Clinical trial NCT03267511
Conditions: Oral Hygiene
Sponsor: GlaxoSmithKline
Start date: 2017-09-25; Completion date: 2017-12-02
Enrollment: 123 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether spherical silica can achieve similar or greater extrinsic dental stain and plaque removal, in comparison to dentifrices containing higher concentrations of standard abrasive silica, and how the addition of 5% sodium tripolyphosphate (STP) enhances cleaning capability.

Detailed description:
This proof of principal (PoP) single centre, randomised, examiner blind, four-treatment arm, parallel design study will be conducted in healthy participants with a propensity for extrinsic dental stain (based on the judgement of the examiner) on the facial surfaces of the anterior teeth. This study will be used to evaluate and compare the extrinsic dental stain and plaque removal of an experimental low abrasivity 0.5% spherical silica dentifrice and a marketed low abrasivity 6% standard silica abrasive dentifrice, and an experimental moderate abrasivity 1% spherical silica / 5% STP dentifrice and a marketed high abrasivity 16% standard abrasive silica / 5% STP dentifrice. Stain will be assessed using an established clinical measure of extrinsic dental stain - the MacPherson modification of the Lobene stain index (MLSI). Particpants will be stratified by baseline MLSI score (total MLSI (area \[A\] × intensity \[I\]) for the facial surfaces of the 4 anterior assessment teeth). Plaque will be assessed using an established clinical measure of plaque - the Turesky Modification of the Quigley Hein Index. Stain and plaque will be assessed at intervals over an 8 week treatment period. Plaque will be assessed at baseline and Week 8 only.

Arms: arm 1: Participants will be instructed to apply experimental dentifrice containing 5% potassium nitrate (KNO3) / 0.2542% sodium fluoride (NaF) dentifrice with 0.5% spherical silica. arm 2: Participants will be instructed to apply experimental dentifrice containing 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% STP. arm 3: Participants will be instructed to apply experimental dentifrice containing 5% KNO3 / 0.2542% NaF dentifrice with 6% abrasive silica. arm 4: Participants will be instructed to apply experimental dentifrice containing 5% KNO3 / 0.2543% NaF dentifrice with 16% abrasive silica and 5% STP.
Interventions: intervention 1: 5% KNO3 / 0.2542% NaF dentifrice with 0.5% spherical silica intervention 2: 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% STP intervention 3: 5% KNO3 / 0.2542% NaF dentifrice with 6% abrasive silica intervention 4: 5% KNO3 / 0.2543% NaF dentifrice with 16% abrasive silica and 5% STP
Intervention descriptions: intervention 1: Participants will be instructed to apply a full brush head of their dentifrice containing 5% KNO3 / 0.2542% NaF dentifrice with 0.5% spherical silica and brush twice daily (morning and evening) for one timed minute (in their usual manner). intervention 2: Participants will be instructed to apply a full brush head of their dentifrice containing 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% STP and brush twice daily (morning and evening) for one timed minute (in their usual manner). intervention 3: Participants will be instructed to apply a full brush head of their dentifrice containing 5% KNO3 / 0.2542% NaF dentifrice with 6% abrasive silica and brush twice daily (morning and evening) for one timed minute (in their usual manner). intervention 4: Participants will be instructed to apply a full brush head of their dentifrice containing 5% KNO3 / 0.2543% NaF dentifrice with 16% abrasive silica and 5% STP and brush twice daily (morning and evening) for one timed minute (in their usual manner).

Protocol documents:
Prot_000.pdf: 
Potassium Nitrate / Sodium Fluoride
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CLINICAL PROTOCOL
A Randomized, Examiner-blind, Proof of Principal Study to 
Investigate the Stain and Plaque Removal Capability of Two 
Experimental 5% Potassium Nitrate Dentifricesin Healthy 
Subjects with the Propensity for Extrinsic Dental Stain
Compound Name:  
5% Potassium Nitrate(KNO
3)/ Sodium 
Fluoride(NaF)
United States (US) Investigational 
New Drug (IND) Number:
N/A
European Clinical Trials Database 
(EudraCT) Number:
N/A
Other Regulatory Agency Identified 
Number:
N/A
Protocol Number:
208078
Phase:
II
 
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Sponsor information
Sponsor Legal Registered Address
GlaxoSmithKline Research & Development 
Limited
980 Great West Road
Brentford
Middlesex, TW8 9GS
UK
Sponsor Contact Address
GlaxoSmithKline Consumer Healthcare (GSK 
CH)
184 Liberty Corner Rd.
Warren, NJ 07059 USA
Tel: 
 
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Document History
Document
Version Date
Summary of Changes 
Original protocol
26-Jul-2017
Not applicable (N/A)
Amendments incorporate all revisions to date, including amendments made at the request of 
country health authorities, institutional review boards(IRBs), etc.  
 
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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:
Jeffrey Milleman
Investigator Qualifications:
DDS, MPA
Investigator Signature:
Date of Signature/ Agreement:
DD/MMM/YYYY
 
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Table of contents
Sponsor information........................................................................................................2
Document History...........................................................................................................3
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT PAGE..............................4
Table of contents.............................................................................................................5
List of tables...................................................................................................................9
SCHEDULE OF ACTIVITIES.....................................................................................10
1 INTRODUCTION........................................................................................................14
1.1
Mechanism of Action.........................................................................................15
1.2
Background and Rationale.................................................................................15
1.2.1
Justification for Conducting the Study...............................................15
1.2.2
Study and Dose Rationale..................................................................15
1.2.3
Safety Data........................................................................................17
2 STUDY OBJECTIVES AND ENDPOINTS.................................................................17
3 STUDY DESIGN AND SUBJECT POPULATION......................................................20
4 SUBJECT SELECTION...............................................................................................21
4.1
Inclusion Criteria...............................................................................................21
4.2
Exclusion Criteria..............................................................................................22
4.3
Randomization Criteria......................................................................................23
4.4
Lifestyle Guidelines...........................................................................................23
4.4.1
Meals and Dietary Restrictions..........................................................24
4.5
Screen Failures..................................................................................................24
4.6
Sponsor’s Qualified Medical Personnel..............................................................24
5 STUDY TREATMENTS..............................................................................................25
5.1
Blinding and Allocation to Treatment/Randomization........................................25
5.2
Breaking the Blind.............................................................................................26
5.3
Subject Compliance...........................................................................................26
5.4
Investigational Product Supplies........................................................................26
5.4.1
Dosage Form and Packaging..............................................................27
5.4.2
Preparation and Dispensing................................................................27
5.5
Administration...................................................................................................27
5.5.1
Medication Errors..............................................................................28
5.6
Investigational Product Storage..........................................................................28
 
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5.7
Investigational Product Accountability...............................................................29
5.7.1
Destruction of Investigational Product Supplies.................................30
5.8
Concomitant Treatments....................................................................................30
6 STUDY PROCEDURES...............................................................................................30
6.1
Study Period......................................................................................................30
6.1.1
Screening -Visit 1.............................................................................30
6.1.2
Baseline MLSI Visit (Day 1) -Visit 2................................................31
6.1.3
Baseline TPI Visit (Day 2) -Visit 3...................................................32
6.1.4
Day 15 (MLSI) -Visit 4.....................................................................33
6.1.5
Day 29 (MLSI) -Visit 5.....................................................................33
6.1.6
Day 57 (MLSI) -Visit 6.....................................................................34
6.1.7
Day 58 (TPI) -Visit 7........................................................................35
6.2
Subject Withdrawal............................................................................................36
7 ASSESSMENTS...........................................................................................................37
7.1
Efficacy.............................................................................................................37
7.1.1
Macpherson Modification of the Lobene Stain Index (MLSI).............37
7.1.2
Turesky Modification of the Quigley Hein Index Dental Plaque 
Assessment (TPI)...............................................................................38
7.2
Safety................................................................................................................39
7.2.1
Oral Soft Tissue (OST) Examination..................................................40
7.2.2
Full Oral Hard Tissue (OHT) Examination.........................................40
8 ADVERSE EVENT AND OTHER EVENTS OF SPECIAL INTEREST 
REPORTING................................................................................................................40
8.1
Definitions of Adverse Events and Serious Adverse Events...............................40
8.1.1
Adverse Event...................................................................................40
8.1.2
Serious Adverse Event.......................................................................41
8.2
Reporting Period................................................................................................42
8.2.1
Adverse Event...................................................................................42
8.2.2
Serious Adverse Event.......................................................................43
8.3
Reporting Procedures.........................................................................................43
8.3.1
Adverse Event...................................................................................44
8.3.2
Serious Adverse Event.......................................................................44
8.3.3
Sponsor’s Reporting Requirements to Regulatory Authorities and 
Ethics Committees.............................................................................45
 
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8.4
Evaluating Adverse Events and Serious Adverse Events....................................45
8.4.1
Severity Assessment..........................................................................45
8.4.2
Causality Assessment.........................................................................46
8.5
Withdrawal Due to an Adverse Event and Serious Adverse Events....................46
8.6
Pregnancy..........................................................................................................47
8.6.1
Time Period for Collecting Pregnancy Information............................47
8.6.2
Action to be Taken if Pregnancy Occurs............................................47
8.7
Follow-up of Adverse Events and Serious Adverse Events.................................47
9 DATA MANAGEMENT..............................................................................................48
9.1
Source Documents/ Data....................................................................................48
9.2
Case Report Form..............................................................................................48
9.3
Data Handling....................................................................................................49
9.3.1
Queries..............................................................................................49
9.4
Processing Patient Reported Outcomes..............................................................50
10 STATISTICAL CONSIDERATIONS AND DATA ANALYSES.................................50
10.1 Sample Size Determination................................................................................50
10.2 Statistical Methods and Analytical Plan.............................................................50
10.2.1
Demographic and Baseline Characteristics.........................................50
10.2.2
Primary Analysis(es)..........................................................................50
10.2.3
Secondary Analysis(es)......................................................................51
10.2.4
Safety Analysis(es)............................................................................51
10.2.5
Other Analysis(es).............................................................................52
10.2.6
Definition of Analysis Populations.....................................................53
10.2.7
Exclusion of Data from Analysis........................................................53
10.2.8
Handling of Dropouts and Missing Data............................................54
10.2.9
Interim Analysis................................................................................54
11 STUDY GOVERNANCE CONSIDERATIONS...........................................................54
11.1 Quality Control..................................................................................................54
11.2 Quality Assurance..............................................................................................54
11.3 Regulatory and Ethical Considerations...............................................................55
11.3.1
Institutional Review Board.................................................................55
11.3.2
Ethical Conduct of the Study..............................................................55
11.3.3
Subject Information and Consent.......................................................55
11.3.4
Subject Recruitment...........................................................................56
 
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11.3.5
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP...........................................................................................56
11.4 Posting of Information on Publicly Available Clinical Trial Registers................57
11.5 Provision of Study Results to Investigators........................................................57
11.6 Records Retention..............................................................................................57
11.7 Conditions for Terminating the Study................................................................58
11.8 Definition of Study End/ End of Study...............................................................58
12 REFERENCES.............................................................................................................58
13 APPENDIX..................................................................................................................60
13.1 Appendix I –Instructions Sheet.........................................................................60
13.2 Appendix II -Abbreviations..............................................................................60
 
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List of tables
Table 1-1
Schedule of Activities........................................................................11
Table 2-1
Study Objectives and Endpoints.........................................................17
Table 13-1
Abbreviations....................................................................................61
 
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SCHEDULE OF ACTIVITIES
The schedule of activities table provides an overview of the protocol visits and procedures.  
The investigator may schedule visits (unplanned visits) in addition to those listed on the 
schedule of activities, in order to conduct evaluations or assessments required to protect the 
well-being of the subject.
 
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Table 13-1
Schedule of Activities
Procedure/Assessment
Screening
Study Period
End of Treatment
Visit 1
Visit 2
Baseline
(MLSI)
Day 1
Visit 3
Baseline
(TPI)
Day 2
Visit 4
Week 2
Day 15 1
days
Visit 5
Week 4
Day 29 2
days
Visit 6
Week 8
Day 57 3
days
Visit 7
Week 8
Day 58 3
days
Informed Consent
X
Minimum 24 hours, maximum of 2 weeks
Demographics,Ethnicity
X
Medical History and Current Medication
X
OST Examination
X
X 
X
X
X
X
X
OHT Examination
X
X
Visual MLSI Stain Assessment of the 12 Anterior Teeth
X
Review Inclusion / Exclusion Criteria
1
X
X 
X
Concomitant Medication
X
X
X
X
X
X
Eligibility 
X
X
Instruct Subjects on the Lifestyle Guidelines and Concomitant Treatment(s)
Sections of the Protocol
X
Brush Anterior Teeth for 30 Seconds with Tap Water Prior to Stain 
Assessment
X
X
X
X
 
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Procedure/Assessment
Screening
Study Period
End of Treatment
Visit 1
Visit 2
Baseline
(MLSI)
Day 1
Visit 3
Baseline
(TPI)
Day 2
Visit 4
Week 2
Day 15 1
days
Visit 5
Week 4
Day 29 2
days
Visit 6
Week 8
Day 57 3
days
Visit 7
Week 8
Day 58 3
days
Full MLSI Stain Assessment of the Anterior Teeth2
X
X
X
X
Repeat MLSI Stain Assessment3
X
X
X
X
Selection of 4 Assessment Teeth
X
Stratification
Minimum 24 hours,maximum of 2 weeks
X
Unsupervised Brushing on Site4
X 
X
X
Plaque Disclosing Followed by Pre-brushing TPI Assessment5
X
X
Randomization and Dispense Study Dentifrice, Timer, Toothbrush and 
Diary/Instructions Card
X
Supervised Brushing on Site6
X
X
X
X
X
Plaque Disclosing Followed by Post-brushing TPI Assessment4
X
X
Repeat TPI Assessment3
X
X
Adverse Events7
X 
X
X
X
X
X
Incidents
8
X 
X
X
X
X
X
Subjects Return Dentifrice, Toothbrush and Diary Card
X
X
X
X
Subject Adherence and Continuance9
X
X
X
X
X
Diary Compliance Check
X
X
X
X
 
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Procedure/Assessment
Screening
Study Period
End of Treatment
Visit 1
Visit 2
Baseline
(MLSI)
Day 1
Visit 3
Baseline
(TPI)
Day 2
Visit 4
Week 2
Day 15 1
days
Visit 5
Week 4
Day 29 2
days
Visit 6
Week 8
Day 57 3
days
Visit 7
Week 8
Day 58 3
days
Study Conclusion
X
Abbreviations: OST= Oral Soft Tissue; OHT = Oral Hard Tissue; MLSI = Macpherson Modification of the Lobene Stain Index; TPI = Turesky Plaque Index.
1At Visit 2 a review of Inclusion Criteria 10 and Exclusion Criteria 12.b and e will be conducted, and at Visit 3 a review of Inclusion Criteria 11 will be conducted.
2At Visit 2 a full MLSI assessment of the 12 anterior teeth will be conducted, at Visits 4, 5 and 6 a full MLSI assessment of the 4 assessment teeth will be conducted
3Five subjects will be randomly selected for repeat MLSI and TPI examinations across each assessment window (a total of 20 repeat MLSI and 10 repeat TPI 
examinations over the duration of the study).
4This will be with a standard fluoride dentifrice administered by the site. Once all efficacy assessments have been completed, subjects will be allowed to brush 
unsupervised prior to leaving the clinical study site.
5Two disclosing rinses with the plaque disclosing solution will be conducted, one prior to the pre-brushing TPI assessment and one prior to the post-brushing TPI 
assessment.
6The supervised brushing at Visits 4, 5,and 6will be conducted following the MLSI stain assessments.
7Any serious adverse event assessed as related to study participation that occurs subsequent to the signing of informed consent and any adverse event subsequent to 
brushing with the standard fluoride dentifrice at Visit 2.For those subjects that don’t brush with the standard fluoride dentifrice at Visit 2adverse eventswill be collected 
from first use of the plaque disclosure solutionat Visit 3.
8Incidents will be collected from first use of the tooth brush, prior to stain assessment.
9Time of each brushing occasion in addition to missed/additional brushings will be captured in the subject diary.
 
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1
INTRODUCTION
Dentifrices are often recommended by dentists to help remove oral debris and dental plaque 
[Pader, 2012]. Dental plaque is a soft, sticky, colourless deposit of bacteria which collects on 
the teeth and along the gingival margin. Bacterial by-products from dental plaque can affect 
the health of the gingiva by causing inflammation of the gingival tissue [Davies, 2008]. 
Gingivitis and periodontal disease can develop when dental plaque accumulates above levels 
compatible with oral health [Marsh, 1992]. Mechanical plaque removal by toothbrushing is 
the most effective way to reduce plaque, and whilst the proper use of a toothbrush is effective 
in removing dental plaque [Pader, 2012], it is understood that the general population will 
brush using an inadequate technique, and for significantly less time thanthe recommended 
and accepted 2 minutes [Gallagher, 2009]. Clinical data support that brushing with a 
dentifrice that has been formulated with chemical and/or abrasive agents to help remove 
plaque, will facilitate,or enhance plaque removal efficacy [Davies, 2008; Parkinson, 2014; 
Ayad, 2015; Parkinson 2015; Feng, 2016]. 
The etiology of stain is multiple but is widely agreed to result from discoloration of plaque 
and pellicle on the surface of the tooth, with the main site for extrinsic stain build up generally 
accepted as the acquired salivary tooth pellicle [Shellis, 2005]. Therefore, plaque removal is 
considered to be an important feature in the prevention of stain build-up and thus careful 
selection of an appropriate abrasive and/or chemotherapeutic agents should be an important 
consideration when formulating dentifrices designed to enhance plaque removal. 
The ability of a dentifrice to help control dental stain is also considered to be a key 
characteristic [Pader, 2012].Extrinsic dental stain removal is typically achieved by the 
inclusion of dental grade abrasives such as silicas and chemical cleaning agents such as 
polyphosphates. A range of parameters have been shown in vitroto affect the stain removal 
and wear properties of abrasives including particle hardness, shape, size, distribution, and 
concentration [Joiner, 2010; Schemehorn, 2011]. Dental grade abrasive silicas are often 
relatively hard abrasives that are typically formulated in anti-sensitivity dentifrices within the 
range of 6-16% and, while effective at cleaning, often lend high abrasivity to dentifrices. 
 
 
 
 It is currently hypothesized that the greater volume of smaller spherical silica 
particles offera higher surface areaof cleaning particles, and whilst further in vitrowork 
should be conducted to elucidate the mode of action of spherical silica, it is prudent to explore 
if these results can also be replicated clinically.
 
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Polyphosphates, such as sodium tripolyphosphate (STP), can also be included as chemical 
cleaning compounds, either on their own or to supplement the physical stain removal offered 
by dental abrasives. Polyphosphates act as chelating ingredients and have been shown to bind 
strongly to the tooth surface, reducing the force of adhesion of adsorbed proteins [Shellis, 
2005] and facilitating stain removal during toothbrushing. In addition, they have been shown 
to desorb salivary proteins from enamel, and inhibit protein adsorption [Rykke, 1988; Rykke 
1990], thereby helping to control stain build up.
 
 
 
 Given that it is of importance that a dentifrice should clean and control 
extrinsic dental stain whilst minimising its abrasive effect [Schemehorn, 2011], particularly 
for people with tooth sensitivity where the softer dentin is exposed [Pickles, 2006]reduced 
abrasivity is considered to be advantageous in anti-sensitivity dentifrices.
This clinical study will compare an experimental low abrasivity 0.5% spherical silica 
dentifrice and a marketed low abrasivity 6% standard abrasive dentifrice, and an experimental 
moderate abrasivity 1% spherical silica / 5% STP dentifrice and a marketed high abrasivity 
16% standard abrasive silica / 5% STP dentifrice. The main aims of this study areto 
determine whether spherical silica can achieve similar or greater extrinsic dental stain and 
plaque removal, in comparison to dentifrices containing higher concentrations of standard 
abrasive silica, and how the addition of 5% STP enhances cleaning capability.This study has 
not been designed to demonstrate the specific contribution that spherical silica or STP, are
having on the overall reduction of stain and plaque.
1.1
Mechanism of Action
Micronized spherical silica is an abrasive cleaning agent and STP is a chelating stain removal 
agent that are currently being investigated in healthy subjects with a propensity for extrinsic 
dental stain. 
1.2
Background and Rationale
1.2.1
Justification for Conducting the Study
Micronized spherical abrasive silica has shown significant potential in vitrofor achieving 
stain and plaque removal. Given that no clinical datahasbeen generated for this technology,it 
is prudent to explore if these results can also be replicated clinically.
1.2.2
Study and Dose Rationale
The test dentifrices have been designed to remove extrinsic dental stain and plaque caused by 
dietary and lifestyle habits, therefore a plaque and stain removal design has been assessed to 
be the most appropriate clinical model for this study.
 
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Stain will be assessed using an established clinical measure of extrinsic dental stain -the 
MacPherson modification [Macpherson, 2000] of the Lobene stain index [Lobene, 1968] 
(MLSI). Subjects will be stratified by baseline MLSI score (total MLSI (A×I) for the facial 
surfaces of the 4 anterior assessment teeth). Plaque will be assessed using an established 
clinical measure of plaque -the Turesky Modification of the Quigley Hein Index, [Turesky, 
1970] (TPI). A plaque disclosing solution will be used to temporarily stain the plaque, thus 
enabling a more accurate assessment.
Stain and plaque will be assessed at intervals over an 8 week treatment period. As stain is the 
primary focus in this study, in addition to the baseline and Week 8 assessments, MLSI 
assessments will also be conducted at Weeks 2 and 4. Plaque will be assessed at baseline and 
Week 8 only.
Plaque removal is expected to be achieved through the physical mode of action of the 
spherical or abrasive silica, as opposedto a chemotherapeutic action. Therefore, a pre-and 
post-brushing TPI assessment has been included in this study.It is expected to see greater 
effects in terms of plaque removal immediately after brushing.
Since the presence of overnight plaque could interfere with the conduct of accurate stain 
measurements, stain and plaque will be assessed on separate days (24 hours, +6 or -2 hours 
apart). Similarly, if stain assessments were to be conducted on the same day, but following 
plaque assessments, residual dye on the tooth surface could also prevent accurate stain scores 
from being measured.
Four of the anterior teeth will be selected for the purpose of stain assessment. Stain 
assessments will be made on the facial surfaces only as these surfaces are considered to be the 
most aesthetically important with respect to dental stain accumulation. The selection of 4 
assessment teeth as opposedto 12, which is typically selected for this model, will allow teeth 
with a greater propensity for stain accumulation to be included in the total MLSI (A×I) scores 
thus enabling greater overall differences to be observed(if it exists)as teeth with low or zero 
stain scores will not be included in the overall total MLSI (A×I). Dental stain and plaque 
largely accumulate in the harder to reach interproximal areas, therefore in addition to analysis 
of the overall total MLSI (A×I) and overall TPI, the interproximal regions have also been 
given focus as an exploratory objective in this study. As most of the stain is removed from the 
body and gingival regions, it is expected that little change in the total gingival MLSI (A×I) 
and total body MLSI (A×I)will be observed, therefore, these variables are not being analysed 
in this study. 
Plaque reductions are normally seen in the hard to reach areas of the mouth, therefore, using 
only 4 test teeth may not provide sufficient data to observe trends for plaque removal. 
Therefore, a full mouth evaluation will be conducted, and all gradable teeth willbeassessed 
for TPI.
A single examiner will perform the dental stain and plaque assessments for all subjects at each 
assessment visit to avoid inter-examiner variability. To assess the repeatability of the stain and 
 
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Potassium Nitrate / Sodium Fluoride
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plaque assessments repeat examinations will be performed by the dental examiner at each 
assessment visit.
According to ICH guidelines, for a study to be classed as truly double blind, not only does the 
examiner (and any appropriate member of staff who may be involved in the dispensing of 
products, analysis of data etc.) need to be blinded 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.
Sensodyne PronamelDaily Protection -Mint Essence has been selected as a reference 
dentifrice in this study as it is the lowest abrasive commercialised dentifrice in the Sensodyne 
range, without STP. Sensodyne Extra Whitening has been selected as a reference dentifrice as 
it is the highest abrasivity commercialized dentifrice in the Sensodyne range, with abrasive 
silica and STP.
The dosage regimen of twice daily use (morning and evening)with a full brush head of 
dentifrice will be the same for all subjects, and has been selectedbased on widely 
recommended oral hygiene practice, and typical consumer habit.
1.2.3
Safety Data
Complete information for the study dentifricesmay be found in the single reference safety 
document (SRSD), which for this study is theSafety Statement (SS).
2
STUDY OBJECTIVES AND ENDPOINTS
Table 2-1
Study Objectives and Endpoints
Objectives
Endpoints
Efficacy
Primary
To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by overall MLSI (A×I), of a 
0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after 8weeks twice daily brushing.
Change from baseline in overall MLSI 
at 8 weeks.
Secondary
To compare the removal of extrinsic 
Change from baseline in overall MLSI 
 
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Potassium Nitrate / Sodium Fluoride
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dental stain, as measured by overall 
MLSI (A×I), of a 0.5% spherical 
silica dentifrice and a marketed 6% 
abrasive silica dentifrice, after 8
weeks twice daily brushing.
at 8 weeks.
To compare the removal of extrinsic 
dental stain, as measured by overall 
MLSI (A×I), of a moderate abrasivity 
1% spherical silica / 5% STP 
dentifrice and a marketed higher 
abrasivity 5% STP whitening 
dentifrice, after 8weeks twice daily 
brushing.
Change from baseline in overall MLSI 
at 8 weeks.
Exploratory
To evaluate the ranking order of 
plaque removal, as measured by TPI, 
of a 0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after a single use.
Change from pre-brushing to post-
brushing TPI after single use.
To evaluate the ranking order of 
plaque removal, as measured by TPI, 
of a 0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after 8weeks twice daily brushing.
Change from baseline (pre-brushing) 
in overall post-brushing TPI at 8 
weeks.
To evaluate the ranking order of
Interproximal plaque removal, as 
measured by TPI, of a 0.5% spherical 
silica dentifrice, a marketed 6% 
abrasive silica dentifrice, a 1% 
sphericalsilica / 5% STP dentifrice, 
and a marketed 16% abrasive silica / 
5% STP dentifrice, after 8 weeks 
twice daily brushing.
Change from baseline (pre-brushing) 
in overall post-brushing interproximal 
TPI at 8 weeks.
To compare the removal of extrinsic 
dental stain, as measured by 
Change from baseline in overall 
interproximal MLSI at 2, 4 and 8 
 
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Potassium Nitrate / Sodium Fluoride
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interproximal (mesial + distal) MLSI 
(A×I), of a 0.5% spherical silica 
dentifrice and a marketed 6% abrasive 
silica dentifrice, after 2, 4 and 8 weeks
twice daily brushing.
weeks.
To compare the removal of extrinsic 
dental stain, as measured by 
interproximal (mesial + distal) MLSI 
(A×I), of a 1% spherical silica / 5% 
STP dentifrice and a marketed 16% 
abrasive silica / 5% STP whitening 
dentifrice, after 2, 4 and 8 weeks
twice daily brushing.
Change from baseline in overall 
interproximal MLSI at 2, 4 and 8 
weeks.
To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by interproximal (mesial + 
distal) MLSI (A×I), of a 0.5% 
spherical silica dentifrice, a marketed 
6% abrasive silica dentifrice, a 1% 
spherical silica / 5% STP dentifrice, 
and a marketed 16% abrasive silica / 
5% STP dentifrice, after 2, 4 and 8 
weekstwice daily brushing.
Change from baseline in overall 
interproximal MLSI at 2, 4 and 8 
weeks.
To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by overall MLSI Area (A), 
of a 0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after 2, 4 and 8 weekstwice daily 
brushing.
Change from baseline in overall MLSI 
Area at 2, 4 and 8 weeks.
To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by overall MLSI Intensity 
(I), of alow abrasivity 0.5% spherical 
silica dentifrice, a marketed low 
abrasivity dentifrice, a moderate 
abrasivity 1% spherical silica / 5% 
STP dentifrice, and a marketed higher 
Change from baseline in overall MLSI 
Intensity at 2, 4 and 8 weeks.
 
