement
Subjects who withdraw from the study post allocation of study product will not be 
replaced.
4.6. Subject and Study Completion
A completed subject is one who has completed all phases of the study.  The end of the 
study is defined as the date of the last subject’s last visit.
5. PRODUCT INFORMATION
5.1. Study Product
The following study products will be supplied by the Clinical Supplies Department, 
GSKCH:
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 29 of 69

Test dentifrice
Control dentifrice
Treatment 
Description
Experimental dentifrice 
containing  
 
stannous fluoride
(
 fluoride)
Dentifrice containing  
 sodium 
monofluorophosphate 
(
 fluoride)
MFC or Commercial 
product
Colgate Cavity Protection 
(USAMarketed Product)
Route of 
administration
Topical oral use
Supervised direct 
application time 
(Test Teeth only)
60 seconds
60 seconds
Supervised direct 
application (Test 
Teeth only) dosing 
instructions
Subjects will directly apply (under supervision) a pea-
sized dose to each of the two qualifying teeth using their 
washed, clean finger by direct application and gently 
rubbing into the tooth’s cervical margin for the allocated 
time.
No rinsing will be permitted.
Supervised brushing 
(Visit 2)
Before leaving the site 
(after all the clinical 
assessments have been 
completed), subjects will  
dose a dry toothbrush with 
a full strip of toothpaste.
Subjects will then brush 
each of the two selected 
sensitive test teeth first, 
followed by the whole 
mouth thoroughly for at 
least 1 minute.
Subjects will be permitted 
to rinse with 5ml tap 
water (kept at room 
temperature) for a 
maximum 5 timed 
seconds.
Before leaving the site (after 
all the clinical assessments 
have been completed), 
subjects will  dose a dry 
toothbrush with a full strip of 
toothpaste
Subjects will brush their 
whole mouth thoroughly for at 
least 1 minute under.
Subjects will be permitted to 
rinse with 5ml tap water (kept 
at room temperature) for a 
maximum 5 timed seconds.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 30 of 69
CCI
CCI
CCI
CCI
CCI

Home use 
instructions
Twice daily 
(morning/ evening)
Subjects will be instructed 
to dose a dry toothbrush 
with a full strip of 
toothpaste.
Subjects will then brush 
each of the two selected 
sensitive test teeth first, 
followed by the whole 
mouth thoroughly for at 
least 1 minute.
Subjects will be permitted 
to rinse with tap water.
Subjects will be instructed to 
dose a dry toothbrush with a 
full strip of toothpaste.
Subjects will then brush the 
whole mouth thoroughly for at 
least 1 minute.
Subjects will be permitted to 
rinse with tap water.
Other items to be supplied by the Clinical Supplies Department, GSKCH:
Name of Item
Purpose
Signal® Family Protection dentifrice 
containing  
 fluoride as sodium 
monofluorophosphate (SMFP), (UK 
marketed product)
Acclimatisation product -to standardize 
oral hygiene practice prior to treatment 
phase.
Subjects will dose thedry toothbrush
providedwith a full strip of toothpaste
and brush teeth for one timed minute 
twice daily (morning and evening).
Aquafresh Clean Control (Everyday 
Clean) toothbrushes (UK marketed 
product)
Toothpaste application by tooth 
brushing
Countdown timers
To ensure accurate brushing/direct 
application duration
Graduated dosing cups
For rinsing with water after brushing
Product usage instructions
To ensure correct product use
Subject Diaries
To document product usage. 
                                               
®Signal is a registered trademark of Unilever plc.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 31 of 69
CCI

5.2. Dose Schedule
During the acclimatisation period, subjects will apply a full brush head of the study
toothpaste and brush for one timed minute twice daily (morning and evening) in their
usual manner. 
At Visit 2 (Post-treatment) subjects will perform a supervised direct application (Test 
teeth only) as described in Section 5.1. 
Subjects will brushwith the study product twice on the day of Baseline (first 
brushing will be supervised at site). Subjects will return to the study site on day 3 
(Visit 3) after six brushings.
5.3. Dose Modification
No dose modification is permitted in this study.
5.4. Product Compliance
A compliance check will be carried out at baseline to confirm that the acclimatisation 
product hasbeen used according to study instructions throughout the acclimatisation 
period.If in the opinion of the investigator there are significant deviations in the 
subjects compliance during the acclimatisation period, this will be captured in the 
eCRF.
Diaries will be completed throughout the treatment period of the study to facilitate 
compliance during the study.
5.5. Precautions
No special precautions are necessary provided the study is carried out inaccordance 
with this protocol.
5.6.Overdose
An overdose is a deliberate or inadvertent administration of a product at a dose higher 
than specified in the protocol.
Overdose is not likely to occur in this study.  Limited quantities of the product will be 
supplied, and closely monitored by the site for each subject.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 32 of 69

Overdose per se is not an AE.  However, any clinical sequelae of an overdose should 
be reported as an AE (and serious adverse event (SAE), if appropriate).  For 
reporting, follow the AE and SAE reporting instructions.
5.7. Rescue Therapy
No rescue therapy is required in this study.
5.8. Product Assignment
Subjects will be assigned to study product in accordance with the randomisation 
schedule generated by the Biostatistics Department, GSKCH, prior to the start of the 
study, using validated internal software.
5.8.1Randomisation
A unique screening number will identify each subject screened for study 
participation.  Screening numbers will be assigned in ascending numerical order as 
each subject signs their consent form.  Subjects who meet all inclusion and exclusion 
criteria will be randomized according to the randomisationschedule.  Randomisation
numbers will be assigned in ascending numerical order as each subject is determined 
to be fully eligible.
Subjects will be stratified according to their maximum baseline Schiff of the two
selected teeth (2 / 3).  Randomisation numbers within each stratum will be assigned in
ascending numerical order according to appearance at the study site on the day
subjects are randomised. The stratification factor will give rise to two strata.
Stratum 1:Subjects with maximum baseline Schiff sensitivity score of 2 for the 
twoselected test teeth
Stratum 2:Subjects with the maximum baseline Schiff sensitivity score of 3 for 
the twoselected test teeth.
Thestudy site will receive two versions of the randomisation schedule, each in a 
sealed envelope and clearly marked as either “For Dispensing” or “Emergency Use 
Only”. 
The “For Dispensing” schedule will contain the list of randomisation numbers only 
and will not include any coded description, just a letter A or B.
The ‘Emergency Use Only’ randomisation schedule will only be removed from the 
sealed envelope in an emergency situation (see Section 5.8.3). This schedule will 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 33 of 69

have a randomisation number followed by the letter A or B. The schedule will have a 
footnote with a key for A or B identifying the two treatments regimen arms. 
However, to maintain the blinding of the study as far as possible, all treatment 
allocations for all randomisation numbers on this randomisation schedule will be 
masked with scratch-off panels. Only the panels required for the unblinding the 
particular subject should be removed.
5.8.2Blinding
Thestudy statistician and other employees of the Sponsor who may influence study 
outcomes are blinded to the product allocation of subjects.The examiner will be 
blinded to the treatment received. To ensure the examinerremains blinded throughout 
the study, the examiner is not permitted in the room whilst product is dispensed.  In 
addition, subjects shouldbe treated in a separate area.  The dispensing staff will not 
be involved in any clinicalassessments during the study.
As the instructions for the two products are slightly different the subjects will be 
given usageinstructions on a separate sheet to the diary.  Only the dispensing staff 
should have sight of the dosing instructions. 
5.8.3Code Breaks
The blind must only be broken in an emergency where it is essential to know which 
product a subject received in order to give the appropriate medical care.  Wherever 
possible the Investigator (or designee) must contact the Sponsor prior to breaking the 
blind.  The investigator must document the reason for breaking the code and sign and 
date the appropriate document.
The study blind must be returned to GSKCH at the end of the study.
5.9. Packaging and Labelling
The acclimatisation product (Signal Family Protection Toothpaste) will be sourced 
from the UK market and supplied in its commercial tube (no overwrapping) with a 
study label affixed. Each subject will receive a sufficient number of tubes to cover 
usage during the acclimatisation phase. 
The study toothpaste tubes [Test dentifrice (Experimental dentifrice containing 
 stannous fluoride, 
 and Control Dentifrice (Colgate cavity 
Protection, fluoride toothpaste, US marketed product)] will be overwrapped in white 
vinyl to obscure any branding on the commercial tube pack. Each tube will have 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 34 of 69
CCI
CCI

study label affixed. Each subject will receive a sufficient number of tubes to cover 
usage during the treatment phase.
The contents of the label will be in accordance with all applicable regulatory 
requirements and will be the responsibility of the Clinical Supplies Department,
GSKCH.
All sundry items willbe supplied in their commercial packaging for dispensing by 
study staff as required. 
Care should be taken with the supplied products and their labels so that they are 
maintained in good condition.  It is important that all labels remain intact and legible 
for the duration of the study. Subjects should be instructed to not remove or deface 
any part of the study label.
5.9.1. Accountability of Product
All products supplied are for use only in this clinical study and should not be used for 
any other purpose.
The investigator or designee will maintain a full record of study product 
accountability. A Product Dispensing Log must be kept current and will contain the 
following information:
The identification of the subject to whom the study product was dispensed.
The date(s) and quantity of the study product dispensed to the subject.
The date(s) and quantity of the study product returned by the subject (if 
applicable).
The inventory must be available for inspection by the study monitor during the study. 
At the end of the study, study product supplies will be verified by the monitor.  Study
 
product supplies will then be either collected by the study monitor or returned by the 
investigator or designee to the GSKCH Clinical Supplies Department or designated 
vendor.
5.9.2. Storageof Product
Study product supplies must be stored in compliance with the label requirements in a 
secure place with limited or controlled access.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 35 of 69

