A Proof of Principal Study to Investigate the Stain Control of Two Stannous Fluoride Dentifrices
Phase: NA
Conditions: Extrinsic Dental Stain, Oral Hygiene
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  An unpublished work subject to trade secret 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 topersons not 
employed by GlaxoSmithKline unless specifically authorized.  Unauthorized 
disclosure of this work is expressly prohibited.
Clinical Protocol
207872
 
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CONFIDENTIAL
SUMMARY INFORMATION



Title:
A Proof of Principal Study to InvestigatetheStain 
Control of Two Stannous Fluoride Dentifrices
Protocol Number:
207872
Sponsor:
GlaxoSmithKline Consumer Healthcare (GSKCH)
St Georges Avenue, Weybridge, Surrey, KT13 0DE,
United Kingdom (UK)
Tel: 
Product Names:
0.454% stannous fluoride (SnF
2) / 5% sodium 
tripolyphosphate (STP) containing dentifrice; 
2.0% abrasive silica
0.454% SnF2 / 5% STP containing dentifrice; 
3.5% abrasive silica
Development Phase:
N/A
Expert Advice Outside of Normal 
Working Hours:
Key Protocol Authors:
PRIMARY CONTACT
Clinical Study Manager:
184 Liberty Corner Rd.
Warren, NJ 07059 USA
Tel:
Biostatistician:
, PhD
Clinical Research:
, BSc
Clinical Supplies:
, MSc

Principal Investigator:
Dr. C.R. Goyal,DMD
Study Site Name & Address:
All Sum Clinical Research1065 
Canadian Place, Unit 102Mississauga, 
OntarioL4W0C2, Canada
Study Site Telephone Number:
Study Examiner:
Dr. 
DMD
 
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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:
Investigator Qualifications:
Investigator Signature:
Date of Signature/ Agreement:
DD/MMM/YYYY
 
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Table of Content
SUMMARY INFORMATION...............................................2
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE..............................................................................3
Table of Content......................................................................4
PROCESS FOR AMENDING THE PROTOCOL...............9
Schedule of Events..................................................................10
PROTOCOL SYNOPSIS FORSTUDY 207872...................11
1. INTRODUCTION...............................................................20
2. OBJECTIVES AND ENDPOINTS....................................22
3. STUDY PLAN.....................................................................24
3.1. Study Design.......................................................................24
3.2. Type and Planned Number of Subjects............................27
3.3. Study Design and Dose Justification.................................27
4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA........................................29
4.1. Inclusion Criteria...............................................................30
4.2. Exclusion Criteria..............................................................31
4.3. Screening/ Baseline Failures..............................................33
4.4. Withdrawal/ Stopping Criteria.........................................33
4.5. Subject Replacement..........................................................34
4.6. Subject and Study Completion..........................................34
5. PRODUCT INFORMATION.............................................35
5.1. Study Product.....................................................................35
5.2. Dose Schedule.....................................................................36
 
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5.3. Dose Modification..............................................................36
5.4. Product Compliance..........................................................36
5.5. Precautions.........................................................................36
5.6. Overdose.............................................................................37
5.7. Rescue Therapy..................................................................37
5.8. Product Assignment...........................................................37
5.8.1 Randomisation....................................................................37
5.8.2. Blinding..............................................................................38
5.8.3. Code Breaks.......................................................................38
5.9. Packaging and Labelling...................................................39
5.9.1. Accountability of Product.................................................39
5.9.2. Storage of Product............................................................40
6. STUDY ASSESSMENTS AND PROCEDURES..............40
6.1. Visit 1 -Screening Visit......................................................40
6.1.1. Telephone Screening.........................................................40
6.1.2. Informed Consent.............................................................40
6.1.3. Demographics....................................................................41
6.1.4. Medical History and Concomitant Medication...............41
6.1.5. Oral Soft Tissue (OST) Examination...............................41
6.1.6.  Full Oral Hard Tissue (OHT) Visual Examination........42
6.1.7.Visual MLSI Stain Assessment........................................42
6.2. Visit 2 -Baseline Visit........................................................42
6.2.1. Oral Soft Tissue (OST) Examination.............................42
6.2.2. Full Oral Hard Tissue (OHT) Examination..................42
6.2.3.Full MLSI Stain Assessment............................................42
6.2.4. Dental Prophylaxis............................................................43
6.2.5.Visual MLSI Stain Assessment........................................43
6.2.6Supervised Product Use....................................................44
6.3. Visit 3 (Week 2)................................................................44
 
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6.3.1.Full MLSI Stain Assessment............................................44
6.3.2.  Supervised Product Use...................................................44
6.4. Visit 4 (Week 4)................................................................44
6.4.1. Full MLSI Stain Assessment............................................44
6.4.2. Dental Prohylaxis (Optional)............................................44
6.4.3. Brushing (Optional)..........................................................44
6.4.4. Study Conclusion..............................................................44
7. SAFETY ASSESSMENTS..................................................45
7.1. Definitions of an Adverse Event and Serious Adverse 
Event.................................................................................45
7.1.1. Adverse Events..................................................................45
7.1.2. Serious Adverse Events.....................................................46
7.2. Recording Adverse Events and Serious Adverse Events.47
7.3. Evaluating Adverse Events and Serious Adverse Events48
7.4. Reporting Adverse Events and Serious Adverse Events..49
7.5. Follow-up of Adverse Events and Serious Adverse Events
..........................................................................................50
7.6. Definition of and Procedure for Reporting Medical Device 
Incidents...........................................................................51
7.6.1. Definition of an Incident...................................................51
7.6.2. Reporting of Incidents and Malfunctions........................51
7.6.3. Follow-up of Incidents......................................................52
7.7. Collection of Pregnancy Information................................53
7.7.1. Time Period for Collecting of Pregnancy Information...53
7.7.2. Action to be Taken if Pregnancy Occurs.........................53
8. DATA MANAGEMENT....................................................54
8.1. Source Documents/ Data....................................................54
8.2. Electronic Case Report Form............................................55
8.3. Data Handling....................................................................56
 
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8.3.1. Data Queries......................................................................56
8.4. Processing Patient Reported Outcomes............................56
9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES....................................................................56
9.1 Sample Size Determination.................................................57
9.2. General Considerations.....................................................57
9.2.1. Definition of Analysis Populations...................................57
9.2.2. Exclusion of Data from Analysis......................................57
9.2.3. Criteria for Evaluation.....................................................58
9.2.4. Criteria for Assessing Efficacy.........................................58
9.2.5. Criteria for Assessing Tolerability...................................58
9.2.6. Handling of Dropouts and Missing Data.........................58
9.3. Statistical Methods and Analytical Plan...........................59
9.3.1. Demographic and Baseline Characteristics.....................59
9.3.2. Primary Analysis...............................................................59
9.3.3. Secondary Analysis...........................................................59
9.3.4. Exploratory Analyses........................................................59
9.3.5. Safety Analyses..................................................................60
10. STUDY GOVERNANCE CONSIDERATIONS.............61
10.1. Posting of Information on Publicly Available Clinical 
Trials Registers................................................................61
10.2. Regulatory and Ethical Considerations, Including the 
Informed Consent............................................................61
10.3. Quality Control (Study Monitoring)...............................61
10.4. Quality Assurance............................................................62
10.5. Conditions for Terminating the Study............................62
10.6. Records Retention............................................................63
 
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10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials 
Registers and Publication................................................64
11. REFERENCES..................................................................66
12. APPENDICES...................................................................68
12.1. Appendix 1........................................................................68
 
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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 
IEC as per country specific requirements. In some countries pre-approval of a minor 
amendment is not requiredand will just be held on file by the sponsor and 
investigator.
 
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Scheduleof Events
Procedure
Pre-screening
Visit 1
Screening
Minimum24 hours, up to a maximum of 2 weeks
Visit 2
Baseline
Day 0
Visit 3
Week 2 
Day 14 2
days
Visit 4
Week 4 
Day 28 2
days
Telephone Screening of Subjects 

Informed Consent

Demographics, Medical History, 
Smoking Status

Current / Concomitant Medication




Oral Soft Tissue (OST) 
Examination


Full Oral Hard Tissue (OHT) 
Examination


Visual MLSI Stain Assessment

Inclusion / Exclusion Criteria


Eligibility 


Brush Anterior Teeth for 30 
Seconds with Tap Water Prior to 
Stain Assessment



Pre-prophylaxis Full MLSI Stain 
Assessment of the Anterior Teeth
1

Stratification / Randomisation

Dental Prophylaxis2

Post-prophylaxis Visual MLSI 
Stain Assessment

Full MLSI Stain Assessment1


Dispense Study Dentifrice, Timer, 
Toothbrush and Diary/Instructions 
Card

Supervised Brushing on Site
3

Adverse Events



Incidents
4


Subject Adherence and 
Continuance


Diary Compliance Check
5


Return Dentifrice, Toothbrush and 
Diary Card


Post Treatment Dental Prophylaxis 
6
Study End

1. Ten subjects will be randomly selected for repeat examinations across each assessment window (a total of 30 repeat 
examinations over the duration ofthe study).
2. AEs will be recorded from and including dental prophylaxis onwards. 
3. Time of first brushing will be captured to distinguish dentifrice AEs from prophylaxis AEs.
4. Incidents will be collected from first use of the tooth brush, prior to stain assessment.
5. Time of each brushing occasion in addition to missed/additional brushings, and changes to smoking status will be 
captured in the subject diary. 
6. Once all efficacyassessments have been completedrandomised subjects who request so will be given a full dental
prophylaxis, and will be recorded in the eCRF.
 