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Potassium Nitrate / Sodium Fluoride
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Template Version Effective: 22-Jun-2017
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abrasivity 5% STP whitening 
dentifrice, after 2, 4 and 8 weeks
twice daily brushing.
Safety 
To evaluate the safety and oral 
tolerability of the test dentifrices when 
used twice daily for 8 weeks.
Adverse Events
Thisis a POPstudydesigned to look at the relative extrinsic dental stain and plaque removal 
performance for all test dentifrices. However, we would expect the following rank order in 
overall MLSI (A×I)to beobserved: the1% spherical silica / 5% STP dentifrice≥16% 
abrasivesilica / 5% STP dentifrice ≥ 0.5% spherical silica dentifrice≥ 6% abrasive silica 
dentifrice.
3
STUDY DESIGNAND SUBJECT POPULATION
This is an 8 week,single-centre, examiner-blind, randomized, four treatment, parallel group 
study conducted in healthy subjects with a propensity for extrinsic dental stain (based on the 
judgement of the examiner).
This PoP study will be used to evaluate and compare the extrinsic dental stain and plaque 
removal of an experimental low abrasivity 0.5% spherical silica dentifrice and a marketed low 
abrasivity 6% standard silica abrasive dentifrice, and an experimental moderate abrasivity 1% 
spherical silica / 5% STP dentifrice and a marketed high abrasivity 16% standard abrasive 
silica / 5% STP dentifrice.This study has not been designed to demonstrate the specific 
contribution that spherical silica or STP, are having on the overall reduction of stain and 
plaque.
Sensodyne PronamelDaily Protection -Mint Essence has been selected as a low abrasivity 
reference dentifrice in this study as it is the lowest abrasive commercialised dentifrice in the 
Sensodyne range, without STP. Sensodyne Extra Whitening has been selected as a high 
abrasivity reference dentifrice as it is the highest abrasivity commercialised dentifrice in the 
Sensodyne range, with abrasive silica and STP.
A sufficient number of subjects will be screened to randomize at least 124 subjects to ensure 
120 evaluable subjects complete the entire study. This will ensure approximately 30 evaluable 
subjects per treatment arm). 
Subjectswill be stratified by their baseline total MLSI (A×I) score of the facial surfaces of 4 
of the 12 anterior teeth (<15 (low); ≥15 (high)).A single dental examiner will perform an 
assessment of the area and intensity of extrinsic dental stain on the facial surfaces of 4 
qualifying teeth selected (based on the judgement of the examiner) from the 6 maxillary and 6 
mandibular anterior teeth (universal numbering: 6-11 and 22-27), using the MLSI, at baseline 
(Visit 2), and following 2, 4 and 8 weeks (Visits 4, 5 and 6) twice daily brushing. Subjects 
 
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will return to the study site the day after baseline (MLSI) and Week 8 visits for pre-and post-
brushing full mouth TPI plaque assessments (Visits 3 and 7) of the facial and lingual surfaces 
of all gradable teeth.
4
SUBJECT SELECTION
This study can fulfill its objectives only if appropriate subjects are enrolled.The following 
eligibility criteria are designed to select subjects for whom participation in the study is 
considered appropriate. All relevant medical and nonmedical conditions should be taken into 
consideration when deciding whether a particular subject is suitable for this protocol.  
4.1
Inclusion Criteria
Subject eligibility should be reviewed and documented by an appropriate member of the 
investigator’s study team before subjects are included in the study
.
Subjects must meet all of the following inclusion criteria to be eligible for enrollment into the 
study:
1. Evidence of a personally signed and dated informed consent document indicating that the 
subjecthas been informed of all pertinent aspects of the study before any assessment is 
performed.
2. Male and female subjects who, at the time of screening
, are between the ages of 18 and 65 
years, inclusive.
3. Subjects who are willing and able to comply with scheduled visits, treatment plan,and 
other study procedures.
4. Good general and mental health with, in the opinion of the investigator or medically 
qualified designeenoclinically significant and relevant abnormalities of medical history 
or oral examinationwhich could impact study outcomes.
5. Good general and mental health with, in the opinion of the investigator or medically 
qualified designeean absenceof any conditionthat would impact on subject safety or 
wellbeing, or affect the subject’s ability to understand and follow study procedures and 
requirements.
6. In the opinion of the investigator or medically qualified designee, at screening, subjects 
must have good oral health.
7. In the opinion of the investigator or medically qualified designee, at screening, subjects 
must haveat least 20natural teeth including the 12 anterior teeth, gradable for TPI 
(Gradable teeth are those where restorative materials cover less than 25%of the tooth 
surface to be graded).
8. In the opinion of the investigator or medically qualified designee, at screening, subjects 
must havethe facial surfaces of at least 4 of the anterior teeth, gradable for the MLSI.
9. In the opinion of the investigator ormedically qualified designee, at screening, subjects 
must havethe presence of extrinsic dental stain (judged to be formed due to dietary 
 
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Potassium Nitrate / Sodium Fluoride
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factors)on the facial surfaces of the anterior teeth, as determined from a visual MLSI stain 
assessment.
10.In the opinion of the investigator,atVisit 2,subjects must haveasufficient level of 
extrinsic dental stain (in the opinion of the examiner) onthe facial surfaces ofthe scorable 
anterior (maxillary and mandibular) teeth.
11.At Visit 3,aminimum overall pre-brushing plaque score (TPI) of ≥2.0.
4.2
Exclusion Criteria
Subjects with any of the following characteristics/conditions will not be included in the study:
1. Subjects who are investigational site staff members directly involved in the conduct of the 
study and their family members, site staff members otherwise supervised by the 
investigator, or subjects who are GSK employees directly involved in the conduct of the 
study.
2. Participation in another clinical studyor receipt of an investigationaldrug(s) within 30 
days prior to study entry and/or during study participation.
3. Subjects who have previously been enrolled in this study. 
4. Acute or chronic medical or psychiatric condition or laboratory abnormality that may 
increase the risk associated with study participation or investigational product 
administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the subject inappropriate for entry into this 
study.
5. Any condition which, in the opinion of the investigator, causes xerostomia.
6. Pregnant female subjects.
7. Breastfeeding female subjects.
8. Known or suspected intolerance or hypersensitivity to the study materials (or closely 
related compounds) or any of their stated ingredients. 
9. Unwillingor unable to comply with the lifestyle guidelines described in this protocol. 
10.Recent history (within the last year) of alcohol or other substance abuse.
11.Subject is unwilling to abstain from tobacco or nicotine-containing productuse (including 
E-cigarettes)during the treatment evaluation period.
12.Subjects using the following mouth rinses, or taking the medications listed below:
a) Regular use of mouthwashes containing ingredients that are known to impart staining. 
For example, chlorhexidine, essential oils or cetylpyridinium chloride (CPC).
b) Use of a chlorhexidine, essential oil or CPC containingmouthwash within 14 days of 
Visit 2 or throughout the study.
c) Current use of Listerine, or any antimicrobial mouth rinse.
d) Use of minocycline, tetracycline or doxycycline within 30 days prior to screening.
e) Use of minocycline, tetracycline or doxycycline between the screening and baseline 
visits.
 
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f) Dailydoses of a medication and/or traditional/herbal ingredients which, 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.
13.Subjects who have the following dental exclusions:
a) Received a dental prophylaxis within 8 weeks of screening.
b) Gross periodontal disease, treatment ofperiodontal disease (including surgery) within 
12 months of screening, scaling or root planning within 3 months of screening.
c) Dental conditions / disease requiring immediate treatment.
d) Usedany professionally dispensed or over the counter bleaching/ whitening products 
(excluding daily use whitening dentifrices) within the past 3 months.
14.Subjects who have the following specific dental exclusions for assessment 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.
e) High levels of calculus deposits which might interfere with plaque assessments at the 
discretionof the investigator.
f) Presence of orthodontic bands or appliances, extensive crowns, partial dentures, or 
fixed retainers.
15.Any subject who, in the judgment of the investigator, should not participate in the study.
4.3
Randomization Criteria
Subjects will be randomized into the study provided they have satisfied all subject selection 
criteria.
4.4
Lifestyle Guidelines
Eligible subjects will continue to use their current dentifrice (according to their normal habit) 
between the screening and baseline visits, and will return to the site for the baseline visit a 
minimum of 24 hours, or up to a maximum of 2 weeks after screening.
 
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Potassium Nitrate / Sodium Fluoride
208078
Final 1.0 Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential
Template Version Effective: 22-Jun-2017
Page 24of 61
Following the supervised brushing with the standard fluoride dentifrice at the baseline (MLSI) 
visit up until completion of the study, subjects must only use the study products provided to 
them. Subjects will abstain from chewing gum and will not use any dental products, including 
home remedies for tooth whitening, other than the study products provided for the duration of 
the study. Subjects will be permitted to use non-antimicrobial dental floss for the removal of 
impacted food only.
On MLSI assessment days (Visits 2, 4, 5 and 6) subjects will attend the study site having 
refrained from all oral hygiene procedures for at least 6 hours.
On TPI assessment days (Visits 3 and 7) subjects will attend the study site having refrained 
from all oral hygiene procedures for 24 hours(+6, or -2 hours; including not brushing the 
eveningbefore).
4.4.1
Meals and Dietary Restrictions
On MLSI assessment days (Visits 2, 4, 5 and 6) and TPI assessment days (Visits 3 and 7) 
subjects will attend the study site having refrained from eating and drinking for at least 2 
hours (with the exception of water), prior to their scheduled visit.
4.5
ScreenFailures
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not subsequentlyrandomized. In order to ensure transparent reporting of screen failure 
subjects, a minimal set of screen failure information will include demography, screen failure 
details (e.g., withdrawal of consent), eligibility criteria, and any serious adverse events
(SAEs). 
Individuals who do not meet the criteria for participation in this study (screen failure) may not 
be re-screened.
4.6
Sponsor’s Qualified Medical Personnel
The contact information for the sponsor
's appropriately qualified medical/dental personnel for 
the study is documented in thestudy contact listin thestudy file.
The contact number can be used by investigational staff if they are seeking advice on 
medical/dental questions or problems; however, it should be used only in the event that the 
established communication pathways between the investigational site and the study team are 
not available.It is therefore intended to augment, but not replace, the established 
communication pathways between the investigational site and the study team for advice on 
medical/dental questions or problems that may arise during the study.The contact number is 
not intended for use by the subject directly, and if a subject calls that number, he or she will 
be directed back to the investigational site.
To facilitate access to appropriately qualified medical/dental personnel on study-related 
medical/dental questions or problems, subjects are provided with a contact card.The contact 
 
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Final 1.0 Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential
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card contains, at a minimum, protocol identifiers, subject study numbers, contact information 
for the investigational site, and contact details in the event that the investigational site staff 
cannot be reached to provide advice on a medical question or problem identified from the 
subject’s healthcare professional other than the investigator.
5
STUDY TREATMENTS
5.1
Blinding and Allocation to Treatment/Randomization
The study statistician, other employees of the sponsor, and vendors 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 isnot 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 untilafter they have left the clinical site. In addition, subjects should
be treated in a separate area. The dispensing staff will not be involved in any efficacy 
assessments during the study.
The randomization list will be prepared using a randomization block design with an equal 
allocation to each of the strata. The clinical study site will beprovided with two versions of 
the randomization schedule, each in a sealed envelope and clearly marked as either “For 
Dispensing” or “Emergency Use Only”. 
The “For Dispensing” schedule will contain the list of randomization numbers only and will 
not include any coded description, just a letter A, B, C or D.
The ‘Emergency Use Only’ randomization schedule will only be removed from the sealed 
envelope in an emergency situation. This schedule will have a randomization number 
followed by the letter A, B, C or D. The schedule will have a footnote with a key for A, B, C 
and D identifying the four treatments arms. However, to maintain the blinding of the study as 
far as possible, all treatment allocations for all randomization numbers on this randomization 
schedule will be masked with scratch-off panels. 
Qualified site personnel will be responsible for randomization and product dispensing. The 
investigational products will be dispensed in a blinded fashion to the subject. A second 
member of site personnel will verify that the correct dentifrice has been dispensed to each 
subject.Subjects will be stratifiedbytheirbaseline total MLSI (A×I) score for the facial 
surfaces of 4 of the 12 anterior teeth (<15 (low); ≥15 (high)), and depending on which strata 
they fall under will be assigned their allocated test product from either the “low” or “high” 
randomization schedule. The strata will be identified as:
Strata 1: Low (MLSI <15)
Strata 2: High (MLSI ≥15)
 
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In accordance with the randomization numbers, the subject will receive the study treatment 
assigned to the corresponding randomization number.
5.2
Breaking the Blind
At the initiation of the study, the study site will be instructed on the method for breaking the 
blind. The method will be a manual process, whereby only scratch-off panels will be removed 
for subjects that require unblinding. Blinding codes should be broken only in emergency 
situations for reasons of subject safety. Whenever possible, the investigator or sub-
investigator should consult with a member of the study team prior to breaking the blind unless 
the delay would endanger the subject’s health. When the blinding code is broken, the reason 
must be fully documented and entered in the CRF.
Any AE or SAEassociated with breaking the blind must be recorded and reported as specified 
in this protocol. The study site is required to inform the ECif the blind is broken. 
5.3
Subject Compliance
Subjects will be asked to bring all tubes of study dentifrice to each study visit for a visual 
compliance check of each product.Any suspected product over use, or underuse will be 
documented in the CRF and subjects will be re-educated on the correct dosing amount and 
instructions.
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 CRF.  
5.4
Investigational Product Supplies
The following study products will be supplied by the Clinical Supplies Department, GSKCH:
Test product 1:5% KNO3 / 0.2542% NaFdentifrice with 0.5% spherical silica
(RDA~38); 
.
Test product 2:5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silicaand 5% 
STP(RDA~58);  
.
Reference Product 1:5% KNO3/ 0.2542% NaF dentifrice with 6% abrasive silica 
(RDA~36); Sensodyne PronamelDaily Protection -Mint Essence ( 
 -USA 
marketed dentifrice).
Reference Product 2:5% KNO3/ 0.2543% NaF dentifrice with 16% abrasive silica 
and 5% STP (RDA~166); Sensodyne Extra Whitening ( 
-USA marketed 
dentifrice).
Other items to be supplied by the Clinical Supplies Department, GSKCH:
Oral-B Sensi Soft Manual Toothbrush(USA marketed)
 
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CCI
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208078
Final 1.0 Clinical Protocol
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Template Version Effective: 22-Jun-2017
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Colgate Cavity Protection(USA marketed) -standard fluoride dentifrice for post-
baseline (MLSI) brushing and Week 7 post-assessmentbrushing
Trace Disclosing Agent -Young Dental Manufacturing
Countdown timers
Rinsing cups
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 beprinted by the study site.
The site will also provide the dental floss.
5.4.1
Dosage Form and Packaging
All test and reference dentifrices are intended for oral use, and will be administered orally as 
detailed in Section 5.5.
The reference dentifrices will be sourced from the US market. The test dentifrices will be
manufactured and filled into white ABL tubes and supplied by GSKCH. 
All test dentifrices will be presented to the clinical study siteintubes that have been 
overwrapped in white vinyl to obscure any branding on the commercial packswith a study 
label affixed.The contents of the label will be in accordance with all applicable regulatory 
requirements and will be the responsibility of the Clinical Supplies Department,GSKCH.
Each subject will receive a sufficient number of tubes to cover usage during the treatment 
phase.
All sundry items, including the Colgate Cavity Protection, will be supplied in their 
commercial packaging for dispensing by study staff as required. 
Care should be taken with the supplied products and their labels so that they are maintained in 
good condition.It is important that all labels remain intact and legible for the duration of the 
study. Subjects should be instructed to not remove or deface any part of the study label.
5.4.2
Preparation and Dispensing 
All investigational product will be dispensed by qualified blinded site personnel according to 
the dosage and administration instruction. The investigational productswill be dispensed in a 
blinded fashion to the subject.A second member of site personnel will verify that the correct 
dentifrice has been dispensed to each subject. A record of the product dispensed to each 
subject will be recorded in a treatment dispensing log, and assigned against each subject 
number.
5.5
Administration
A record of the administration of the study products will be kept using adispensing log and 
the CRF.
 
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Subjects will be instructed to self-administer their investigational product according to the 
product use instructions provided to the subject(full toothbrush head for one timed minute, 
twice a day).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.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 the baselineTPI visit(Visit 3), and subjects will 
conduct a supervised brushingfor one timed minute. This will be repeated again at Visits 4, 5, 
6 and 7.
5.5.1
Medication Errors
Medication errors may result, in this study, from the administration or consumption of: 
the wrong product,
by the wrong subject, 
at the wrong time, 
or at the wrong dosage strength (other examples of concern may be added based on 
the investigational product administration, such as inadvertent exposure).  
Such medication errors occurring to a study participant are to be captured in the CRF.  In the 
event of medication dosing error, the sponsor should be notified immediately.
Medication errors are reportable irrespective of the presence of an associated AE/SAE, 
including:
Medication errors involving subject exposure to the investigational product;
Potential medication errors or uses outside of what is foreseen in the protocol that 
do or do not involve the participating subject.
Whether or not a medication error is accompanied by an AE, as determined by the 
investigator, the medication error and, if applicable, any associated adverse event(s) is 
captured on an adverse event (AE) CRF page.
5.6
Investigational Product Storage
The investigator, or an approved representative, will ensure that all investigational products 
including any comparator and marketed products are stored in a secured area with controlled 
access under required storage conditions and in accordance with applicable regulatory 
requirements and product label.  
Site systems must be capable of measuring and documenting (for example, via a log), at a 
minimum, daily minimum and maximum temperatures for all site storage locations (as 
applicable, including frozen, refrigerated, and/or room-temperature products). This should be 
 
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Potassium Nitrate / Sodium Fluoride
208078
Final 1.0 Clinical Protocol
GlaxoSmithKline Consumer Healthcare Confidential
Template Version Effective: 22-Jun-2017
Page 29of 61
captured from the time of investigational product receipt throughout the study.Even for 
continuous monitoring systems, a log or site procedure that ensures active daily evaluation for 
excursions should be available.The operation of the temperature-monitoring device and 
storage unit (for example, refrigerator), as applicable, should be regularly inspected to ensure 
it is maintained in working order. 
Any excursions from the product-label storage conditions should be reported upon discovery.  
The site should actively pursue options for returning the product to the storage conditionsas 
described in the labeling, as soon as possible. Deviations from the storage requirements, 
including any actions taken, must be documented and reported to the Sponsor.  
Once an excursion is identified, the investigational product must be quarantined and not used 
until the Sponsor provides documentation of permission to use the investigational product. It 
will not be considered a protocol deviation if the sponsor approves the use of the 
investigational product after the temperature excursion.Use of the investigational product 
prior to sponsor approval will be considered a protocol deviation.  Specific details regarding 
information the site should report for each excursionwill be provided to the site. 
Site staff will instruct subjects on the proper storage requirements for take-home 
investigational products. 
5.7
Investigational Product Accountability
All products supplied are for use only in this clinical study and should not be used for any 
other purpose.
Study products must be received by a designated person at the study site, handled and stored 
safely and properly, and kept in a secured location to which only the staff have access. Upon 
receipt, all study treatments should be stored according to the instructions specified on the 
treatment labels.Clinicalsupplies are to be dispensed only in accordance with the protocol.
The clinical study site must maintain adequate records documenting the receipt, use, loss, or 
other disposition of the investigational product supplies.All study drugs will be accounted for 
using a drug accountability form/record. 
At the end of the study subjects will return all study products back to the clinical study site, 
which will be verified by the monitor. Study product supplies will then be either collected by 
the study monitor or returned by the investigator or designee to the designated third party 
vendor.
The inventory must be available for inspection by the study monitor during the study. 
Monitoring of treatments accountability will be performed by the field monitor during site 
visits and at the completion of the study.
 
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5.7.1
Destruction of Investigational Product Supplies 
All investigational study treatments and the Colgate Cavity Protection dentifriceshipped for 
this clinical study will be returned to the Sponsor at the termination of the study.At the 
conclusion of the study, the Principal Investigator or an appropriate designee, and a 
representative of GSKCH will inventory all used and unused investigational study treatment.
The study treatment inventory record for returned study treatment will then be completed. All 
investigational product for this clinical study (empty containers), as well as all unused study 
product will be shipped to thedesignated vendor using the return instructions provided. 
5.8
Concomitant Treatments
Details of any relevant dental, medical or surgical history (within the last year),including 
allergies or drugsensitivity, will be recorded in the CRF.
All concomitant and/or traditional/herbal ingredients takenduring the study must be recorded 
in the CRF with indication, unit dose, daily dose, and start and stop dates of administration.
All subjects will be questioned about concomitant treatment at each clinic visit.
Treatments taken within 30 days before the first dose of study investigational product will be 
documented as a prior treatment.Treatments taken after the first dose of study investigational 
product will be documented as concomitant treatments.
Subjects will be asked not to have any non-emergency dental treatment during the study 
(including prophylaxis). Subjects will be withdrawn if they start a course of minocycline, 
tetracycline or doxycycline during the study period.
6
STUDY PROCEDURES
6.1
Study Period
6.1.1
Screening-Visit 1
Subjects will be admitted to the clinical site at least 24 hours prior toDay1dosing.
The following procedures/assessments will take place in the order listed below(where 
possible),and recorded in the CRF:
Obtain written 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 documenting a written consent will be provided by the 
investigator or by GSKCH. The investigator, or designee, should sign and date the 
consent form to confirm that theconsent processwas completed correctly. The 
 
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subject, will be provided with a copy of their signed and dated consent form and any 
other written information which they should be instructed to retain.
If, during a subject’s participation in the study, any new information becomes 
available that may affect the subject’s willingness to participate in the study, each 
ongoing subject should receive a copy of this new information and be re-consented 
into the study. Subjects will be provided with a copy of the signed and dated amended 
consent form. The date of consent will be recorded on the CRF.
Collect demography andethnicity.
Collect medical history, including history of illegaldrug, alcohol and tobacco use.
Obtain complete medication history of all prescription or nonprescription drugs, and 
dietary and herbal supplements taken within 30 daysprior to the planned first dose.
Full oral soft tissue (OST)examinationconducted byaqualified dental examiner.
Full oral hard tissue(OHT) examination conducted byaqualified dental examiner.
VisualMLSI stain assessmentof the facial (maxillary and mandibular) surfacesby a 
qualified dental examiner.
Review Inclusion and Exclusion criteria. Pregnancy status will be confirmed verbally 
by the subject.
Confirmation of subject eligibility.
To prepare for study participation, instruct subjects on the use of the Lifestyle 
Guidelinesand Concomitant Treatment(s)sections of the protocol.
6.1.2
BaselineMLSI Visit (Day 1) -Visit 2
Subjects will be admitted to the clinical site at least 24hours following the Screening visit.
Subjects will attend the study site having refrained from all oral hygiene procedures for at 
least 6 hours, and from eating anddrinking for at least 2 hours (with the exception of water), 
prior to their scheduled visit.
The following procedures will be completedin the following order (where possible), and 
recorded in the CRF:
Review changes in the subject’s medical history including concomitant medication 
since Screening.
Review of Inclusion Criteria 10, and Exclusion Criteria 12.b and e.
Full OHT and OST examinationsconducted by a medically qualified examiner. 
Record any changes since the Screening visit in the CRF.
Confirmsubject eligibility and continuance.
Supervised brushing of the anterior teeth for 30 seconds using a wetted toothbrush, 
followed by flossing.
Full MLSI stain assessment of the facial (maxillary and mandibular) teethconducted
by a qualified dental examiner.
 
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4 eligible assessment teeth selectedby a qualified dental examiner.
Repeat full MLSI stainassessment of the 4 assessment teeth for selected subjects.
Stratification (based on total MLSI score of the 4 facial surfacesof the 4 eligible 
assessment teeth).
Unsupervised brushing with standard fluoride dentifrice.
AEs and incidents.Assess symptoms by spontaneous reporting of adverse events and 
by asking the subjects to respond to a non-leading question such as “How do you
feel?”
6.1.3
Baseline TPI Visit (Day 2) -Visit 3
Subjects will be admitted to the clinical site 24 hours(+6, or -2 hours; including not brushing 
the evening before)after Visit 2, and will be requested to refrainfrom eating and drinking for 
at least 2 hours (with the exception of water),prior to their scheduled visit.
Prior to randomization the following procedures/assessments will be completedin the 
following order (where possible),and recorded in the CRF:
Review changes in the subject’s medical history including concomitant medication 
sincethe previous visit.
Review of Inclusion Criteria 11.
Confirmation of subject adherence and continuance.Full OST examination conducted 
by a medically qualified examiner.
Subjects disclose plaque by rinsing with plaque disclosure solution.
Pre-brushing full mouth TPI assessment of all gradable teeth, conductedby a 
qualified dental examiner.
Randomization.
Following randomization,the following procedures/assessments will be completedin the 
following order(where possible), and recorded in the CRF:
Dispense study dentifrice, toothbrush and diary/ instructions card.
Supervised brushing with subject’s allocated dentifrice.The time of brushing will be 
entered in the CRF. 
Subjects disclose plaque for a second time by rinsing with plaque disclosure solution.
Post-brushingfull mouthTPI assessment of all gradableteeth, conducted by a 
qualified dental examiner.
Repeat TPI assessment conducted by a qualified dental examiner, for selected 
subjects.
Post assessment brushing with standard fluoride dentifrice and toothbrush (if 
requested by the subject).
 