6. STUDY ASSESSMENTS AND PROCEDURES
This section lists the procedures and parameters of each planned study assessment.  
The exact timing of each assessment is listed in the Schedule of Events section.
Adherence to the study design requirements, including all assessments and 
procedures are essential and required for study conduct.
6.1. Visit 1 -Screening Visit
6.1.1. Informed Consent
The investigator, or designee, must obtain written (signed and dated by the subject) 
informed consent from each subject prior to their participationin this study after 
adequate explanation of the aims, methods, objectives, and potential hazards of the 
study.
The investigator, or designee, must also explain to the subjects that they are 
completely free to refuse to enter the study or to withdraw from it at any time.  
Appropriate forms for documenting a written consent will be provided by the 
investigator or by GSKCH.  The investigator, or designee, should sign and date the 
consent form to confirm that the consent process was completed correctly.  The 
subject will be provided with a copy oftheir signed and dated consent form and any 
other written information which they should be instructed to retain.
If, during a subject’s participation in the study, any new information becomes 
available that may affect the subject’s willingness to participate in the study, each 
ongoing subject should receive a copy of this new information and be re-consented 
into the study. Subjects or should be provided with a copy of the signed and dated 
amended consent form. The date of consent will be recorded on the CRF.
6.1.2. Demographics
The following demographic parameters will be captured by the Investigator or 
designee and recorded on the CRF: year of birth, age, gender, andrace.
6.1.3. Medical History and Concomitant Medication
Medical history will be assessed as related to the inclusion/exclusion criteria by the 
Investigator or medically qualified designee.  Details of any relevant medical or 
surgical history (within the last year),including allergies or drug sensitivity, will be 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 36 of 69

recorded on the CRF.  Any concomitant therapy taken in the 30 days priorto the 
Screening Visit and throughout the study will also be recorded.
6.1.4.Oral Soft Tissue (OST) Examination
Where possible, this procedure should be conducted by a single trained dental 
examiner.The examination will be accomplished by direct observation and palpation 
withretraction aids as appropriate. The examiner will include examination of the 
LabialMucosa (including lips), Buccal Mucosa, and Mucogingival folds, Gingival 
Mucosa, Hard Palate, Soft Palate, Tonsilar Area, Pharyngeal Area, Tongue, 
Sublingual Area,Submandibular Area and Salivary Glands. The results of the 
examination will berecorded in the CRF as either normal or abnormal with details of 
any abnormalities. Abrief description of any abnormality observed by the examiner 
or reported by the subjectat the application site following the administration of the 
acclimatisation or treatmenttoothpastes will be recorded as an AE. 
AnOST examination will be conducted at everystudy visit prior to any clinical 
assessments.While it is preferable to use the same OST examiner throughout the 
study, to facilitate subject flow, OST examinations may be carried out by different 
examiners.
6.1.5.Oral Hard Tissue (OHT) Visual Examination
A suitable qualified individual will perform an examination of the oral hard tissue to
confirm that the subject has a minimum of 20 natural teeth and to evaluate dentition
exclusions. The examination will be performed by direct observation.
6.1.6.Eligible Tooth Assessment
Eligible tooth assessment will include an oral hard tissue examination (visual 
assessment only to evaluate dentition exclusions -see Exclusion Criteria 8 and 9);
erosion, abrasionand/or gingival recession; gingival index; tooth mobility and 
qualifying evaporative airassessment.Assessments will be carried out by the 
Investigator or medically qualified designee against the inclusion/exclusion criteria 
and recorded in the CRF.
6.1.6.1.  Erosion, Abrasion and Recession (EAR) assessment
The presence of cervical erosion, abrasionand/or gingival recession[Addy, 2000]
will be determined on the facial surfaces of individual teeth.Teeth exhibiting EAR 
will be assessed to ensure they do notmeet any of thegeneral dentition exclusion 
criteria and the specific dentition exclusion criteria for test teeth (see Exclusion 
Criteria 8 and 9).
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 37 of 69

6.1.6.2.Modified Gingival Index (MGI)Assessment
The MGI is a non-invasive visual evaluation of gingival health[Lobene, 1986]scored
on a scale of 0-4. MGI will be assessed for the facial gingiva adjacent to the test area
(exposed dentine) only of teeth exhibiting facial cervical erosion, abrasion and/or
recession at the Screening visit.MGI = 0 is required for eligibleteeth.
Score
Description
0
Absence of inflammation
1
mild inflammation; slightchange in colour, little change in colour; little 
change in texture of any portion of the marginal or papillary gingival unit.
2
mild inflammation; criteria as above but involving the entire marginal or 
papillar gingival unit.
3
moderate inflammation; glazing, redness, edema, and/or hypertrophy of 
the marginal or papillary gingival unit.
4
severe inflammation; marked redness, edema and/or hypertrophy of the 
marginal or papillary gingival unit, spontaneous bleeding, congestion, or 
ulceration.
6.1.6.3.Tooth MobilityAssessment
The clinical mobility assessment will only be performed on teeth exhibiting facial 
cervical erosion, abrasion and/or recession and that have a MGI = 0. Clinicalmobility 
will be classified in the following way (based on a modification to the MillerIndex) 
[Laster, 1975]and the degree of mobility will be recorded. A clinical mobilityof ≤1 
is required for eligible teeth.
Degree 0
No movement or mobility of the crown of the tooth < 0.2mm in a 
horizontal direction.
Degree 1
Mobility of the crown of the tooth 0.2 –1mm in a horizontal direction
Degree 2
Mobility of the crown of the tooth exceeding 1mm in a horizontal 
direction
Degree 3
Mobility of the crown of the tooth in a vertical direction as well.
6.1.6.4. Qualifying Evaporative air Sensitivity
The screening dentist will assess sensitivity by a simple air blast on the facial surface 
of all teeth that meet the EAR, MGI and mobility criteria. This assessment is made by 
directing a one second application of air from a standard dental syringe perpendicular 
to the tooth surface approximately1-2 mm coronal to the free gingival margin and 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 38 of 69

from a distance of approximately 1cm. Following the air blast, the dentist will ask the 
subject if they experienced sensitivity. In order to qualify, the subject should confirm 
they experienced sensitivity and a simple “yes/no” response will be recorded.
6.1.7. Acclimatisation Product Supervised Brushing
Subjects will apply a strip of dentifrice to cover the head of the toothbrush provided 
and brush teeth for one timed minute. 
6.2. Visit 2 –Baseline (Pre-treatment)
6.2.1. Oral Soft Tissue (OST) Examination
Complete as described in Section 6.1.5.
6.2.2. Tactile Assessment (Yeaple probe)
Tactile assessments will be performed by a single trained examiner.
Testing shall begin at 10 g and increase by 10 g with each successive challenge until a 
"yes" response is recorded. The force setting which elicited the “yes” response will be 
repeated.  If a second "yes" is not obtained, the force setting will be increased by 10 g 
and continue until a force is found which elicits two consecutive "yes" responses.  If 
no sensitivity is found below the session maximum, the tooth is disqualified from 
further testing.  The gram setting, which elicits the two consecutive “yes” responses, 
will be recorded as the threshold.
At thisvisit(pre-treatment)the upper test limit is 20g.  If no pain response is found, 
the threshold will be recorded as >20 g and the tooth will be disqualified from further 
tactile testing. 
The recording/calibration assistantor examiner will make adjustments and record the 
micro-amperage force setting and subject
's responses onto the source document.  The 
assistant will not give verbal cues to the examiner (the individual applying the probe 
tip to the tooth) other than when it is okay to proceed as this may bias the subject
's 
response.  For example, if the assistant feels that the subject did not give a true 
response, they may then elect to repeat the same force setting without telling the 
examiner.  In this respect the examiner is also blinded, to avoid investigator bias.  
Since this places more responsibility on the assistant, it is imperative that the assistant 
be well trained in this procedure.  It is also possible that the investigator may be 
unsure of the reliability of the subject
's response.  In this case, the investigator may 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 39 of 69