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PROTOCOL SYNOPSIS FOR STUDY 207872

Brief Summary
This proof of principal (PoP) single centre, randomised, examiner blind, four-
treatment arm, parallel design study will be used to evaluate and compare the stain 
build up of two 0.454% stannous fluoride (SnF2) / 5% sodium tripolyphosphate (STP) 
dentifrices of differing abrasivity levels, with a marketedstandard fluoride dentifrice
and a marketed SnF
2dentifrice. 
Stain will be assessedfollowinga full professionaldentalprophylaxis, at intervals 
over a 4 week treatment period, using an establishedclinical measure of extrinsic 
dental stain-the MacPherson modification[Macpherson, 2000] of the Lobene stain 
index [Lobene, 1968] (MLSI).Subjects will be stratified by pre-prophylaxis MLSI 
score (total MLSI Area x Intensity(A×I)for the facial surfaces of the 12 anterior 
teeth)and smoking status.
The study will be conducted in healthy subjects with a propensity for extrinsic dental 
stain (in the opinionof the examiner)on the facial surfaces of the anterior teeth.
 
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Objectivesand Endpoints
Objectives
Endpoints
Primary
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI (A×I), of 
two experimental 0.454% SnF2 / 5% 
STP dentifrices with that of a 
marketed standard fluoride 
dentifrice, after 4weeks twice daily 
use.
Overall MLSI at week 4.
Secondary
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI (A×I), of 
two experimental 0.454% SnF2 / 5% 
STP dentifrices with that of a 
marketed SnF2 dentifrice, after 4 
weeks twice daily use.
Overall MLSI at week 4.
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI (A×I), of 
a marketed SnF
2 dentifrice with that 
of a marketed standard fluoride 
dentifrice, after 4 weeks twice daily 
use.
Overall MLSI at week 4.
Exploratory
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI (A×I), of 
an experimental 0.454% SnF
2 / 5% 
STP, 2.0% abrasive silica dentifrice
with that of an experimental 0.454% 
SnF2 / 5% STP, 3.5% abrasive silica 
dentifrice, after 4 weeks twice daily 
use.
Overall MLSI at week 4.
 
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To evaluate and compare the build 
up of extrinsic tooth stain , as 
measured by overall MLSI (A×I), of 
two experimental 0.454% SnF2 / 5% 
STP dentifrices with that of a 
marketed standard fluoride dentifrice 
and a marketed SnF
2 dentifrice, after 
2weeks twice daily use.
OverallMLSI at week 2.
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall Interproximal 
(Distal + Mesial) MLSI, of two 
experimental 0.454% SnF
2 / 5% STP 
dentifrices with that of a marketed 
standard fluoride dentifrice and a 
marketed SnF2dentifrice, after 2 and 
4 weeks twice daily use.
Overall Interproximal (Distal + 
Mesial) MLSI at weeks2 and 4.
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI Area (A), 
of two experimental moderate 
abrasivity 0.454% SnF
2 / 5% STP 
dentifrices with that of a marketed 
standard fluoride dentifrice and a 
marketed SnF2dentifrice, after 2 and 
4weeks twice daily use.
OverallMLSI Area at weeks2 
and 4.
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI Intensity 
(I), of two experimental moderate 
abrasivity 0.454% SnF2 / 5% STP 
dentifrices with that of a marketed 
standard fluoride dentifrice and a 
marketed SnF2dentifrice, after 2 and 
4weeks twice daily use.
OverallMLSI Intensity at weeks
2 and 4.
 
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Study Design
Overall Design
This is a single-centre, examiner-blind, randomised, four treatment, parallel group 
study, stratified by baseline total MLSI (A×I) score for the facial surfaces of at least 
11 of the 12 anterior teeth (<45 (low);≥45 (high)) and smoking status (smoker;non
smoker). A single dental examiner will perform a full MLSIassessment of the area 
and intensity of extrinsic dental stain on the facial surfaces of the 6 maxillary and 6 
mandibular anterior teeth (universal numbering: 6-11 and 22-27), and the lingual 
surfaces of the 6 mandibular anterior teeth (universal numbering: 22-27), at baseline
(Visit 2), and following 2 and 4weeks twice dailybrushing (Visits 3 and 4).
Potential subjects will be pre-screened via telephone and later attend a screening visit 
during which they 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)
examination, afulloral hard tissue (OHT)examinationand a visual MLSI stain 
assessment. Subjects deemed(in the opinion of the examiner)to have a sufficient 
level ofextrinsicdental staining (assessed to be formed due to ingestionof food or 
drinks, or use of tobacco products)on the facial surfaces ofthe scorable anterior 
(maxillary and mandibular) teeth, as well as meeting all other study criteria,will be 
considered as eligible to proceed with the study. Eligiblesubjects will continue to use 
their own dentifrice at home until theirbaseline visit. Prior to the baseline visit,
subjects will be asked to abstain from oral hygienefor at least 6 hours.
At baseline, each subject will undergo an OST anda fullOHT, and thenbrush their 
anterior teeth for 30 seconds using a wetted toothbrush (with tap water), prior to 
undergoing afull MLSI stain assessment. Subjects deemed (in the opinion of the 
examiner)to have a sufficient level of extrinsic dental stainon the facial surfaces of
the scorable anterior (maxillary and mandibular) teeth, who continue to meet all study
 
criteria, will be stratified (based on pre-prophylaxis baseline total MLSI(A×I)score 
and smoking status)and randomised to treatment. The stratification factor will give 
rise to four strata:
MLSI Score High(≥45), Smoker
MLSI Score Low(<45), Smoker
MLSI Score High(≥45), Non Smoker
MLSI Score Low(<45), Non Smoker
A dental hygienist will professionally clean each subject’s teeth using a conventional 
 
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dental prophylaxis paste followed by flossing(carried out by the hygienist)to remove 
all visible stain, plaque,debris, and all sub-and supra-gingival calculusfrom the 
anterior teeth. A second dental examiner will confirm all sub-and supra-gingival 
calculus, visible stain (Total MLSI(A×I)= 0), plaque and debris has been removed 
from the facial, palatal/lingual surfaces of the anterior teeth (visually and by tactile 
assessment using a dental explorer).Subjects will then be requested to brush twice 
daily (morning and evening) with theirallocated study dentifrice for the next 4weeks. 
They will receive verbal and written product usage instructions. First product usewill 
be supervised on site, with a furthersupervised brushingat Visit 3. Subjects will be 
asked to record each product use in a diary, and note any significant changes to diet 
or smoking status, medications and healthduring the course of the study, and 
confirmed by the site at each visit.  
Subjects will return to the site atVisits 3 and 4,having abstained from oral hygiene
for at least 6 hours prior to their visit. Subjects will brush their anterior teeth for 30 
seconds using a wetted toothbrush, prior to undergoing a full MLSI stain assessment. 
Subjects will be asked to bring their study dentifrice, toothbrush and completed diary 
to each visit to facilitate compliance checks.
Randomised subjects who request sowill be offered a full mouth dental prophylaxis 
on completion of Visit 4procedures, or on completion of the visit where they exit the 
study.
Repeat examinationswill be performed by the dental examiner at each full MLSI 
assessment visit. Ten subjects will be randomly selected for repeat examinations 
across each assessment window (a total of 30 repeat examinations over the duration 
of the study) at Visits 2 (pre-prophylaxis), 3 and 4. There will be a minimum of 10 
minutes, and a maximum of 30 minutes between repeatability examinations.
Pre-screening
Prior to the screening visit, telephone screening of interested subjects will be 
conducted by the site using a telephone script. 
Visit 1 -Screening Visit
The following assessments will be conducted:
Written informed consent.
Review inclusion/exclusion criteria.
Review of the oral care products the subject is currently using to confirm they 
do not contain any restricted ingredients.
Demographics, current/concomitant medications, medical historyand 
smoking status captured.
 
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Oral examinations including an OSTandafullOHT examination.
Visual MLSI stain assessmentof the facial (maxillary and mandibular) 
surfaces only.
Confirmation of subject eligibility.
Visit 2 -Baseline Visit
The following assessments will be conducted:
Review of current/concomitant medications.
Review inclusion/ exclusion and confirmation of subject eligibility and 
continuance.
Full OST examination.
Full OHT examination.
Supervised brushing of theanterior teeth for 30 seconds using a wetted 
toothbrush.
Pre-prophylaxis full MLSI stain assessmentof the facial (maxillary and 
mandibular) and lingual (mandibular) surfaces.
Stratification(based on total MLSI score of the facial surfacesonly)and 
randomisation.
Full professional dental prophylaxis.
Post-prophylaxis visual MLSI stain assessment of the facial (maxillary and 
mandibular) and lingual (mandibular) surfacesto confirm overall MLSI = 0.
Dispensation of studydentifrice, toothbrush and diary/instructions card.
Supervised brushing with subject’s allocated dentifrice.
AEs and Incidents following supervised brushing.
Visit 3 -Week 2
The following assessments will be conducted:
Subjects return study dentifrice, toothbrushand diary cardto the clinicalsite.
Review of current/concomitant medications, AEs and incidents.
Review of completed diary to confirm timing of each brushing occasion in 
addition to missed/additional brushings, and potential changes to smoking 
status.
Confirmation of subject adherence and continuance.
Supervised brushing of theanterior teeth for 30 seconds using a wetted 
toothbrush.
Full MLSI stain assessmentof the facial (maxillary and mandibular) and 
lingual (mandibular) surfaces.
Supervised brushing with subject’s allocated dentifrice.
AEs and Incidents following supervised brushing.
 