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AEs and incidents captured. Assess symptoms by spontaneous reporting of adverse 
eventsand by asking the subjects to respond to a non-leading question such as “How 
do you feel?”
6.1.4
Day 15(MLSI)-Visit 4
Subjects will be admitted to the clinical sitehaving refrained from all oral hygiene procedures 
for at least 6 hours, and from eating and drinking for at least 2 hours (with the exception of 
water), prior to their scheduled visit.
The following procedures/assessments will be completedin the following order(where 
possible), and recorded in the CRF:
Subjects return study dentifrice, toothbrush, and diary card to the clinical site.
Review changes in the subject’s medical history including concomitant medication
sincethe previous visit.
Review of completed diary to confirm timing of each brushing occasion in addition to 
missed/additional brushings.
AEs and incidents captured.Assess symptoms by spontaneous reporting of adverse 
events and by asking the subjects to respond to a non-leading question such as “How 
do you feel?
Confirmation of subject adherence and continuance.
Full OST examination conducted byamedically qualified examiner.
Supervised brushing of the anterior teeth for 30 seconds using a wetted toothbrush, 
followed by flossing.
Full MLSI stain assessment of the 4 assessment teeth by a qualified dental examiner.
Repeat full MLSI stain assessment of the 4 assessment teeth for selected subjects.
Supervised brushing withsubject’s allocated dentifrice for 60 seconds.
AEs and incidents captured.Assess symptoms by spontaneous reporting of adverse 
events and by asking the subjects to respond to a non-leading question such as “How 
do you feel?”
6.1.5
Day 29 (MLSI) -Visit 5
Subjects will be admitted to the clinical sitehaving refrained from all oral hygiene procedures 
for at least 6 hours, and from eating and drinking for at least 2hours (with the exception of 
water), prior to their scheduled visit.
The following procedures/assessments will be completed in the following order and recorded 
in the CRF:
Subjects return study dentifrice, toothbrush, and diary card to the clinical site.
Review changes in the subject’s medical history including concomitant medication 
sincethe previous visit.
 
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Review of completed diary to confirm timing of each brushing occasion in addition to 
missed/additional brushings.
AEs and incidents captured.Assesssymptoms by spontaneous reporting of adverse 
events and by asking the subjects to respond to a non-leading question such as “How 
do you feel?
Confirmation of subject adherence and continuance.
Full OST examination conducted by a medically qualified examiner.
Supervised brushing of the anterior teeth for 30 seconds using a wetted toothbrush, 
followed by flossing.
Full MLSI stain assessment of the 4 assessment teethby a qualified dental examiner.
Repeat full MLSI stain assessment of the 4 assessment teeth for selected subjects.
Supervised brushing withsubject’s allocated dentifrice for 60 seconds.
AEs and incidents captured.Assess symptoms by spontaneous reporting of adverse 
events and by asking the subjects to respond to a non-leading question suchas “How 
do you feel?”
6.1.6
Day 57 (MLSI) -Visit 6
Subjects will be admitted to the clinical sitehaving refrained from all oral hygiene procedures 
for at least 6 hours, and from eating and drinking for at least 2 hours (with the exception of 
water), prior to their scheduled visit.
The following procedures/assessments will be completed in the following orderand recorded 
in the CRF:
Subjects return study dentifrice, toothbrush, and diary card to the clinical site.
Review changes in the subject’s medical history including concomitant medication 
sincethe previous visit.
Review of completed diary to confirm timing of each brushing occasion in addition to 
missed/additional brushings.
AEs and incidents captured.Assess symptoms by spontaneous reporting of adverse 
events and by asking the subjects to respond to a non-leading question such as “How 
do you feel?
Confirmation of subject adherence and continuance.
Full OST examination conducted by a medically qualified examiner.
Supervised brushing of the anterior teeth for 30 seconds using a wetted toothbrush, 
followed by flossing.
Full MLSI stain assessment of the 4 assessment teethby a qualified dental examiner.
Repeat full MLSI stain assessment of the 4 assessment teeth for selected subjects.
Supervised brushing withsubject’s allocated dentifrice for 60 seconds.
 
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AEs and incidents captured.Assess symptoms by spontaneous reporting of adverse 
events and by asking the subjects to respond to a non-leading question suchas “How 
do you feel?”
6.1.7
Day 58 (TPI) -Visit 7
Subjects will be admitted to the clinical site 24 hours(+6, or -2 hours; including not brushing 
the evening before)after Visit 2, and will be requested to refrainfrom eating and drinking for 
at least 2 hours(with the exception of water),prior to their scheduled visit.
The following procedures/assessments will be completed in the following order and recorded 
in the CRF:
Subjects return study dentifrice, toothbrush, and diary card to the clinical site.
Review changes in the subject’s medical history including concomitant medication 
sincethe previous visit.
Review of completed diary to confirm timing of each brushing occasion in addition to 
missed/additional brushings.
AEs and incidents captured.Assess symptoms by spontaneous reporting of adverse 
events and by asking the subjects to respond to a non-leading question such as “How 
do you feel?
Confirmation of subject adherence and continuance.
Full OSTconducted by a qualified dental examiner.
Subjects disclose plaque by rinsing with plaque disclosure solution.
Pre-brushingfull mouthTPI assessment of all gradable teeth, conductedby a qualified 
dental examiner.
Supervised brushing with subject’s allocated dentifrice.
AEs and incidents captured following supervised brushing.
Subjects disclose plaque for a second time by rinsing with plaque disclosure solution.
Post-brushing full mouth TPI assessment of all gradable teeth, conductedby a 
qualified dental examiner.
Repeat TPI assessmentconductedby a qualified dental examiner.
Post assessment brushing with standard fluoride dentifrice and toothbrush (if requested 
by the subject).
AEs and incidents captured.Assess symptoms by spontaneous reporting of adverse 
events and by asking the subjects to respondto a non-leading question such as “How 
do you feel?
Study conclusion.
If a subject has any clinically significant, study-related abnormalities at the conclusion of a 
scheduled inpatient portion of the study, the GSK CH medical monitor (or designated 
representative) should be notified and depending on the abnormality, the subject may be asked 
 
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to remain at the clinical site until such abnormalities are deemed not clinically significant, or 
it issafe for outpatient follow-up.If the subject is unable or unwilling to remain at the clinical 
site and/or when outpatient follow-up is deemed appropriate, the GSK CH medical monitor 
(or designated representative) should be so notified, and the investigator should make every 
effort to arrange follow-up evaluations at appropriate intervals to document the course of the 
abnormalities.
6.2
Subject Withdrawal
At the end of the study subjects will be evaluated to determine if they completed all study 
procedures or if they were discontinued from the study early. If the subject discontinued at 
any point during the study, the primary reason for withdrawal should be recorded on the Study 
Conclusion page of the CRF by selecting one of the options below.
1.
Subject did not meet study criteria
2.
Adverse event
3.
Subject lost to followup
4.
Protocol Violation
5.
Withdrawal of informed consent
6.
Other
Subjects may withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the investigator or sponsor for safety or, behavioral 
reasons, or the inability of the subject to comply with the protocol-required schedule of study 
visits or procedures at a given study site.  
The following circumstances require discontinuation of study treatment and/or premature 
subject withdrawal:
Protocol violation that may impact the outcome of the subject’s safety
Withdrawal of informed consent
Subject lost to follow-up 
Unblinding of the subject 
Pregnancy
Death
If a subject is discontinued or prematurely withdraws from the study, reasons for 
discontinuation or withdrawal and associated date must be documented in the relevant 
section(s) of the CRF. 
 
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If a subject does not return for a scheduled visit, every effort should be made to contact the 
subject. The Investigator or site staff should attempt to contact the subject twice.After two 
attempts, clinical site staff must send a registered letter. If no response is received from the 
subject, the subject will beconsidered lost to follow up. All attempts to contact the subject 
and information received during contact attempts must be documented in theCRF. In any 
circumstance, every effort should be made to documentsubject outcome, if possible. The 
investigator should inquire about the reason for withdrawal, request that the subject return all
study products(used and unused), and follow-up with the subject regardingany unresolved 
AEs.
It may be appropriate for the subject to return to the clinical site for final safety assessments. 
Subjects shouldbe questioned regarding their reason for withdrawal. An OST may be 
conductedat the investigator’s discretion.
Lack of completion of all or any of the early termination procedures will not be viewed as 
protocol deviations so long as the subject’s safety was preserved.
If the subject withdraws from the study and also withdraws consent for disclosure of future 
information, no further evaluations should be performed and no additional data should be 
collected. The sponsor may retain and continue to use any data collected before such 
withdrawal of consent.
7
ASSESSMENTS
Every effort should be made to ensure that protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances, outside the control of the investigator that may make it unfeasible toperform 
the test. In these cases, the investigator must take all steps necessary to ensure the safetyand 
well-being of the subject.When a protocol-required test cannot be performed, the investigator 
will document the reason for the missed test and any corrective and preventative actions that 
he or she has taken to ensure that required processes are adhered to as soon as possible.The 
study team must be informed of these incidents in a timely manner.
7.1
Efficacy
The following efficacy assessments will be performed at times defined in the Study 
Proceduressection of this protocol.  
7.1.1
Macpherson Modification of the Lobene Stain Index (MLSI)
Stain assessments will be performed by a single clinical examiner, in the same room with 
consistent light levels, throughout the study to facilitate standardization of the assessments. 
Subjects will brush their anterior teeth with a wetted toothbrush for 30 seconds prior to each 
stain assessment. Teeth will be air dried prior to the assessment, and during the assessment as 
needed. 
 
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The facial surfaces of each assessable tooth is divided 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 facial surfaces:distal facial area; body facial area; 
mesial facial area 
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
7.1.1.1 Repeatability of the MLSI Assessment
To assess the repeatability of the stain assessments,replicate examinations will be performed 
by the samequalified dental examiner at each assessment visit. Five subjects will be randomly 
selected for repeat MLSI assessments across each assessment window (a total of 20 repeat 
MLSI assessments over the duration of the study). Every effort should be made to ensure the 
examiner does not refer to the results of the assessment completed prior to the repeat 
assessment. The results of the initial assessment will not be visible to the examiner or scribe 
when the repeat assessment is carried out.
7.1.2
Turesky Modification of the Quigley Hein Index Dental Plaque 
Assessment (TPI)
Thequalified dentalexaminer must ensure that the subjects taking part in this exercise have 
been appropriately informed and have consented to take part to this activity.
 
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The dental examiner will use the Turesky Modification of the Quigley Hein Index [Turesky 
1970], to assess plaque on all gradable teethfor the full mouth. Only natural teeth devoid of 
restorations which would prevent plaque grading can be assessed. This means no crowns, 
bridges, and teeth withrestorations which, in the investigator’s judgment would prevent an 
accurate grading. Wisdom teeth are not to be assessed.
The plaque will first be disclosed using a dye solution (provided by site). Subjects will then 
rinse with 5 millilitres (mL) of Trace Disclosing Agentfor 10 seconds to disclose any residual 
plaque. They will expectorate and rinse with 10 mL of water for 10 seconds and expectorate 
again. Plaque will be assessed with each tooth being divided into 6 areas including the 
mesiofacial, facial, distofacial, mesiolingual, lingual and distolingual surfaces.
Disclosed plaque will be scored as follows and recorded in the CRF:
Score 
Description 
0 
No plaque 
1 
Slight flecks of plaque at the cervical margin of the tooth 
2 
A thin continuous band of plaque (1 mm or smaller) at the cervical margin of the tooth 
3 
A band of plaque wider than 1 mm but covering less than 1/3 of the crown of the tooth 
4 
Plaque covering at least 1/3 but less than 2/3 of the crown of the tooth 
5 
Plaque covering 2/3 or more of the crown of the tooth 
7.1.2.1 Repeatability of the Plaque Assessment
To assess the repeatability of the TPI assessments, replicate examinations will be performed 
by the samequalified dental examiner at each assessment visit.Five subjects will be randomly 
selected for repeat TPI examinations across each assessment window (a total of 10 repeat TPI 
examinations over the duration of the study).Repeatability assessments will be a minimum of 
10 minutes between repeat plaque assessments of the same subject. The results of the initial 
assessment will not be visible to the examiner or scribe when the repeat assessment is carried 
out.
7.2
Safety
The following safety assessments will be performed at times defined in the Study Procedures
section of this protocol.  
 
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7.2.1
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 with retraction aids as 
appropriate. The examiner will include examination of the Labial Mucosa (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 be recorded in the CRF as either normal or abnormal with 
details of any abnormalities. A brief description of any abnormality observed by the examiner 
or reported by the subject at the application site following and study procedures or 
administration of the treatment dentifrices will be recorded as an AE. 
An OST examination will be conducted at each visit prior to any clinical assessments. While 
it is preferable to use the same OST examiner throughout the study, to facilitate subject flow, 
OST examinations may be carried out by different examiners.
7.2.2
Full Oral Hard Tissue (OHT) Examination
Where possible, this procedure should be conducted by a single dental examiner or clinically 
qualified designee for all subjects. Subjects with evidence of gross intraoral neglect or the 
need for extensive dental therapy will be excluded.
The OHT examination will assess grossly carious lesions or signs of erosive wear, enamel 
irregularities, tooth fracture, gross decay, decalcification and faulty restorations. Observations 
will be listed as “Absent”or “Present”and conditions noted as present will be described. 
Examination findings will be described and documented in the CRF. Any observation that 
changes from “Absent”to “Present”from the screening assessment must be recorded as an 
AE.
8
ADVERSE EVENT AND OTHER EVENTS OF SPECIAL 
INTEREST REPORTING
8.1
Definitions of Adverse Events and Serious Adverse Events
8.1.1
Adverse Event
An AE is any untoward medical occurrence in a clinical study participant, temporally 
associated with the use of astudy product, whether or not considered related to the study 
product.
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a study treatment.
Events Meeting the AE Definition:  
 
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Any abnormal safety assessments (eg, OST findings, including those that worsen 
from baseline, considered clinically significant in the medical and scientific judgment 
of the investigator (ie, not related to progression of underlying disease).
Exacerbation of a chronic or intermittent pre-existing condition including either an 
increase in frequency and/or intensity of the condition.
New conditions detected or diagnosed after study treatment administration even 
though it may have been present before the start of the study.
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction.
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study 
treatment or a concomitant medication. Overdose per se will not be reported as an 
AE/SAE unless it is an intentional overdose taken with possible suicidal/self-harming 
intent. Such overdoses should be reported regardless of sequelae.
"Lack of efficacy" per se will not be reported as an AE or SAE. Such instances will be 
captured in the efficacy assessments. However, the signs, symptoms, and/or clinical 
sequelae resulting from lack of efficacy will be reported as AE or SAE if they fulfill 
the definition of an AE or SAE. 
Events NOTmeeting the AE definition: 
Any abnormal safety assessments which are associated with the underlying disease, 
unless judged by the investigator to be more severe than expected for the subject’s 
condition. 
The disease/disorder being studied or expected progression, signs, or symptoms of the 
disease/disorder being studied, unless more severe than expected for the subject’s 
condition. 
Medical or surgical procedure (e.g., endoscopy, appendectomy) is not the AE. The 
condition that leads to the procedure is an AE (e.g., appendicitis).
Situations where an untoward medical occurrencedid 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. 
8.1.2
Serious Adverse Event
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met (e.g., hospitalization for signs/symptoms of the disease under study, death 
due to progression of disease).
A serious adverse event is any untoward medical occurrence at any dose that:
Results in death
Is life-threatening
 
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The term 
'life-threatening
' in the definition of 
'serious
' refers to an event in which 
the participant was at risk of death at the time of the event. It does not refer to an 
event, which hypotheticallymight have caused death, if it were more severe;
Requires inpatient hospitalization or prolongation of existing hospitalization
In general, hospitalization signifies that the participant has been detained (usually 
involving at least an overnight stay) atthe hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AE. If a complication prolongs hospitalization or fulfills any 
other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered serious.
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.
Results in persistent or significant disability/incapacity
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions.
This definition is not intended to include experiencesof relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (eg, sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption.
Results in congenital anomaly/birth defect
Other situations
Medical or scientific judgment should be exercised in deciding whether SAE 
reporting is appropriate in other situations such as important medical events that 
may not be immediately life-threatening or result in death or hospitalization but 
may jeopardize the participant or may require medical or surgical intervention to 
prevent one of the other outcomes listed in the above definition. These events 
should usually be considered serious.
Examples of such events include invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization, or development of 
drug dependency or drug abuse.
8.2
Reporting Period
8.2.1
Adverse Event
AEs will be collected from first unsupervised brushing with the standard fluoride dentifrice at 
Visit 2, and until 5days following last administration of the investigational product.For those 
subjects that don’t brush withthe standard fluoride dentifrice at Visit 2,AEs will be collected 
 
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from first useof the plaque disclosure solution, and until 5 days following last administration
of the investigational product.
Medical occurrences that begin before the start of study treatment but after obtaining 
informed consent will be recorded on the Medical History/Current Medical Conditions section 
of the case report form (CRF) not the AE section.
8.2.2
Serious Adverse Event
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 provides informed consent, 
which is obtained prior to the subject’s participation in the study, i.e., prior to undergoing any 
study-related procedure and/or receiving investigational product and until 5days following 
last administration of the investigational product.
SAEs assessed as not relatedto study participation (e.g., investigational product, protocol 
mandated procedures, invasive tests, or change in existing therapy) or notrelated to a GSK 
concomitant medication will be recorded from thetime of signing the ICFand until 5 days 
following last administration of the investigational product. 
8.3
Reporting Procedures
The investigator and anydesigneesareresponsible for detecting, documenting and reporting 
events that meet the definition of an AE or SAEand remain responsible for following up on 
AEs that are serious, considered related to the study treatment or the study, or that caused the 
participant to discontinue the study treatment. 
The investigator is to report all directly observed AEs and all AEs spontaneously reported by 
the study subject. In addition, each study subjectwill be questioned about AEs. 
Each AE is to be assessed to determine if it meets the criteria for SAEs.If an SAE occurs, 
expedited reporting will follow local and international regulations, as appropriate.
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (eg, hospital progress notes, laboratory, and diagnostics reports) related to the 
event.
The investigator or site staff will then record all relevant information regarding an AE/SAE in 
the CRF.
It is notacceptable for the investigator to send photocopies of the participant’s medical 
records to GSK in lieu of completion of the GSK /AE/SAECRF page.
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.
 
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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).
Medical conditions reported prior to the time period for reporting AEs/SAEs should be 
recorded as part of the subject’s medical history.
AEs elicited by the investigator in a standard manner at the study visits should also be 
recorded in the AE section of the CRF. Care will be taken not to introduce bias when 
detecting AE and/or SAE. Open-ended and non-leading verbal questioning of the participant 
is the preferred method to inquire about AEoccurrence.
8.3.1
Adverse Event
All AEs will be reported on the AE page(s) of the CRFby the investigator or site staff.  It 
should be noted that the form for collection of SAE information is not the same as the AE
CRF.Where the same data are collected, the forms must be completed in a consistent manner. 
For example, the same AE termshould be used on both forms. AE should be reported using 
concise medical terminology on the CRF as well as on the form for collection of SAE 
information.
8.3.2
Serious Adverse Event
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 
Criterion for seriousness.
The following are desirable and are of particular relevance for investigator and GSK CH 
assessment of the SAE report:
Date of onset of AE 
Date AE stopped, if relevant
Study product start date
Study product end date if relevant
Action taken on study product
Outcome if known
 
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The SAE form, completed as fully as possible, must be e-mailed to the GSK CH Clinical 
Operations Safety Reporting email box with the study number and subject numberin the 
subject line of the email immediately and under no circumstance should this exceed 24 
hoursafter study site personnel learn of the event. The investigator will submit any updated 
SAE data to the sponsor, immediately andunder no circumstance should this exceed 24 
hours of it being available. The GSK CH Study Manager should also be notified of the 
situation by telephone or email.
EmailSerious Adverse Events to:
The GSK CH Study Manager or designee will be responsible for forwarding the SAE form to 
the Case Management Group, Global Clinical Safety and Pharmacovigilance mailbox 
The initial report will be followed up with more information as relevant, or as requested by 
the GSK CH study manager.
8.3.3
Sponsor’s Reporting Requirements to Regulatory Authorities and 
Ethics Committees
GSK has a legal responsibility to notify, as appropriate, the local regulatory authority and 
other regulatory authorities about the safety of a productunder clinical investigation. Prompt 
notification of SAEs by the investigator to GSK is essential so thatlegal obligations and 
ethical responsibilities towards the safety of subjects are met.
GSK will comply with country specific regulatory requirements relating to safety reporting to 
the regulatory authority, IRB and investigators.
Investigator safety reports must be prepared for suspected unexpected serious adverse 
reactions (SUSAR) according to local regulatory requirements and sponsor policy and 
forwarded to investigators as necessary.
An investigator who receives an investigator safety report describing a SAE or other specific 
safety information eg, summary or listing of SAE) from the sponsor will review and then file 
it along with the Safety Statement and will notify the IEC, if appropriate according to local 
requirements.
8.4
Evaluating Adverse Events and Serious Adverse Events
8.4.1
Severity Assessment
The investigator or designee will make an assessment of severity for each AE and SAE 
reported during the study and will assign it to one of the following categories:
 
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Mild:  An event that is easily tolerated by the subject, causing minimal discomfort and 
not interfering with everyday activities.
Moderate:  An event that is sufficiently discomforting to interfere with normal 
everyday activities
Severe:  An event that prevents normal everyday activities. 
Note: An AE that is assessed as severe will not be confused with an SAE. Severity is a 
category utilized for rating the intensity of an event; and both AEs and SAEs can be assessed 
as severe. For example, a headache may be severe (interferes significantly with the subject
's 
usual function) but would not be classified as serious unless it met one of the criteria for 
SAEs, listed above. 
8.4.2
Causality Assessment
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements.For each AE/SAE, the investigator must document in the medical notes that 
he/she has reviewed the AE/SAE and has provided an assessment of causality.The 
investigator’s assessment of causality must be provided for all AEs (serious and non-serious); 
the investigator must record the causal relationship in theCRF, as appropriate, and report such 
an assessment in accordance with the SAE reporting requirements if applicable.
A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out.
Generally, the facts (evidence) or arguments to suggest a causal relationship should be 
provided.
The investigator will use clinical judgment to determine the relationship and will also consult 
the Safety Statement and/or Product Information, for marketed products, in the determination 
of his/her assessment. Alternative causes, such as underlying disease(s), concomitant therapy, 
other risk factors, and the temporal relationship of the event to the study product will be 
considered and investigated.
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 informationand send an SAE follow-up report with the updated 
causality assessment. 
8.5
Withdrawal Due to an Adverse Event and Serious Adverse 
Events
Withdrawal due to AEs should be distinguished from withdrawal due to other causes, 
according to the definition of AE noted earlier, and recorded on the appropriate AE CRF
page. 
 
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When a subject withdraws because of an SAE, the SAE must be reported in accordance with 
the reporting requirements defined below.
8.6
Pregnancy
8.6.1
Time Period for Collecting Pregnancy Information
Pregnancy information will be collected on all pregnancies reported following administration 
of any study product and until 5 days after the lastdose.
8.6.2
Action to be Taken if Pregnancy Occurs
The investigator will collect pregnancy information on any subject who becomes pregnant 
while participating in the study after administration of the investigational productor washout 
product. The investigator will record pregnancy information on the appropriate form and e-
mail itto the GSK CH Clinical Operations Safety Reporting email box 
 within 24 hours of learning of the subject becoming pregnant. The GSK 
CH Study Manager or designee will be responsible for forwarding the SAE form to the Case 
Management 
Group, Global Clinical Safety and Pharmacovigilance mailbox 
The subject will be followed to determine the outcome of the pregnancy. Information on the 
status of the mother and infant / neonate (including concomitant medications taken by the 
mother during the pregnancy) will be forwarded by the investigator to the GSK CH Clinical 
Operations Safety Reporting email boxand the GSK CH Study Manager or designee will 
forward this information to the Case Management Group, Global Clinical Safety and 
Pharmacovigilance group mailbox at GSK
. Generally, follow-up will 
be no longer than 6 to 8 weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported.
While pregnancy itself is not considered to be an AE, abnormal pregnancy outcomes (eg, 
spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are 
considered to be and should be recorded as an SAE.
Any female participant who becomes pregnant while participating will discontinue study 
treatment.
8.7
Follow-up of Adverse Events and Serious Adverse Events
After the initial report, the investigator is required to proactively follow up with each subject 
and provide further information on the subject’s condition.
All AEs/SAEs will be followed until resolution, until the condition stabilizes, until the event 
is otherwise explained, or until the subject is lost to follow-up.  
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as may be indicated or as requested by GSK to elucidate as 
 
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fully as possible the nature and/or causality of the AE or SAE.This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals.
New or updated information will be recorded in the originally completed CRF.
The investigator will submit any updated SAE data to GSK within 24 hours of receipt of the 
information.
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 GSK by emailing the 
information to the GSK CH Clinical Operations Safety Reporting email box 
. The GSK CH Study Manager or designee will be responsible for 
forwarding theinformation to theCase Management Group, Global Clinical Safety and 
Pharmacovigilance group mailbox at GSK
The investigator will submit any updated SAE data to GSK within the designated reporting 
time frames.
9
DATA MANAGEMENT
As used in this protocol, the term CRF should be understood to refer to either a paper form or 
an electronic data record or both, depending on the data collection method used in this study. 
For this study subject data will be entered into an electronicCRF using a validated data 
system.
9.1
Source Documents/ Data
The source documents (e.g., hospital records, clinical andoffice charts, memoranda, subjects’ 
diaries or evaluation checklists,recorded data from automated instruments, microfiches, x-
rays, subject files involved in the clinical study) which contain the source of data recorded in 
the CRF should be specified in Section 6.  The CRF and diarycan be used as a source 
document at the discretion of data management.
Each subject will be assigned and identified by a unique Number. Any reference made to an 
individual subject within the study must be done using the unique Screening Number.
9.2
Case Report Form
A CRF is a printed, optical, or electronic document designed to record all of the protocol 
required information to be reported to the sponsor on each trial subject.
 
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For each subject who has given informed consent/assent and has been screened, CRF must be 
completed and signed by the Principal Investigator (or authorized designee) to certify that the 
data are complete and correct.  
Management of clinical data will be performed in accordance with Third Party BDM Vendor 
applicable standards and data cleaning procedures with oversight by GSK CH to ensure 
integrity of the data e.g., removing errors and inconsistencies in the data.In order to protect 
the privacy of subjects, no Personally Identifiable Information (PII) (including the subject
's 
name or initials or full birth date) is to be recorded in the CRF or aspart of the query text.
All CRF pages should be completed during a subject assessment when the CRF hasbeen 
designated as the source.Data that is sourced elsewhere should be entered into the CRF in an 
agreed upon timeframe between the Investigator and Sponsor.  
GSK CH will obtain and retain all CRFs and associated study data at the completion of the 
study. 
9.3
Data Handling
Documentation of all data management activities should allow step-by-step retrospective 
assessment of data quality and study performance. 
Any changes or corrections to data will be performed in the Electronic Data Capture (EDC) 
System, and it will include rationale for changes. The EDC system has an audit trail, which 
will provide a complete record of the changes and corrections endorsed by the Investigator. 
Any corrections to the entries made to the paper source documents must be dated, initialed, 
and explained (if necessary) and should not obscure the original entry. 
Adverse events will be coded using MedDRA (Medical Dictionary for Regulatory Activities) 
and concomitant medications terms (if applicable) using an internal validated medication 
dictionary, GSKDrug.  
9.3.1
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 CRF data, in addition to the 
queries already programmed and generated by the system, to raise manual queries as needed 
for site clarification or correction. The Clinical Dictionary Development and Management 
Group will raise queries as needed on safety data to code the terms (Adverse Events and 
Drugs) appropriately. 
The study monitor at the study site will review the CRFs in accordance with the monitoring 
plan, and any queries will be generated in the EDC System to the Investigator or designee, 
enabling the errors to be addressed in parallel with Data Management review. The study 
monitor can also run reports and listings on the CRFs, to raise manual queries as needed for 
site clarification or correction.
 