then opt to re-probe at the same force setting.  This can be indicated to the assistant 
by a non-verbal signal (i.e. a hand gesture).
Theevaporative airstimulus(withSchiffSensitivityScore)shouldfollow the tactile 
assessment,with a minimum offive minutes in between each assessment type to 
allow recoverytime.
6.2.2.1 Subject Response
The probe tip should be placed perpendicular to the buccal surface and moved in a 
slow motion while drawn across the tooth surface in order to ensure application of the 
stimulus across the sensitive area of the exposed dentine.  After each challenge, 
subjects will be asked to indicate whether the sensation caused pain or discomfort.  
Only "yes" and "no" are acceptable answers.  The examiner will tell the subject that 
they should indicate "yes" only if they feel PAIN or DISCOMFORT each time the 
probe is applied to their tooth.  The subject may respond "yes" if they feel pressure, 
so it is important to remind them, as much as necessary, that they will feel pressure 
but to only respond "yes" if they feel pain or discomfort.  If the subject fails to give a 
definite answer, the examiner should re-prompt them to provide a “yes” or “no” 
response.  If they continue to be reluctant, their uncertainty shouldbe indicated on the 
score sheet and the next stimulus should be at the next step in the upward direction.  
The gram setting, which elicits the two consecutive “yes” responses, will be recorded 
as the threshold.
The evaporative air stimulus should follow the tactile assessment, with a minimum of 
five minutes in between each assessment type to allow recovery time.
6.2.2.2 Calibration of the Yeaple Probe
A digital video disc (DVD) demonstration of this procedure will be provided. 
Eitherof the two proceduresdescribed below are preferred; however other 
comparable proceduresmay be acceptable. 
Themicroamp settings will vary from day to day (partly due to battery power
consumption), but the difference should not be significant. Thus, previous probe
settings will serve as a guide. Calibration should start at the lowest microamp setting
and then increase.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 40 of 69

1. The yeaple probe is fixed to a clamp attached to a ring stand so that the probetip is 
vertical. A small paper cup attached with cotton thread is balanced overthe end of 
the yeaple probe, without the probe tripping. The probe dial is setto the microamp 
setting and water is fed into the paper cup using a dropperuntil the probe trips. 
The gram setting is recorded and the yeaple probe resetto the next microamp 
value. The procedure is repeated until data has beencollected to more than 80 
grams.
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 zerograms. 
The probe dial is set to the microamp setting and the gram setting isincreased on 
the balance until the probe trips. The gram setting is recordedand 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
grams. This calibration should be repeated three times, and the averageof the three
used for the day’s settings.
The settings will be recorded on the yeaple probe calibration record. This form must
also be dated and initialled by whoever performs the calibration. For convenience a
separate form should be used for each probe (record the unit’s serial number on the
form). This record will serve as the guide for the force setting for that day’s
examinations.
6.2.3. Evaporative Air Sensitivity Assessment 
This assessment will be conducted by a single examiner for all subjects at each visit 
by directing a maximum onesecondapplication of air from adental air syringe to the 
exposed dentinesurface from a distance of approximately 1 cm. The examiner should 
takeappropriate measures to isolate the test tooth surface in order to prevent stimulus
exposure to adjacent tooth or surrounding soft tissue.Response to this stimulus will 
be evaluated using the SchiffSensitivityScale.
The examiner will assess the evaporative air sensitivity of all clinically eligible teeth 
identified at Screening (teeth that qualified on EAR, MGI and tooth mobility criteria, 
and had none of the dentition exclusions), that qualified for the tactile assessment 
using the Schiff Sensitivity Scale.  Two test teeth will be selected according to 
specific eligibilitycriteria in an individual subject.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 41 of 69

6.2.3.1. Schiff Sensitivity Scale
This is an examiner based index[Schiff, 1994], scored immediately following 
administration of the evaporative airstimulus.  This scale focuses on a combination of 
specific, observable, physical, behavioural and verbal responses from the subject as a 
result of the stimulation of exposed dentine, rather than solely an oral request from 
the subject to discontinue stimulation and may facilitate discrimination. Those teeth 
which meet the tactile threshold inclusion criterion (tactile threshold ≤ 20g) will be 
assessed.  The examiner will indicate the subject’s response to the evaporative air
stimulus, after the stimulation of each individual tooth, using the Schiff Sensitivity 
Scale as follows.  
0
Subject doesnot 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 stimulusto be painful, 
and requests discontinuation of the stimulus
Those teeth which meet the required tactile threshold (Yeaple ≤ 20g) should then be 
assessed by evaporative air stimulus.When twoteeth that meet the study criteria are 
identified, no further testing is necessary.
6.2.4. Selection of Two Test Teeth
Two test teeth will be selected by the examinerthat meetsthe inclusion criteria.
6.2.5. Study treatment direct application 
Subjects will apply (under supervision, the supervising person should be someone 
other than the examiner undertaking the assessments) a pea-sized dose to each of the 
two qualifying teeth using their washed, clean finger by direct application and gently 
rubbing into the tooth’s cervical margin for the allocated time.  
No rinsing will be permitted.
See Section 5.1 for dosing instructions.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 42 of 69

6.3. Visit 2 (Post-treatment)
6.3.1. Oral Soft Tissue (OST) Examination
Complete as described in Section 6.1.5.
6.3.2. Tactile Assessment (Yeaple probe)
Tactile assessment will be conducted as described in Section 6.2.2 of the two selected 
test teeth only.  At Visit 2 (post-treatment), the upper force setting will be 80g.  If no 
sensitivity is found, the threshold will be recorded as >80g.
6.3.3. Evaporative Air Sensitivity Assessment
The evaporative air assessment should follow the tactile assessment with a minimum 
of 5 mins between the last tactile assessment and the first evaporative air assessment 
to allowthe teethrecovery time.
6.3.3.1. Schiff Sensitivity Scale
Theexaminer will record the subjects’ response to each of the two selected test teeth
immediately following administration of the evaporative airstimulusas described in 
Section 6.2.3. 
6.3.3.2. Supervised brushing 
At Visit 2, before leaving the site (after all the clinical assessments have been 
completed), all subjects will brush their whole mouth for at least one minute under 
supervision with the assigned treatment according to instructions in section 5.1for 
test dentifrice or control dentifrice. Subjects will be permitted to rinse with 5ml tap 
water (kept at room temperature) for a maximum 5 timed seconds.
6.4. Visit 3(Day3)
6.4.1. Oral Soft Tissue (OST) Examination
Complete as described in section 6.1.5.
6.4.2. Tactile Assessment (Yeaple Probe)
Tactile assessment will be conducted as described in section 6.2.2of the two selected 
test teeth only.  At visit 3, the upper force setting will be 80g.  If no sensitivity is 
found, the threshold will be recorded as >80g.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 43 of 69

6.4.3. Evaporative Air Sensitivity Assessment
The evaporative air assessment should follow the tactile assessment with a minimum 
of 5 mins between the last tactile assessment and the first evaporative air assessment 
to allow the teeth recovery time.
6.4.3.1. Schiff Sensitivity Scale
The examiner will record the subjects’response to each of the two selected test teeth 
immediately following administration of the evaporative air stimulus as described in 
section 6.2.3. 
6.4.4. Study Conclusion
Subjects will be evaluated to determine if they completed all study procedures or if 
they were discontinued from the study early.  If the subject discontinued at any point 
during the study, the primary reason for withdrawal should be recorded on the study 
conclusion page of the crf by selecting one of the options below.
Subject did not meet study criteria
Adverse event
Lost to follow up
Protocol violation
Withdrawal of consent
Other
7. SAFETY ASSESSMENTS
7.1. Definitions of an Adverse Event and Serious Adverse Event 
7.1.1. Adverse Events
The investigator or site staff will be responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE.
Adverse Event Definition:
An AE is any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use of an investigational 
or washout product, whether or not considered related to the investigational or 
washout product.
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 an investigational or 
washout product.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 44 of 69