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Visit 4-Week 4 (LSLV)
The following assessments will be conducted:
Subjects return study dentifrice, toothbrush and diary cardto the clinicalsite.
Review of current/concomitant medications, AEs and incidents.
Review of completed diary to confirm timing of each brushing occasion in 
addition to missed/additional brushings, and potential changes to smoking 
status.
Confirmation of subject adherence and continuance.
Supervised brushing of theanterior teeth for 30 seconds using a wetted 
toothbrush.
Full MLSI stain assessmentof the facial (maxillary and mandibular) and 
lingual (mandibular) surfaces.
Post assessment brushing with study dentifrice and tooth brush (if requested 
by the subject).
Post treatment dental prophylaxis (if requested by the subject).
AE’s and incidentscaptured.
Study end.
Type and Planned Number of Subjects
A sufficient number of subjects will be screened to randomise at least 220subjects to 
ensure 200 evaluable subjects complete the study. This will ensure approximately 50 
evaluable subjects per treatment arm.
This study has not been formally powered to make any claims, and is appropriately 
sized as a PoP study for the purpose of observing meaningful trends.

Diagnosis and Main Criteria for Inclusion
Subjects aged 18-65 years of age, with a minimum of 16natural teeth(including the 
12 anterior teeth)and in good general health with a propensity forextrinsic dental 
stain.At Screening and Baseline subjects must have the facial surfaces, and 
mandibular lingual surfaces, of at least 11 of the 12 anterior teeth, gradable for MLSI
(four sites per tooth), with sufficient extrinsic dental stain(in the opinion of the 
examiner)on the facial surfaces ofthe scorable anterior (maxillary and mandibular)
teeth.
 
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Product Information
The following study products will be supplied by the Clinical Supplies Department, 
GSKCH:
Test Product 1
Test Product 2 Reference Product 1
Reference Product 2
Product Name 
Experimental 
dentifrice 
containing 
0.454% SnF2 / 
5% STP; 2.0% 
abrasive silica 
(RDA~58)
Experimental 
dentifrice 
containing 
0.454% SnF2 / 
5% STP; 3.5% 
abrasive silica 
(RDA~77)
Dentifrice containing
1000ppm fluoride as 
Sodium 
Monofluorophosphate 
(SMFP; Colgate 
CavityProtection®, 
Canada Marketed 
dentifrice) 
moderate abrasivity 
(RDA~80)
Dentifrice containing 
0.454% SnF2
(SensodyneComplete 
Protection, Canada 
Marketed dentifrice) 
higher abrasivity 
(RDA~120)
Short Product 
Name
Test dentifrice 
(RDA~58)
Test dentifrice
(RDA~77)
Reference dentifrice 
(RDA~80)
Reference dentifrice 
(RDA~120)
Product 
Formulation 
Code (MFC)
Commercially 
Available
Commercially 
Available
Dose
Aribbon ofdentifrice, covering the length of the toothbrush head
Route of 
Administration
Oral
Dosing 
Instructions
Brush twice daily (morning and evening) with the allocatedstudy dentifricefor 1 
timed minute
Statistical Methods
For the relevant stain variable, the various scores will be averaged over the regions 
under consideration. These include:
Overall MLSI -calculated as the mean MLSI (A×I) score over all gingival, 
body, mesial and distal sites on the facial surfaces of the six maxillary anterior 
teeth and six mandibular anterior teeth, and the lingual surfaces of the six 
mandibular anterior teeth.
Interproximal MLSI -calculated as the mean MLSI (A×I) score over all 
interproximal (mesial+distal) sites on the facial surfaces of the six maxillary 
anterior teeth and six mandibular anterior teeth, and the lingual surfaces of the 
six mandibular anterior teeth.
 
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Overall MLSI Area -calculated as mean MLSI (A) score all gingival, body, 
mesial and distal sites on the facial surfaces of the six maxillary anterior teeth 
and six mandibular anterior teeth, and the lingual surfaces of the six 
mandibular anterior teeth. 
Overall MLSI Intensity -calculated as mean MLSI (I) score all gingival, 
body, mesial and distal sites on the facial surfaces of the six maxillary anterior 
teeth and six mandibular anterior teeth, and the lingual surfaces of the six 
mandibular anterior teeth. 
Primary and Secondary Efficacy
The primary and secondary variableswill be overall MLSI at Week 4. These
variableswill be analysed using analysis of covariance (ANCOVA) with treatment 
and smoking status as factor, and appropriate pre-prophylaxis baseline mean MLSI 
score as a covariate. Adjusted means and treatment differences between the test 
products and the marketed standard fluoride dentifrice will be provided together with 
their 95%CIs and p-values. 
Exploratory Efficacy
Exploratory variables include overall MLSI Intensity score at Week2, and 
Interproximal MLSI score, overall MLSI Area score and overall MLSI Intensity score 
at Weeks 2 and 4. Each of these variables will be analysed using the same ANCOVA 
model as the primary analysis.
 
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1. INTRODUCTION
One of the main functions of a dentifrice is to help control extrinsic dental stain
[Pader, 2012], typicallyachieved by the inclusion of dental grade abrasivessuch as 
silica’s.Polyphosphates, such as sodium tripolyphosphate (STP), can also beincluded
as chemical cleaning compounds,tosupplement the physical stain removal offeredby 
dental abrasives. Polyphosphates act as chelating ingredientsand have been shown to 
bind strongly to the tooth surface, reducingthe force ofadhesion of adsorbed proteins 
[Shellis, 2005] andfacilitating stainremoval duringtoothbrushing. In addition, they
have been shown to desorb salivary proteins fromenamel, and inhibit protein 
adsorption [Rykke, 1997], thereby helping to control stain build up. 
Extrinsic (surface) dental stain is primarily caused by chromagens(originating inthe 
diet,or from smoking ormedications)binding to proteinaceous compounds found in 
the salivarypellicle [Schuurs, 2013], and is a common finding in the adult population. 
The etiology of stain is multiplebut iswidely agreed toresultfrom discoloration of 
plaque and pellicle on the surface of the tooth, with the mainsite for extrinsic stain 
build up generally accepted as the acquired salivary toothpellicle [Shellis, 2005].
Stannous fluoride(SnF
2)hasbeen incorporated into oral hygiene products indicated 
forthe reliefof dentinal hypersensitivity (DH) since the 1960s [Tinanoff, 1990; 
Thrash, 1994; Schiff,2005; Baig, 2005; Paraskevas, 2006; Schiff, 2006]. The 
stannous salts found in dentifrice formulations havehistorically been associated with
undesirable dental staining withlong-term use [Tinanoff, 1995].GSKCH currently 
markets a 0.454% SnF2dentifrice in Canada as Sensodyne Complete Protection. In 
order to control against the known staining effects of stannoussalts, 5% STP was 
included in a moderate to high abrasivity formulation, as measured by a Relative 
Dentine Abrasivity (RDA) of ~120. 
Two clinical studies were conducted on the now marketed dentifrice to evaluate the 
buildup of extrinsic dental stain, followingprofessional prophylaxis.In an 8 week 
study a marketed SnF
2dentifrice; RDA~146 (Crest Pro-Health
*) exhibited greater 
stain build up compared to the test SnF
2dentifrice, and no statistically significant 
differences in dental stain buildup were observed between thethentest SnF2
dentifrice and a standardfluoride dentifrice; RDA~80(ColgateCavity Protection), 
after 8 weeks twice daily use [GSKCH study  
]. In a longer use 24 weeks 
study, a statistically significant difference in favour of the SnF
2dentifrice versus the 
                                               
*Crest Pro-Health is a registered trademark of Proctor and Gamble.
Colgate is a registered trademark of the Colgate-Palmolive group.
 
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samestandardfluoride dentifrice (ColgateCavity Protection®)was observed after 24 
weeks twice daily use [GSKCH study  
]. 
It is an important compromise that a dentifrice should be able to control extrinsic
dentalstainwhile minimising itsabrasive effect [Schemehorn, 2011], particularly for 
people with tooth sensitivity where the softer dentin is exposed[Pickles, 2006]. 
Therefore, a lower abrasivity dentifrice is considered to be more appropriate for DH 
sufferers.GSKCH have therefore developed two experimental dentifrice formulations 
which have lower RDA values of ~52 and RDA of ~80, to support an overall lower 
abrasion/ enamel protectionproposition.
 
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2. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI (A×I), of 
two experimental 0.454% SnF2 / 5% 
STP dentifrices with that of a 
marketed standard fluoride 
dentifrice, after 4weeks twice daily 
use.
Overall MLSI at week 4.
Secondary
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI (A×I), of 
two experimental 0.454% SnF2 / 5% 
STP dentifrices with that of a 
marketed SnF2 dentifrice, after 4 
weeks twice daily use.
Overall MLSI at week 4.
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI (A×I), of 
a marketed SnF
2 dentifrice with that 
of a marketed standard fluoride 
dentifrice, after 4 weeks twice daily 
use.
Overall MLSI at week 4.
Exploratory
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI (A×I), of 
an experimental 0.454% SnF
2 / 5% 
STP, 2.0% abrasive silica dentifrice
with that of an experimental 0.454% 
SnF2 / 5% STP, 3.5% abrasive silica 
dentifrice, after 4 weeks twice daily 
use.
Overall MLSI at week 4.
 
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To evaluate and compare the build 
up of extrinsic tooth stain , as 
measured by overall MLSI (A×I), of 
two experimental 0.454% SnF2 / 5% 
STP dentifrices with that of a 
marketed standard fluoride dentifrice 
and a marketed SnF
2 dentifrice, after 
2weeks twice daily use.
OverallMLSI at week 2.
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall Interproximal 
(Distal + Mesial) MLSI, of two 
experimental 0.454% SnF
2 / 5% STP 
dentifrices with that of a marketed 
standard fluoride dentifrice and a 
marketed SnF2dentifrice, after 2 and 
4 weeks twice daily use.
Overall Interproximal (Distal + 
Mesial) MLSI at weeks2 and 4.
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI Area (A), 
of two experimental moderate 
abrasivity 0.454% SnF2 / 5% STP 
dentifrices with that of a marketed 
standard fluoride dentifrice and a 
marketed SnF2dentifrice, after 2 and 
4weeks twice daily use.
OverallMLSI Area at weeks2 
and 4.
To evaluate and compare the build 
up of extrinsic tooth stain, as 
measured by overall MLSI Intensity 
(I), of two experimental moderate 
abrasivity 0.454% SnF2 / 5% STP 
dentifrices with that of a marketed 
standard fluoride dentifrice and a 
marketed SnF2dentifrice, after 2 and 
4weeks twice daily use.
OverallMLSI Intensity at weeks
2 and 4.
 