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9.4
Processing Patient Reported Outcomes
Patient reported outcome (PRO) data may be collected from diary cards, questionnaires,etc, 
and entered into the sponsor’s clinical data management system (DMS). In instances where 
the PRO data is entered into the DMS by GSK CH, the PROs will be anonymizedas agreed 
and documented prior to study initiation. PROs that are source will be retained by the 
investigator and certified copies will be sent to GSK CH. 
Inorder to protect the privacy of subjects, no Personally Identifiable Information (PII) 
(including the subject
's name or initials or birth date) is to be recorded on all PRO’s that will 
be forwarded to GSK CH.
10
STATISTICAL CONSIDERATIONS AND DATA ANALYSES
10.1
Sample Size Determination
10.2
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 finalization of the protocol and prior to 
study unblinding as appropriate.
Treatment differences in the study variables will be tested with the null hypothesis:
H0: there is no treatment difference versus the alternate hypothesis
H1: there is a treatment difference.
10.2.1
Demographic and Baseline Characteristics
Descriptive statistics (number of subjects, mean, standard deviation, median, minimum and 
maximumfor continuous variables, and frequency and percentage for categorical variables) 
will be provided for demographic baseline characteristics concomitant medication, medical 
history and compliance. 
10.2.2
Primary Analysis(es) 
The primary efficacy variable is thechange from baseline in overall MLSI score. The primary 
time-point is 8 weeks. 
 
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The overall MLSI (AxI) for each subject is derived at a tooth site level first before averaging 
over all the teeth sites assessed. The change from baseline is derived from theindividual sites 
first before calculating the average changeacross the sites assessed. 
The change from baseline in overall MLSI will be analysed using analysisof covariance 
(ANCOVA) with treatment as a fixed effectand baseline overall MLSI asa covariate.
The assumption of normality and homogeneity of variance in the ANCOVA modelwill be 
investigated.Violation of this assumption will be overcome using a suitable data 
transformation or a non-parametric technique (eg Wilcoxon Rank Sum testor Van Elteren 
Test).
There are no comparisons for the primary objective as the main objective is to look at the rank 
order of the treatments in level of stain reductionafter 8 weeks of treatment.This will be 
achieved via the adjusted means and confidence intervals for the means alongwith plots of 
MLSI over time. The hypothesis is that the test products will reduce stain to a greater extent 
than the reference products.
Two comparisons of interest will be done under secondary and exploratory objectives. These 
comparisons are: -
Test Product 1 vs Reference Product 1
Test Product 2 vs Reference Product 2.
Analyses at weeks 2 and 4 form part of the exploratory objectives.
10.2.3
Secondary Analysis(es)
Secondary analyses are covered in the primary
 analysis.
10.2.4
Safety Analysis(es)
Safety population will be used for safety assessments. Safety analyses will beperformed 
according to the treatment that the subject received (using variable ATRT).All AEs will be 
reviewed by the Clinical Research Scientist orDesignee prior to database lock and unblinding 
and will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). During 
this review stage, AEs willbe further categorized as oral or non-oral. AEs will be listed and 
summarized bytreatment received. Serious AEs will also be listed. AEs will be regarded as 
treatmentemergent if they occur on or after the first treatment application at the baseline visit.
The following AEs tables split by treatment will be produced:
Listing of all AEs (Randomized and Non-Randomized Subjects)
 
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Treatment emergent AEs by Oral/Non-Oral Preferred Term (PT)
Treatment emergent AEs by System Organ Class (SOC) and PT
Treatment emergent AEs by Intensity presented by System Organ Class (SOC) and PT
Treatment emergent treatment related AEs by Oral/Non-Oral
Listing of SAEs (if there are none a null listing will be produced; ifthere are more 
than 5 treatment emergent SAEsa table will beproduced instead by SOC and PT)
Non-serious treatment emergent AEs by SOC and PT (only produced if thereare more 
than 5 SAEs).
Listing of incidents (if there is none a null listing will be produced).
Further information related to safety also includes a table and listing of OST data.  The table 
will show changes in abnormality pre and post treatment. A table of exposure not needed in 
this study as it is a single use study.
10.2.5
Other Analysis(es)
10.2.5.1Exploratory variables
Change from Baseline in interproximal MLSI (AxI) stain score at weeks 2,4 and 8
Change from Baseline in overall area (A) stain score at weeks 2,4 and 8
Change from Baseline in overall intensity (I) stain score at weeks 2,4 and 8
Change from Baseline (Pre-treatment) in overall TPIfor day 2 post-treatment, week 8 
pre-treatment and week 8-post treatment
Change from Baseline (Pre-treatment) in interproximal TPI for day 2 post-treatment, 
week 8 pre-treatment and week 8 post-treatment
Repeatability stain score
Repeatability plaque score
10.2.5.2Definition of exploratory variables
All stain variables will be derived in a similar way based onrelevant tooth sites and analyzed 
as per the primary variable using the appropriate baseline value as a covariate.The 
interproximal stain sites are the mesial and distal tooth sites.
The overall TPI for each subject is derived at a tooth site level first before averaging over all
the teeth sites assessed. The change from baseline is derived at the individual sites first before 
calculating the average changeacross the sites assessed. 
 
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The interproximal TPI is based on themesial and distal tooth sites.The interproximal TPI 
score and change from baseline calculated in the same way as for the overall TPI.
10.2.5.3Analysis of exploratory variables
The change from baseline in TPI variableswill be analysed using analysisof covariance 
(ANCOVA) with treatment and MLSI stratification as fixed effectsand appropriate baseline 
(pre-treatment) TPI asa covariate.
The repeatstain and plaqueassessments will be compared to the original assessmentsand will 
not be used in any efficacy analysis.The first and second assessments on each tooth site will 
be crosstabulated.A weighted Kappa coefficient (κ), along with the 95% CI will be 
calculated to assessthe intra-examiner reliability. Fleiss-Cohen weighted kappa will be 
calculated for therepeatability analysis. Reliability will be deemed
Excellent if κ > 0.75
Fair to good if 0.4 ≤ κ ≤ 0.75
Poor if κ <0.4
All subjects who have repeatability data will be included in this analysis.
10.2.6
Definition of Analysis Populations
All assessments of safety will be based on the safety population, defined as all subjects who 
are randomized and receive at least one dose of study treatment during the study. Safety 
population summaries will be presented by treatment received.
The primary population for efficacy assessment will be the intent-to-treat (ITT) population, 
defined as all subjects who are randomized, receive the study treatment at least once and 
provide at least one post-baseline (post treatment) assessment of efficacy. All ITT population 
summaries and analyses will be presented by treatment randomized.
No Per Protocol population analysis will be performed for this study as it is purely an 
exploratory Proof of Principal study.
Repeatability population will be defined as any subject who has a repeat stain or plaque 
assessment. The repeat stain and plaque populations will be separate populations.
10.2.7
Exclusion of Data from Analysis 
Exclusion of any data from the analyses will be determined during a Blind Data Review 
Meeting prior to database lock. Any reasons for exclusion from an analysis population will be 
listed, if applicable.
 
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10.2.8
Handling of Dropouts and Missing Data 
Subjects who withdraw from the study early will be included in the study analysis up to the 
point of withdrawal. Subjects who withdraw will not be replaced. No data will be imputed in 
the case of dropouts or missing data.
10.2.9
Interim Analysis
No interim analysis is planned for this study
11
STUDY GOVERNANCE CONSIDERATIONS
11.1
Quality Control 
In accordance with applicable regulations including GCP, and GSK procedures, GSK or 
designee (i.e. third party vendor) monitors will contact the site prior to the start of the study to 
review with the site staff the protocol, study requirements, and their responsibilities to satisfy 
regulatory, ethical, and GSK requirements.
When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the CRF will serve as the source 
document.
GSK or designee will monitor the study and site activity to verify that the:
Data are authentic, accurate, and complete.
Safety and rights of subjects are being protected.
Study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements.
The extent and nature of monitoring will be described in a written monitoring plan on file at 
GSK CH. The investigator (or designee) agrees to allow the monitor direct access to all 
relevant documents and agrees to co-operate with the monitor to ensure that any problems 
detected in the course of these monitoring visits are resolved.
11.2
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 
 
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findings/relevant issues and to implement any corrective and/or preventative actions to 
address any findings/issues identified.
The investigatorwill notify GSK CH or its agents immediately of any regulatory inspection 
notification in relation to the study. Furthermore, the investigator will cooperate with GSK 
CH or its agents to prepare the study site for the inspection and will allow GSK CH or its 
agent, whenever feasible, to be present during the inspection. The investigator will promptly 
apply copies of the inspection finding to GSK CH or its agent. Before response submission to 
the regulatory authority, the investigator will provide GSK CH or its agents with an 
opportunity to review and comment on responses to any such findings. 
The sponsor will be available to help investigators prepare for an inspection.
11.3
Regulatory and Ethical Considerations
11.3.1
Institutional Review Board 
It is the responsibility of the investigator to have prospective approval of the study protocol, 
protocol amendments, informed consent documents, safety statement (including any updates) 
and other relevant documents, e.g.,recruitment advertisements, if applicable, from the IRB. 
All correspondence with the IRB should be retained in the investigator file.Copies of IRB 
approvals should be forwarded to GSK CH prior to the initiation of the study, and also when 
subsequent amendments to the protocol are made.
The only circumstance in which an amendment may be initiated prior to IRBapproval is 
where the change is necessary to eliminate apparent immediate hazards to the subjects.In that 
event, the investigator must notify the IRBand GSK CH in writing immediately after the 
implementation.
11.3.2
Ethical Conductof the Study
The study will be conducted in accordance with legal and regulatory requirements, as well as 
the general principles set forth in the International Ethical Guidelines for Biomedical 
Research Involving Human Subjects (Council for International Organizations of Medical 
Sciences 2002), guidelines for GCP (ICH 1996and revision 2), and the Declaration of 
Helsinki (World Medical Association 2013). 
In addition, the study will be conducted in accordance with the protocol, the ICH guideline on 
GCP, and applicable local regulatory requirements and laws.
11.3.3
Subject Information and Consent
All parties will ensure protection of subject personal data and will not include subject names 
or other identifiable data in any reports, publications, or other disclosures, except where 
required by laws. 
 
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When study data are compiled for transfer to GSK CH and other authorized parties, subject 
names, addresses, and other identifiable data will be replaced by numerical codes based on a 
numbering system provided by GSK CH inorder to de-identify study subjects.  
The study site will maintain a confidential list of subjects who participated in the study, 
linking each subject’s numerical codeto his or her actual identity.In case of data transfer, 
GSK CH will maintain high standards of confidentiality and protection of subjects’ personal 
data consistent with applicable privacy laws.
The informed consentdocuments must be in compliance with ICH GCP, local regulatory 
requirements, and legal requirements, including applicable privacy laws.
The informed consentdocuments used during the informed consent process must be reviewed 
and approved by the sponsor, approved by the IRB before use, and available for inspection.
The investigator must ensure that each study subject,is fully informed about the nature and 
objectives of the study and possible risks associated with participation. 
The investigator, or a person designated by the investigator, will obtain written informed 
consent from each subjectbefore any study-specific activity isperformed.  The investigator 
will retain the original of each subject
's signedinformed consentdocument.
11.3.4
Subject Recruitment 
Advertisements approved by IRBsand investigator databases may be used as recruitment 
procedures.Use of IRBapproved, generic, prescreening questionnaire to assess basic subject 
characteristics to determine general eligibility for this study is allowed.This generic 
questionnaire may be used by sites as a phone script and/or to review internal databases to 
identify subjects.  
GSKCH will have an opportunity to review and approve the content of any study recruitment 
materials directed to potential study subjects before such materials are used. 
11.3.5
Reporting of Safety Issues and Serious Breaches of the Protocol or 
ICH GCP 
Within GSK CH a serious breach is defined as a breach likely to affect to a significant degree 
the safety and rights of a subject or the reliability and robustness of the data generated in GSK 
CH-sponsored human subject research studies. 
In the event of any prohibition or restriction imposed (i.e., clinical hold) by an applicable 
competent authority in any area of the world, or if the investigator is aware of any new 
information that might influence the evaluation of the benefits and risks of the investigational
product, GSK CH should be informed immediately. 
In addition, the investigator will inform GSK CH immediately of any urgent safety measures 
taken by the investigator to protect the study subjects against any immediate hazard, and of 
any serious breaches of this protocol or of ICH GCP that the investigator becomes aware of.
 
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11.4
Posting of Information on Publicly Available Clinical Trial 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollmentof subjects begins in accordance with applicable GSK processes.
11.5
Provision of Study Results to Investigators
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the clinical study report.The investigator will be provided 
reasonable access to statistical tables, figures, and relevant reports and will have the 
opportunity to review the complete study results at a GSK site or other mutually-agreeable 
location.
GSK will also provide the investigator with the full summary of the study results.The 
investigator is encouraged to share the summary results with the study subjects, as 
appropriate.
The procedures and timing for public disclosure of the results summary and for development 
of a manuscript for publication will be in accordance with GSK Policy.
A manuscript will be progressed for publication in the scientific literature if the results 
provide important scientific or medical knowledge.
11.6
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 orall 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 atrue 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 acceptablequality control process exists for making 
these reproductions.
The investigator must assure that the subject’s anonymity will be maintained. On CRFs or 
other documents submitted to GSK CH, subjects should not be identified by their names or 
initials, but by an identification code. The investigator should keep a separate log of subjects’ 
 
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codes, names and addresses. Documents not for submission to GSK CH, e.g. subjects’ written 
consent forms, should be maintained by the investigator in strict confidence.
Records and documents, including signed ICF, pertaining to the conduct of this study must be 
retained by the investigator for 25 years from the issue of the final Clinical Study Report 
(CSR)/ equivalent summaryunless local regulations or institutional policies require a longer 
retention period. The minimum retention time will meet the strictest standard applicable to 
that site for the study, as dictated by any institutional requirements or local laws or 
regulations, GSK standards/procedures, and/or institutional requirements.  
No study document should be destroyed without a prior written agreement between GSK CH 
and the investigator. The investigator must notify GSK of any changes in the archival 
arrangements, including, but not limited to, archival at an off-site facility or transfer of 
ownership of the records in the event the investigator is no longer associated with the site.
11.7
Conditions for Terminating the Study 
Premature termination of this study may occur because of a regulatory authority decision,
change in opinion of the IRB, or investigational product safety problems, or at the discretion 
of GSK CH. In addition, GSK CH retains the right to discontinue development of KNO3/ 
NaF dentifricesat any time. 
If a study is prematurely terminated, GSK CH willpromptly notify the investigator.After 
notification, the investigator must promptly contact all participating subjects and should 
assure appropriate therapy/ follow-up for the subjects. As directed by GSK CH, all study 
materials must be collected and allCRFscompleted to the greatest extent possible. Where 
required by the applicable regulatory requirements, GSK CH should inform the regulatory 
authority(ies) and the investigator should promptly inform the IRB and provide the IRBa 
detailed written explanation of the termination or suspension. 
If the IRBterminates or suspends its approval/favorable opinion of a trial, the investigator 
should promptly notify the GSK CH and provide GSK CH with a detailed written explanation 
of the termination or suspension.
Upon completion or premature discontinuation of the study, the GSK CH monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in accordance 
with applicable regulations including GCP, and GSK CH Standard Operating Procedures.
11.8
Definition of Study End/End of Study 
The end of the study will be the date of the Last Subject Last Visit (LSLV). For this study the 
LSLV will date will be the primary completion date (PCD).
12
REFERENCES
 
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1. Ayad F, Mateo LR, Dillon R, Miller JM, Pilch S, Stewart B. Randomized clinical trial of 
two oral care regimens in reducing and controlling established dental plaque and 
gingivitis. American Journal of Dentistry 2015: Sep; 28 Spec No A:27A-32A. 
2. Davies, R. M. Toothpaste in the control of plaque/gingivitis and periodontitis. 
Periodontology 2000. 2008; 48: 23-30.
3. Feng X, He T, Cao M, He Y,  Ji N. A randomized clinical trial to assess anti-plaque 
effects of an oral hygiene regimen with a stannous-containing sodium fluoride dentifrice, 
advanced manual toothbrush, and CPC rinse. American Journal of Dentistry 2016: Apr; 
29(2): 120-124.
4.
5. ICH Topic6 Guideline for Good Clinical Practice CPMP/ICH/135/95 17th July 1996.
6. Joiner A. Whitening toothpastes: a review of the literature. J Dent 2010; 38(suppl 2): e17-
24.
7. Lobene, RR. Effect of Dentifrices on Tooth Stains with Controlled Brushing. Journal of 
American Dentistry 1968: 77; 849-855.
8. 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.
9. Marsh PD. Microbiological aspects of the chemical control of plaque and gingivitis. 
J.Dent.Res. 1992; 71: 1431-1438.
10.Pader M. Dentifrices. Kirk-Othmer. Encyclopedia of Chemical Technology. 1–9. 
Published Online: 13 April 2012.
11.Parkinson et al. AADR, Charlotte, NC, USA. 2014 (Abstr 1362); 
12.Parkinson et al. IADR 93rd General Session, Boston, MA, USA. 2015 (Abstr 1639)
13.Pickles MJ. Toothwear. In: Duckworth RM, ed. The teeth and their environment. 
Monographs in Oral Science, Vol. 19. Basel: Karger, 2006; 86-104.
14.Rykke M, Rolla G, Sonju T. Effect of pyrophosphateon protein adsorption to 
hydroxyapatite in vitro and on pellicle formation in vivo. Scand J Dent Res 1988; 96:517-
522.
15.Rykke M, Rolla G. Desorption of acquired enamel pellicle in vivo by pyrophosphate. 
Scand J Dent Res 1990; 98:211-214.
16.Schemehorn BR, Moore MH, Putt MS. Abrasion, polishing, and stain removal 
characteristics of various commercial dentifrices in vitro. J Clin Dent 2011; 22: 11-18.
17.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.
18.Turesky S, Gilmore ND, Glickman I. Reduced plaque formation by the chloromethyl 
analogue of Vitamin C. J Periodontol 1970; 41: 41-44.
19.World Medical Association Declaration of Helsinki,59th General Assembly, Seoul 2008.
 
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13
APPENDIX
13.1
Appendix I –Instructions Sheet
INSTRUCTIONS FOR PRODUCT USE
Brush twice a day (morning and evening).
Each time you brush:
Dispense a ribbon of toothpaste covering the length of the toothbrush head (see below 
picture).
Set your timer for 1 minute, and then brush your teeth in your usual manner for 1 timed 
minute.
Record each brushingon the diary card. Note any changes to these brushing procedures 
and reasons for changes (e.g. missed brushings, extra brushings) in the ‘Comments’ 
column.
Record any changes in yourhealthandmedications (prescription and over the counter 
medications),or treatmentson the diary card. 
Bring your diarycard (completed and not completed), toothpaste and toothbrush to the 
next study visit.
13.2
Appendix II -Abbreviations
The following is a list of abbreviations that may be used in the protocol. 
 
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Table 13-1
Abbreviations
Abbreviation
Term
AE
adverse event
ANCOVA
analysis of covariance
CI
confidence interval
CPC
cetylpyridinium chloride
CRF
case report form
DMS
data management system
EDC
electronic data capture
FSFV
first subject firstvisit
GCP
Good Clinical Practice
GSK CH
GlaxoSmithKline Consumer Healthcare
ICH
International Conference on Harmonisation
IND
investigational new drug application
IRB
institutional review board
ITT
intent-to-treat
KNO3
potassium nitrate
LSLV
last subject last visit 
MedDRA
medical Dictionary for Regulatory Activities
mL
milliliters 
MLSI
Macpherson modification of the Lobene Stain Index
N/A
not applicable
NaF
sodium fluoride
OHT 
oral hard tissue
OST
oral soft tissue
PI
principal investigator
PII
personally identifiable information
PT
preferred term
PRO
Patient reported outcome
SAE
serious adverse event
SOC
system organ class
SOP
standard operating procedure
SS
safety statement
STP 
sodium tripolyphosphate
SUSAR
suspected unexpected serious adverse reactions
TPI
Turesky modification of the Quigley Hein Index
USA
United States of America
 
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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 
 
 
24-Aug-2017 09:06:19
 
Clinical Operations Approval
Approved
21-Aug-2017 10:35:05
Biostatistics Approval
208078 Protocol
21-Aug-2017 10:22:00
 
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PPD
PPD
PPD

SAP_001.pdf: 
Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan 05Oct2017 
 
 
Property of GSK Consumer Healthcare 
Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of GSK 
Template Version Effective: 15-Jul-2017 
Page 1 of 49 
 
 
STATISTICAL REPORTING AND ANALYSIS PLAN  
 
 
 
 
A RANDOMIZED, EXAMINER-BLIND, PROOF OF PRINCIPAL STUDY 
TO INVESTIGATE THE STAIN AND PLAQUE REMOVAL CAPABILITY 
OF TWO EXPERIMENTAL 5% POTASSIUM NITRATE DENTIFRICES 
IN HEALTHY SUBJECTS WITH THE PROPENSITY FOR EXTRINSIC 
DENTAL STAIN 
 
 
 
Protocol Number: 208078  
Phase: 
II 
 
 
 
 
 
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Final Statistical Reporting and Analysis plan  05Oct2017 
 
 
 
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Document History 
 
Document 
Version Date 
Summary of Changes (New analysis or Change 
in planned analysis) 
Original Analysis Plan 05-Oct-2017 
Not applicable (N/A) 
 
 
 
 
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Final Statistical Reporting and Analysis plan  05Oct2017 
 
 
 
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Table of contents 
Document History ............................................................................................................... 2 
Table of contents ................................................................................................................. 
3 
1 Summary of Key Protocol Information 
................................
............................................... 5 
1.1 Study Design 
.......................................................................................................... 5 
1.2 Study Objectives 
.................................................................................................... 6 
1.3 Treatments 
................................
................................
............................................... 
8 
1.4 Sample Size Calculation 
................................
.......................................................... 9 
2 Planned Analyses 
............................................................................................................... 9 
2.1 Interim Analysis 
..................................................................................................... 9 
2.2 Final Analyses ......................................................................................................... 
9 
3 Considerations for Data Analyses and Data Handling Conventions 
................................... 9 
3.1 Baseline Definition 
................................
................................
.................................. 9 
3.2 Subgroups/Stratifications 
........................................................................................ 9 
3.3 Timepoints and Visit Windows 
................................
............................................. 
10 
4 Data Analysis 
................................................................................................................... 10 
4.1 Populations for Analysis 
....................................................................................... 10 
4.1.1 
Subject Disposition 
................................
............................................... 
10 
4.1.2 
Protocol Deviations 
.............................................................................. 11 
4.1.3 
Analysis Populations 
............................................................................ 11 
4.2 Subject Demographics and Other Baseline Characteristics 
................................... 
12 
4.2.1 
Demographic Characteristics 
................................
................................ 
12 
4.2.2 
General Medical History 
................................
....................................... 12 
4.3 Study Product Compliance and Use of Other Therapy ......................................... 12 
4.3.1 
Study Product Compliance 
................................................................... 12 
4.3.2 
Prior and Concomitant Medication 
....................................................... 
13 
4.4 Analysis of Efficacy .............................................................................................. 
13 
4.4.1 
Primary Efficacy Endpoint 
................................................................... 13 
4.4.2 
Secondary Efficacy Variables 
...............................................................
 14 
4.5 Analysis of Secondary Objectives 
................................
......................................... 14 
4.5.1 
Efficacy 
................................
................................
................................. 14 
4.6 Analysis of Exploratory Objectives 
...................................................................... 14 
4.6.2 
Handling of Missing Values/Censoring/Discontinuations 
.................... 
15 
4.7 Analysis of Safety 
................................................................................................ 15 
 
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Final Statistical Reporting and Analysis plan  05Oct2017 
 
 
 
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4.7.1 
Adverse Events and Serious Adverse Events 
........................................ 
15 
4.7.2 
Other Safety Variables 
................................
.......................................... 
17 
4.8 Analysis of Other Variables 
.................................................................................. 17 
5 Changes to the Protocol Defined Statistical Analysis Plan 
............................................... 
17 
6 Abbreviation 
................................
................................
...................................................... 18 
7 Attachment 1: List of Data Displays 
................................
................................................. 
19 
8 Appendix 1: Template for Tables, Figures and Listings 
................................................... 20 
 
 
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Potassium Nitrate / Sodium Fluoride 
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Final Statistical Reporting and Analysis plan  05Oct2017 
 
 
 
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The purpose of this Statistical Reporting and Analysis Plan (RAP) is to describe the planned 
analyses  and  outputs to  be  
included  
in  
the  Clinical  Study  Report  for Protocol  208078. The 
RAP will be finalized prior to data base freeze and treatment code un-blinding. 
1 
Summary of Key Protocol Information 
The purpose of this trial is to demonstrate the efficacy and safety of 5% Potassium Nitrate 
(KNO3) / Sodium Fluoride (NaF) to treat the symptoms of extrinsic dental stain. Efficacy will 
be demonstrated through evaluating and comparing the extrinsic dental stain and plaque 
removal of an experimental low abrasivity 0.5% spherical silica dentifrice and a marketed low 
abrasivity 6% standard silica abrasive dentifrice, and an experimental moderate abrasivity 1% 
spherical silica / 5% sodium tripolyphosphate (STP) dentifrice and a marketed high abrasivity 
16% standard abrasive silica / 5% STP dentifrice.  Safety will be demonstrated through 
assessment of the incidence of adverse events (AEs).  
1.1  
Study Design 
 
This is an 8 week, single-centre, examiner-blind, randomized, four treatment, parallel group 
study conducted in healthy subjects with a propensity for extrinsic dental stain (based on the 
judgement of the examiner). 
 
This proof of principle (PoP) study will be used to evaluate and compare the extrinsic dental 
stain  and  plaque removal  of  an  experimental low  abrasivity  0.5%  spherical  silica  dentifrice 
and  a  marketed  
low abrasivity  6%  standard  silica  abrasive  dentifrice,  and  an  experimental 
moderate  abrasivity  1%  spherical  silica  
/  5%  STP  dentifrice  and  a  marketed  high  abrasivity 
16%  standard  abrasive silica  /  5%  STP  dentifrice.  This  study  has  not  been  designed  to 
demonstrate  
the  specific contribution  
that  spherical  silica  or  STP,  are  having  on  
the overall 
reduction of stain and plaque. 
 
A sufficient number of subjects will be screened to randomize at least 124 subjects to ensure 
120 evaluable subjects complete the entire study. This will ensure approximately 30 evaluable 
subjects per treatment arm). 
 