Events meeting AE definition include:
Any abnormal laboratory test results (if applicable) or other safety 
assessments, including those that worsen from baseline, and felt to be 
clinically significant in the medical and scientific judgment of the 
investigator.
Exacerbation of a chronic or intermittent pre-existing condition including 
either an increase in frequency and/or intensity of the condition.
New condition(s) detected or diagnosed after study product administration 
even though it may have been present prior to the start of the study.
Signs, symptoms, or the clinical sequelae of a suspected interaction.
Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
study product or a concomitantmedication (overdose per se will not be 
reported as an AE/SAE).
Events NOT meeting definition of an AE include:
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/ condition being studied or expected progression, signs, 
or symptoms of the disease/disorder being studied, unless more severe than 
expected for the subject’s condition.. 
Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition 
that leads to the procedure is an AE.
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.
7.1.2. Serious Adverse Events
Serious Adverse Event is defined as any untoward medical occurrence that, at 
any dose:
A. Results in death
B. Is life-threatening
NOTE: 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.
C. Requires hospitalization or prolongation of existing hospitalization
NOTE: In general, hospitalization signifies that the subject has been detained 
(usually involving at least an overnight stay) at the hospital or emergency 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 45 of 69

ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or out-patient 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.
D. Results in disability/incapacity
NOTE: 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 or prevent everyday life functions but do not constitute a substantial 
disruption.
E. Is a congenital anomaly/birth defect
F. Other Situations
Medical or scientific judgment should be exercised in deciding whether 
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 should also be considered serious.
Examples of such events are 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 or reports of spontaneous abortion.
7.2. RecordingAdverse Eventsand Serious Adverse Events
Recording of adverse events and serious adverse events:
The investigator or site staff will be responsible for detecting, documenting 
and reporting events that meet the definition of an AE or SAE. 
The investigator or site staff will then record all relevant information 
regarding an AE/SAE in the CRF.
There may be instances when copies of medical records for certain cases are 
requested by GSK.  In this instance, all subject identifiers, with the exception 
of the subject number, will be blinded on the copies of the medical records 
prior to submission of to GSK.
The investigator will attempt to establish a diagnosis of the event based on 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 46 of 69

signs, symptoms, and/or other clinical information.  In such cases, the 
diagnosis will be documented as the AE/SAE and not the individual 
signs/symptoms. Clinical AEs will be described by diagnosis and not by 
symptoms when possible (e.g., upper respiratory tract infection, seasonal 
allergy, etc. instead of runny nose).
AEs will be collected from the start of the investigational product and until 5
days following last administration of the study product.
SAEs will be collected over the same time period as stated above for AEs.  
However, any SAEs assessed as relatedto study participation (e.g., 
investigational product, protocol mandated procedures, invasive tests, or 
change in existing therapy) or related to a GSK concomitant medication will 
be recorded from the time a subject consents to participate in the study up to 
and including any follow-up contact.  
Medical conditions reported prior to the time period for reporting AEs/SAEs 
should be recorded as part of the subject’s medical history.
7.3. Evaluating Adverse Eventsand Serious Adverse Events
Assessment of Intensity:
The investigator or designee will make an assessment of intensity for each AE and 
SAE reported during the study and will assign it to one of the following categories:
Mild:  An event that is easily tolerated by 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. -an AE that is 
assessed as severe will not be confused with an SAE. Severity is a category 
utilized for rating the intensity of an event; and both AEs and SAEs can be 
assessed as severe.
Note: An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE.
Assessment of Causality:
The investigator is obligated to assess the relationship between study product 
and the occurrence of each AE/SAE.
A "reasonable possibility" is meant to convey that there are facts/evidence or 
arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.
The investigator will use clinical judgment to determine the relationship.
Alternative causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the 
event tothe study product will be considered and investigated.
The investigator will also consult the Investigator Brochure (IB) and/or 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 47 of 69

Product Information, for marketed products, in the determination of his/her 
assessment.
For each AE/SAE the investigator must document in the medical notes 
(source document) or CRF that he/she has reviewed the AE/SAE and has 
provided an assessment of causality.
There may be situations when an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK.  However, it is 
very important that the investigator always make an assessment of 
causality for every event prior to the initial transmission of the SAE data 
to GSK.
The investigator may change his/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly.
The causality assessment is one of the criteria used when determining 
regulatory reporting requirements.
7.4. Reporting Adverse Eventsand Serious Adverse Events
AE Reporting to GSKCH:
AEs will be recorded in the AE section of the CRF. 
Medical conditions recorded by the subject on a diary
 card or similar 
document that meet the definition of an AE must also be recorded in the AE 
section of the CRF, if not previously well-characterized by the investigator in 
the subject’s medical history. 
AEs elicited by the investigator in a standard manner at the study visits should 
also be recorded in the AE section of the CRF.  The investigator or designee 
must ask the subject the following question during each visit including any 
follow-up visits:  “Have you felt unwell, experienced any symptoms or taken 
any medication (since your last visit) (today) (since your last dose) (since the 
last session)?”
The medically qualified investigator should review adverse events in a timely 
manner; this review should be documented in writing in the source document 
or in the CRF. 
After the study is completed at a given site, and the site has received their 
study data on Compact Discs (CDs), the electronic data collection tool will be 
removed from the internetto prevent the entry of new data or changes to 
existing data.
SAE Reporting to GSKCH:
A paper copy of the SAE form provided in the investigator study master file should 
be completed as fully as possible. 
It is essential to enter the following information: 
Protocol and subject identifiers
Subject’s demography
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 48 of 69

Description of events, with diagnosis if available
Investigator opinion of relationship to study product (see section 8.3)
Criterion for seriousness.
The following are desirable and are of particular relevance for investigator and 
GSKCH assessment of the SAE report:
Date of onset of AE 
Date AE stopped, if relevant
Study product start date
Study product end date if relevant
Action taken on study product
Outcome if known
The SAE form, completed asfully as possible, and SAE fax cover sheet must be 
faxed or e-mailed to the appropriate GSKCH Study Manager as soon as possible, but 
not later than 24 hoursafter study site personnel learn of the event. The GSKCH 
Study Manager should be notified of the situation by telephone or email.
Fax Serious Adverse Events to:
UK: 
The GSKCH Study Manager will be responsible for forwarding the SAE form to the 
Case Management Group, Global Clinical Safety and Phamacovigilance, the Medical 
Director responsible for the study and other GSKCH personnel as appropriate via 
email.
The initial report will be followed up with more information as relevant, or as 
requested by the GSKCH study manager.
7.5. Follow-up of Adverse Eventsand Serious Adverse Events
Follow-up of AEs and SAEs:
After the initial report, the investigator is required to proactively follow up 
with each subject and provide further information on the subject’s condition.
All AEs/SAEs will be followed until resolution, until the condition stabilizes, 
until the event is otherwise explained, or until the subject is lost to follow-up.  
The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations as may be indicated or as 
requested by GSK to elucidate as fully as possible the nature and/or causality 
of the AE or SAE.
Investigators are not obliged to actively seek AEs or SAEs in former subjects.  
However, if the investigator learns of any SAE, including the death,at any 
time after a subject has been discharged from the study, and considers the 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 49 of 69
PPD

event reasonably related to the investigational product or study participation, 
the investigator will promptly notify GSKCH.
The investigator will submit any updated SAE data to GSK within the 
designated reporting time frames.
Regulatory and ethics reporting requirements for SAEs:
The investigator will promptly report all SAEs to GSKCH within the 
designated reporting timeframes (within 24 hours of learning of the event).  
GSKCH 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 GSKCH is essential so that legal obligations and ethical 
responsibilities towards the safety of subjects are met.
GSKCH will comply with country specific regulatory requirements relating to 
safety reporting to the regulatory authority, IECand investigators.
Investigator safety reports are prepared according to GSKCH policy and are 
forwarded to investigators as necessary.  An investigator safety report is 
prepared for a SAE(s) that is both attributable to investigational product and 
unexpected.  The purpose of the report is tofulfill specific regulatory and 
GCP requirements, regarding the product under investigation.
An investigator who receives an investigator safety report describing a SAE(s) 
or other specific safety information (e.g., summary of listing of SAEs) from 
GSKCH will file it with the Investigator Brochure (or safety statement) and 
will notify the IEC, if appropriate according to local requirements.
7.6. Definition of and Procedure for Reporting Medical Device 
Incidents
Medical devices are being provided by GSKCH for use in thisstudy; the medical 
device in this study is the study toothpaste (Test Dentifrice).  GSKCH medical device 
incidents, including those resulting from malfunctions of the device, must be 
detected, documented, and reported by the investigator on the CRF throughout the 
study.
7.6.1. Definition of an Incident
Definition of an Incident:
Any malfunction or deterioration in the characteristics and/or performance of 
a device, as well as any inadequacy in the labelling or the instructions for use 
which, directly or indirectly, might lead to or might have lead to the death of a 
patient or user or of other persons or to a serious deterioration in their state of 
health.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 50 of 69