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3. STUDY PLAN
3.1. Study Design
Overall Design
This is a single-centre, examiner-blind, randomised, four treatment, parallel group 
study, stratified by baseline total MLSI (A×I) score for the facial surfaces of at least 
11 of the 12 anterior teeth (<45 (low);≥45 (high)) and smoking status (smoker;non
smoker). A single dental examiner will perform a full MLSI assessment of the area 
and intensity of extrinsic dental stain on the facial surfaces of the 6 maxillary and 6 
mandibular anterior teeth (universal numbering: 6-11 and 22-27), and the lingual 
surfaces of the 6 mandibular anterior teeth (universal numbering: 22-27), at baseline
(Visit 2), and following 2 and 4weeks twice dailybrushing (Visits 3 and 4).
Potential subjects will be pre-screened via telephone and later attend a screening visit 
during which they 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)
examination, afulloral hard tissue (OHT)examinationand a visual MLSI stain 
assessment. Subjects deemed to have a sufficient level of extrinsic dental staining (in 
the opinion of the examiner), assessed to be formed due to ingestionof food or 
drinks, or use of tobacco products)for the facial surfaces ofthe scorable anterior 
(maxillary and mandibular) teeth, as well as meeting all other study criteria,will be 
considered as eligible to proceed with the study. Eligiblesubjects willcontinue to use 
their own dentifrice at home until theirbaseline visit. Prior to the baseline visit,
subjects will be asked to abstain from oral hygienefor at least 6 hours.
At baseline, each subject will undergo an OST and a full OHT, and thenbrush their 
anterior teeth for 30 seconds using a wetted toothbrush (with tap water), prior to 
undergoing afull MLSI stain assessment. Subjects with a sufficient level of extrinsic 
dental stain (in the opinion of the examiner)on the facial surfaces ofthe scorable 
anterior (maxillary and mandibular) teeth, who continue to meet all study
 criteria, will 
be stratified (based on pre-prophylaxis baseline total MLSI(A×I)score and smoking 
status)and randomised to treatment. The stratification factor will give rise tofour 
strata:
MLSI Score High(≥45), Smoker
MLSI Score Low(<45), Smoker
MLSI Score High(≥45), Non Smoker
 
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MLSI Score Low(<45), Non Smoker
A dental hygienist will professionally clean each subject’s teeth using a conventional 
dental prophylaxis paste followed by flossing(carried out by the hygienist)to remove 
all visible stain, plaque,debris, and all sub-and supra-gingival calculusfrom the 
anterior teeth. A second dental examiner will confirm all sub-and supra-gingival 
calculus, visible stain (Total MLSI(A×I)= 0), plaque and debris has been removed 
from the facial, palatal/lingual surfaces of the anterior teeth (visually and by tactile 
assessment using a dental explorer).Subjects will then be requested to brush twice 
daily (morning and evening) with theirallocated study dentifrice for the next 4weeks. 
They will receive verbal and written product usage instructions. First product usewill 
be supervised on site, with a furthersupervised brushingat Visit 3. Subjects will be 
asked to record each product use in a diary, and note any significant changes to diet 
or smoking status, medications and healthduring the course of the study, and 
confirmed by the site at each visit.  
Subjects will return to the site atVisits 3 and 4,having abstained from oral hygiene
for at least 6 hours prior to their visit. Subjects will brush their anterior teeth for 30 
seconds using a wetted toothbrush, prior to undergoing a full MLSI stain assessment. 
Subjects will be asked to bring their study dentifrice, toothbrush and completed diary
cardto each visit to facilitate compliance checks.
Randomised subjects who request sowill be offered a full mouth dental prophylaxis 
on completion of Visit 4procedures, or on completion of the visit where they exit the 
study.
Repeat examinationswill be performed by the dental examiner at each full MLSI 
assessment visit. Ten subjects will be randomly selected for repeat examinations 
across each assessment window (a total of 30 repeat examinations over the duration 
of the study) at Visits 2 (pre-prophylaxis), 3 and 4. There will be a minimum of 10 
minutes, and a maximum of 30 minutes between repeatability examinations.
Pre-screening
Prior to the screening visit, telephone screening of interested subjects will be 
conductedby the siteusing a telephone script. 
Visit 1-Screening Visit
The following assessments will be conducted:
Written informed consent.
Review inclusion/exclusion criteria.
Review of the oral care products the subject is currently using to confirm they 
do not contain any restricted ingredients.
 
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Demographics, current/concomitant medications, medical historyand 
smoking status captured.
Oral examinations including an OSTandafullOHT examination.
VisualMLSI stain assessmentof the facial (maxillary and mandibular) 
surfaces.
Confirmation of subject eligibility.
Visit 2 -Baseline Visit
The following assessments will be conducted:
Review of current/concomitant medications.
Confirmation of subject eligibility and continuance.
Full OST examination.
Full OHT examination.
Supervised brushing of theanterior teeth for 30 seconds using a wetted 
toothbrush.
Pre-prophylaxis full MLSI stain assessmentofthe facial (maxillary and 
mandibular) and lingual (mandibular) surfaces.
Stratification(based on total MLSI score of the facial surfaces only)and 
randomisation.
Full professional dental prophylaxis.
Post-prophylaxis visual MLSI stain assessment of the facial (maxillary and 
mandibular) and lingual (mandibular) surfaces to confirm overall MLSI = 0.
Dispensation of study dentifrice, toothbrush, timer and diary/instructions card.
Supervised brushing with subject’s allocated dentifrice.
AEs and Incidents following supervised brushing.
Visit 3 -Week 2
The following assessments will be conducted:
Subjects return study dentifrice, toothbrush, and diarycardto the clinicalsite.
Review of current/concomitant medications, AEs and incidents.
Review of completed diary to confirm timing of each brushing occasion in 
addition to missed/additional brushings, and potential changes to smoking 
status.
Confirmation of subject adherence and continuance.Supervised brushing of 
theanterior teeth for 30 seconds using a wetted toothbrush.
Full MLSI stain assessmentof the facial (maxillary and mandibular) and 
lingual (mandibular) surfaces.
Supervised brushing with subject’s allocated dentifrice.
AEs and Incidents following supervised brushing.
 
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Visit 4-Week 4 (LSLV)
The following assessments will be conducted:
Subjects return study dentifrice, toothbrush, timer and diarycardto the 
clinicalsite.
Review of current/concomitant medications, AEs and incidents.
Review of completed diary to confirm timing of each brushing occasion in 
addition to missed/additional brushings, and potential changes to smoking 
status.
Confirmation of subject adherence and continuance.
Supervised brushing of theanterior teeth for 30 seconds using a wetted 
toothbrush.
Full MLSI stain assessmentof the facial (maxillary and mandibular) and 
lingual (mandibular) surfaces.
Post assessment brushing with study dentifrice and tooth brush (if requested 
by the subject).
Post treatment dental prophylaxis (if requested by the subject).
AE’s and incidentscaptured.
Study end.
3.2. Type and Planned Number of Subjects
A sufficient number of subjects will be screened to randomise at least 220subjects to 
ensure 200 evaluable subjects complete the study. This will ensure approximately 50 
evaluable subjects per treatment arm.
This study has not been formally powered to make any claims, and is appropriately 
sized as a PoP study for the purpose of observing meaningful trends.

3.3. Study Design and Dose Justification
This PoP single centre, randomised, examiner blind, four-treatment arm, parallel 
design study will be used to evaluate and compare the stain build up of two 0.454% 
SnF2/ 5% STPdentifrices of differing abrasivity levels, with a marketedstandard 
fluoride dentifriceand a marketed SnF
2dentifrice. 
Stain will be assessedfollowinga full professionaldentalprophylaxis, at intervals 
over a 4 week treatment period, using an establishedclinical measure of extrinsic 
dental stain-the MacPherson modification[Macpherson, 2000] of the Lobene stain 
index [Lobene, 1968] (MLSI).Subjects will be stratified by pre-prophylaxis MLSI 
 
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score (total MLSI (A×I)for the facial surfaces of the 12 anterior teeth)and smoking 
status.
Since STP has been included in the test dentifrices to prevent SnF
2from contributing 
to extrinsic dental stain, and not to directly reduce extrinsic stain caused by dietary 
and lifestyle habits, a stain build updesign has been assessed to be the most 
appropriate clinical model for this study.
A 4 week treatment period has been selected for this study, as 4 weeks has been 
assessed to be a sufficient period of time to establish statistically significant between 
treatment differences for stain build up with this specific dentifrice technology. A 
previous 8 week study conducted by GSKCH demonstrated that although there was 
an increase in stain build up from Week 4 to 8, the between treatment differences 
observed at Week 4 were similar to those at Week 8 [GSKCH study  
]. Stain 
assessments will also be conducted at Week 2, as this time-point was not included in 
earlier studies [GSKCH studies  
and  
]. Therefore, it is of interest 
to assess the performance of the commercialised and experimental SnF
2dentifrices at 
this time-point.
Stain assessments will be made on the facial and lingual surfaces of the anterior teeth 
as these surfaces are considered the most aesthetically importantwith respect to 
dental stain accumulation.Dental stain largely builds up in the harder to reach 
interproximal areas, therefore in addition to analysis of the total MLSI (A×I) the 
interproximal regions have also beengiven focus as an exploratory objectivein this 
study. As most of the stain is removed from the body and gingival regions, we would 
expect to see little change in the total gingival MLSI(A×I)and total body MLSI
(A×I), therefore, these variables arenot being analysed in this study. Furthermore, 
separate analysis of the facial and lingual surfaces are not of focus in this study. As 
the facial teeth are the most brushed we would expect to see little stain build up on 
the facial surfaces in comparison to the lingual surfaces,with little difference 
expected between the total MLSI (A×I) and total lingual MLSI (A×I).
A single examiner will perform the dental stain assessments for all subjects at the 
baseline, Week2 and 4 visits to avoid inter-examiner variability.To assess the 
repeatability of the stain assessments 30repeat examinationswill be performed by the 
dental examinerover the duration of the study.
The dosage regimen of twice daily use (morning and evening) will be the same for all 
subjects,and has been selectedbased on widely recommended oral hygiene practice, 
and typical consumer habit.
 