Subjects will be stratified by their baseline total Macpherson modification of the Lobene stain 
index (MLSI (Area×Intensity)) score of the facial surfaces of 4 of the 12 anterior teeth (<15 
(low); ≥15  (high)).  A  single dental  examiner  will  perform  an  assessment  of  the  area  and 
intensity of extrinsic dental stain on the facial surfaces of 4 qualifying teeth selected (based on 
the  judgement  of  the  examiner)  from  the  6  maxillary  and  6  mandibular  anterior  teeth 
(universal numbering: 6-11 and 22-27), using the MLSI, at baseline 
(Visit 2), and following  2, 4 and 8  weeks (Visits 4, 5 and 6) twice daily  brushing. Subjects 
will return to the study site the day after baseline (MLSI) and Week 8 visits for pre- and post-
 
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brushing full  mouth Turesky  modification  of  the  Quigley  Hein  Index  (TPI)  plaque 
assessments (Visits 3 and 7) of the facial and lingual surfaces of all gradable teeth. 
1.2  
Study Objectives 
 
Objectives 
Endpoints 
Primary Objective 
Primary Endpoint 
• To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by overall MLSI (A×I), of 
a 0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after 8 weeks twice daily brushing. 
• Change from baseline in overall MLSI 
at 8 weeks. 
Secondary Objectives 
Secondary Endpoints 
Efficacy 
 
• To compare the removal of extrinsic 
dental stain, as measured by overall 
MLSI (A×I), of a 0.5% spherical 
silica dentifrice and a marketed 6% 
abrasive silica dentifrice, after 8 
weeks twice daily brushing 
• Change from baseline in overall MLSI at 
8 weeks. 
 
• To compare the removal of extrinsic 
dental stain, as measured by overall 
MLSI (A×I), of a moderate abrasivity 
1% spherical silica / 5% STP 
dentifrice and a marketed higher 
abrasivity 5% STP whitening 
dentifrice, after 8 weeks twice daily 
brushing.
 
• Change from baseline in overall MLSI at 
8 weeks. 
Exploratory Objectives 
Exploratory Endpoints 
• To evaluate the ranking order of 
plaque removal, as measured by TPI, 
of a 0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after a single use. 
• Change from pre-brushing to post-
brushing TPI after single use. 
 
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Objectives 
Endpoints 
• To evaluate the ranking order of 
plaque removal, as measured by TPI, 
of a 0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after 8 weeks twice daily brushing. 
• Change from baseline (pre-brushing) in 
overall post-brushing TPI at 8 weeks. 
• To evaluate the ranking order of 
Interproximal plaque removal, as 
measured by TPI, of a 0.5% spherical 
silica dentifrice, a marketed 6% 
abrasive silica dentifrice, a 1% 
spherical silica / 5% STP dentifrice, 
and a marketed 16% abrasive silica / 
5% STP dentifrice, after 8 weeks 
twice daily brushing.
 
• Change from baseline (pre-brushing) in 
overall post-brushing interproximal TPI 
at 8 weeks. 
• To compare the removal of extrinsic 
dental stain, as measured by 
interproximal (mesial + distal) MLSI 
(A×I), of a 0.5% spherical silica 
dentifrice and a marketed 6% 
abrasive silica dentifrice, after 2, 4 
and 8 weeks twice daily brushing.
 
• Change from baseline in overall 
interproximal MLSI at 2, 4 and 8 weeks. 
• To compare the removal of extrinsic 
dental stain, as measured by 
interproximal (mesial + distal) MLSI 
(A×I), of a 1% spherical silica / 5% 
STP dentifrice and a marketed 16% 
abrasive silica / 5% STP whitening 
dentifrice, after 2, 4 and 8 weeks 
twice daily brushing.
 
• Change from baseline in overall 
interproximal MLSI at 2, 4 and 8 weeks. 
• To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by interproximal (mesial + 
distal) MLSI (A×I), of a 0.5% 
spherical silica dentifrice, a marketed 
6% abrasive silica dentifrice, a 1% 
spherical silica / 5% STP dentifrice, 
and a marketed 16% abrasive silica / 
5% STP dentifrice, after 2, 4 and 8 
• Change from baseline in overall 
interproximal MLSI at 2, 4 and 8 weeks. 
 
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Objectives 
Endpoints 
weeks twice daily brushing.
 
• To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by overall MLSI Area (A), 
of a 0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after 2, 4 and 8 weeks twice daily 
brushing.
 
• Change from baseline in overall MLSI 
Area at 2, 4 and 8 weeks. 
• To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by overall MLSI Intensity 
(I), of a low abrasivity 0.5% spherical 
silica dentifrice, a marketed low 
abrasivity dentifrice, a moderate 
abrasivity 1% spherical silica / 5% 
STP dentifrice, and a marketed higher 
abrasivity 5% STP whitening 
dentifrice, after 2, 4 and 8 weeks 
twice daily brushing.
 
• Change from baseline in overall MLSI 
Intensity at 2, 4 and 8 weeks. 
Safety Objective 
Safety Endpoint 
• To evaluate the safety and oral 
tolerability of the test dentifrices 
when used twice daily for 8 weeks. 
• Adverse Events 
1.3  
Treatments 
The following study products will be supplied by the Clinical Supplies Department, GSK CH:  
 
• Test product 1: 5% KNO3 / 0.2542% NaF dentifrice with 0.5% spherical silica 
           (RDA~38);  
 
 
• Test product 2: 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% 
           STP (RDA~58);  
. 
 
• Reference Product 1: 5% KNO3 / 0.2542% NaF dentifrice with 6% abrasive silica 
           (RDA~36); Sensodyne Pronamel Daily Protection - Mint Essence ( 
 - USA 
           marketed dentifrice). 
 
• Reference Product 2: 5% KNO3 / 0.2543% NaF dentifrice with 16% abrasive silica 
 
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           and 5% STP (RDA~166); Sensodyne Extra Whitening ( 
 - USA marketed 
           dentifrice). 
1.4  
Sample Size Calculation 
A sufficient number of subjects will be screened to randomize at least 124 subjects to ensure 
120 evaluable subjects complete the entire study. This will ensure approximately 30 evaluable 
subjects per treatment arm.  
2 
Planned Analyses 
2.1  
Interim Analysis 
No interim analysis is planned. 
2.2 
Final Analyses 
The final planned primary  analyses will be performed  after  
the completion of the following 
sequential steps: 
1. All subjects have completed the study as defined in the protocol. 
2. All required database cleaning activities have been completed and database has been 
locked. 
3. All criteria for unblinding the randomization codes have been met and the randomization 
codes have been distributed. 
3  
Considerations for Data Analyses and Data Handling 
Conventions 
3.1  
Baseline Definition 
For all endpoints the baseline value will be the latest pre-dose assessment with a non-missing 
value.  
3.2  
Subgroups/Stratifications 
Subjects will be stratified by their baseline total MLSI (A×I) score for the facial surfaces of 4 
of the 12 anterior teeth (<15 (low); ≥15 (high)), and depending on which strata they fall under 
 
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will  be  assigned  
their  allocated  
test  product  
from  either  
the  “low”  or  “high”  
randomization 
schedule. The strata will be identified as: 
Strata 1: Low (MLSI <15) 
Strata 2: High (MLSI ≥15) 
Efficacy  variables  will  be  analysed  accounting  
for  
strata. Subgroups are not defined for this 
trial. 
3.3  
Timepoints and Visit Windows 
Time windows required for this study are as the following: 
• Visit 2 (MLSI Baseline) is minimum 24 hours and maximum two weeks from Visit 1 
(Screening) 
• Visit 3 (TPI Baseline) is 24 hours after Visit 2 
• Visit 4 (Week 2) is 14 ± 1 days from Visit 2. 
• Visit 5 (Week 4) is 28 ± 2 days from Visit 2. 
• Visit 6 (Week 8) is 56 ± 3 days from Visit 2. 
• Visit 7 (Week 8) is 57 ± 3 days from Visit 2. 
Visits outside of the above time windows will be reviewed during the Blinded Data Review 
Meeting (BDRM). 
4 
Data Analysis 
Data analysis will be performed by inVentiv Health Clinical. The statistical analysis software 
used will be SAS version 9.4 (Studio).   
Prior to database closure a BDRM will be conducted in which various aspects of the trial will 
be discussed and agreed.  
Unless otherwise described below, all listings will be produced for all randomized subjects.   
4.1  
Populations for Analysis 
Tables  described  
in  
this  section  other  
than  disposition will  be  produced  for  all  randomized 
subjects. 
4.1.1 Subject Disposition 
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not  subsequently  randomized.  A  summary  will  be  provided  of  the  number  of  subjects 
screened and the number of screen failures with reasons why subjects were not randomized.  
 
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Subject disposition will be summarized as the number and percentage of subjects (out of the 
number  of  
randomized  subjects)  who  complete  
the  study,  with  
the  number  who  discontinue 
broken down by reason for discontinuation (Table 14.1.1). The table will also summarize the 
number and percent of subjects assigned to each analysis population (refer to section 4.1.3).   
Subject  disposition  including  the  subject  status  (completer,  Yes/No),  critical  demographic 
data  (age,  sex,  race, ethnicity),  the  duration  of  treatment  before  discontinuation  and  the 
specific  reason  for  discontinuation,  will  be  listed  in for  randomized  subjects (Listing 
16.2.1.1.1) by treatment group and in for non-randomized subjects (Listing 16.2.1.1.2).  
4.1.2 Protocol Deviations 
Important  protocol deviations  (including  deviations related  to study  inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be listed. 
Protocol  deviations will  be  
tracked  by  
the  study  
team  
throughout  
the  conduct  of  
the  study. 
Data will be reviewed prior to unblinding and hard lock of the database to ensure all important 
deviations are captured and categorised. 
Violations that influence  the  efficacy  outcome will  be  given  in  the  “Review  Listing 
Requirement  (RLR)”  document  and important violations  will  be  identified  in  blinded  data 
review stage. 
All protocol deviations will be listed (Listing 16.2.2).   
4.1.3 Analysis Populations 
Five analysis populations are defined.   
Population 
Definition / Criteria 
Analyses 
Evaluated 
All Screened 
Subjects 
• All subjects who enter the study and sign 
the informed consent form. This 
population includes screen failures as well 
as those that are randomized. 
• Disposition, AE 
listing 
Randomized 
• All subjects who are randomized and may 
or may not receive the application of the 
study products. 
• Any subject who receives a treatment 
randomization number will be considered 
to have been randomized. 
• Protocol violations 
Safety 
• Comprise of all subjects who are 
randomized and receive at least one dose 
of study treatment. 
• This population will be based on the 
treatment the subject actually received. 
• Safety Population 
 
 
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Population 
Definition / Criteria 
Analyses 
Evaluated 
Intent-To-Treat  • Comprises of all randomized subjects who 
receive the study treatment at least once 
and provide at least one post-baseline 
(post treatment) assessment of efficacy. 
• This population will be based on the 
treatment to which the subject was 
randomize 
• Efficacy 
Repeatability 
• Any subject who has a repeat stain or 
plaque assessment. The repeat stain and 
plaque populations will be separate 
populations. 
• Repeatability 
Population 
 
The  numbers  of  subjects  included  in  each  of  the  analysis  populations,  and  the  number 
excluded from each population (except repeatability population) broken  down by the reason 
for  exclusion  will  be  presented  
(Table  14.1.3).  
  Subjects  excluded  
from  any  of  
the  analysis 
populations will be listed (Listing 16.2.3.1), with the reason for exclusion.   
4.2  
Subject Demographics and Other Baseline Characteristics 
Demographic and baseline characteristics summaries will be produced for the ITT and Safety 
populations by treatment group. 
4.2.1 Demographic Characteristics 
Categorical demographic variables include sex, race, strata and ethnicity.  These variables will 
be summarized by the number and percentage of subjects with each relevant characteristic in 
each treatment group.  Age will be summarized by the mean, standard deviation (SD), median 
(med),  minimum (min) and  maximum (max) values  in  each  treatment  group.    All 
demographic information will be tabulated in Table 14.1.4.1 for the Safety population, Table 
14.1.4.2 for the ITT population and listed in Listing 16.2.4.1. 
4.2.2 General Medical History 
Medical diagnoses/surgeries will be listed in Listing 16.2.4.2, with start date and end date or 
ongoing at the start of study drug.    
4.3 Study Product Compliance and Use of Other Therapy 
4.3.1 Study Product Compliance 
Brushing  compliance  (using  study  products  twice  daily)  will  be  listed  and  checked at  the 
blinded data review (BDR) stage for evaluation of protocol violations. 
 
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4.3.2 Prior and Concomitant Medication 
Prior medications will be listed by subject, with, indication, dose, dose form, frequency, route, 
start  date  and  end  date  (Listing  16.2.5.5). Prior  medications  are  defined  as  those  stopped 
before the first administration of the study products.  Concomitant medications will be listed 
similarly (Listing 16.2.5.6). Concomitant medications are defined as those ongoing or started 
on or after the first administration of the study products. 
4.4 
Analysis of Efficacy  
4.4.1 Primary Efficacy Endpoint 
4.4.1.1 Primary Efficacy Endpoint Definition 
The primary efficacy variable is the change from baseline in overall MLSI score. The primary 
time-point is 8 weeks. The overall MLSI (AxI) for each subject is derived at a tooth site level 
first before averaging over all the non-missing teeth sites assessed. The change from baseline 
is derived from the individual sites first before calculating the average change across the sites 
assessed.  
4.4.1.2 Statistical Hypothesis, Model, and Method of Analysis 
 
The primary objective is to evaluate the ranking order in extrinsic dental stain removal, as 
measured by overall MLSI (A×I), of a 0.5% spherical silica dentifrice, a marketed 6% 
abrasive silica dentifrice, a 1% spherical silica / 5% STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, after 8 weeks twice daily brushing. 
Summary statistics including mean, SD, median, min, max will be provided for baseline and 
Week 8 by randomized treatment group (Table 14.2.2.1).The change from baseline in overall 
MLSI will  be  analyzed  using  analysis  of  covariance  (ANCOVA)  with  
treatment  as  a  fixed 
effect and baseline overall MLSI as a covariate.  
There are no comparisons for the primary objective as the main objective is to look at the rank 
order  of  
the  
treatments  
in  
level  of  stain  reduction  after  8  weeks  of  
treatment.  This  will  be 
achieved via the adjusted means and confidence intervals (CIs) for the means along with plots 
of MLSI over time. Adjusted means of all treatments will be provided together with their 95% 
CIs and p-values (Table 14.2.2.2). 
The  assumption  of  normality  and  homogeneity  of  variance  
in  
the  ANCOVA  model  will  be 
investigated.  Violation  of  this  assumption  will be  overcome  using  a  suitable  data 
transformation or a non-parametric technique (e.g. Wilcoxon Rank Sum test). 
 
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4.4.1.3 Supportive Analyses 
Not Applicable 
4.4.2 Secondary Efficacy Variables 
The secondary efficacy variable is same as the primary efficacy variable.  
4.5 Analysis of Secondary Objectives 
4.5.1 
Efficacy 
The hypothesis is that the test products will reduce stain to a similar, or greater extent than the 
reference products. 
Two comparisons of interest will be done under the secondary objectives. These comparisons 
are:- 
Test Product 1 vs Reference Product 1 
Test Product 2 vs Reference Product 2. 
The change from baseline in overall MLSI at Week 8 will be analyzed using ANCOVA with 
treatment as a fixed effect and baseline overall MLSI as a covariate. 
From the  above ANCOVA model,  
treatment  differences  between  groups  
(Test Product 1 vs 
Reference Product 1 and Test Product 2 vs Reference Product 2), 95% CIs and p-values, will 
be provided (Table 14.2.2.2). 
The  assumption  of  normality  and  homogeneity  of  variance  
in  
the  ANCOVA model will  be 
investigated. Violation  of  this  assumption  will  be  overcome  using  a  suitable  data 
transformation or a non-parametric technique (e.g. Wilcoxon Rank Sum test). 
4.6 Analysis of Exploratory Objectives 
4.6.1.1 Exploratory Efficacy Endpoint Definition 
The exploratory variables are;  
• Change from baseline in overall interproximal MLSI (AxI) stain score at Weeks 2, 4 
and 8 
• Change from baseline in overall area (A) stain score at Weeks 2, 4 and 8 
• Change from baseline in overall intensity (I) stain score at Weeks 2, 4 and 8 
• Change from baseline (pre-treatment) in overall TPI for Day 2 post-treatment, Week 8 
pre-treatment and Week 8-post treatment 
 
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• Change from baseline (pre-treatment) in interproximal TPI  
for  Day 2 post-treatment, 
Week 8 pre-treatment and Week 8 post-treatment 
All  stain  variables  will  be  derived  in  a  similar  way  based  on  relevant  tooth  sites.  The 
interproximal stain sites are the mesial and distal tooth sites. 
The overall TPI for each subject is derived at a tooth site level first before averaging over all 
the teeth sites assessed. The change from baseline is derived at the individual sites first before 
calculating the average change across the sites assessed.  
The  
interproximal  TPI  
is  based  on  
the  mesial  and  distal  
tooth  sites.  The  
interproximal TPI 
score and change from baseline are calculated in the same way as for the overall TPI. 
4.6.1.2 Analysis of Exploratory Variables 
Summary statistics including mean, SD, median, min, and max will be provided for week 2 
and week 4 by randomized treatment group (Table 14.2.2.1). 
All stain variables will be analyzed as per the primary efficacy variable using the appropriate 
baseline values as a covariate.  
The  change  from  baseline  in  TPI  variables will  be analyzed using  analysis of  covariance 
(ANCOVA) with treatment and MLSI stratification as fixed effects and appropriate baseline 
(pre-treatment) TPI as a covariate.  
From  ANCOVA  model,  
the  adjusted  mean  
for  each  
treatment  group  will  be  provided  with 
95% CIs and corresponding p-values.  
Results for overall interproximal  MLSI  
(A×I) score, overall MLSI  area score, overall MLSI 
intensity score, overall TPI score and  overall Interproximal TPI Score  will be presented in 
Table  14.2.3.1,  14.2.3.2, Table  14.2.4.1,  14.2.4.2, Table  14.2.5.1,  14.2.5.2, Table  14.2.6.1, 
14.2.6.2 and Table 14.2.7.1, 14.2.7.2 respectively.  
4.6.2 
Handling of Missing Values/Censoring/Discontinuations 
 
Missing data will not be replaced or imputed. Dropouts will be included in analyses up to the 
point of discontinuation. 
4.7 
Analysis of Safety 
4.7.1 
Adverse Events and Serious Adverse Events 
All summaries of safety will be performed using the safety population and will be analyzed 
based  on  treatment  actually  received. No formal  statistical  testing will  be performed  on 
summary comparisons related to safety related measurements.  
 
 
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All AEs will be coded using the medical dictionary for regulatory activities (MedDRA). AEs 
will be classified by system organ class (SOC) and by preferred term (PT). In addition, prior 
to database lock all AEs will be reviewed by the Clinical Research Director (or designee) and 
categorized  as  either  oral  or  non-oral.  Safety  will  be  assessed  based  on  any  oral AEs (this 
includes those that are identified as treatment  emergent oral soft tissue  
(OST) abnormalities 
and spontaneously reported oral AEs). Any new or worsening OST condition that occurs after 
the OST examinations at Screening will be recorded as an AE. 
 
AEs will  be  summarized  using  descriptive  statistics  (frequency  
tables)  by treatment  group. 
Summary tables will indicate both the number of events and the number (percent) of subjects 
involved.  Summaries  of AEs  will  
include  only  
treatment emergent  adverse  events  
(TEAEs) 
unless otherwise noted. TEAEs are defined as new AEs that occur on or after the date/time of 
the  first  supervised  use  of  the  randomized  treatment  (or  events  aggravated  in  severity 
following treatment). Events with an onset date/time prior to first use of a treatment will be 
considered  as  non-treatment  emergent. Listing  of  AEs  (including  non-treatment  emergent 
from All Subjects) will be provided.  
 
The following summary tables and listings will be presented by treatment group. 
• Table of treatment emergent AEs by SOC and Preferred Term (Table 14.3.1.1.1) 
• Table  of  treatment  emergent  AEs  by  Oral/Non-Oral  and  Preferred  Term (Table 
14.3.1.1.2) 
• Table of treatment emergent treatment related AEs by SOC and Preferred Term  
(Table 14.3.1.3.1)  
• Table  of  Treatment  emergent  
treatment  
related  AEs  by  Oral/Non-Oral  and  Preferred 
Term (Table 14.3.1.3.2) 
• Table of  Non-serious treatment emergent AEs by SOC and PT (only produced if there 
are more than 5 SAEs) (Table 14.3.1.4) 
• Listing  of  all  AEs  (including  all  subjects: Listing  16.2.7.1.1 for  all  randomized 
subjects; Listing 16.2.7.1.2 for non-randomized subjects) 
• Listing of death (Listing 14.3.2.1) 
• Listing of non-fatal SAEs (Listing 14.3.2.2) 
• Listing of treatment emergent AEs leading to withdrawal (Listing 14.3.2.3) 
• Listing of treatment emergent AEs classified as oral (Listing 14.3.2.4) 
In the event that there is nothing to report a null listing will be produced.  
 
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4.7.2 
Other Safety Variables 
All incidents captured in the study will be listed (Listing 16.2.7.2). Oral soft issue data will be 
listed (Listing 16.2.7.3) 
4.8 
Analysis of Other Variables 
To assess the repeatability of the stain and TPI assessments, replicate examinations will be 
performed by the same qualified dental examiner at each assessment visit. Five subjects will 
be randomly selected for repeat MLSI and TPI assessments across each assessment window. 
The repeat stain and plaque assessments will be compared to the original assessments and will 
not be used in any efficacy analysis. The first and second assessments on each tooth site will 
be  cross tabulated. A  weighted  Kappa  coefficient  (κ),  along  with  the  95%  CI  will  be 
calculated  to assess the  intra-examiner  reliability.  Fleiss-Cohen  weighted  kappa  will  be 
calculated for the repeatability analysis. Reliability will be deemed  
• Excellent if κ > 0.75 
• Fair to good if 0.4 ≤ κ ≤ 0.75 
• Poor if κ <0.4 
All  
subjects  who  have  
repeatability  data will be  
included in this analysis. Results for repeat 
MLSI area  and  intensity assessments  will  be  in Table  14.2.8.1  and Table  14.2.8.2 
respectively.  Also result for repeat TPI assessment will be Table 14.2.8.3. 
5 
Changes to the Protocol Defined Statistical Analysis Plan 
Changes from the originally planned statistical analysis specified in the protocol are outlined 
in Table 1. 
 
Table 1 
Changes to Protocol Defined Analysis Plan 
Protocol 
Reporting & Analysis Plan 
Statistical Analysis section 
Statistical Analysis Plan 
Rationale for Changes 
• Sect
ion 10.2.1:  
Descr
ipt
ive stat
ist
ics (number of 
sub
jects, mean, standard dev
iat
ion, 
med
ian, m
in
imum and max
imum for 
cont
inuous var
iab
les, and frequency 
and percentage for categor
ica
l 
var
iab
les) w
i
l
l be prov
ided for 
demograph
ic base
l
ine character
ist
ics 
concom
itant med
icat
ion, med
ica
l 
h
istory and comp
l
iance.  
 
• We are not prov
id
ing 
descr
ipt
ive stat
ist
ics for 
concom
itant med
icat
ions, 
med
ica
l h
istor
ies and 
comp
l
iance. 
• Summary tab
les are not 
requ
ired for report
ing 
 
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Protocol 
Reporting & Analysis Plan 
Statistical Analysis section 
Statistical Analysis Plan 
Rationale for Changes 
• 10.2.4- Safety Ana
lys
is(es) 
L
ist
ing of SAEs (
if there are none a 
nu
l
l 
l
ist
ing w
i
l
l be produced; 
if there 
are more than 5 treatment emergent 
SAEs a tab
le w
i
l
l be produced 
instead by SOC and PT)
 
• Ana
lys
is of Safety 
L
ist
ing of death (L
ist
ing 
14.3.2.1); L
ist
ing of non-fata
l 
SAEs (L
ist
ing 14.3.2.2) 
 
• As per RAP temp
late and 
l
ist of requ
ired TLF 
l
ist for 
Ora
l stud
ies, two 
l
ist
ings 
have been added 
in RAP.  
• 10.2.6 Def
in
it
ion of Ana
lys
is 
Popu
lat
ions 
 
• We have added two 
popu
lat
ions 
in RAP wh
ich 
are a
l
l screened sub
jects 
and random
ized popu
lat
ion.  
• We w
i
l
l requ
ire these 
popu
lat
ion for some TLFs.  
• Safety Ana
lys
is(es) 
 
• The be
low tab
le 
is not 
inc
luded 
in the RAP:
 
Treatment emergent AEs by 
Intens
ity presented by 
System Organ C
lass (SOC) 
and PT 
 
• It 
is not requ
ired s
ince 
it 
is 
study dependent and not 
requ
ired for th
is study.   
 
6 
Abbreviation   
 
Abbreviation Term 
AE 
adverse event 
TEAE 
treatment-emergent adverse event 
ANCOVA 
analysis of covariance 
CI 
confidence interval 
ITT 
intent-to-treat 
KNO3 
potassium nitrate 
NaF 
sodium fluoride 
STP 
sodium tripolyphosphate 
MedDRA 
medical Dictionary for Regulatory Activities 
MLSI 
Macpherson modification of the Lobene Stain Index 
OST 
oral soft tissue 
SAE 
serious adverse event 
 
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Abbreviation Term 
SOC 
system organ class 
PT 
preferred term 
TPI 
Turesky modification of the Quigley Hein Index 
A 
Area 
I 
Intensity  
SD 
standard deviation  
Med 
median 
Min 
minimum 
Max 
maximum 
RLR 
review listing requirement 
BDRM 
blinded data review meeting 
SAS 
statistical analysis system 
GSK CH 
GlaxoSmithKline Consumer Healthcare 
POP 
proof of principle  
7 
Attachment 1: List of Data Displays 
 
Study 208078_L
ist of 
Outputs.xlsx
 
 
 
 
 
 
 
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Final Statistical Reporting and Analysis plan 05Oct2017 
 
 
Property of GSK Consumer Healthcare 
Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of GSK 
Template Version Effective: 15-Jul-2017 
Page 20 of 49 
8 
Appendix 1: Template for Tables, Figures and Listings 
This is a guideline which will give the guidance of treatment labels that will be used for the table header and in the figures, listings and in 
the footnotes.  
The treatment labels for the column heading will be as follow: 
• Test Product 1 
• Test Product 2 
• Reference Product 1 
• Reference Product 2 
The treatment comparison will be in below order; 
Test Product 1 Vs Test Product 2 
Reference Product 1 Vs Reference Product 2  
The below footnotes will be used for each outputs; 
Test Product 1: 5% KNO3 / 0.2542% NaF dentifrice with 0.5% spherical silica (RDA~38) 
Test Product 2: 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% STP (RDA~58) 
 
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Reference Product 1: Sensodyne Pronamel Daily Protection  (RDA~36). 
Reference Product 2: Sensodyne Extra Whitening (RDA~166).  
 