7.6.2. Reporting of Incidents and Malfunctions
Incident Reporting to GSKCH:
All incidents must be reported to GSKCH within 24 hours (or sooner if 
possible) of the investigator or designee becoming aware of the situation.
Any medical device incident occurring during the study will be documented in 
the subject
's medical records, in accordance with the investigator
's normal 
clinical practice, and on the appropriate Incident Report Form.  Inaddition, 
for incidents fulfilling the definition of an AE or an SAE, the appropriate AE 
CRF page or SAE form will be completed and reported as per the AE and 
SAE reporting sections.
The Incident Report Form will be completed as thoroughly as possible and
signed by the investigator before transmittal to GSKCH.  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 faxed or emailed to the 
appropriate GSKCH Study Manager as soon as possible, but not later than 
24 hoursafter study site personnel learn of the event. If there is an SAE, the 
completed SAE pages should be sent together with this report form.  
However, if a copy of the SAE report is sent with this form, this does not 
replace the procedure to report an SAE.  The original Incident Report Form 
will remain with the subject’s records.
The GSKCH Study Manager should be notified of the situation by telephone 
or email.
Fax the Incident Report Forms to:
UK: 
The GSKCH Study Manager will be responsible for forwarding the Incident 
Report Form to the Case Management Group, Global Clinical Safety and 
Pharmacovigilance, the Medical Director responsible for the study and other 
GSKCH personnel as appropriate.
The initial report will be followed up with more information as relevant, or as 
requested by the GSKCH study manager.
Reporting of Malfunctions to GSKCH:
The investigator will follow the following directions regarding device failure 
(malfunction):
Notify GSKCH immediately.
Schedule the subject to return to the site promptly to return the failed device.
Record any incidents on the CRF and Incident Report Form following 
instructions given in the section above.
Return the failed device to the sponsor as soon as possible, including 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 51 of 69
PPD

documentation of the details of the failure.
7.6.3. Follow-up of Incidents
Follow-up of Incidents:
During the study:
All incidents will be followed until resolution of the event, until the condition 
stabilizes, until the condition is otherwise explained, or until the subject is lost 
to follow-up. This applies to all subjects, including those withdrawn 
prematurely. The investigator is responsible for ensuring that follow-up 
includes any supplemental investigations as may be indicated to elucidate as 
completely as practical the nature of the incident.
New or updated information will be recorded on the originally completed 
form with all changes signed and dated by
 the investigator.
After the study:
Investigators are not obligated to actively seek reports of incidents in former 
subjects.  However, if the investigator learns of any incident at any time after 
a subject has been discharged from the study, and such incident is reasonably 
related to a GSKCHmedical device provided for the study, the investigator 
will promptly notify GSKCH.
Regulatory and Ethics Reporting Requirements for Incidents:
The investigator will promptly report all incidents occurring with any GSKCH 
medical device provided for usein the study within 24 hours. GSKCH has a 
legal responsibility to notify appropriate regulatory bodies and other entities 
about certain safety information relating to medical devices being used in 
clinical studies. Prompt notification of incidents by the investigator to 
GSKCH is essential in order to meet legal obligations and ethical 
responsibility towards the safety of subjects.
The investigator, or responsible person according to local requirements, will 
comply with the applicable local regulatory requirements relating to the 
reporting of incidents to the IEC.
7.7. Collection of Pregnancy Information
7.7.1. Time Period for Collecting of Pregnancy Information
Collection of Pregnancy Information:
Pregnancy information will be collected on all pregnancies reported following 
administration of any investigational product (or washout product). 
Information on pregnancy identified during the screening phase and prior to 
investigational product (or washout product) administration does not need to 
be collected.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 52 of 69

7.7.2. Action to be Taken if Pregnancy Occurs
Action to be Taken:
The investigator will collect pregnancy information on any subject who 
becomes pregnant while participating in the study after administration of the 
investigational product (or washout product). The investigator will record 
pregnancy information on the appropriate form and submit it to GSKCH 
within 2 weeks of learning of the subject becoming pregnant. The subject will 
be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and infant / neonate (including concomitant medications 
taken by the mother during the pregnancy) will be forwarded to GSKCH. 
Generally, follow-up will be no longer than 6 to 8 weeks following the 
estimated delivery date. Any termination of the pregnancy will be reported.
While pregnancy itself is not considered to be an AE, any pregnancy 
complication or elective termination for medical reasons will be recorded as 
an AE or SAE.
A spontaneous abortion is always considered to be an SAE and will be 
reported as such. An SAE occurring in association with a pregnancy, brought 
to the investigator’s attention after the subject completed the study and 
considered by the investigator as possibly related to the investigational 
product, must bepromptly forwarded to GSK.
While the investigator is not obliged to actively seek this information in 
former study participants, he or she may learn of an SAE through spontaneous 
reporting.
If the subject becomes pregnant during the study they willbe withdrawn from 
the study and this should be recorded in the appropriate section of the CRF.
8. DATA MANAGEMENT
For this study subject data will be entered into an electronic case report form, using a 
GSKCH validated data system.
8.1. Source Documents/ Data
The source documents (e.g. hospital records, clinical and office charts, laboratory 
notes, memoranda, subjects’ diaries or evaluation checklists, pharmacy dispensing 
records, recorded data from automated instruments, microfiches, photographic 
negatives, microfilm or magnetic media, x-rays, subject files and records kept at the 
pharmacy, at the laboratory and at the medico-technical departments involved in the 
clinical study) which contain the source of data recorded in the CRF should be 
specified in the Source Document Designation Form.  In some cases the CRF can be 
used as a source document.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 53 of 69

Each subject will be assigned and identified by a unique Screening Number. Any 
reference made to an individual subject within the study must be done using the 
unique Screening Number.
8.2. Electronic Case Report Form
A CRF is a printed, optical, or electronic document designed to record all of the 
protocol required information to be reported to the sponsor on each trial subject.
For each subject who has given informed consent/assent and has been screened, CRF 
must be completed and signed by the Principal Investigator (or authorized designee) 
to certify that the data are complete and correct.  
Management of clinical data will be performed in accordance with applicable 
GSKCH standards and data cleaning procedures to ensure the integrity of the data e.g. 
removing errors and inconsistencies in the data. 
In order to protect the privacy of subjects, no Personally Identifiable Information 
(PII) (including the subject
's name or initials or birth date) is to be recorded in the 
CRF or as part of the query text.
Adverse events and concomitant medications terms (if applicable) will be coded 
using MedDRA (Medical Dictionary for Regulatory Activities) and an internal 
validated medication dictionary, GSKDrug.  
Subject data will be entered into GSKCH defined CRFs and transmitted electronically 
to GSKCH in a validated (21 CFR Part 11 compliant) web-based electronic data 
capture system (InForm
TM).
All CRF pages should be completed during a subject assessment when the CRF has 
been designated as the source.  Data that is sourced elsewhere should be entered into 
the CRF in an agreed upon timeframe between the Investigator and Sponsor.  
The CRFs (including queries, query responses and audit trails) will be retained by 
GSKCH. Site data archived compact discs (CD(s)) prepared by a third party will be 
sent to the investigator to maintain as the investigator copy following the 
decommissioning of the study.
8.3. Data Handling
Documentation of all data management activities should allow step-by-step 
retrospective assessment of data quality and study performance. Any changes or 
corrections to data will be performed in the Electronic Data Capture (EDC) System, 
and it will include rationale for changes. The EDC system has an audit trail, which 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 54 of 69