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Sensodyne Complete Protection has been selected as a reference dentifrice in this 
study as it is acommercialised SnF
2containing dentifrice. Colgate Cavity Protection®
has been selected as areference comparator as it ismarketed globally, does not 
contain any ingredients known to impart extrinsic dental stain, andis considered to be
representative of a moderate abrasivity standard, daily use fluoride dentifrice.Two 
recent stain build up studies have been conducted by GSKCH, which contain both the 
commercialised SnF2dentifrice and Colgate Cavity Protection®, providing us with a 
recent benchmark of relative and expected performance at the Week 4 time-point. 
According to ICH guidelines, for a study to be classed as trulydouble blind, not only 
does the examiner (and any appropriate member of staff who may be involved in the 
dispensing of products, analysis of data etc.) need to be blinded to the treatment the 
subject receives, but the test products must be identical in every way (colour, flavour, 
appearance, packaging). Given it is almost impossible to ensure identical appearance, 
taste and packaging for all of the dentifrices evaluated in this study, the level of 
blindness for this study is described as ‘examiner blind’ only.
The study 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 examiner remains blinded throughout 
thestudy, the examiner is not permitted in the room whilst product is dispensed. All 
study products will be overwrapped to conceal any labelling. In addition, subjects will 
be treated in a separate areaand instructed not to share their allocated treatment with 
the examiner. The dispensing staff will not be involved in any clinical assessments 
during the study.
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 subject eligibility is provided in the Safety Statement 
and on the product label.
Deviations from inclusion and exclusion criteria are not allowed as they can 
potentially jeopardise the scientific integrity of the study, regulatory acceptability,or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is 
essential.
 
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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 between 18 and 65 years inclusive.
3. COMPLIANCE
Understands and is willing, 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) Noclinically significant and relevant abnormalities of medical history or oral 
examinationwhich could impact study outcomes.
b) Absenceof any condition that would impact on subject safety or wellbeing, or 
affect the subject’s ability to understand and follow study procedures and 
requirements.
5. DENTAL HEALTH
In the opinion of the investigator or medically qualified designee
At screening:
a) Good oral health.
b) At least 16 natural teeth including the 12 anterior teeth.
c) The facial surfaces, and mandibular lingual surfaces, of at least 11 of the 12 
anterior teeth, gradable for the MLSI.
d) Presence of extrinsic dental stain (judged to be formed due to dietary factors, 
or use of tobacco products)on the facial surfaces of the anterior teeth, as 
determined from a visual stain assessment.
 
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At baseline:
e) A sufficient level of extrinsic dental stain(in the opinion of the examiner)on 
the facial surfaces ofthe scorable anterior (maxillary and mandibular)teeth.
4.2. Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply:
1. PREGNANCY
Women whoare known to be pregnant, or who are intending to become pregnant 
over the duration of the study. Since this study is not being conducted under an IND 
this information will be self-reported, and not diagnosed through the conduct of 
urinary pregnancy testing.

2. BREAST-FEEDING
Women who are breast-feeding.
3. SUBSTANCE ABUSE
Recent history (within the last year) of alcohol or other substance abuse.
4. CONCURRENT MEDICATION 
a) Currentregular use of mouthwashes containing ingredients that are known 
to impart staining. For example, chlorhexidine or cetylpyridinium chloride 
(CPC).
b) Use of minocycline, tetracycline or doxycycline within 30 days prior to 
screening.
c) Use of minocycline, tetracycline or doxycycline between the screening and 
baseline visit.
d) Dailydoses of a medication and/or traditional/herbal ingredientswhich, in 
the opinion of the investigator, may affect study outcomes. For example, 
drugs or supplements containing metal ions known to impart staining to 
the enamel.
 
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5. 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 ofthe investigator, causes 
xerostomia.
6. ALLERGY/ INTOLERANCE
Known or suspected intolerance or hypersensitivity to the study materials (orclosely 
related compounds) or any of their stated ingredients.
7. CLINICAL STUDY/ EXPERIMENTAL PRODUCT
a) Participation in another clinical study or receipt of an investigational drug 
within 30days of the screening visit.
b) Previous participation in this study.
8. GENERAL DENTITION EXCLUSIONS
a) Dental prophylaxis within 8 weeks of screening.
b) Gross periodontal disease, treatment of periodontal disease (including 
surgery) within 12 months of screening, scaling or root planning within 3 
months of screening.
c) Use of any professionally dispensed or over the counter bleaching/
whitening products (excluding daily use whitening dentifrices) within the 
past3 months.
9. SPECIFIC DENTITION EXCLUSIONS FOR TEST TEETH
a) Any tooth which, in the opinion of the investigator, appears to be non vital 
based on changes in the intrinsic colour.
b) Tooth with evidence of current or recent caries, or reported treatment of 
decay in 12 months of screening.
c) Tooth with exposed dentine which, in the opinion of the investigator, 
could impact grading of extrinsic dental stain; tooth with deep, defective 
or facial restorations; tooth used as an abutment for fixed or removable 
partial dentures; tooth with full crown or veneer, orthodontic bands or 
cracked enamel. 
d) Tooth with surface irregularities, discoloration due to trauma, tetracycline 
stain, restorations, or hypo or hyperplasic areas which, in the opinion of 
the investigator, would prevent consistent grading of extrinsic dental stain.
 
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10. PERSONEL
An employee of the sponsor or the study site or members of their immediatefamily.
11. OTHER
Any subject who, in the judgment of the investigator, should not participate in the 
study.
4.3. Screening/ Baseline Failures
Screen failures are defined as subjects who consent to participate in the study butare 
never subsequently randomised.In order to ensure transparent reporting of screen 
failure subjects, a minimal set of screen failure information is requiredto be entered 
into the electronic case report form(eCRF):
Consent
Demography 
Study conclusion form (reason must include documentation of 
inclusion/exclusion criteria that was failed)
AE forms (Yes/No and specifics if Yes)
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. If the reason for removal of a subject from the study is an AE, 
the principal specific event or test will be recorded in the eCRF. 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 stabilises, is otherwise explained, or the 
subject is lost to follow-up. Should there be any subject circumstances, which in the 
opinion of the investigatorcould 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 a\s possible.
 
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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.
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 least 2 telephone calls). The contact attempt should be 
documented in the subject’s record.
Should the subject continue to be unreachable, only then will he/she be 
considered to have withdrawn from the study with a primary reason of “Lost 
to Follow-up”.
Should asituation arisefora randomised subject, which in the opinion of the 
investigatorcould affect study outcomes (e.g. excessive alcohol consumption), the 
following actions must be taken:
Baseline visit: every attempt will be made to reschedule the subject. If they 
cannot be reappointed they will be withdrawn from the study. No clinical 
efficacy measures will be performed. The subject should not be replaced.
Week 2 visit: every attempt will be made to reschedule the subject. If they 
cannot be reappointed they will continue in the study. No stain assessments 
will be performed at this visit.
Week 4 visit: every attempt will be made to reschedule the subject. If they 
cannot be reappointed they will be withdrawn from the study. No stain 
assessmentswill be performed. The subjectshould not be replaced.
4.5. Subject Replacement
Subjects who withdraw from the study post-randomisation 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.
 
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5. PRODUCT INFORMATION
5.1. Study Product
The following study products will be supplied by the Clinical Supplies Department, 
GSKCH:
Test Product 1
Test Product 2 Reference Product 1
Reference Product 2
Product Name 
Experimental 
dentifrice 
containing 
0.454% SnF2 / 
5% STP; 2.0% 
abrasive silica 
(RDA~58)
Experimental 
dentifrice 
containing 
0.454% SnF2 / 
5% STP; 3.5% 
abrasive silica 
(RDA~77)
Dentifrice containing
1000ppm fluoride as 
Sodium 
Monofluorophosphate 
(SMFP; Colgate 
CavityProtection®, 
Canada Marketed 
dentifrice) 
moderate abrasivity 
(RDA~80)
Dentifrice containing 
0.454% SnF2
(SensodyneComplete 
Protection, Canada 
Marketed dentifrice) 
higher abrasivity 
(RDA~120)
Short Product 
Name
Test dentifrice 
(RDA~58)
Test dentifrice 
(RDA~77)
Reference dentifrice 
(RDA~80)
Reference dentifrice 
(RDA~120)
Product 
Formulation 
Code (MFC)
Commercially 
Available
Commercially 
Available
Dose
Aribbon ofdentifrice, covering the length of the toothbrush head
Route of 
Administration
Oral
Dosing 
Instructions
Brush twice daily (morning and evening) with the allocatedstudy dentifricefor 1 
timed minute
Other items to be supplied by the Clinical Supplies Department, GSKCH:
Name of Item
Purpose
Oral-B Sensi Soft Manual Toothbrush
Dentifrice application by tooth brushing.
Countdown timers
To ensure accurate brushing.
In addition to the test dentifrice, toothbrush and countdown timer all subjects will be 
supplied with a diary card/instructions. The diary card/instructions will be printed by 
the study site.
 