 
 
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Protocol 208078    
  
  
  
  
  
  
  
  
 
                            Program Run Date: DDMMMYYYY 
Table 14.1.1 
Subject Disposition 
All Screened Subjects 
Study Population: All Screened Subjects (N=xxx) 
 
Test Product 1   
N (%) 
 
Test Product 2 
N (%) 
Reference Product 1 
N (%) 
 
Reference Product 2 
N (%) 
Overall 
  N (%) 
 
TOTAL SUBJECTS SCREENED 
 
 
 
 
  xxx 
SUBJECTS NOT RANDOMIZED 
 
 
 
 
  xxx  (xx.x) 
       DID NOT MEET STUDY CRITERIA  
 
 
 
  xxx  (xx.x) 
       ADVERSE EVENT 
 
 
 
 
  Xxx  (xx.x) 
       LOST TO FOLLOW UP 
 
 
 
 
  xxx  (xx.x) 
       PROTOCOL VIOLATION 
 
 
 
 
  Xxx  (xx.x) 
       WITHDRAWAL OF CONSENT 
 
 
 
 
  Xxx  (xx.x) 
       OTHER 
 
 
 
 
  Xxx  (xx.x) 
  
SUBJECTS RANDOMIZED 
  xxx 
  xxx 
  xxx 
  xxx 
  xxx 
   COMPLETED STUDY 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    DID NOT COMPLETE STUDY 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
       DID NOT MEET STUDY CRITERIA   xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
       ADVERSE EVENT 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
       LOST TO FOLLOW-UP 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
       PROTOCOL VIOLATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
 
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Test Product 1   
N (%) 
 
Test Product 2 
N (%) 
Reference Product 1 
N (%) 
 
Reference Product 2 
N (%) 
Overall 
  N (%) 
       WITHDRAWAL OF CONSENT 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
       OTHER 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
 
 
 
 
 
 
SAFETY POPULATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
ITT POPULATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
 
Percentages for non-randomized category are based on number of screened subjects; percentages for randomized category are based on number of 
randomized subjects 
                                                                                                                           
  
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Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
Table 14.1.3 
Analysis Populations  
All Randomized Population 
Study Population: All Randomized Population (N=xxx) 
 
Test Dentifrice 
(RDA-58) 
  N (%) 
 
Test Dentifrice 
(RDA-77) 
   N (%) 
 Reference Dentifrice 
(RDA-80) 
      N (%) 
 
 Reference Dentifrice 
(RDA-120) 
    N (%) 
  Overall 
  
  N (%) 
 
 
 
NUMBER OF SUBJECTS EXCLUDED 
FROM SAFETY POPULATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    Reason 1 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    Reason 2 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    ... 
 
 
 
 
 
NUMBER OF SUBJECTS EXCLUDED 
FROM ITT POPULATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    Reason 1 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    Reason 2 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    ... 
 
 
 
 
 
 
 
 
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Protocol: 208078                                                                                                           Program Run Date: DDMMMYYYY 
Table 14.1.4.1.1 
Demographic and Baseline Characteristics 
Safety Population 
 
Study Population: Safety Population (N=xxx) 
 
 
Test Product 1    
N (%) 
 
Test Product 2 
N (%) 
...... 
... 
 
OVERALL 
(N=xx) 
SEX N (%) 
 
 
 
 
     MALE 
     FEMALE 
 
RACE N (%) 
        XX (XX.X) 
        XX (XX.X) 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
        XX (XX.X) 
     AFRICAN AMERICAN/AFRICAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
     AMERICAN INDIAN OR ALASKAN NATIVE 
        XX (XX.X) 
        XX (XX.X) 
 
        XX (XX.X) 
     ASIAN - CENTRAL/SOUTH ASIAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
 
        XX (XX.X) 
     ASIAN - EAST ASIAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
     ASIAN - SOUTH EAST ASIAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
     NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
     WHITE - ARABIC/NORTH AFRICAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
     WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
 
 
 
... 
 
ETHNICITY N (%) 
 
 
 
 
     HISPANIC OR LATINO 
        XX (XX.X) 
        XX (XX.X) 
 
        XX (XX.X) 
     NOT HISPANIC OR LATINO 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
 
 
 
... 
 
AGE (YEARS) 
 
 
... 
 
     N 
        XX 
        XX 
... 
        XX 
     MEAN 
        XX.X 
        XX.X 
... 
        XX.X 
     SD 
        XX.XX 
        XX.XX 
... 
        XX.XX 
 
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     MEDIAN 
        XX.X  
        XX.X  
........ 
        XX.X  
     MINIMUM 
        XX 
        XX 
…………. 
        XX 
     MAXIMUM 
        XX 
        XX 
... 
        XX 
 
 
 
 
 
STRATIFICATION 
 
 
 
 
   STRATA 1: LOW (MLSI <15) 
      XX (XX.X) 
       XX (XX.X) 
 
        XX (XX.X) 
   STRATA 2: HIGH (MLSI ≥15) 
      XX (XX.X) 
       XX (XX.X) 
 
        XX (XX.X) 
                                                                                                                             Page x of y 
                                                                                                          
 
 
 
 
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Protocol 208078  
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMMYYYY 
 
Table 14.2.2.1 
Summary of Overall MLSI Score 
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
 
 
Test Product 1 
(N=XX) 
Test Product 2 
(N=XX) 
…………….. 
Overall 
(N=XXX) 
 
Visit 
 
Observed 
Value 
 
Change from 
Baseline 
Observed 
Value 
 
Change from 
Baseline 
…………………….. 
Observed Value 
 
Change from 
Baseline 
BASELINE N  
XX      ... 
 
XX      ... 
 
…………….. 
XX      ... 
 
 
MEAN  
X.XX    ... 
 
X.XX    ... 
 
…………………….. 
X.XX    ... 
 
 
SD 
X.XXX    ... 
 
X.XXX    ..
. 
 
…………….. 
X.XXX    ... 
 
 
MEDIAN                                         
X.XX    ... 
 
X.XX    ... 
 
…………………….. 
X.XX    ... 
 
 
MINIMUM X.XX    ... 
 
X.XX    ... 
 
…………….. 
X.XX    ... 
 
 
MAXIMUM X.XX    ... 
 
X.XX    ... 
 
…………………….. 
X.XX    ... 
 
WEEK 2 
N 
XX 
XX 
XX 
XX 
…………….. 
XX 
XX 
 
MEAN 
X.XX 
X.XX 
X.XX 
X.XX 
…………………….. 
X.XX 
X.XX 
 
SD 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
…………….. 
X.XXX 
X.XXX 
 
MEDIAN                                         
X.X 
X.X 
X.X 
X.X 
…………………….. 
X.X 
X.X 
 
MINIMUM X.X 
X.X 
X.X 
X.X 
…………….. 
X.X 
X.X 
 
MAXIMUM X.X 
X.X 
X.X 
X.X 
…………………….. 
X.X 
X.X 
WEEK 4 
SAME AS 
ABOVE 
 
 
 
 
 
 
 
 
 
 
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                                                                                                                           Page x of y                                 
                                                                                                         
  
 
 
 
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Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMMYYYY 
 
 
Table 14.2.2.2 
Statistical Analysis of Overall Change Baseline in MLSI Score   
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
Visit 
 
Test Product 1 
(N=XX) 
Test Product 2 
(N=XX) 
Reference Product 1 
(N=XX) 
Reference Product 1 
(N=XX) 
WEEK 2 
ADJUSTED MEANS (SE)[1] 
X.XX (X.XXX) 
X.XX (X.XXX) 
X.XX (X.XXX) 
X.XX (X.XXX) 
 
95 % CI [1] 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
 
P-VALUE [1] 
0.XXXX 
0.XXXX 
0.XXXX 
0.XXXX 
 
COMPARISON                       DIFFERENCE (SE) [1,2]              95% CI [1]                  P-VALUE [1] 
 
TEST PRODUCT 1 VS REFERENCE 
PRODUCT 1  
X.XX (X.XXX) 
(X.XX, X.XX) 
0.XXXX 
 
TEST PRODUCT 2 VS REFERENCE 
PRODUCT 2 
X.XX (X.XXX) 
(X.XX, X.XX) 
0.XXXX 
 
 
 
 
 
 
WEEK 4 
SAME AS ABOVE 
 
 
 
 
 
  
 
 
 
 
    [1] From ANCOVA with treatment as factors and baseline overall MLSI score as a covariate 
    [2] Difference is first named treatment minus second named treatment such that a negative difference favours the first named treatment 
                                                                                                                           Page x of y   
                                                                                                        
  
Programming note: The same summary would be provided for the Week 8 also.  
 
 
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Protocol 208078  
  
  
  
  
  
  
  
  
  
 
             PROGRAM RUN DATE: DDMMMYYYY 
 
Table 14.2.6.1 
Summary of TPI Score 
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
Visit 
TimePoint 
 
Test Product 1 
(N=XX) 
Test Product 2 
(N=XX) 
……………… 
Overall 
(N=XX) 
 
 
 
Observed 
Values 
Change from 
Pre-brushing 
Observed 
Values 
Change from 
Pre-brushing 
……………… 
Observed Values 
Change from 
Pre-brushing 
BASELINE 
PRE- 
BRUSHING 
N  
XX       
 
XX       
 
……………… 
XX       
 
 
 
MEAN  
X.XX     
 
X.XX     
 
……………… 
X.XX     
 
 
 
SD 
X.XXX     
 
X.XXX     
 
……………… 
X.XXX     
 
 
 
MEDIAN                                         
X.XX   
 
X.XX   
 
……………… 
X.XX   
 
 
 
MINIMUM 
X.XX    
 
X.XX    
 
……………… 
X.XX    
 
 
 
MAXIMUM 
X.XX    
 
X.XX    
 
……………… 
X.XX    
 
 
 
 
 
 
 
 
……………… 
 
 
 
POST- 
BRUSHING 
N  
XX       
XX       
XX       
XX       
……………… 
XX       
XX       
 
 
MEAN  
X.XX     
X.XX     
X.XX     
X.XX     
……………… 
X.XX     
X.XX     
 
 
SD 
X.XXX     
X.XXX     
X.XXX     
X.XXX     
……………… 
X.XXX     
X.XXX     
 
 
MEDIAN                                         
X.XX   
X.XX   
X.XX   
X.XX   
……………… 
X.XX   
X.XX   
 
 
MINIMUM 
X.XX    
X.XX    
X.XX    
X.XX    
……………… 
X.XX    
X.XX    
 
 
MAXIMUM 
X.XX    
X.XX    
X.XX    
X.XX    
……………… 
X.XX    
X.XX    
 
 
 
 
 
 
 
 
 
 
WEEK 8 
SAME AS 
ABOVE 
 
 
 
 
 
 
 
 
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Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMMYYYY 
 
 
Table 14.2.6.2 
Statistical Analysis of Overall Change from Baseline (Pre-brushing) in TPI Score   
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
Visit 
 
Test Product 1 
(N=XX) 
Test Product 2 
(N=XX) 
Reference Product 1 
(N=XX) 
Reference Product 1 
(N=XX) 
BASELINE POST-BRUSHING ADJUSTED MEANS (SE)[1] 
X.XX (X.XXX) 
X.XX (X.XXX) 
X.XX (X.XXX) 
X.XX (X.XXX) 
 
95 % CI [1] 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
 
P-VALUE [1] 
0.XXXX 
0.XXXX 
0.XXXX 
0.XXXX 
 
COMPARISON                       DIFFERENCE (SE) [1,2]              95% CI [1]                  P-VALUE [1] 
 
TEST PRODUCT 1 VS REFERENCE 
PRODUCT 1  
X.XX (X.XXX) 
(X.XX, X.XX) 
0.XXXX 
 
TEST PRODUCT 2 VS REFERENCE 
PRODUCT 2 
X.XX (X.XXX) 
(X.XX, X.XX) 
0.XXXX 
 
 
 
 
 
 
WEEK 8 PRE-BRUSHING 
SAME AS ABOVE 
 
 
 
 
 
WEEK 8 POST-BRUSHING 
 SAME AS ABOVE 
 
 
 
 
    [1] From ANCOVA with treatment and MLSI stratification as factors and appropriate baseline (Pre-treatment) TPI score as a covariate 
    [2] Difference is first named treatment minus second named treatment such that a negative difference favours the first named treatment 
                                                                                                                           Page x of y   
                                                                                                        
  
Programming note: The same summary would be provided for the Week 8 pre-brushing and Week 8 post-brushing also.  
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 33 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMMYYYY 
Table 14.2.8.1 
Repeatability for MLSI Intensity Score 
Repeatability Population 
 
Study Population: Repeatability Population (N=XX) 
 
 
Initial \ Repeated 
Missing 
0 
1 
2 
3 
 
Missing  
xx 
xx 
xx 
xx 
xx 
 
0 
xx 
xx 
xx 
xx 
xx 
 
1 
xx 
xx 
xx 
xx 
xx 
 
2 
xx 
xx 
xx 
xx 
xx 
 
3 
xx 
xx 
xx 
xx 
xx 
Kappa 
0.xx 
 
 
 
 
 
95% CI 
(0.xx, 0.xx) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intensity Score: 0=No Stain; 1=light Stain; 2=Moderate Stain; 3=Heavy Stain. Missing means non-scorable. 
                                                                                                                       Page x of y 
                                                                                                    
 
 
 
Note to Programmer: For Table 14.2.8.2 and 14.2.8.3, use area and TPI scoring descriptions in footnote.  
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 34 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMYYYY 
 
Table 14.3.1.1.1 
Treatment Emergent Adverse Event by SOC and Preferred Term 
Safety Population 
Study Population: Safety Population (N=xx) 
SOC  
   Preferred Term 
 
Test Product 1 
(N=XX) 
Test Product 2 
(N=XX) 
Reference Product 1 
(N=XX) 
Reference Product 1 
(N=XX) 
Overall 
(N=XX) 
 
n (%) 
nAE 
n (%)     nAE 
n (%)     nAE 
n (%)     nAE 
n (%) 
nAE 
NUMBER OF SUBJECTS WITH 
AT LEAST ONE AE 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
NUMBER OF SUBJECTS WITH 
NO AE 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
 
 
 
 
 
 
 
 
SKIN AND SUBCUTANEOUS 
TISSUE DISORDERS 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
  ERYTHEMA 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
  DERMATITIS 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
 
 
 
 
 
 
GASTROINTESTINAL SYSTEM 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
  ABDOMINAL PAIN 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
  DRY MOUTH 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
  VOMITTING 
 
 
 
Etc. 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
n (%) = Number (percent) of subjects nAE = Number of adverse events. 
                                                                                                                        Page x of y                                    
                                                                                                      
 
  
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 35 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMYYYY 
 
Listing 16.1.7 
Randomization Information 
All Randomized Population 
Stratum 1: Low (MLSI <15)  
Subject 
Number 
Age/Sex/ Race [1] 
Randomization Number 
Treatment Randomized [2] 
Date of Randomization  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
[2] A= Reference Product 1; B= Reference Product 2; C= Test Product 1; D= Test Product 2.  
The block size for this randomization was used 8.  
                                                                                                                        Page x of y                                    
                                                                                                      
 
 
 
 
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Type 
Version 
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Effective Date 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 36 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMYYYY 
 
Listing 16.2.1.1.1 
Subject Disposition 
All Randomized Population 
 
Subject 
Age/Sex/ Race 
[1] 
Ethnicity 
Screening 
Date 
Treatment 
Start Date 
and Time 
Date of 
Completion or 
Withdrawal 
Duration of 
Treatment 
(Days) [2] 
Completed  
Primary 
Reason for 
Withdrawal 
Further Details [3] 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
[2] Treatment duration is calculated as date of completion or withdrawal minus treatment start date.  
[2] Further details of reasons for withdrawal. 
                                                                                                                        Page x of y                                    
                                                                                                      
 
 
 
 
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Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 37 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.2 
All Protocol Deviations 
All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age/Sex/Race[1] Deviation 
Sequence 
Start Date/Time 
End Date/Time 
Protocol Deviation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
 
                                                                                                               Page x of y                             
                                                                                                       
 
 
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 38 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMYYYY 
 
Listing 16.2.3.1 
Exclusion from Analysis Population 
All Randomized population 
 
Subject 
Number 
Age/Sex/Race[1] 
Treatment Start Date and 
Time 
Safety Population  
ITT Population 
Reasons for Exclusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male ; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
 
                                                                                                                        Page x of y        
                                                                                                      
 
Programming Note for Listing 16.2.3.1: This listing is based on population definition document. 
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 39 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.4.1 
Demographic Characteristics 
 All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age 
(years) 
Sex 
Race 
Ethnicity  
Stratification 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                                               Page x of y        
                                                                                                       
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 40 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.4.2 
Medical History and Current Medical Conditions 
 All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Age/Sex/Race 
[1] 
Any Medical History?  Medical Condition 
Start Date 
Ongoing? 
End Date 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
 
                                                                                                               Page x of y                             
                                                                                                       
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 41 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.5.6 
Concomitant Medications and Non-drug Therapies Taken During Treatment 
 All Randomized Population  
Subject 
Number 
Age/Sex/Race[1] Sequence 
Number 
Treatment 
[GSK Drug 
Synonym] 
Reason for 
Treatment 
Route of 
Administration 
Dose per 
Administration 
Frequency 
Start Date 
(Study Day [2]) 
End Date/ Ongoing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage.  
[2] Study day relative to the date of randomization. 
                                                                                                               Page x of y          
                                                                                                       
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 42 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.6.1 
Individual MLSI Stain Index 
All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age/Sex/Race[1] Visit  
Tooth Number 
(universal/FDI) 
Surface 
Site 
Intensity 
Score[2] 
Area Score[3] 
Area x Intensity 
Score 
Change from 
Bassline Score  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage.                                                      
[2] Intensity Score: 0=No Stain; 1=light Stain;2=Moderate Stain; 3=Heavy Stain. Missing means non-scorable; X=Missing.                              
[3] Area Score: 0=No Stain; 1=Stain covering upto 1/3 of region; 2=Stain covering upto 1/3 of region, and no more than 2/3 of region; 3=Stain covering 
more than 2/3 of region; X=Missing 
                                                                                                               Page x of y        
                                                                                              
 
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 43 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.6.2 
Individual Turesky Plaque Index (TPI) 
All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age/Sex/Race[1] Visit  
PRE/POST 
Tooth Number 
(universal/FDI) 
Surface 
Site 
TPI Score [2] 
Average Whole Mouth 
TPI 
Change from 
Bassline Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage.                                                      
[2] 0 = No plaque; 1 = Slight flecks of plaque at the cervical margin of the tooth; 2 = A thin continuous band of plaque (1 mm or smaller) at the 
cervical margin of the tooth; 3 = A band of plaque wider than 1 mm but covering less than 1/3 of the crown of the tooth; 4 = Plaque covering at least 1/3 
but less than 2/3 of the crown of the tooth; 5 = Plaque covering 2/3 or more of the crown of the tooth; X = Missing Tooth; N = Not Scorable                            
                                                                                                               Page x of y        
                                                                                              
 
 
 
 
 
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Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 44 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
           Program Run Date: DDMMYYYY 
 
Listing 16.2.7.1.1 
All Adverse Events 
All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age/Sex/
Race[1] 
Adverse Event 
(Preferred Term) 
(System Organ 
Class) 
 
Start Date 
/Study 
Day[2] 
Start 
Time 
End 
Date 
End 
Time 
Frequency 
/Intensity
[3] 
Related 
to Study 
Product? 
Action 
Taken re 
Study 
Product 
Outcome 
Serious? 
Withdrew?
[4] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
@@ Adverse events with verbatim text ending in this are classified as Oral AEs. 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
[2] Study day is the day relative to start of treatment, day 1 being the day of first treatment. 
[3] INT = Intermittent and SGLE = Single. 
[4] Did subject withdraw from study as a result of this adverse event? 
                                                                                                                                                                                                                                                                      Page x of y 
                                                                                                           
 
 
 
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Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 45 of 49 
 
Programming Note for Listing 16.2.7.1.2: 
• Repeat the same layout for listing 16.2.7.1.2 
• Population should be used ‘Non randomized Subjects’ 
• The fourth column should be only ‘Start Date’ 
• Add footnote ‘Only SAEs are collected for non randomized subjects’ 
• Delete the footnote related to study day and adjust the numbers accordingly. 
 
 
 
 
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Type 
Version 
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Effective Date 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 46 of 49 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.7.3 
Oral Soft Tissue Examination  
All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age/Sex/Race[1] 
Visit  
Area 
Condition  
 Details 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage.                                                      
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 47 of 49 
Protocol 208078                  
  
  
  
  
  
  
  
 
   Program Run Date: DDMMYYYY 
Figure 14.2.1 
Overall MLSI (A×I) Score Mean (±SE) Plot over Time by Treatment 
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
 
 
Mean and SE plotted are from summary statistics in T 14.2.2.1.1 
                                                                                                                            Page x of y       
0
0.5
1
1.5
2
2.5
0
2
4
6
8
Overall MLSI (AxI) Score
Time Point
TEST Product 1
Reference Product 1
TEST Product 2
Reference Product 2
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 48 of 49 
Protocol 208078                  
  
  
  
  
  
  
  
 
   Program Run Date: DDMMYYYY 
Figure 14.2.2 
Overall TPI Score Mean (±SE) Plot over Time by Treatment 
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
 
 
Mean and SE plotted are from summary statistics in T 14.2.5.1.1 
0
0.5
1
1.5
2
2.5
Overall TPI Score
Time Point
TEST Product 1
Reference Product 1
TEST Product 2
Reference Product 2
Pre
Baseline
Post
 
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208078 
Draft Statistical Reporting and Analysis plan  05Oct 2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 49 of 49 
                                                                                                                                        Page x of y    
Programming Note: Please repeat figure for the Week 8 also.  
    
 
 
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Effective Date 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
Property of GSK Consumer Healthcare 
Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of GSK 
Template Version Effective: 15-Jul-2017 
Page 1 of 53 
STATISTICAL REPORTING AND ANALYSIS PLAN 
A RANDOMIZED, EXAMINER-BLIND, PROOF OF PRINCIPAL STUDY 
TO INVESTIGATE THE STAIN AND PLAQUE REMOVAL CAPABILITY 
OF TWO EXPERIMENTAL 5% POTASSIUM NITRATE DENTIFRICES 
IN HEALTHY SUBJECTS WITH THE PROPENSITY FOR EXTRINSIC 
DENTAL STAIN 
Protocol Number: 208078 
Phase: 
II 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
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Page 2 of 53 
Document History 
 
Document 
Version Date 
Summary of Changes (New analysis or Change 
in planned analysis) 
Original Analysis Plan 05-Oct-2017 
Not applicable (N/A) 
RAP Amendment 
Version 1.0 
21-Nov-2017 
Add brushing compliance listing in RAP rather 
than cover it in BDRM.  
Add eCRF comments listing  
Added major Protocol deviation table 
Amend the text of section 3.3 (Timepoints and 
Visit Window)  
Added the text in repeatability population of 
section 4.1.3   
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 3 of 53 
Table of contents 
Document History ............................................................................................................... 2 
Table of contents ................................................................................................................. 
3 
1 Summary of Key Protocol Information 
................................
............................................... 5 
1.1 Study Design 
.......................................................................................................... 5 
1.2 Study Objectives 
.................................................................................................... 6 
1.3 Treatments 
................................
................................
............................................... 
8 
1.4 Sample Size Calculation 
................................
.......................................................... 9 
2 Planned Analyses 
............................................................................................................... 9 
2.1 Interim Analysis 
..................................................................................................... 9 
2.2 Final Analyses ......................................................................................................... 
9 
3 Considerations for Data Analyses and Data Handling Conventions 
................................... 9 
3.1 Baseline Definition 
................................
................................
.................................. 9 
3.2 Subgroups/Stratifications 
........................................................................................ 9 
3.3 Timepoints and Visit Windows 
................................
............................................. 
10 
4 Data Analysis 
................................................................................................................... 10 
4.1 Populations for Analysis 
....................................................................................... 10 
4.1.1 
Subject Disposition 
................................
............................................... 
10 
4.1.2 
Protocol Deviations 
.............................................................................. 11 
4.1.3 
Analysis Populations 
............................................................................ 11 
4.2 Subject Demographics and Other Baseline Characteristics 
................................... 
12 
4.2.1 
Demographic Characteristics 
................................
................................ 
12 
4.2.2 
General Medical History 
................................
....................................... 13 
4.3 Study Product Compliance and Use of Other Therapy ......................................... 13 
4.3.1 
Study Product Compliance 
................................................................... 13 
4.3.2 
Prior and Concomitant Medication 
....................................................... 
13 
4.4 Analysis of Efficacy .............................................................................................. 
13 
4.4.1 
Primary Efficacy Endpoint 
................................................................... 13 
4.4.2 
Secondary Efficacy Variables 
...............................................................
 14 
4.5 Analysis of Secondary Objectives 
................................
......................................... 14 
4.5.1 
Efficacy 
................................
................................
................................. 14 
4.6 Analysis of Exploratory Objectives 
...................................................................... 15 
4.6.2 
Handling of Missing Values/Censoring/Discontinuations 
.................... 
16 
4.7 Analysis of Safety 
................................................................................................ 16 
 
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Potassium Nitrate / Sodium Fluoride 
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4.7.1 
Adverse Events and Serious Adverse Events 
........................................ 
16 
4.7.2 
Other Safety Variables 
................................
.......................................... 
17 
4.8 Analysis of Other Variables 
.................................................................................. 17 
5 Changes to the Protocol Defined Statistical Analysis Plan 
............................................... 
17 
6 Abbreviation 
................................
................................
...................................................... 19 
7 Attachment 1: List of Data Displays 
................................
................................................. 
20 
8 Appendix 1: Template for Tables, Figures and Listings 
................................................... 21 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
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Page 5 of 53 
The purpose of this Statistical Reporting and Analysis Plan (RAP) is to describe the planned 
analyses  and  outputs to  be  
included  
in  
the  Clinical  Study  Report  for Protocol  208078. The 
RAP will be finalized prior to data base freeze and treatment code un-blinding. 
1 
Summary of Key Protocol Information 
The purpose of this trial is to demonstrate the efficacy and safety of 5% Potassium Nitrate 
(KNO3) / Sodium Fluoride (NaF) to treat the symptoms of extrinsic dental stain. Efficacy will 
be demonstrated through evaluating and comparing the extrinsic dental stain and plaque 
removal of an experimental low abrasivity 0.5% spherical silica dentifrice and a marketed low 
abrasivity 6% standard silica abrasive dentifrice, and an experimental moderate abrasivity 1% 
spherical silica / 5% sodium tripolyphosphate (STP) dentifrice and a marketed high abrasivity 
16% standard abrasive silica / 5% STP dentifrice.  Safety will be demonstrated through 
assessment of the incidence of adverse events (AEs).  
1.1  
Study Design 
 
This is an 8 week, single-centre, examiner-blind, randomized, four treatment, parallel group 
study conducted in healthy subjects with a propensity for extrinsic dental stain (based on the 
judgement of the examiner). 
 
This proof of principle (PoP) study will be used to evaluate and compare the extrinsic dental 
stain  and  plaque removal  of  an  experimental low  abrasivity  0.5%  spherical  silica  dentifrice 
and  a  marketed  
low abrasivity  6%  standard  silica  abrasive  dentifrice,  and  an  experimental 
moderate  abrasivity  1%  spherical  silica  
/  5%  STP  dentifrice  and  a  marketed  high  abrasivity 
16%  standard  abrasive silica  /  5%  STP  dentifrice.  This  study  has  not  been  designed  to 
demonstrate  
the  specific contribution  
that  spherical  silica  or  STP,  are  having  on  
the overall 
reduction of stain and plaque. 
 