will provide a complete record of the changes and corrections endorsed by the 
Investigator.
8.3.1. Data Queries
Programmed edit checks will be generated automatically, asthe data is being entered 
into the system. Data Management will also run reports and listings on the CRF data, 
in addition to the queries already programmed and generated by the system, to raise 
manual queries as needed for site clarification or correction. The Clinical Dictionary 
Development and Management Group will raise queries as needed on safety data to 
code the terms (Adverse Events and Drugs) are reported appropriately. 
The study monitor at the study site will review the CRFs in accordance with the 
monitoring plan, and any queries will be generated in the EDC System to the 
Investigator or designee, enabling the errors to be addressed in parallel with Data 
Management review. Monitor can also run reports and listings on the CRFs, to raise 
manual queries as needed for site clarification or correction
8.4. Processing Patient Reported Outcomes
Patient reported outcome (PRO) data are collected directly from the subject PRO 
measures e.g. diary cards, questionnaires etc, and entered into the sponsor’s clinical 
data management system (DMS) by the study site representative. In instances where 
the PRO data is entered into the DMS by GSKCH, the PROs will be anonymised, and 
forwarded to GSKCH for entry, as agreed and documented ahead of the study
 
starting. PROs that are source will be retained by the investigator and certified copies 
will be sent to GSKCH. 
In order to protect the privacy of subjects, no Personally Identifiable Information 
(PII) (including the subject
's name or initials or birth date) is to be recorded on all 
PRO’s that will be forwarded to GSKCH.
9. STATISTICAL CONSIDERATIONS AND DATA ANALYSES
9.1 Sample Size Determination
Change from baseline in Schiff Sensitive Score will be used to evaluate treatment
effects with regard to the primary objective. A sufficient number of subjects will be
screened in order to ensure that 92 evaluable subjects per group complete the study.
With 92 evaluable subjects per group, it will be possible to detect a mean difference
of 0.25 (SD=0.5198) in change from baseline in Schiff sensitive score after 3 days use
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 55 of 69

between treatments with 90% power. The estimate of SD was obtained from a review 
of GSKCH studies[GSKCH Study 205710; GSKCH Study205697,GSKCH Study 
205084]. Thesample size is based on carrying out two-tailed two sample t-test at a 
5% significancelevel and assumes that the group variances are equal.
Therefore, allowing for dropouts approximately 190 subjects will be randomised to
ensure approximately 184 subjects (approximately 92 per arm) complete the study.
9.2.General Considerations
9.2.1.Definition of Analysis Populations
All assessments of safety will be based on the safety population, defined as all 
subjects who are randomised and receive at least one dose of study treatment during 
thestudy. Safety population summaries will be presented by treatment received.
The primary population for efficacy assessment will be the intent-to-treat (ITT) 
population, defined as all subjects who are randomized, receive the study treatment at 
least once and provide at least one post-baseline (post treatment) assessment of 
efficacy. All ITT population summaries and analyses will be presented by treatment 
randomized.
The per protocol (PP) population is defined as all subjects in the ITT population who 
haveat least one assessment of efficacy considered unaffected by protocol violations.
PP analysis will be performed only on those data considered unaffected by protocol 
violations. 
Efficacy analysis on the PP population will be performed on the clinical sensitivity 
measures (tactile threshold and Schiff sensitivity score) only if there is more than 
10% difference in the number of subjects between PP and ITT populations.A 
decision on whether a PP analysis will be performed will be made prior to study 
unblinding.
9.2.2.Exclusion of Data from Analysis
Any of the following will be considered a protocol violation which may warrant 
exclusion of data or the subject from efficacy analysis:
Violation of inclusion or exclusion criteria that are deemed to affect efficacy.
Medical history which is deemed to affect efficacy.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 56 of 69

Use of prohibited treatment or medication before or during the study, which is 
felt to affect the assessment of efficacy. 
Not receiving randomised treatment.
Treatment non-compliance
Assessments outside the scheduled time windows
Protocol deviations captured in CRF.
Any other reason identified likely to affect efficacy
Protocol violations which warrant exclusion from efficacy analysis will be identified 
between the statistician and medical director or designee ahead of database lock and 
breaking the study blind.
9.2.3.Criteria for Evaluation
DH measures captured in the study will be used for efficacy evaluations of the study 
treatments. OST abnormalities, incidents and AEs reported in the study will be used
for safety evaluations of the study treatments.
9.2.4.Criteria for Assessing Efficacy
The success criterion for this study is to observe a statistically significant greater 
reduction in evaporative air sensitivity (Schiff Sensitivity Scale) for subjects using the 
experimental  
 stannous fluoride dentifrice, compared touse of a dentifrice 
containing  
 sodium monofluorophosphate, after 3 days use.
9.2.5.Criteria for Assessing Tolerability
The assessment for safety will be based on OST abnormalities, incidentsand AEs 
reported following dosing with study treatment.
9.2.6.Handling of Dropouts and Missing Data
Subjects who withdraw from the study early will be included in the study analysis up 
to the point of withdrawal. Subjects who withdraw will notbe replaced. No data will 
be imputed in the case of dropouts or missing data.
9.2.7.Other Issues
An interim analysis is not planned for this study.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 57 of 69
CCI
CCI

9.3. Statistical Methods and Analytical Plan
Additional details ofthe proposed statistical analysis will be documented in the 
statistical analysis plan (SAP), which will be written following finalization of the 
protocol and prior to study unblinding / analysis (as appropriate).
All statistical analyses will be conductedunder the null hypothesis (H0) of no
difference between treatments versus the alternate hypothesis (H1) of a difference
between treatments. All tests will be two sided with a significance level of 5%.
9.3.1.Demographic and Baseline Characteristics
Descriptive statistics (number of subjects, mean, standard deviation, median, 
minimum and maximum for continuous variables, and frequency and percentage for 
categorical variables) will be provided for demographic and baseline characteristics.
9.3.2.Primary Analysis
9.3.2.1 Schiff Sensitivity Scorefollowing three days of treatment
The change from baseline in Schiff sensitivity score after 3 days use will be the 
primary efficacy variable. This will becalculated as the subject level mean change 
(on two teeth) from Baseline (pre-treatment) of the two selected test teeth..
The change from baseline in Schiff sensitivity score will be analysed using analysis 
of covariance (ANCOVA) with treatment included as a factor and baseline Schiff 
sensitivity score included as a covariate. Note that since the Baseline Schiff 
sensitivity score was included as a covariate, the Baseline Schiff stratificationvalue 
was not included in the model. The adjusted mean for each treatment, and difference 
between treatments together with their 95% confidence interval and p-value for the 
between treatments comparison, will be provided. In addition, to assess efficacy 
within treatments, the adjusted mean change frombaseline (with 2-sided 95% CIs) 
and p-values from the above model will bepresented.
The assumption of normality and homogeneity of variance in ANCOVA model will 
be investigated. Violation of these assumptions may be overcome using suitable 
transformation or performing a non-parametric test (e.g., the Wilcoxon Rank Sum 
test).
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 58 of 69

9.3.3.Secondary Analyses
9.3.3.1 Schiff Sensitivity Score following a single use
The secondary analysis for the change from baseline in Schiff Sensitivity Score will 
be conducted after a single use using the same model as the primary analysis, with 
similar statistics reported.
9.3.3.2 Tactile sensitivity followinga single use and 3 daystreatment
The secondary efficacy variable, tactile threshold will becalculated as the subject 
level mean change (on two test teeth) from Baseline (pre-treatment) after a single use 
and after 3 days use. This will be analysed using analysis of covariance (ANCOVA) 
with treatment and Schiff sensitivity strata included as a factorsand baseline tactile
score included as a covariate. The adjusted mean for each treatment, and difference 
between treatments together with their 95% confidence interval and p-value for the 
between treatments comparison, will be provided. In addition, to assess efficacy 
within treatments, the adjusted mean change frombaseline (with 2-sided 95% CIs) 
and p-values from the above model will bepresented.
For allsecondary analyses, the assumption of normality and homogeneity of variance 
in ANCOVA model will be investigated. Violation of these assumptions may be 
overcome using suitable transformation or performing a non-parametric test (e.g., the 
Wilcoxon Rank Sum test).
9.3.4.Safety Analyses
For the assessment of safety/tolerability, incidentsand AEs will be listed. AEs will be 
summarised by treatment group. AEs will be regarded as treatment emergent if they 
occur on or after the first treatment application at the baseline visit. 
10. STUDY GOVERNANCE CONSIDERATIONS
10.1.Posting of Information on Publicly Available Clinical Trials 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 59 of 69