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CCI
CCI

5.2. Dose Schedule
During the treatment period, subjectswill apply a full brush head of theirallocated 
dentifrice, brush for one timed minute (in their usual manner) and expectorate.
The dosage regimen of twice daily treatment (morning and evening) will be applied 
during the treatment period.Subjects will be offered the opportunity to brush 
unsupervised with theirallocated dentifrice at Visit 4,after completing all visit 
procedures.
5.3. Dose Modification
No dose modification is permitted in this study.
5.4. Product Compliance
A record of the administration of the study products will be kept using adispensing 
log and the eCRF.
To ensure that subjects understand the dose of dentifrice to be used, staff will 
demonstrate what is meant by a ‘full ribbon’ (i.e. covering the length of the 
toothbrush head) at thebaseline visit, and a supervised brushing will be carried outat 
Visit 3(at the end of the visit procedures).  
Subjects will receive a brushing instruction/diary sheet. This will outline the brushing 
instructions and will be used to record the date and time of each brushing occasion 
during the treatment period. Subjects will also be asked to note any missed brushings, 
and to use the diary to record any significant changes to diet or smoking status. 
Subjects will be provided with a diary at baseline,which they will return ateach visit 
to the study site. The number of missed or extra brushings will be recorded in the 
eCRF.  
Subjects will also be asked to bring all tubes of study dentifrice to each study visit for 
a visual compliance check of each product.
5.5. Precautions
No special precautions are necessary provided the study is carried out in accordance 
with this protocol.
 
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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.
Overdose per se is not an AE. However, any clinical sequelae of an overdose should 
be reported as an AE (and serious adverseevent (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 productin accordance with the randomisation 
schedule generated byinVentiv Healthprior to the start of the study, using validated 
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 randomised according to the randomisation schedule. Randomisation 
numbers will be assigned in ascending numerical order as each subject is determined 
to be fully eligible.
Subjects with a sufficient level of extrinsic dental stain (in the opinion of the 
examiner)on the facial surfaces ofthe scorable anterior (maxillary and mandibular) 
teeth, who continue to meet all study
 criteria, will be stratified (based on pre-
prophylaxis baseline total MLSI(A×I)score and smoking status)andrandomised to 
treatment. The stratification factor will give rise to four strata:
MLSI Score High, Smoker
MLSI Score Low, Smoker
MLSI Score High, Non Smoker
 
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MLSI Score Low, Non Smoker
The randomisation list will be prepared using a randomisation block design with an 
equal allocation to each of the strata.The study 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 willcontain the list of randomisation numbers only 
and will not include any codeddescription, just a letter A,B, Cor D.
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 
have a randomisation number followed by the letter A, B,Cor D. The schedule will 
have a footnote with a key for A,B,Cand D identifying the three treatments. 
However, to maintain the blinding of the study as far as possible, alltreatment 
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.
5.8.2.Blinding
The study statistician, other employees of the sponsor, andvendors acting on behalf 
of the sponsor,whomay influence study outcomes are blinded to the product 
allocation of subjects.The examiner will be blinded to the treatment received. To 
ensure the examinerremains blinded throughout the study, the examiner is not 
permitted in the room whilst product is dispensed, and subjects will be asked not to 
remove study products from their bags outside of the dispensing room and until they 
are home.In addition, subjects shouldbe treated in a separate area. The dispensing 
staff will not be involved in any efficacy assessments during the study.
5.8.3.Code Breaks
The blind must only be broken in an emergency where it is essential to know which 
product a subject received in order to givethe 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 randomisation schedulesmust be returned toGSKCH at the end of the study.
 
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5.9. Packaging and Labelling
The reference dentifrices (Colgate CavityProtection®and Sensodyne Complete 
Protection)will be sourced from the Canadian market.The test dentifrices will be
manufactured, filled and supplied by GSKCH. 
Alldentifrices, will beoverwrapped in white vinyl to obscure any branding on the 
commercial packs. Each tube will have one English label and one French label 
affixed. Eachsubject will receive a sufficient number of tubes to cover usage during 
the treatment phase.
The contents of the label will bein accordance with all applicable regulatory 
requirements and will be the responsibility of the Clinical Supplies Department,
GSKCH.
All sundry items will be supplied in their commercial packaging for dispensing by 
study staff as required. 
Care should betaken 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 thestudy label.
5.9.1. Accountability of Product
All products supplied are for use only in this clinical study and should notbe used for 
any other purpose.
Completion of diaries will be the responsibilityof subjects, after they have been 
dispensed subjects will be asked to take them home and bring them back to the 
clinical site for each study visit.
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 datesand quantity of the study product dispensed to the subject.
The datesand quantity of the study product returned by the subject (if 
applicable).
 
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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 eithercollected 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.
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.Telephone Screening
Prior to the screening visit, telephone screening of interested subjects will be 
conducted using a telephone script. This will be conducted by the site recruitment 
staff or designee.  
6.1.2. Informed Consent
The investigator, or designee, must obtain written (signed and dated by the subject) 
informed consent from each subject participating in this study after adequate 
explanation of the aims, methods, objectives, and potential hazards of the study.
The investigator, or designee, must also explain to the subjects that they are 
completely free to refuse to enter the study or to withdraw from it at any time.  
Appropriate forms for documentinga 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 
subjectwill be provided with a copy of their signed and dated consent form and any 
other written information which they should be instructed to retain.
 
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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. Subjectsshould be provided with a copy of the signed and dated 
amended consent form. The date of consent will be recorded on the eCRF.
6.1.3. Demographics
The following demographic detail willbe captured by the Investigator or designee 
and recorded on the eCRF: year of birth, genderandrace.
6.1.4. Medical History and Concomitant Medication
Medical history will be assessed asrelated to the inclusion/exclusion criteria by the 
Investigator or medically qualified designee.Details of any relevant dental, medical 
or surgical history (within the last year),including allergies or drug sensitivity, will 
be recorded on the eCRF. Anyconcomitant therapy taken in the 30 days priorto the 
Screening Visit and throughout the study will also be recorded.
6.1.5.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 eCRF 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 followingdental 
prophylaxis oradministration of the treatmentdentifrices will be recorded as an AE. 
AnOST examination will be conducted at Visits 1 and 2,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.
 
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6.1.6.Full 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 16natural teeth and to evaluate dentition
exclusions. The examination will be performed by direct observation.
6.1.7.Visual MLSI Stain Assessment 
Avisual assessment of the 12 anterior teeth forstainwill be performed (individual 
tooth scores will not be recorded)to determineeligibility.Eligible subjects will be 
deemedto have asufficient level of extrinsic dental stain (in the opinion of the 
examiner)on the scorable surfaces of the anterior (maxillary andmandibular)teeth.
6.2. Visit 2 -Baseline Visit
6.2.1. Oral Soft Tissue (OST) Examination
Complete as described in Section 6.1.5.
6.2.2. Full Oral Hard Tissue (OHT) Examination
Complete as described in Section 6.1.6.
6.2.3.Full MLSI Stain Assessment
Stain assessments will be performed by a single clinical examiner, in the same room 
with consistent light levels,throughout the study to facilitate standardisation of the 
assessments. Subjects will brush their anterior teeth with a wettedtoothbrush for 30 
seconds prior to each stain assessment. Teeth will be air dried prior to the assessment, 
and during the assessment as needed. 
The facial and lingual surfaces of each assessable tooth isdivided into four regions. 
The ‘gingival’region is defined as a crescent-shaped band, approximately 2 mm 
wide, adjacent to the free margin of the gingiva and extending to the crest of the 
interdental papillae of the adjacent teeth. The ‘body’of the tooth is then sub-divided 
into three regions on the facial surfaces.
Maxillary and mandibular facialsurfaces:distal facial area; body facial 
area; mesial facial area 
Mandibular lingual surfaces: distal lingual area; body lingual area; mesial 
lingual area 
 
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Extrinsic dental stain will be scored in each area using the MSLI [MacPherson, 
2000], with grades of 0-3 assigned for each category of intensity and area. 
Stain Intensity:intensity will be scored separately for the ‘gingival’and ‘body’areas 
of each assessable tooth as follows. 
Score 0 = No stain 
Score 1 = Light stain 
Score 2 = Moderate stain 
Score 3 = Heavy stain
Stain Area:area will be scored separately for the ‘gingival’and ‘body’areas of each 
assessable tooth as follows. 
Score 0 = No stain 
Score 1 = Stain covering up to 1/3 of region 
Score 2 = Stain covering up to 1/3 of region, and no more than 2/3 of region 
Score 3 = Stain covering more than 2/3 of region
6.2.4. Dental Prophylaxis
Randomised subjects will receive full mouth professional dental cleaning (using 
conventional prophylaxis paste), followed by flossingcarried out by the hygienist, to 
remove all sub-and supra-gingival calculus, plaque and debris from the teeth, with 
particular focus on the anterior teeth. A second dental professional willconfirm all 
sub-and supra-gingival calculus, visible stain (MLSI = 0), plaque and debris has been 
removed from the facial, palatal/lingualsurfaces of the anterior teeth (visually and by 
tactile assessment using a dental explorer). If necessary, additional dental cleaning 
will be carried out to achieve this.
Dental prophylaxis may be carried out by differentdentalhygienists to facilitate 
subject flow.
6.2.5.VisualMLSI Stain Assessment
Avisual stain assessment will be performed to confirm the presence of no stain 
(MLSI=0) on the eligible surfaces of the anterior (maxillary andmandibular)teeth.
 