A sufficient number of subjects will be screened to randomize at least 124 subjects to ensure 
120 evaluable subjects complete the entire study. This will ensure approximately 30 evaluable 
subjects per treatment arm). 
 
Subjects will be stratified by their baseline total Macpherson modification of the Lobene stain 
index (MLSI (Area×Intensity)) score of the facial surfaces of 4 of the 12 anterior teeth (<15 
(low); ≥15  (high)).  A  single dental  examiner  will  perform  an  assessment  of  the  area  and 
intensity of extrinsic dental stain on the facial surfaces of 4 qualifying teeth selected (based on 
the  judgement  of  the  examiner)  from  the  6  maxillary  and  6  mandibular  anterior  teeth 
(universal numbering: 6-11 and 22-27), using the MLSI, at baseline 
(Visit 2), and following  2, 4 and 8  weeks (Visits 4, 5 and 6) twice daily  brushing. Subjects 
will return to the study site the day after baseline (MLSI) and Week 8 visits for pre- and post-
 
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brushing full  mouth Turesky  modification  of  the  Quigley  Hein  Index  (TPI)  plaque 
assessments (Visits 3 and 7) of the facial and lingual surfaces of all gradable teeth. 
1.2  
Study Objectives 
 
Objectives 
Endpoints 
Primary Objective 
Primary Endpoint 
• To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by overall MLSI (A×I), of 
a 0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after 8 weeks twice daily brushing. 
• Change from baseline in overall MLSI 
at 8 weeks. 
Secondary Objectives 
Secondary Endpoints 
Efficacy 
 
• To compare the removal of extrinsic 
dental stain, as measured by overall 
MLSI (A×I), of a 0.5% spherical 
silica dentifrice and a marketed 6% 
abrasive silica dentifrice, after 8 
weeks twice daily brushing 
• Change from baseline in overall MLSI at 
8 weeks. 
 
• To compare the removal of extrinsic 
dental stain, as measured by overall 
MLSI (A×I), of a moderate abrasivity 
1% spherical silica / 5% STP 
dentifrice and a marketed higher 
abrasivity 5% STP whitening 
dentifrice, after 8 weeks twice daily 
brushing.
 
• Change from baseline in overall MLSI at 
8 weeks. 
Exploratory Objectives 
Exploratory Endpoints 
• To evaluate the ranking order of 
plaque removal, as measured by TPI, 
of a 0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after a single use. 
• Change from pre-brushing to post-
brushing TPI after single use. 
 
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Objectives 
Endpoints 
• To evaluate the ranking order of 
plaque removal, as measured by TPI, 
of a 0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after 8 weeks twice daily brushing. 
• Change from baseline (pre-brushing) in 
overall post-brushing TPI at 8 weeks. 
• To evaluate the ranking order of 
Interproximal plaque removal, as 
measured by TPI, of a 0.5% spherical 
silica dentifrice, a marketed 6% 
abrasive silica dentifrice, a 1% 
spherical silica / 5% STP dentifrice, 
and a marketed 16% abrasive silica / 
5% STP dentifrice, after 8 weeks 
twice daily brushing.
 
• Change from baseline (pre-brushing) in 
overall post-brushing interproximal TPI 
at 8 weeks. 
• To compare the removal of extrinsic 
dental stain, as measured by 
interproximal (mesial + distal) MLSI 
(A×I), of a 0.5% spherical silica 
dentifrice and a marketed 6% 
abrasive silica dentifrice, after 2, 4 
and 8 weeks twice daily brushing.
 
• Change from baseline in overall 
interproximal MLSI at 2, 4 and 8 weeks. 
• To compare the removal of extrinsic 
dental stain, as measured by 
interproximal (mesial + distal) MLSI 
(A×I), of a 1% spherical silica / 5% 
STP dentifrice and a marketed 16% 
abrasive silica / 5% STP whitening 
dentifrice, after 2, 4 and 8 weeks 
twice daily brushing.
 
• Change from baseline in overall 
interproximal MLSI at 2, 4 and 8 weeks. 
• To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by interproximal (mesial + 
distal) MLSI (A×I), of a 0.5% 
spherical silica dentifrice, a marketed 
6% abrasive silica dentifrice, a 1% 
spherical silica / 5% STP dentifrice, 
and a marketed 16% abrasive silica / 
5% STP dentifrice, after 2, 4 and 8 
• Change from baseline in overall 
interproximal MLSI at 2, 4 and 8 weeks. 
 
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Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
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Objectives 
Endpoints 
weeks twice daily brushing.
 
• To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by overall MLSI Area (A), 
of a 0.5% spherical silica dentifrice, a 
marketed 6% abrasive silica 
dentifrice, a 1% spherical silica / 5% 
STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, 
after 2, 4 and 8 weeks twice daily 
brushing.
 
• Change from baseline in overall MLSI 
Area at 2, 4 and 8 weeks. 
• To evaluate the ranking order in 
extrinsic dental stain removal, as 
measured by overall MLSI Intensity 
(I), of a low abrasivity 0.5% spherical 
silica dentifrice, a marketed low 
abrasivity dentifrice, a moderate 
abrasivity 1% spherical silica / 5% 
STP dentifrice, and a marketed higher 
abrasivity 5% STP whitening 
dentifrice, after 2, 4 and 8 weeks 
twice daily brushing.
 
• Change from baseline in overall MLSI 
Intensity at 2, 4 and 8 weeks. 
Safety Objective 
Safety Endpoint 
• To evaluate the safety and oral 
tolerability of the test dentifrices 
when used twice daily for 8 weeks. 
• Adverse Events 
1.3  
Treatments 
The following study products will be supplied by the Clinical Supplies Department, GSK CH:  
 
• Test product 1: 5% KNO3 / 0.2542% NaF dentifrice with 0.5% spherical silica 
           (RDA~38);  
. 
 
• Test product 2: 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% 
           STP (RDA~58);  
. 
 
• Reference Product 1: 5% KNO3 / 0.2542% NaF dentifrice with 6% abrasive silica 
           (RDA~36); Sensodyne Pronamel Daily Protection - Mint Essence ( 
 - USA 
           marketed dentifrice). 
 
• Reference Product 2: 5% KNO3 / 0.2543% NaF dentifrice with 16% abrasive silica 
 
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           and 5% STP (RDA~166); Sensodyne Extra Whitening ( 
 - USA marketed 
           dentifrice). 
1.4  
Sample Size Calculation 
A sufficient number of subjects will be screened to randomize at least 124 subjects to ensure 
120 evaluable subjects complete the entire study. This will ensure approximately 30 evaluable 
subjects per treatment arm.  
2 
Planned Analyses 
2.1  
Interim Analysis 
No interim analysis is planned. 
2.2 
Final Analyses 
The final planned primary  analyses will be performed  after  
the completion of the following 
sequential steps: 
1. All subjects have completed the study as defined in the protocol. 
2. All required database cleaning activities have been completed and database has been 
locked. 
3. All criteria for unblinding the randomization codes have been met and the randomization 
codes have been distributed. 
3  
Considerations for Data Analyses and Data Handling 
Conventions 
3.1  
Baseline Definition 
For all endpoints the baseline value will be the latest pre-dose assessment with a non-missing 
value.  
3.2  
Subgroups/Stratifications 
Subjects will be stratified by their baseline total MLSI (A×I) score for the facial surfaces of 4 
of the 12 anterior teeth (<15 (low); ≥15 (high)), and depending on which strata they fall under 
 
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will  be  assigned  
their  allocated  
test  product  
from  either  
the  “low”  or  “high”  
randomization 
schedule. The strata will be identified as: 
Strata 1: Low (MLSI <15) 
Strata 2: High (MLSI ≥15) 
Efficacy  variables  will  be  analysed  accounting  
for  
strata. Subgroups are not defined for this 
trial. 
3.3  
Timepoints and Visit Windows 
Time windows for this study are as the following: 
• Visit 2 (MLSI Baseline) is minimum 24 hours and maximum two weeks from Visit 1 
(Screening) 
• Visit 3 (TPI Baseline) is 24 hours after Visit 2 
• Visit 4 (Week 2) is 14 ± 1 days from Visit 2. 
• Visit 5 (Week 4) is 28 ± 2 days from Visit 2. 
• Visit 6 (Week 8) is 56 ± 3 days from Visit 2. 
• Visit 7 (Week 8) is 57 ± 3 days from Visit 2. 
 
All  data will  be  accepted  
for  
the  analysis.  Deviations from  
the  scheduled  visit  window are 
considered to be minor.   
4 
Data Analysis 
Data analysis will be performed by inVentiv Health Clinical. The statistical analysis software 
used will be SAS version 9.4 (Studio).   
Prior to database closure a BDRM will be conducted in which various aspects of the trial will 
be discussed and agreed.  
Unless otherwise described below, all listings will be produced for all randomized subjects.   
4.1  
Populations for Analysis 
Tables  described  
in  
this  section  other  
than  disposition will  be  produced  for  all  randomized 
subjects. 
4.1.1 Subject Disposition 
Screen failures are defined as subjects who consent to participate in the clinical study but are 
not  subsequently randomized.  A  summary  will  be  provided  of  the  number  of  subjects 
screened and the number of screen failures with reasons why subjects were not randomized.  
 
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Subject disposition will be summarized as the number and percentage of subjects (out of the 
number  of  
randomized  subjects) who  complete  
the  study,  with  
the  number  who  discontinue 
broken down by reason for discontinuation (Table 14.1.1). The table will also summarize the 
number and percent of subjects assigned to each analysis population (refer to section 4.1.3).   
Subject  disposition  including  the  subject  status  (completer,  Yes/No), critical  demographic 
data  (age,  sex,  race, ethnicity), the  duration  of  treatment  before  discontinuation and  the 
specific  reason  for  discontinuation, will  be  listed  in for  randomized  subjects (Listing 
16.2.1.1.1) by treatment group and in for non-randomized subjects (Listing 16.2.1.1.2).  
4.1.2 Protocol Deviations 
Important  protocol deviations  (including  deviations related  to  study  inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be listed. 
Protocol  deviations will  be  
tracked  by  
the  study  
team  
throughout  
the  conduct  of  
the  study. 
Data will be reviewed prior to unblinding and hard lock of the database to ensure all important 
deviations are captured and categorised. 
Violations that  influence  the  efficacy  outcome will  be  given in  the  “Review  Listing 
Requirement  (RLR)”  document  and important violations  will  be  identified  in  blinded  data 
review stage. 
The number and percentage of subjects with any important protocol deviations and with each 
type of major protocol deviations will be presented by treatment (Table 14.1.2). All protocol 
deviations will be listed (Listing 16.2.2).  
4.1.3 Analysis Populations 
Five analysis populations are defined.   
Population 
Definition / Criteria 
Analyses Evaluated 
All Screened 
Subjects 
• All subjects who enter the study 
and sign the informed consent 
form. This population includes 
screen failures as well as those 
that are randomized. 
• Disposition, AE listing 
Randomized 
• All subjects who are randomized 
and may or may not receive the 
application of the study products. 
• Any subject who receives a 
treatment randomization number 
will be considered to have been 
randomized. 
• Protocol violations 
Safety 
• Comprise of all subjects who are 
randomized and receive at least 
one dose of study treatment. 
• Safety Analysis 
 
 
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Population 
Definition / Criteria 
Analyses Evaluated 
• This population will be based on 
the treatment the subject actually 
received. 
Intent-To-Treat  • Comprises of all randomized 
subjects who receive the study 
treatment at least once and 
provide at least one post-baseline 
(post treatment) assessment of 
efficacy. 
• This population will be based on 
the treatment to which the 
subject was randomize 
• Efficacy 
Repeatability 
• Any subject who has a repeat 
stain or plaque assessment. The 
repeat stain and plaque 
populations will be separate 
populations. MLSI repeatability 
population and TPI repeatability 
population will be subset of the 
repeatability population.  
• Repeatability Analysis 
 
 
 
 
 
The  numbers  of  subjects  included  in  each  of  the  analysis  populations,  and  the  number 
excluded from each population (except repeatability population) broken  down by the reason 
for  exclusion  will  be  presented  
(Table  14.1.3).  
  Subjects  excluded  
from  any  of  
the  analysis 
populations will be listed (Listing 16.2.3.1), with the reason for exclusion.   
4.2  
Subject Demographics and Other Baseline Characteristics 
Demographic and baseline characteristics summaries will be produced for the ITT and Safety 
populations by treatment group. 
4.2.1 Demographic Characteristics 
Categorical demographic variables include sex, race, strata and ethnicity.  These variables will 
be summarized by the number and percentage of subjects with each relevant characteristic in 
each treatment group.  Age will be summarized by the mean, standard deviation (SD), median 
(med),  minimum (min) and  maximum (max) values  in  each  treatment  group.    All 
demographic information will be tabulated in Table 14.1.4.1 for the Safety population, Table 
14.1.4.2 for the ITT population and listed in Listing 16.2.4.1. 
 
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4.2.2 General Medical History 
Medical diagnoses/surgeries will be listed in Listing 16.2.4.2, with start date and end date or 
ongoing at the start of study drug.    
4.3 Study Product Compliance and Use of Other Therapy 
4.3.1 Study Product Compliance 
Brushing compliance (using study products twice daily) will be listed (Listing 16.2.5.1). This 
listing will include expected number of brushing, actual number of brushing and percentage of 
compliance. 
4.3.2 Prior and Concomitant Medication 
Prior medications will be listed by subject, with, indication, dose, dose form, frequency, route, 
start  date  and  end  date  (Listing  16.2.5.5). Prior  medications are  defined  as  those  stopped 
before the first administration of the study products.  Concomitant medications will be listed 
similarly (Listing 16.2.5.6). Concomitant medications are defined as those ongoing or started 
on or after the first administration of the study products. 
4.4 
Analysis of Efficacy  
4.4.1 Primary Efficacy Endpoint 
4.4.1.1 Primary Efficacy Endpoint Definition 
The primary efficacy variable is the change from baseline in overall MLSI score. The primary 
time-point is 8 weeks. The overall MLSI (AxI) for each subject is derived at a tooth site level 
first before averaging over all the non-missing teeth sites assessed. The change from baseline 
is derived from the individual sites first before calculating the average change across the sites 
assessed.  
4.4.1.2 Statistical Hypothesis, Model, and Method of Analysis 
 
The primary objective is to evaluate the ranking order in extrinsic dental stain removal, as 
measured by overall MLSI (A×I), of a 0.5% spherical silica dentifrice, a marketed 6% 
abrasive silica dentifrice, a 1% spherical silica / 5% STP dentifrice, and a marketed 16% 
abrasive silica / 5% STP dentifrice, after 8 weeks twice daily brushing. 
Summary statistics including mean, SD, median, min, max will be provided for baseline and 
Week 8 by randomized treatment group (Table 14.2.2.1).The change from baseline in overall 
MLSI will  be  analyzed  using  analysis of  covariance  (ANCOVA)  with treatment as a  fixed 
effect and baseline overall MLSI as a covariate.  
 
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There are no comparisons for the primary objective as the main objective is to look at the rank 
order  of  
the  
treatments  
in  
level  of  stain  reduction  after  8  weeks  of  
treatment.  This  will  be 
achieved via the adjusted means and confidence intervals (Cis) for the means along with plots 
of MLSI over time. Adjusted means of all treatments will be provided together with their 95% 
Cis and p-values (Table 14.2.2.2). 
The  assumption  of  normality  and  homogeneity  of  variance  
in  
the  ANCOVA  model will  be 
investigated. Violation  of  this  assumption  will  be  overcome  using  a  suitable  data 
transformation or a non-parametric technique (e.g. Wilcoxon Rank Sum test). 
4.4.1.3 Supportive Analyses 
Not Applicable 
4.4.2 Secondary Efficacy Variables 
The secondary efficacy variable is same as the primary efficacy variable.  
4.5 Analysis of Secondary Objectives 
4.5.1 
Efficacy 
The hypothesis is that the test products will reduce stain to a similar or greater extent than the 
reference products. 
Two comparisons of interest will be done under the secondary objectives. These comparisons 
are:- 
Test Product 1 vs Reference Product 1 
Test Product 2 vs Reference Product 2. 
The change from baseline in overall MLSI at Week 8 will be analyzed using ANCOVA with 
treatment as a fixed effect and baseline overall MLSI as a covariate. 
From the  above ANCOVA model,  
treatment  differences  between  groups  
(Test Product 1 vs 
Reference Product 1 and Test Product 2 vs Reference Product 2), 95% Cis and p-values, will 
be provided (Table 14.2.2.2). 
The  assumption  of  normality  and  homogeneity  of  variance  
in  
the  ANCOVA model will  be 
investigated. Violation  of  this  assumption  will  be  overcome  using  a  suitable  data 
transformation or a non-parametric technique (e.g. Wilcoxon Rank Sum test). 
 
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4.6 Analysis of Exploratory Objectives 
4.6.1.1 Exploratory Efficacy Endpoint Definition 
The exploratory variables are;  
• Change from baseline in overall interproximal MLSI (AxI) stain score at Weeks 2, 4 
and 8 
• Change from baseline in overall area (A) stain score at Weeks 2, 4 and 8 
• Change from baseline in overall intensity (I) stain score at Weeks 2, 4 and 8 
• Change from baseline (pre-treatment) in overall TPI for Day 2 post-treatment, Week 8 
pre-treatment and Week 8-post treatment 
• Change from baseline (pre-treatment) in interproximal TPI  
for  Day 2 post-treatment, 
Week 8 pre-treatment and Week 8 post-treatment 
All  stain  variables  will  be  derived  in  a  similar  way  based  on  relevant  tooth  sites.  The 
interproximal stain sites are the mesial and distal tooth sites. 
The overall TPI for each subject is derived at a tooth site level first before averaging over all 
the teeth sites assessed. The change from baseline is derived at the individual sites first before 
calculating the average change across the sites assessed.  
The  
interproximal  TPI  
is  based  on  
the  mesial  and  distal  
tooth  sites.  The  
interproximal  TPI 
score and change from baseline are calculated in the same way as for the overall TPI. 
4.6.1.2 Analysis of Exploratory Variables 
Summary statistics including mean, SD, median, min, and max will be provided for week 2 
and week 4 by randomized treatment group (Table 14.2.2.1). 
All stain variables will be analyzed as per the primary efficacy variable using the appropriate 
baseline values as a covariate.  
The  change  from baseline in  TPI  variables will  be analyzed using  analysis of  covariance 
(ANCOVA) with treatment and MLSI stratification as fixed effects and appropriate baseline 
(pre-treatment) TPI as a covariate.  
From  ANCOVA  model,  
the  adjusted  mean  
for  each  
treatment  group  will be  provided  with 
95% Cis and corresponding p-values.  
Results for overall interproximal MLSI (A×I) score, overall MLSI  area score, overall MLSI 
intensity score, overall TPI score and  overall Interproximal TPI Score  will be presented in 
Table  14.2.3.1,  14.2.3.2, Table  14.2.4.1,  14.2.4.2, Table  14.2.5.1,  14.2.5.2, Table  14.2.6.1, 
14.2.6.2 and Table 14.2.7.1, 14.2.7.2 respectively.  
 
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4.6.2 
Handling of Missing Values/Censoring/Discontinuations 
 
Missing data will not be replaced or imputed. Dropouts will be included in analyses up to the 
point of discontinuation. 
4.7 
Analysis of Safety 
4.7.1 
Adverse Events and Serious Adverse Events 
All summaries of safety will be performed using the safety population and will be analyzed 
based  on  treatment  actually  received. No formal  statistical  testing will  be performed  on 
summary comparisons related to safety related measurements.  
 
All Aes will be coded using the medical dictionary for regulatory activities (MedDRA). Aes 
will be classified by system organ class (SOC) and by preferred term (PT). In addition, prior 
to database lock all Aes will be reviewed by the Clinical Research Director (or designee) and 
categorized  as  either  oral  or  non-oral.  Safety  will  be  assessed  based  on  any  oral Aes (this 
includes  
those  
that  are  
identified as treatment  emergent oral soft tissue  
(OST) abnormalities 
and spontaneously reported oral Aes). Any new or worsening OST condition that occurs after 
the OST examinations at Screening will be recorded as an AE. 
 
Aes will  be  summarized  using  descriptive  statistics  (frequency  
tables)  by treatment  group. 
Summary tables will indicate both the number of events and the number (percent) of subjects 
involved.  Summaries  of Aes  will  
include  only  
treatment emergent  adverse  events  (TEAEs) 
unless otherwise noted. TEAEs are defined as new Aes that occur on or after the date/time of 
the  first  supervised  use  of  the  randomized  treatment  (or  events  aggravated  in  severity 
following treatment). Events with an onset date/time prior to first use of  a treatment will be 
considered  as  non-treatment  emergent. Listing  of  Aes  (including  non-treatment  emergent 
from All Subjects) will be provided.  
 
The following summary tables and listings will be presented by treatment group. 
• Table of treatment emergent Aes by SOC and Preferred Term (Table 14.3.1.1.1) 
• Table  of  treatment  emergent  Aes  by  Oral/Non-Oral  and  Preferred  Term  (Table 
14.3.1.1.2) 
• Table of treatment emergent treatment related Aes by SOC and Preferred Term  
(Table 14.3.1.3.1)  
• Table  of  Treatment  emergent  
treatment  related  Aes  by  Oral/Non-Oral  and  Preferred 
Term (Table 14.3.1.3.2) 
• Table of  Non-serious treatment emergent Aes by SOC and PT (only produced if there 
are more than 5 SAEs) (Table 14.3.1.4) 
 
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• Listing  of  all  Aes (including  all  subjects: Listing  16.2.7.1.1 for  all  randomized 
subjects; Listing 16.2.7.1.2 for non-randomized subjects) 
• Listing of death (Listing 14.3.2.1) 
• Listing of non-fatal SAEs (Listing 14.3.2.2) 
• Listing of treatment emergent Aes leading to withdrawal (Listing 14.3.2.3) 
• Listing of treatment emergent Aes classified as oral (Listing 14.3.2.4) 
In the event that there is nothing to report a null listing will be produced.  
4.7.2 
Other Safety Variables 
All incidents captured in the study will be listed (Listing 16.2.7.2). Oral soft issue data will be 
listed (Listing 16.2.7.3). All eCRF comments will be listed (Listing 16.2.3). 
4.8 
Analysis of Other Variables 
To assess the repeatability of the stain and TPI assessments, replicate examinations will be 
performed by the same qualified dental examiner at each assessment visit. Five subjects will 
be randomly selected for repeat MLSI and TPI assessments across each assessment window. 
The repeat stain and plaque assessments will be compared to the original assessments and will 
not be used in any efficacy analysis. The first and second assessments on each tooth site will 
be  cross tabulated. A  weighted  Kappa  coefficient  (κ),  along  with  the  95%  CI  will  be 
calculated  to  assess the  intra-examiner  reliability.  Fleiss-Cohen weighted  kappa  will  be 
calculated for the repeatability analysis. Reliability will be deemed  
• Excellent if κ > 0.75 
• Fair to good if 0.4 ≤ κ ≤ 0.75 
• Poor if κ <0.4 
All subjects who have repeatability data will be  
included in this analysis. Results for repeat 
MLSI area  and  intensity assessments  will  be  in Table  14.2.8.1  and Table  14.2.8.2 
respectively.  Also result for repeat TPI assessment will be Table 14.2.8.3. 
5 
Changes to the Protocol Defined Statistical Analysis Plan 
Changes from the originally planned statistical analysis specified in the protocol are outlined 
in Table 1. 
 
Table 1 
Changes to Protocol Defined Analysis Plan 
Protocol 
Reporting & Analysis Plan 
Statistical Analysis section 
Statistical Analysis Plan 
Rationale for Changes 
 
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Protocol 
Reporting & Analysis Plan 
Statistical Analysis section 
Statistical Analysis Plan 
Rationale for Changes 
• Sect
ion 10.2.1:  
Descr
ipt
ive stat
ist
ics (number of 
sub
jects, mean, standard dev
iat
ion, 
med
ian, m
in
imum and max
imum for 
cont
inuous var
iab
les, and frequency 
and percentage for categor
ica
l 
var
iab
les) w
i
l
l be prov
ided for 
demograph
ic base
l
ine character
ist
ics 
concom
itant med
icat
ion, med
ica
l 
h
istory and comp
l
iance.  
 
• We are not prov
id
ing 
descr
ipt
ive stat
ist
ics for 
concom
itant med
icat
ions, 
med
ica
l h
istor
ies and 
comp
l
iance. 
• Summary tab
les are not 
requ
ired for report
ing 
• 10.2.4- Safety Ana
lys
is(es) 
L
ist
ing of SAEs (
if there are none a 
nu
l
l 
l
ist
ing w
i
l
l be produced; 
if there 
are more than 5 treatment emergent 
SAEs a tab
le w
i
l
l be produced 
instead by SOC and PT)
 
• Ana
lys
is of Safety 
L
ist
ing of death (L
ist
ing 
14.3.2.1); L
ist
ing of non-fata
l 
SAEs (L
ist
ing 14.3.2.2) 
 
• As per RAP temp
late and 
l
ist of requ
ired TLF 
l
ist for 
Ora
l stud
ies, two 
l
ist
ings 
have been added 
in RAP.  
• 10.2.6 Def
in
it
ion of Ana
lys
is 
Popu
lat
ions 
 
• We have added two 
popu
lat
ions 
in RAP wh
ich 
are a
l
l screened sub
jects 
and random
ized popu
lat
ion.  
• We w
i
l
l requ
ire these 
popu
lat
ion for some TLFs.  
• Safety Ana
lys
is(es) 
 
• The be
low tab
le 
is not 
inc
luded 
in the RAP:
 
Treatment emergent Aes by 
Intens
ity presented by 
System Organ C
lass (SOC) 
and PT 
 
• It 
is not requ
ired s
ince 
it 
is 
study dependent and not 
requ
ired for th
is study.   
• 10.2.6 Def
in
it
ion of Ana
lys
is 
Popu
lat
ions 
 
• We have added two 
subsets popu
lat
ion for 
repeatab
i
l
ity popu
lat
ion 
in 
RAP. 
• It 
is not poss
ib
le to keep the 
repeated sub
jects for sta
in 
and p
laque assessment 
under the same popu
lat
ion. 
Therefore we have 
deve
loped subset 
popu
lat
ion for MLSI and TPI 
repeatab
i
l
ity.  
 