10.2.Regulatory and Ethical Considerations, Including the Informed 
Consent
The study will be conducted in accordance with all applicable regulatory 
requirements, and with GSK policy.
The study will also be conducted in accordance with ICH Good Clinical Practice 
(GCP), all applicable subject privacy requirements, and the guiding principles of the 
current version of the Declaration of Helsinki.  This includes, but is not limited to, the 
following:
Before initiating a trial, the investigator/institution should have written and 
dated approval/favorable opinion from the IEC for thetrial protocol (including 
amendments), written informed consent form, consent form updates, subject 
recruitment procedures (e.g., advertisements), investigator brochure/ safety 
statement (including any updates) and any other written information to be 
provided to subjects. A letter or certificate of approval will be sent by the 
investigator to the sponsor prior to initiation of the study, and also when 
subsequent amendments to the protocol are made.
Signed informed consent  to be obtained for each subject before participation 
in the study (and for amendments as applicable)
Investigator reporting requirements (e.g. reporting ofAEs/SAEs/protocol 
deviations to IEC.
GSK will provide full details of the above procedures, either verbally, in 
writing, or both.
10.3.Quality Control (Study Monitoring)
In accordance with applicable regulations including GCP, and GSK procedures, GSK 
or designee (i.e. third party vendor) monitors will contact the site prior to the start of 
the study to review with the site staff the protocol, study requirements, and their 
responsibilities to satisfy regulatory, ethical, and GSK requirements.
When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the CRF will serve as the 
source document.
GSK or designee will monitor the study and site activity to verify that the:
Data are authentic, accurate, and complete.
Safety and rights of subjects are being protected.
Study is conducted in accordance with the currently approved protocol and 
any other study agreements, GCP, and all applicable regulatory requirements.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 60 of 69

The extent and nature of monitoring will be described in a written monitoring plan on 
file at GSKCH. The investigator (or designee) agrees to allow the monitor direct 
access to all relevant documents and agrees to co-operate with the monitor to ensure 
that any problems detected in the course of these monitoring visits are resolved.
10.4.Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK 
may conduct a quality assurance assessment and/or audit of the site records, and the 
regulatory agencies may conduct a regulatory inspection at any time during or after 
completion of the study. 
In the event of an assessment, audit or inspection, the investigator (and institution) 
must agree to grant the advisor(s), auditor(s) and inspector(s) direct access to all 
relevant documents and to allocate their time and the time of their staff to discuss the 
conduct of the study, any findings/relevant issues and to implement any corrective 
and/or preventative actions to address any findings/issues identified.
The sponsor will be available to help investigators prepare for an inspection.
10.5.Conditions for Terminating the Study
Upon completion or premature discontinuation of the study, the GSKCH monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in 
accordance with applicable regulations including GCP, and GSKCH Standard 
Operating Procedures.
Both GSKCH and the Investigator reserve the right to temporarily suspend or 
prematurely discontinue this study at any time for reasons including, but not limited 
to, safety or ethical issues or severe non-compliance. For multicenter studies (if 
applicable), this can occur at one or more or at all sites.  
If the trial is prematurely terminated or suspended for any reason, the investigator site 
should promptly inform the trial subjects and should assure appropriate therapy/ 
follow-up for the subjects. Where required by the applicable regulatory requirements, 
GSKCH should inform the regulatory authority(ies). 
In addition: 
If the investigator terminates or suspends a trial without prior agreement of 
GSKCH, the investigator site should promptly inform the sponsor and the 
IEC, and should provide the sponsor and the IECa detailed written 
explanation of the termination or suspension.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 61 of 69

If the GSKCH terminates or suspends a trial, the investigator should promptly 
inform the IEC and provide the IEC a detailed written explanation of the 
termination or suspension. 
If the IEC terminates or suspends its approval/favorable opinion of a trial, the 
investigator shouldpromptly notify the GSKCH and provide GSKCH with a 
detailed written explanation of the termination or suspension.
10.6.Records Retention
Following closure of the study, the investigator must maintain all site study records 
(except for those required by local regulations to be maintained elsewhere), in a safe 
and secure location.  
The records (study/ site master file) must be maintained to allow easy and timely 
retrieval, when needed (e.g., for a GSK audit or regulatory inspection) and must be 
available for review in conjunction with assessment of the facility, supporting 
systems, and relevant site staff.
Where permitted by local laws/regulations or institutional policy, some or all of these 
records can be maintained in a format other than hard copy (e.g., microfiche, scanned, 
electronic); however, caution needs to be exercised before such action is taken. 
The investigator must ensure that all reproductions are legible and are a true and 
accurate copy of the original and meet accessibility and retrieval standards, including 
re-generating a hard copy, if required.  Furthermore, the investigator must ensure 
there is an acceptable back-up of these reproductions and that an acceptable quality 
control process exists for making these reproductions.
The investigator must assure that the subject’s anonymity will be maintained.  On 
CRFs or other documents submitted to GSKCH, 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 GSKCH, e.g. subjects’ written consent forms, should be maintained by the 
investigator in strict confidence.
GSK will inform the investigator of the time period for retaining these records to 
comply with all applicable regulatory requirements (GSKCH recommends that 
documents be kept for 10 years). The investigator is also required to keep subject 
identification codes on file for at least 15 years after completion or discontinuation of 
the study. The minimum retention time willmeet the strictest standard applicable to 
that site for the study, as dictated by any institutional requirements or local laws or 
regulations, GSK standards/procedures, and/or institutional requirements.  
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 62 of 69

No study document should be destroy
ed without a prior written agreement between 
GSKCH and the investigator. The investigator must notify GSK of any changes in the 
archival arrangements, including, but not limited to, archival at an off-site facility or 
transfer of ownership of the records in the event the investigator is no longer 
associated with the site.
10.7.Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials Registers 
and Publication
Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the clinical study report.  The investigator will be 
provided reasonable access to statistical tables, figures, and relevant reports and will 
have the opportunity to review the complete study results at a GSK site or other 
mutually-agreeable location.
GSK will also provide the investigator with the full summary of the study results.  
The investigator is encouraged to share the summary results with the study subjects, 
as appropriate.
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK Policy.
A manuscript willbe progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge.
11. REFERENCES
Addy M., Dentine Hypersensitivity: definition, prevalence, distribution and aetiology. 
In Tooth Wear and Sensitivity; 2000; pp 239–248.
Addy M., Mostafa P., Absi E., Adams D., Cervical dentin hypersensitivity. Etiology 
and management with particular reference to dentifrice. In Rowe NH, ed. Proceedings 
of Symposiumon Hypersensitive Dentin. Origin and Management. University of 
Michigan, Ann Arbor, MI,; 1985; pp 146–167.
Ayad F., Ayad N., Zhang Y. P., DeVizio W., Cummins D., Mateo L. R., Comparing 
the Efficacy in Reducing Dentin Hypersensitivity of a New Toothpaste Containing 
8.0% Arginine, Calcium Carbonate, and 1450 ppm Fluoride to a Commercial 
Sensitive Toothpaste Containing 2% Potassium Ion: An Eight-Week Clinical Study 
on Canadian Ad. J. Clin. Dent.2009, 10-16, 10–16.
Brannstrom M., Astrom A., A Study on the Mechanism of Pain Elicited From the 
Dentin. J. Dent. Res.1964, 43, 619–625.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 63 of 69

Canadian Advisory Board, Consensus-Based Recommendations for the Diagnosis 
and Management. Joournal Can. Dent. Assoc.2003, 69, 221–226.
Chaknis P., Pangakos F., DeVizio W., SowinskiJ., Petrone D., Proskin H., 
Assessment of hypersensitivity reduction of a dentifrice containing 0.3% triclosan, 
2% PVM/MA copolymer, 0.243% NaF and specially designed silica as compared to a 
dentifrice containing 0.454% stannous fluoride, sodium hexametaphosphate and zinc 
lactate to. Am. J. Dent.2011, 24, 14–20.
Dababneh R. H., Khouri a T., Addy M., Dentine hypersensitivity -an enigma? A 
review of terminology, mechanisms, aetiology and management. Br. Dent. J.1999, 
187, 606–611; discussion 603.
Docimo R., Montesani L., Maturo P., Costacurta M., Bartolino M., Zhang Y. P., 
DeVizio W., Delgado E., Cummins D., Dibart S., et al., Comparing the efficacy in 
reducing dentin hypersensitivity of a new toothpaste containing 8.0% arginine, 
calcium carbonate, and 1450 ppm fluoride to a benchmark commercial desensitizing 
toothpaste containing 2% potassium ion: An eight-week clinical study . J. Clin. Dent.
2009, 20, 137–143.
Du M., Jiang H., Tai B., He T., Chang J., Sun L., De-sensitizing effect of a stannous 
containingsodium fluoride novel dentifrice. J Dent Res2011, 90, Poster Session.
Fischer C., Fischer R. G., Wennberg A., Prevalence and distribution of cervical 
dentine hypersensitivity in a population in Rio de Janeiro, Brazil. J. Dent.1992, 20, 
272–276.
Flynn J., Galloway R., Orchardson R., The incidence of “hypersensitive” teeth in the 
West of Scotland. J. Dent.1985, 13, 230–236.
Fu Y., Li X., Que K., Wang M., Hu D., Mateo L. R., DeVizio W., Zhang Y. P., 
Instant dentin hypersensitivity relief of a new desensitizing dentifrice containing 
8.0% arginine, a high cleaning calcium carbonate system and 1450 ppm fluoride: a 3-
day clinical study in Chengdu, China. Am. J. Dent.2010, 23 Spec No, 20A—27A.
Graf H., Galasse R., Morbidity, prevalence and intraoral distribution of 
hypersensitive teeth. J. Dent. Res.1977, 56, A162.
GSKCH Study RH01324, GSKCH Clinical Study Report, RH01324.
GSKCH Study RH01327, GSKCH Clinical Study Report, RH01327.
GSKCH Study 
.
GSKCH Study 
.
GSKCH Study Z7871335, GSKCH Clinical Study Report, Z7871335.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 64 of 69
CCI
CCI