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6.2.6 Supervised Product Use
After stratification and randomisation subjects willperform asupervised brushing. 
See Section 5.1 for dosing and instructions.
6.3. Visit 3 (Week 2)
6.3.1.Full MLSI Stain Assessment
See Section 6.2.3.
6.3.2. Supervised Product Use
See Section 5.1 for dosing and instructions.
6.4. Visit4(Week 4)
6.4.1. FullMLSI Stain Assessment
See Section 6.2.3.
6.4.2. Dental Prohylaxis (Optional)
Randomised subjects who request sowill be offered a full mouth dental prophylaxis 
on completion of Visit 4procedures, or on completion of the visit where they exit the 
study.See Section 6.2.4.
6.4.3. Brushing (Optional)
Following all study procedures, unsupervised brushing will be permitted with the 
study dentifrice and tooth brush (if requested by the subject).
6.4.4. Study Conclusion
At Visit 4, 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 eCRF by selecting one of the 
options below.
1.
Subject did not meet study criteria
2.
Adverse Event
 
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3.
Lost to Follow Up
4.
Protocol Violation
5.
Withdrawal of Consent
6.
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
productor clinical procedure, whether or not considered related to the 
investigational productorclinical procedure(eg. dental prophylaxis).
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 investigationalor 
clinical procedure(eg. dental prophylaxis).
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 anincrease 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 concomitant medication (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. 
 
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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:
Results in death
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.
Requires hospitalisation or prolongation of existing hospitalisation
NOTE: In general, hospitalisation signifies that the subject has been detained 
(usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or out-patient setting. Complications that occur during 
hospitalisation are AEs. If a complication prolongs hospitalisation or fulfills 
any otherserious criteria, the event is serious. When in doubt as to whether 
“hospitalisation” occurred or was necessary, the AE should be considered 
serious.
Hospitalisation for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.
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.
Is a congenital anomaly/birth defect
 
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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 
hospitalisation but may jeopardise the subject or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These 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 hospitalisation 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 eventsthat 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 eCRF.
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this instance, all subject identifiers, with the exception 
of the subject number, will be blinded on the copies of the medical records 
prior to submission to GSK.
The investigator will attempt to establish a diagnosis of the event based on 
signs, symptoms, and/or other clinical information. In such cases, the 
diagnosis will be documented as the 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 dental prophylaxis 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.
 
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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 
utilised 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 to the study product will be considered and investigated.
The investigator will also consult the Safety Assessmentor 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 eCRF 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.
 
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7.4. Reporting Adverse Eventsand Serious Adverse Events
AE Reporting to GSKCH:
AEs will be recorded in the AE section of the eCRF. 
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 eCRF, if not previously well-characterised 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 eCRF. 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 eCRF. 
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 internet to 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
Description of events, with diagnosis if available
Investigator opinion of relationship to study product (see section8.3)
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
 
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The SAE form, completed as fully 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:
US: 
Email Serious Adverse Eventsto:
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 stabilises, 
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 
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 
 
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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, IEC and 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 to fulfill 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 safety statementand 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 this study; the medical 
device in this study is the toothbrush. GSKCH medical device incidents, including 
those resulting from malfunctions of the device, must be detected, documented, and 
reported by the investigator on the eCRF 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 led tothe death of a 
patient or user or of other persons or to a serious deterioration in their state of 
health.
7.6.2. Reporting of Incidents and Malfunctions
Incident Reporting to GSKCH:
All incidents must be reported to GSKCHwithin 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. In addition, for 
incidents fulfilling the definition of an AE or an SAE, the appropriate AE 
eCRF page or SAE form will be completed and reportedas per the AE and 
SAE reporting sections.
 
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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 Managershould be notified of the situation by telephone 
or email.
Fax the Incident Report Forms to:
US: 
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 eCRF and Incident Report Form following 
instructions given in the section above.
Return the failed device to the sponsor as soon as possible, including 
documentation of the details of the failure.
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 
stabilises, 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.
 
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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 anytime after a 
subject has been discharged from the study, and such incident is reasonably 
related to a GSKCH medical 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 use in 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 
GSKCHis 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 Collectingof Pregnancy Information
Collection of Pregnancy Information:
Pregnancy information will be collected on all pregnancies reported following 
administration of any investigational product. Information on pregnancy 
identified during the screening phase and prior to investigational product 
administrationdoes not need to be collected.
7.7.2. Action to be Taken ifPregnancy 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.The investigator will record pregnancy information on 
the appropriate form and submit it tothe followingGSKCHmailbox:
Pregnancy informationmust be submitted within2 weeks of learning of the 
subject becoming pregnant. 
The subject will be followed to determine the outcome of the pregnancy. 
 
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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 be promptly 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 should be withdrawn 
from the study and this should be recorded in the appropriate section of the 
eCRF.
8. DATA MANAGEMENT
For this study subject data will be entered into an electroniccase report form, using 
an inVentiv Healthor GSKCH validated data system.
8.1. Source Documents/ Data
The source documents (e.g. screening telephone script, hospital records, clinical and 
office charts, 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 eCRF should be specified in the Source Document Designation Form.In some 
cases the eCRF can be used as a source document.
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.
 
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8.2. Electronic Case Report Form
ACRF 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, 
eCRF must be completed and signed by the Principal Investigator (or authorised 
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
'sname or initials or birth date) is to be recorded in the 
eCRF 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 eCRFs and transmitted 
electronically to GSKCH in a validated (21 CFR Part 11 compliant) web-based 
electronic data capture system.
All eCRF pages should be completed during a subject assessment when the eCRF has 
been designated as the source. Data that is sourced elsewhere should be entered into 
the eCRF in an agreed upon timeframe between the Investigator and Sponsor.  
At the conclusion of the study, the occurrence of any protocol deviations will be 
determined. After these actions have been completed and the database has been 
declared to be complete and accurate, it will be locked and made available for data 
analysis. Any changes to the database after that time can only be made by joint 
written agreement between the GSKCH Principal Clinical Research Scientist, the 
Project Statistician and the Project Data Manager with the authorization from Head of 
Clinical Research.
Throughout the duration of the study,eCRFs (including queries, query responses and 
audit trails) will be retained byinVentiv Health. Following decommissioning of the 
studysite data archived compact discs (CD(s)) prepared byinVentiv Health will be 
sent to the investigatorand GSKCH.
 
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8.3. Data Handling
Documentation of alldata management activities should allow step-by-step 
retrospective assessment of data quality and study performance. Any changes or 
corrections to data will be performed in the Electronic Data Capture (EDC) System, 
and it will include rationale for changes. The EDC system has an audit trail, which 
will provide a complete record of the changes and corrections endorsed by the 
Investigator.
8.3.1. Data Queries
Programmed edit checks will be generated automatically, as the data is being entered 
into the system. Data Management will also run reports and listings on the eCRF 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 clinical site will review the eCRFs in accordance with the 
monitoring plan, and any queries will be generated in the EDC System to the 
Investigator or designee, enabling the errors to be addressed in parallel with Data 
Management review. The study monitor can also run reports and listings on the 
eCRFs, to raisemanual 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. PRO’s 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 orbirth date) is to be recorded on all 
PRO’s that will be forwarded to GSKCH.
9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES
All statistical activities will be conducted by inVentiv Health under the guidance of 
GSKCH.
 
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9.1 Sample SizeDetermination
A sufficient number of subjects will be screened to randomise at least 220subjects to 
ensure 200 evaluable subjects complete the study. This will ensure approximately 50 
evaluable subjects per treatment arm.
This study has not been formallypowered to make any claims, and is appropriately 
sized as a PoP study for the purpose of observing meaningful trends.
9.2.General Considerations
9.2.1.Definition of Analysis Populations
The All Subjects population includes all subjects who enter the study and sign the 
informed consent form. This population includes screen failures as well as those that 
are randomised.
The Safety population will include all subjects who are randomised and receive at 
least one dose of investigational product and will bereported by treatment received.
The Intent-To-Treat (ITT) population will include all subjects who are randomised, 
receive at least one dose of investigational product and have at least one post-baseline 
efficacy evaluation and will be reported by randomised treatment.
The Per Protocol (PP) population will include all subjects inthe ITT population who 
have at least one efficacy assessment considered unaffected by protocol violations.
Efficacy assessments considered affected by protocol violations will be excluded 
from PP analysis.
Repeatability subjects are those subjects that have an initial and a repeat stain 
assessment.
The primary population for assessment of efficacy will be the ITT population. A PP 
analysis will be performed on the primary variable only if more than 20% of the 
subjects in the ITT population are excluded from the PP population.
The Safety population will be used for all safety and tolerability reporting.
9.2.2.Exclusion of Data from Analysis
Thefollowingwill be considered as major protocol deviations leading to the 
exclusion of subjects / data for PP analysis:
 
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Deviation from the inclusion/exclusion criteria likely toaffect efficacy.
The use of prohibited medication likely to affect efficacy.
Not receiving randomised treatment
Other deviations likely to result in exclusion from the PP population will be detailed 
in the statistical analysis plan (SAP).
Protocol violations deemed to affect efficacy will be identified between the 
Biostatistician and Clinical Research Director or designee, ahead of breaking the 
study blind.
9.2.3.Criteria for Evaluation
Efficacy will be evaluated by the ITT or PP population. Safetywill be assessed by the 
safety population.
9.2.4.Criteria for Assessing Efficacy
Efficacy will be evaluated based on the ranking performance of the study treatments 
on the stainvariables.The minimum requirement will be similar, or lower levels of 
stain for at least one of the experimental products compared to the standard fluoride 
dentifrice (Colgate Cavity Protection®). The marketed SnF
2 dentifrice (Sensodyne
Complete Protection)will be expected to demonstrate a comparable, or statistically 
significantly better performance on the stain parameters versus the experimental 
products and Colgate Cavity Protection®.
9.2.5.Criteria for Assessing Tolerability
The safety profile of the study treatments will be assessed with respect to adverse 
events (AEs) and oral soft tissue (OST) abnormalities.
9.2.6. Handling of Dropouts and Missing Data
Subjects who withdraw from the study early will beincluded in the statistical analysis 
up to the time pointwhen they withdraw. Missing data will not be replaced.
 