He T., Barker M. L., Qaqish J., Sharma N., Fast onset sensitivity relief of a 0.454% 
stannous fluoride dentifrice. J. Clin. Dent.2011a, 22, 46–50.
He T., Chang J., Cheng R., Sun L., Instant and Rapid Sensitivity Relief of a Stannous 
fluoride Dentifrice. J. Dent. Res.2011b, 90.
Holland G. R., Narhi M. N., Addy M., Gangarosa L., Orchardson R., Guidelines for 
the design and conduct of clinical trials on dentine hypersensitivity. J. Clin. 
Periodontol.1997, 24, 808–813.
Laster L., Laudenbach K. W., Stoller N. H., An evaluation of clinical tooth mobility 
measurements. J. Periodontol.1975, 46, 603—607.
Leight R., Bowman J., Barlow A., Dentinal Hypersensitivity: Evidence for a “No 
Treatment” Effect. J. Dent. Res.2008, 87, Abstract No 3498.
Lobene R. R., Weatherford T., Ross N. M., Lamm R. A., Menaker L., A modified 
gingival index for use in clinical trials. Clin. Prev. Dent.1986, 8, 3–6.
Mason S., Hughes N., SufiF., Bannon L., Maggio B., North M., Holt J., A 
comparative clinical study investigating the efficacy of a dentifrice containing 8% 
strontium acetate and 1040 ppm fluoride in a silica base and a control dentifrice 
containing 1450 ppm fluoride in a silica base to provide immediate relief of dentin 
hyp. J. Clin. Dent.2010, 21, 42—48.
Nathoo S., Delgado E., Zhang Y. P., DeVizio W., Cummins D., Mateo L. R., 
Comparing the efficacy in providing instant relief of dentin hypersensitivity of a new 
toothpaste containing 8.0% arginine, calcium carbonate, and 1450 ppm fluoride 
relative to a benchmark desensitizing toothpaste containing 2% potassium ion and 
1450 ppm . J. Clin. Dent.2009, 20, 123—130.
Ni L., He T., Chang J., Cheng R., Sun L., -sensitizing effect of a Stannous containing 
sodium fluoride toothpaste. In IADR, San Diego, Poster Session; 2011.
Orchardson R., Changes in extracellular fluid composition which excite axons. J. 
Physiol.1975, 245, 14P—16P.
Orchardson R., Collins W. J. ., Clinical features of hypersensitive teeth. Br. Dent. J.
1987, 162, 253–256.
Parkinson C., Hughes N., Jeffery P., Jain R., Kennedy L., Qaqish J., Gallob J. T., S 
M., The efficacy of an experimental dentifrice containing 0.454% w/w stannous 
fluoride in providing relief fropm the painof dentin hypersensitivity: An 8-week 
clinical study. Am. J. Dent.2013, 26, 25A –31A.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 65 of 69

Pashley D., Tay F., Haywood V., Collins M., Drisko C., Consensus-based 
recommendations for the diagnosis and management of dentin hypersensitivity. 
Compend Cont Edu Dent2008, 29, 1–35.
Polson A. M., Caton J. G., Yeaple R. N., Zander H. A., Histological determination of 
probe tip penetration into gingival sulcus of humans using an electronic pressure-
sensitive probe. J. Clin. Periodontol.1980, 7, 479–488.
Rees J. S., The prevalence of dentine hypersensitivity in general dental practice in the 
UK. J. Clin. Periodontol.2000, 27, 860–865.
Schiff T., Dotson M., Cohen S., Efficacy of a dentifrice containing potassium nitrate, 
soluble pyrophosphate, PVM/MA copolymer, and sodium fluoride on dentinal 
hypersensitivity: a twelve-week study. J. Clin. Dent.1994, 5, 87–92.
Schiff T., Zhang Y., DeVizio W., Stewart B., Chaknis P., Petrone M., Volpe A., 
Proskin H., A randomized clinical trial of the desensitizing efficacy of three 
dentifrices. Compend. Contin. Educ. Dent.2000a, 27, 4–10.
Schiff T., Bonta Y., Proskin H., DeVizio W., Petrone M., Volpe A., Desensitizing 
efficacy of a new dentifrice containing 5.0% potassium nitrate and 0.454% stannous 
fluoride. Am. J. Dent.2000b, 13, 111–115.
Schiff T., Saletta L., Baker R., Winston J., He T., Desensitizing effect of a stabilized 
stannous fluoride/Sodium hexametaphosphate dentifrice. Compendium of continuing 
education in dentistry. Compend. Contin. Educ. Dent.2005, 26, 35–40.
Schiff T.,He T., Sagel L., Baker R., Efficacy and Safety of a Novel Stabilized 
Stannous Fluoride and Sodium Hexametaphosphate. J. Contemp Dent. Pract. Pract.
2006, 7, 1–10.
Schiff T., Delgado E., Zhang Y. P., Cummins D., DeVizio W., Mateo L. R., Dentin 
hypersensitivity: Effective treatment with an in-office desensitizing paste containing 
8% arginine and calcium carbonate. Am. J. Dent.2009, 22.
Seltzer S., Bender I., The Dental Pulp: Biologic Considerations in Dental 
Procedures; JP Lippincott, 1975.
Sharma N., Roy S., Kakar A., Greenspan D. C., Scott R., A clinical study comparing 
oral formulations containing 7.5% calcium sodium phosphosilicate (novamin??), 5% 
potassium nitrate, and 0.4% stannous fluoride for the management of dentin 
hypersensitivity. J. Clin. Dent.2010, 21, 88–92.
Sharma N., Roy S., Kakar A., Greenspan D., Scott R., Instant Sensitivity Relief of a 
Stannous containing Sodium Fluoride Dentifrice. J. Dent. Res.2011, 90, Oral 
Presentation.
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 66 of 69

West N. X., Addy M., Jackson R. J., Ridge D. B., Dentine hypersensitivity and the 
placebo response. A comparison of the effect of strontium acetate, potassium nitrate 
and fluoride toothpastes. J. Clin. Periodontol.1997, 24, 209–215. 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 67 of 69

12. APPENDICES
12.1. Appendix 1 -Abbreviations and Trademarks
Abbreviations
ANCOVA
Analysis of Covariance
AE 
AdverseEvent
CD
Compact Disc
CRF
Case Report Form
DH
Dentinal Hypersensitivity
DMS
Data Management System
EAR
Erosion, Abrasion or facial/gingival Recession
EDC
Electronic Data Capture
GCP
Good Clinical Practice
GSKCH
GlaxoSmithKline Consumer Healthcare
ICH
International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
ITT
Intention to Treat
MedDRA
Medical Dictionary for Regulatory Activities
MGI
Modified GingivalIndex
OHT
Oral Hard Tissue Examination
OST
Oral Soft Tissue Examination
PII
Personally Identifiable Information
PP
Per Protocol
SAE
Serious Adverse Event
PRO
Patient Reported Outcome
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 68 of 69

 
 
SIGNATURE PAGE 
 
  
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
28-Aug-2016 15:37:22
 
Biostatistics Approval
Clinical Operations Approval
26-Aug-2016 11:05:18
Approved
207212 Clinical Protocol
26-Aug-2016 06:03:15
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
28-Aug-2016 15:37:31
 
eldo_controlled
3.0; Most-Recent; Effective; CURRENT
207212 Clinical Protocol
Auto Issue
090032d580c0ede6
Page 69 of 69
PPD
PPD
PPD