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9.3. Statistical Methods and Analytical Plan
Additional details of the proposed statistical analysis will be documented in the 
statistical analysis plan (SAP), which will be written following finalisation of the 
protocol and prior to study unblinding.
9.3.1.Demographicand Baseline Characteristics
Descriptive statistics (number of subjects, mean, standard deviation, median, 
minimum and maximum for continuous variable, and frequency and percentage for 
categorical variables) will be provided for demographic and baseline data.
9.3.2. Primary Analysis
The primary variablewill be overall MLSI at Week 4. This variable will be analysed 
using analysis of covariance (ANCOVA) with treatment and smoking status as factor, 
and pre-prophylaxis baseline mean MLSI score as thecovariate. Adjusted means and 
treatment differences between thetwotest products and the marketed standard 
fluoride dentifrice,and the treatment difference between the marketed SnF2 dentifrice
and the marketed standard fluoride dentifricewill be provided together with their 
95%CIs and p-values.
The assumption of residual normality in ANCOVA analysis will be investigated. If 
violated, data transformation or a non-parametric method (e.g., the Wilcoxon rank 
sum test) will be applied. 
9.3.3. Secondary Analysis
The secondary variableswill beoverall MLSI (A×I) at Week 4 forthetreatment 
differencesbetween the two test products and the marketed SnF2 dentifrice,and the 
treatment difference between the marketed SnF2 dentifriceand the marketed standard 
fluoride dentifrice.
These will be analysed and results summarised in the same way as per the primary 
variable but with the appropriate baseline term as the covariate.
9.3.4.Exploratory Analyses
Exploratory variables include overall MLSI Intensity score at Week2, and 
Interproximal MLSI score, overall MLSI Area score and overall MLSI Intensity score 
at Weeks 2 and 4. Each of these variables will be analysed using the same ANCOVA 
 
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model as in the primary analysiswith the appropriate baseline termas thecovariate. 
Adjusted means of all treatments and treatment differences will be provided together 
with their 95%CIs and p-values.
9.3.5. Safety Analyses
For the assessment of safety and tolerability, treatment emergent AEs will be 
summarised by treatment group. AEs andincidents will be listed. No inferential 
analyses will be performed to compare treatments with respect to safety data.
The safety profile of the study treatments will be assessed with respect to AEs. OST 
abnormalities are included as AEs if they appear or worsen after the initial 
assessment.
All safety data will be reported for the Safety population as per actual treatment 
received. All subjects screened will be included in the list of AEs.
All AEs will be reviewed by the Clinical Research Director or Designee prior to 
database freeze and will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). During this review stage, AEs will be further categorised as 
oral or non-oral.
AEs will be regarded as treatment emergentif they occur on or after the start date and 
time of the first treatment usage (as determined by start date and time from the 
EXPOSURE/dispensing panel; if this date is missing a suitable alternative will be 
used eg date and time of randomisation). All other AEs prior to this will be 
considered non-treatment emergent.
The following summary tables and listings will be presented by treatment group.
Table of treatment emergent AEs by Oral/Non-Oral  and Preferred Term
Table of  treatment emergent AEs by SOC and Preferred Term
Table of Treatment emergent treatment related AEs by Oral/Non-Oral and 
Preferred Term
Table of  treatment emergent treatment related AEs by SOC and Preferred Term
Listing of all AEs (including Non-treatment emergent from All Subjects)
Listing of SAEs
Listing of incidents 
In the event that there is nothing to report a null listing will be produced.
 
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No inferential analyses will be performed to compare treatments with respect to 
safety.
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.
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), allapplicable subject privacy requirements, and the guiding principles of the 
current version of the Declaration of Helsinki. This includes, but isnot limited to, the 
following:
Before initiating a trial, the investigatorshould have written and dated 
approval/favourable opinion from the IEC for the trial protocol (including 
amendments), written informed consent form, consent form updates, subject 
recruitment procedures (e.g., advertisements), 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 of AEs/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, the 
study monitor will contact the site prior to the start of the study to review with the site 
 
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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 eCRF will serve as the 
source document.
The study monitor will monitor the study and siteactivity to verify that the:
Data are authentic, accurate, and complete.
Safety and rights of subjects are being protected.
Study is conducted in accordance with the currently approved protocol and 
any other study agreements, GCP, and all applicable regulatory requirements.
The extent and nature of monitoring will be described in a written monitoring plan on 
file at 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 studymonitor 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(SOPs).
 
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Both GSKCHandthe 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. 
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. 
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 IEC a detailed written 
explanation of the termination or suspension.
If the GSKCH terminates or suspends a trial, the investigator should promptly 
inform the IEC and provide the IEC a detailed written explanationof the 
termination or suspension. 
If the IEC terminates or suspends its approval/favourable opinion of a trial, 
the investigator should promptly 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.
 
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The investigator must assure that the subject’sanonymity will be maintainedon 
eCRFs or other documents submitted to inVentiv Health,GSKCH,or any other 
GSKCH approved vendors. 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 submissiontoinVentiv
Health,GSKCH, or any other GSKCH approved vendors, e.g. subjects’ written 
consent forms, should be maintained by the investigator in strict confidence.
GSKCH 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 will meet the strictest standard applicable to 
that site for the study, as dictated by any institutional requirements or local laws or 
regulations, GSKCHstandards/procedures, and/or institutional requirements.  
No study document should be destroyed without a prior written agreement between 
GSKCH and the investigator. The investigator must notify GSKCHof 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 approvalof 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.
GSKCHwill also provide the investigator with the fullsummary 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 bein accordance with GSK Policy.
 
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A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge.
 
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11. REFERENCES
Baig A, He T. A novel dentifrice technology for advanced oral health protection: A 
review of technical and clinical data. Compend Contin Educ Dent 2005;26 (Suppl 
1):4-11.
GSKCH Study 
 
 2013.
GSKCH Study 
 
 2016.
ICH Topic 6 Guideline for Good Clinical Practice CPMP/ICH/135/95 17th July 
1996.
Lobene, RR. Effect of Dentifrices on Tooth Stains with Controlled Brushing 
Journal of American Dentistry 1968: 77; 849-855.
Macpherson LM, Stephen KW, Joiner A, Schäfer F, Huntington E.  Comparison of 
a conventional and modified tooth stain index. J Clin Periodontol.2000:Nov; 
27(11):854-9.
Mason S, Hughes N, Layer T. Considerations for the development of over-the-
counter dentifrices for the treatment and relief of dentin sensitivity. J Clin Dent
2009; 20(Spec Iss): 167-173.
Pader M. Dentifrices. Kirk-Othmer. Encyclopedia of Chemical Technology. 1–9. 
Published Online: 13 April 2012.
Paraskevas S, van der Weijden GA. A review of the effects of stannous fluoride on 
gingivitis. J Clin Periodontol 2006;33:1-13.
Pickles MJ. Toothwear. In: Duckworth RM, ed. The teeth and their environment. 
Monographs in Oral Science, Vol. 19. Basel: Karger, 2006; 86-104.
Schemehorn BR, Moore MH, Putt MS. Abrasion, polishing, and stain removal 
characteristics of various commercial dentifrices in vitro. J Clin Dent2011; 22: 11-
18.
Schuurs A. Pathology of the hard dental tissue.  Wiley Press, 2013. p224.
Shellis RP, Addy M, Rees GD.In vitro studies on the effect of sodium 
tripolyphosphate on the interactions of stain and salivary protein with 
hydroxyapatite.J Dent 2005: 33; 313-324.
 
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CCI
CCI
CCI
CCI

Thrash WJ, Dodds MW, Jones DL. The effect of stannous fluoride on dentinal 
hypersensitivity. Int Dent J 1994;44 (Suppl 1):107-118.
Tinanoff N. Review of the antimicrobial action of stannous fluoride. JClin Dent 
1990;2:22-27.
Tinanoff N. Progress regarding the use of stannous fluoride in clinical dentistry.J 
Clin Dent 1995;6 (Spec No.): 37-40.
 
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12. APPENDICES
12.1. Appendix 1 
Abbreviations
AE 
Adverse Event
CD
Compact Disc
CRO
Contract Research Organisation
eCRF
Electronic Case Report Form
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
IRB
Institutional Review Board
ITT
Intention to Treat
MLSI
Macpherson Modification to the Lobene Stain Index
NaF
Sodium Fluoride
OHT
Oral Hard Tissue
OST
Oral Soft Tissue
PII
Personally Identifiable Information
PP
Per Protocol
RDA
Relative Dentin Abrasivity
SAE
Serious Adverse Event
SMFP
Sodium Monofluorophosphate
STP
Sodium Tripolyphosphate
SnF2
Stannous Fluoride
SOP
Standard Operating Procedure
PRO
Patient Reported Outcome
 
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SIGNATURE PAGE 
 
  
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
25-May-2017 11:14:22
 
Approved
30-May-2017 04:37:00
Clinical Operations Approval
25-May-2017 11:05:21
Approved
Biostatistics Approval
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25-May-2017 11:04:50
 
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PPD
PPD
PPD
PPD