 
 
 
 
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6 
Abbreviation   
 
Abbreviation Term 
AE 
adverse event 
TEAE 
treatment-emergent adverse event 
ANCOVA 
analysis of covariance 
CI 
confidence interval 
ITT 
intent-to-treat 
KNO3 
potassium nitrate 
NaF 
sodium fluoride 
STP 
sodium tripolyphosphate 
MedDRA 
medical Dictionary for Regulatory Activities 
MLSI 
Macpherson modification of the Lobene Stain Index 
OST 
oral soft tissue 
SAE 
serious adverse event 
SOC 
system organ class 
PT 
preferred term 
TPI 
Turesky modification of the Quigley Hein Index 
A 
Area 
I 
Intensity  
SD 
standard deviation  
Med 
median 
Min 
minimum 
Max 
maximum 
RLR 
review listing requirement 
BDRM 
blinded data review meeting 
SAS 
statistical analysis system 
GSK CH 
GlaxoSmithKline Consumer Healthcare 
POP 
proof of principle  
 
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7 
Attachment 1: List of Data Displays 
 
Study 208078_L
ist of 
Outputs.xlsx
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
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Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
Property of GSK Consumer Healthcare 
Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of GSK 
Template Version Effective: 15-Jul-2017 
Page 21 of 53 
8 
Appendix 1: Template for Tables, Figures and Listings 
This is a guideline which will give the guidance of treatment labels that will be used for the table header and in the figures, listings and in 
the footnotes.  
The treatment labels for the column heading will be as follow: 
• Test Product 1 
• Test Product 2 
• Reference Product 1 
• Reference Product 2 
The treatment comparison will be in below order; 
Test Product 1 Vs Test Product 2 
Reference Product 1 Vs Reference Product 2  
The below footnotes will be used for each outputs; 
Test Product 1: 5% KNO3 / 0.2542% NaF dentifrice with 0.5% spherical silica (RDA~38) 
Test Product 2: 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% STP (RDA~58) 
 
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Reference Product 1: Sensodyne Pronamel Daily Protection  (RDA~36). 
Reference Product 2: Sensodyne Extra Whitening (RDA~166).  
 
 
 
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Protocol 208078    
  
  
  
  
  
  
  
  
 
                            Program Run Date: DDMMMYYYY 
Table 14.1.1 
Subject Disposition 
All Screened Subjects 
Study Population: All Screened Subjects (N=xxx) 
 
Test Product 1   
N (%) 
 
Test Product 2 
N (%) 
Reference Product 1 
N (%) 
 
Reference Product 2 
N (%) 
Overall 
  N (%) 
 
TOTAL SUBJECTS SCREENED 
 
 
 
 
  xxx 
SUBJECTS NOT RANDOMIZED 
 
 
 
 
  xxx  (xx.x) 
       DID NOT MEET STUDY CRITERIA  
 
 
 
  xxx  (xx.x) 
       ADVERSE EVENT 
 
 
 
 
  Xxx  (xx.x) 
       LOST TO FOLLOW UP 
 
 
 
 
  xxx  (xx.x) 
       PROTOCOL VIOLATION 
 
 
 
 
  Xxx  (xx.x) 
       WITHDRAWAL OF CONSENT 
 
 
 
 
  Xxx  (xx.x) 
       OTHER 
 
 
 
 
  Xxx  (xx.x) 
  
SUBJECTS RANDOMIZED 
  xxx 
  xxx 
  xxx 
  xxx 
  xxx 
   COMPLETED STUDY 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    DID NOT COMPLETE STUDY 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
       DID NOT MEET STUDY CRITERIA   xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
       ADVERSE EVENT 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
       LOST TO FOLLOW-UP 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
       PROTOCOL VIOLATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
 
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Test Product 1   
N (%) 
 
Test Product 2 
N (%) 
Reference Product 1 
N (%) 
 
Reference Product 2 
N (%) 
Overall 
  N (%) 
       WITHDRAWAL OF CONSENT 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
       OTHER 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
 
 
 
 
 
 
SAFETY POPULATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
ITT POPULATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
REPEATABILITY POPULATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
   MLSI REPEATABILITY POPULATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
   TPI REPEATABILITY POPULATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
 
Percentages for non-randomized category are based on number of screened subjects; percentages for randomized category are based on number of 
randomized subjects 
                                                                                                                           
  
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Protocol 208078    
  
  
  
  
  
  
  
  
  
 
            Program Run Date: DDMMYYYY 
Table 14.1.2 
Incidence of Major Protocol Deviations  
All Randomized Population 
 
Study Population: All Randomized Population (N=xxx) 
 
 
Test Product 1   
N (%) 
 
Test Product 2 
N (%) 
Reference Product 1 
N (%) 
 
Reference Product 2 
N (%) 
  Overall 
  
  N (%) 
 
 
 
NUMBER OF SUBJECTS WITH AT 
LEAST ONE IMPORTANT PROTOCOL 
DEVIATIONS  
 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    DEVIATIONS 1 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    DEVIATIONS 2 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    DEVIATIONS 3 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    DEVIATIONS 4 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    ... 
 
 
 
 
 
 
 
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Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
Table 14.1.3 
Analysis Populations  
All Randomized Population 
Study Population: All Randomized Population (N=xxx) 
 
Test Dentifrice 
(RDA-58) 
  N (%) 
 
Test Dentifrice 
(RDA-77) 
   N (%) 
 Reference Dentifrice 
(RDA-80) 
      N (%) 
 
 Reference Dentifrice 
(RDA-120) 
    N (%) 
  Overall 
  
  N (%) 
 
 
 
NUMBER OF SUBJECTS EXCLUDED 
FROM SAFETY POPULATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    Reason 1 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    Reason 2 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    ... 
 
 
 
 
 
NUMBER OF SUBJECTS EXCLUDED 
FROM ITT POPULATION 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    Reason 1 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    Reason 2 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
  xxx  (xx.x) 
    ... 
 
 
 
 
 
 
 
 
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Protocol: 208078                                                                                                           Program Run Date: DDMMMYYYY 
Table 14.1.4.1 
Demographic and Baseline Characteristics 
Safety Population 
 
Study Population: Safety Population (N=xxx) 
 
 
Test Product 1    
N (%) 
 
Test Product 2 
N (%) 
...... 
... 
 
OVERALL 
(N=xx) 
SEX N (%) 
 
 
 
 
     MALE 
     FEMALE 
 
RACE N (%) 
        XX (XX.X) 
        XX (XX.X) 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
        XX (XX.X) 
     AFRICAN AMERICAN/AFRICAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
     AMERICAN INDIAN OR ALASKAN NATIVE 
        XX (XX.X) 
        XX (XX.X) 
 
        XX (XX.X) 
     ASIAN - CENTRAL/SOUTH ASIAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
 
        XX (XX.X) 
     ASIAN - EAST ASIAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
     ASIAN - SOUTH EAST ASIAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
     NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
     WHITE - ARABIC/NORTH AFRICAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
     WHITE - WHITE/CAUCASIAN/EUROPEAN HERITAGE 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
 
 
 
... 
 
ETHNICITY N (%) 
 
 
 
 
     HISPANIC OR LATINO 
        XX (XX.X) 
        XX (XX.X) 
 
        XX (XX.X) 
     NOT HISPANIC OR LATINO 
        XX (XX.X) 
        XX (XX.X) 
... 
        XX (XX.X) 
 
 
 
... 
 
AGE (YEARS) 
 
 
... 
 
     N 
        XX 
        XX 
... 
        XX 
     MEAN 
        XX.X 
        XX.X 
... 
        XX.X 
     SD 
        XX.XX 
        XX.XX 
... 
        XX.XX 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 28 of 53 
     MEDIAN 
        XX.X  
        XX.X  
........ 
        XX.X  
     MINIMUM 
        XX 
        XX 
…………. 
        XX 
     MAXIMUM 
        XX 
        XX 
... 
        XX 
 
 
 
 
 
STRATIFICATION 
 
 
 
 
   STRATA 1: LOW (MLSI <15) 
      XX (XX.X) 
       XX (XX.X) 
 
        XX (XX.X) 
   STRATA 2: HIGH (MLSI ≥15) 
      XX (XX.X) 
       XX (XX.X) 
 
        XX (XX.X) 
                                                                                                                             Page x of y 
                                                                                                          
 
 
 
 
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Effective Date 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 29 of 53 
Protocol 208078  
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMMYYYY 
 
Table 14.2.2.1 
Summary of Overall MLSI Score 
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
 
 
Test Product 1 
(N=XX) 
Test Product 2 
(N=XX) 
…………….. 
Overall 
(N=XXX) 
 
Visit 
 
Observed 
Value 
 
Change from 
Baseline 
Observed 
Value 
 
Change from 
Baseline 
…………………….. 
Observed Value 
 
Change from 
Baseline 
BASELINE N  
XX      ... 
 
XX      ... 
 
…………….. 
XX      ... 
 
 
MEAN  
X.XX    ... 
 
X.XX    ... 
 
…………………….. 
X.XX    ... 
 
 
SD 
X.XXX    ... 
 
X.XXX    ..
. 
 
…………….. 
X.XXX    ... 
 
 
MEDIAN                                         
X.XX    ... 
 
X.XX    ... 
 
…………………….. 
X.XX    ... 
 
 
MINIMUM X.XX    ... 
 
X.XX    ... 
 
…………….. 
X.XX    ... 
 
 
MAXIMUM X.XX    ... 
 
X.XX    ... 
 
…………………….. 
X.XX    ... 
 
WEEK 2 
N 
XX 
XX 
XX 
XX 
…………….. 
XX 
XX 
 
MEAN 
X.XX 
X.XX 
X.XX 
X.XX 
…………………….. 
X.XX 
X.XX 
 
SD 
X.XXX 
X.XXX 
X.XXX 
X.XXX 
…………….. 
X.XXX 
X.XXX 
 
MEDIAN                                         
X.X 
X.X 
X.X 
X.X 
…………………….. 
X.X 
X.X 
 
MINIMUM X.X 
X.X 
X.X 
X.X 
…………….. 
X.X 
X.X 
 
MAXIMUM X.X 
X.X 
X.X 
X.X 
…………………….. 
X.X 
X.X 
WEEK 4 
SAME AS 
ABOVE 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 30 of 53 
                                                                                                                           Page x of y                                 
                                                                                                         
  
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 31 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMMYYYY 
 
 
Table 14.2.2.2 
Statistical Analysis of Overall Change Baseline in MLSI Score   
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
Visit 
 
Test Product 1 
(N=XX) 
Test Product 2 
(N=XX) 
Reference Product 1 
(N=XX) 
Reference Product 1 
(N=XX) 
WEEK 2 
ADJUSTED MEANS (SE)[1] 
X.XX (X.XXX) 
X.XX (X.XXX) 
X.XX (X.XXX) 
X.XX (X.XXX) 
 
95 % CI [1] 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
 
P-VALUE [1] 
0.XXXX 
0.XXXX 
0.XXXX 
0.XXXX 
 
COMPARISON                       DIFFERENCE (SE) [1,2]              95% CI [1]                  P-VALUE [1] 
 
TEST PRODUCT 1 VS REFERENCE 
PRODUCT 1  
X.XX (X.XXX) 
(X.XX, X.XX) 
0.XXXX 
 
TEST PRODUCT 2 VS REFERENCE 
PRODUCT 2 
X.XX (X.XXX) 
(X.XX, X.XX) 
0.XXXX 
 
 
 
 
 
 
WEEK 4 
SAME AS ABOVE 
 
 
 
 
 
  
 
 
 
 
    [1] From ANCOVA with treatment as factors and baseline overall MLSI score as a covariate 
    [2] Difference is first named treatment minus second named treatment such that a negative difference favours the first named treatment 
                                                                                                                           Page x of y   
                                                                                                        
  
Programming note: The same summary would be provided for the Week 8 also.  
 
 
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Effective Date 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 32 of 53 
Protocol 208078  
  
  
  
  
  
  
  
  
  
 
             PROGRAM RUN DATE: DDMMMYYYY 
 
Table 14.2.6.1 
Summary of TPI Score 
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
Visit 
TimePoint 
 
Test Product 1 
(N=XX) 
Test Product 2 
(N=XX) 
……………… 
Overall 
(N=XX) 
 
 
 
Observed 
Values 
Change from 
Pre-brushing 
Observed 
Values 
Change from 
Pre-brushing 
……………… 
Observed Values 
Change from 
Pre-brushing 
BASELINE 
PRE- 
BRUSHING 
N  
XX       
 
XX       
 
……………… 
XX       
 
 
 
MEAN  
X.XX     
 
X.XX     
 
……………… 
X.XX     
 
 
 
SD 
X.XXX     
 
X.XXX     
 
……………… 
X.XXX     
 
 
 
MEDIAN                                         
X.XX   
 
X.XX   
 
……………… 
X.XX   
 
 
 
MINIMUM 
X.XX    
 
X.XX    
 
……………… 
X.XX    
 
 
 
MAXIMUM 
X.XX    
 
X.XX    
 
……………… 
X.XX    
 
 
 
 
 
 
 
 
……………… 
 
 
 
POST- 
BRUSHING 
N  
XX       
XX       
XX       
XX       
……………… 
XX       
XX       
 
 
MEAN  
X.XX     
X.XX     
X.XX     
X.XX     
……………… 
X.XX     
X.XX     
 
 
SD 
X.XXX     
X.XXX     
X.XXX     
X.XXX     
……………… 
X.XXX     
X.XXX     
 
 
MEDIAN                                         
X.XX   
X.XX   
X.XX   
X.XX   
……………… 
X.XX   
X.XX   
 
 
MINIMUM 
X.XX    
X.XX    
X.XX    
X.XX    
……………… 
X.XX    
X.XX    
 
 
MAXIMUM 
X.XX    
X.XX    
X.XX    
X.XX    
……………… 
X.XX    
X.XX    
 
 
 
 
 
 
 
 
 
 
WEEK 8 
SAME AS 
ABOVE 
 
 
 
 
 
 
 
 
                                                                                                                            Page x of y                                
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 33 of 53 
                                                                                                         
  
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 34 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMMYYYY 
 
 
Table 14.2.6.2 
Statistical Analysis of Overall Change from Baseline (Pre-brushing) in TPI Score   
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
Visit 
 
Test Product 1 
(N=XX) 
Test Product 2 
(N=XX) 
Reference Product 1 
(N=XX) 
Reference Product 1 
(N=XX) 
BASELINE POST-BRUSHING ADJUSTED MEANS (SE)[1] 
X.XX (X.XXX) 
X.XX (X.XXX) 
X.XX (X.XXX) 
X.XX (X.XXX) 
 
95 % CI [1] 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
(X.XX, X.XX) 
 
P-VALUE [1] 
0.XXXX 
0.XXXX 
0.XXXX 
0.XXXX 
 
COMPARISON                       DIFFERENCE (SE) [1,2]              95% CI [1]                  P-VALUE [1] 
 
TEST PRODUCT 1 VS REFERENCE 
PRODUCT 1  
X.XX (X.XXX) 
(X.XX, X.XX) 
0.XXXX 
 
TEST PRODUCT 2 VS REFERENCE 
PRODUCT 2 
X.XX (X.XXX) 
(X.XX, X.XX) 
0.XXXX 
 
 
 
 
 
 
WEEK 8 PRE-BRUSHING 
SAME AS ABOVE 
 
 
 
 
 
WEEK 8 POST-BRUSHING 
 SAME AS ABOVE 
 
 
 
 
    [1] From ANCOVA with treatment and MLSI stratification as factors and appropriate baseline (Pre-treatment) TPI score as a covariate 
    [2] Difference is first named treatment minus second named treatment such that a negative difference favours the first named treatment 
                                                                                                                           Page x of y   
                                                                                                        
  
Programming note: The same summary would be provided for the Week 8 pre-brushing and Week 8 post-brushing also.  
 
 
 
Document Name 
 
Type 
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Effective Date 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 35 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMMYYYY 
Table 14.2.8.1 
Repeatability for MLSI Intensity Score 
MLSI Repeatability Population 
 
Study Population: MLSI Repeatability Population (n=XX) 
 
 
Initial \ Repeated 
Missing 
0 
1 
2 
3 
 
Missing  
xx 
xx 
xx 
xx 
xx 
 
0 
xx 
xx 
xx 
xx 
xx 
 
1 
xx 
xx 
xx 
xx 
xx 
 
2 
xx 
xx 
xx 
xx 
xx 
 
3 
xx 
xx 
xx 
xx 
xx 
Kappa 
0.xx 
 
 
 
 
 
95% CI 
(0.xx, 0.xx) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Intensity Score: 0=No Stain; 1=light Stain; 2=Moderate Stain; 3=Heavy Stain. Missing means non-scorable. 
                                                                                                                       Page x of y 
                                                                                                    
 
 
 
Note to Programmer: For Table 14.2.8.2 and 14.2.8.3, use area and TPI scoring descriptions in footnote.  
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 36 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMYYYY 
 
Table 14.3.1.1.1 
Treatment Emergent Adverse Event by SOC and Preferred Term 
Safety Population 
Study Population: Safety Population (N=xx) 
SOC  
   Preferred Term 
 
Test Product 1 
(N=XX) 
Test Product 2 
(N=XX) 
Reference Product 1 
(N=XX) 
Reference Product 1 
(N=XX) 
Overall 
(N=XX) 
 
n (%) 
nAE 
n (%)     nAE 
n (%)     nAE 
n (%)     nAE 
n (%) 
nAE 
NUMBER OF SUBJECTS WITH 
AT LEAST ONE AE 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
NUMBER OF SUBJECTS WITH 
NO AE 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
 
 
 
 
 
 
 
 
SKIN AND SUBCUTANEOUS 
TISSUE DISORDERS 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
  ERYTHEMA 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
  DERMATITIS 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
 
 
 
 
 
 
GASTROINTESTINAL SYSTEM 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
  ABDOMINAL PAIN 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
  DRY MOUTH 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
  VOMITTING 
 
 
 
Etc. 
xx (xx.x) 
xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x)    xx 
xx (xx.x) 
xx 
n (%) = Number (percent) of subjects nAE = Number of adverse events. 
                                                                                                                        Page x of y                                    
                                                                                                      
 
  
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 37 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMYYYY 
 
Listing 16.1.7 
Randomization Information 
All Randomized Population 
Stratum 1: Low (MLSI <15)  
Subject 
Number 
Age/Sex/ Race [1] 
Randomization Number 
Treatment Randomized [2] 
Date of Randomization  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
[2] A= Reference Product 1; B= Reference Product 2; C= Test Product 1; D= Test Product 2.  
The block size for this randomization was used 8.  
                                                                                                                        Page x of y                                    
                                                                                                      
 
 
 
 
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Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 38 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMYYYY 
 
Listing 16.2.1.1.1 
Subject Disposition 
All Randomized Population 
 
Subject 
Age/Sex/ Race 
[1] 
Ethnicity 
Screening 
Date 
Treatment 
Start Date 
and Time 
Date of 
Completion or 
Withdrawal 
Duration of 
Treatment 
(Days) [2] 
Completed  
Primary 
Reason for 
Withdrawal 
Further Details [3] 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
[2] Treatment duration is calculated as date of completion or withdrawal minus treatment start date.  
[2] Further details of reasons for withdrawal. 
                                                                                                                        Page x of y                                    
                                                                                                      
 
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 39 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.2 
All Protocol Deviations 
All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age/Sex/Race[1] Deviation 
Sequence 
Start Date/Time 
End Date/Time 
Protocol Deviation 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
 
                                                                                                               Page x of y                             
                                                                                                       
 
 
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 40 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.3 
eCRF Comments  
All Randomized Population 
Treatment Group: Test Product 1 
 
Subject Number 
Age/Sex/Race[1] 
Visit Name 
Section 
Item 
Comments  
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
 
                                                                                                               Page x of y                             
                                                                                                       
 
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 41 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
             Program Run Date: DDMMYYYY 
 
Listing 16.2.3.1 
Exclusion from Analysis Population 
All Randomized population 
 
Subject 
Number 
Age/Sex/Race[1] 
Treatment Start Date and 
Time 
Safety Population  
ITT Population 
Reasons for Exclusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male ; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
 
                                                                                                                        Page x of y        
                                                                                                      
 
Programming Note for Listing 16.2.3.1: This listing is based on population definition document. 
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 42 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.4.1 
Demographic Characteristics 
 All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age 
(years) 
Sex 
Race 
Ethnicity  
Stratification 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
                                                                                                               Page x of y        
                                                                                                       
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 43 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.4.2 
Medical History and Current Medical Conditions 
 All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Age/Sex/Race 
[1] 
Any Medical History?  Medical Condition 
Start Date 
Ongoing? 
End Date 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
 
                                                                                                               Page x of y                             
                                                                                                       
 
 
 
Document Name 
 
Type 
Version 
Document Identifier 
Effective Date 
 
 
 
 
Reason For Issue 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 44 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.5.1 
Brushing Compliance 
 All Randomized Population  
Treatment Group: Test Product 1 
 
Subject Number 
Age/Sex/Race [1] 
Period 
Expected Number of 
Brushing [2] 
Actual Number Brushing 
[3] 
Compliance [4] 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
[2] Expected Number of Brushing = 2*Number of Days between the Two Visits; 
[3] Actual Number of Brushing = Expected Number – Missed brushing + Additional Brushing; 
[4] Compliance = Actual Number / Expected Number *100 (%) 
 
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208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 45 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.5.6 
Concomitant Medications and Non-drug Therapies Taken During Treatment 
 All Randomized Population  
Subject 
Number 
Age/Sex/Race[1] Sequence 
Number 
Treatment 
[GSK Drug 
Synonym] 
Reason for 
Treatment 
Route of 
Administration 
Dose per 
Administration 
Frequency 
Start Date 
(Study Day [2]) 
End Date/ Ongoing 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage.  
[2] Study day relative to the date of randomization. 
                                                                                                               Page x of y          
                                                                                                       
 
 
 
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208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 46 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.6.1 
Individual MLSI Stain Index 
All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age/Sex/Race[1] Visit  
Tooth Number 
(universal/FDI) 
Surface 
Site 
Intensity 
Score[2] 
Area Score[3] 
Area x Intensity 
Score 
Change from 
Bassline Score  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage.                                                      
[2] Intensity Score: 0=No Stain; 1=light Stain;2=Moderate Stain; 3=Heavy Stain. Missing means non-scorable; X=Missing.                              
[3] Area Score: 0=No Stain; 1=Stain covering upto 1/3 of region; 2=Stain covering upto 1/3 of region, and no more than 2/3 of region; 3=Stain covering 
more than 2/3 of region; X=Missing 
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208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 47 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.6.2 
Individual Turesky Plaque Index (TPI) 
All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age/Sex/Race[1] Visit  
PRE/POST 
Tooth Number 
(universal/FDI) 
Surface 
Site 
TPI Score [2] 
Average Whole Mouth 
TPI 
Change from 
Bassline Score 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage.                                                      
[2] 0 = No plaque; 1 = Slight flecks of plaque at the cervical margin of the tooth; 2 = A thin continuous band of plaque (1 mm or smaller) at the 
cervical margin of the tooth; 3 = A band of plaque wider than 1 mm but covering less than 1/3 of the crown of the tooth; 4 = Plaque covering at least 1/3 
but less than 2/3 of the crown of the tooth; 5 = Plaque covering 2/3 or more of the crown of the tooth; X = Missing Tooth; N = Not Scorable                            
                                                                                                               Page x of y        
                                                                                              
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 48 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
 
           Program Run Date: DDMMYYYY 
 
Listing 16.2.7.1.1 
All Adverse Events 
All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age/Sex/
Race[1] 
Adverse Event 
(Preferred Term) 
(System Organ 
Class) 
 
Start Date 
/Study 
Day[2] 
Start 
Time 
End 
Date 
End 
Time 
Frequency 
/Intensity
[3] 
Related 
to Study 
Product? 
Action 
Taken re 
Study 
Product 
Outcome 
Serious? 
Withdrew?
[4] 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
@@ Adverse events with verbatim text ending in this are classified as Oral AEs. 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage. 
[2] Study day is the day relative to start of treatment, day 1 being the day of first treatment. 
[3] INT = Intermittent and SGLE = Single. 
[4] Did subject withdraw from study as a result of this adverse event? 
                                                                                                                                                                                                                                                                      Page x of y 
                                                                                                           
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 49 of 53 
 
Programming Note for Listing 16.2.7.1.2: 
• Repeat the same layout for listing 16.2.7.1.2 
• Population should be used ‘Non randomized Subjects’ 
• The fourth column should be only ‘Start Date’ 
• Add footnote ‘Only SAEs are collected for non randomized subjects’ 
• Delete the footnote related to study day and adjust the numbers accordingly. 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 50 of 53 
Protocol 208078    
  
  
  
  
  
  
  
  
  
  
            Program Run Date: DDMMYYYY 
 
Listing 16.2.7.3 
Oral Soft Tissue Examination  
All Randomized Population 
Treatment Group: Test Product 1 
 
Subject 
Number 
Age/Sex/Race[1] 
Visit  
Area 
Condition  
 Details 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A1 = African American/African Heritage, A2 = American Indian Or Alaskan Native,A3 = Asian-
Central/South Asian Heritage, A4 = Asian-East Asian Heritage, A5 = Asian-Japanese Heritage, A6 = Asian-South East Asian Heritage, N = Native Hawaiian Or 
Other Pacific Islander, W1 = White-Arabic/North African Heritage, W2 = White - White/Caucasian/European Heritage.                                                      
 
 
 
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208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 51 of 53 
Protocol 208078                  
  
  
  
  
  
  
  
 
   Program Run Date: DDMMYYYY 
Figure 14.2.1 
Overall MLSI (A×I) Score Mean (±SE) Plot over Time by Treatment 
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
 
 
Mean and SE plotted are from summary statistics in T 14.2.2.1.1 
                                                                                                                            Page x of y       
0
0.5
1
1.5
2
2.5
0
2
4
6
8
Overall MLSI (AxI) Score
Time Point
TEST Product 1
Reference Product 1
TEST Product 2
Reference Product 2
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 52 of 53 
Protocol 208078                  
  
  
  
  
  
  
  
 
   Program Run Date: DDMMYYYY 
Figure 14.2.2 
Overall TPI Score Mean (±SE) Plot over Time by Treatment 
Intent-to-Treat Population 
Study Population: Intent-to-Treat Population (N=XX) 
 
 
Mean and SE plotted are from summary statistics in T 14.2.5.1.1 
0
0.5
1
1.5
2
2.5
Overall TPI Score
Time Point
TEST Product 1
Reference Product 1
TEST Product 2
Reference Product 2
Pre
Baseline
Post
 
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208078 
Final Statistical Reporting and Analysis plan Amendment  21NOV2017 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 53 of 53 
                                                                                                                                        Page x of y    
Programming Note: Please repeat figure for the Week 8 also.  
    
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Addendum 1, 01FEB2018 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 1 of 10 
 
 
STATISTICAL REPORTING AND ANALYSIS PLAN  
Addendum 1 
 
 
 
 
A RANDOMIZED, EXAMINER-BLIND, PROOF OF PRINCIPAL STUDY 
TO INVESTIGATE THE STAIN AND PLAQUE REMOVAL CAPABILITY 
OF TWO EXPERIMENTAL 5% POTASSIUM NITRATE DENTIFRICES 
IN HEALTHY SUBJECTS WITH THE PROPENSITY FOR EXTRINSIC 
DENTAL STAIN 
 
 
 
Protocol Number: 208078  
Phase: 
II 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Addendum 1, 01FEB2018 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 2 of 10 
Document History 
 
Document 
Version Date 
Summary of Changes (New analysis or Change 
in planned analysis) 
Original Analysis Plan 05-Oct-2017 
Not applicable (N/A) 
RAP Amendment 
Version 1.0 
21-Nov-2017 
Add brushing compliance listing in RAP rather 
than cover it in BDRM.  
Add eCRF comments listing  
Added major Protocol deviation table 
Amend the text of section 3.3 (Timepoints and 
Visit Window)  
Added the text in repeatability population of 
section 4.1.3   
 
RAP Addendum 
Version 1.0 
01-Feb-2018 
Add the figure based on the Adjusted mean change 
from baseline for MLSI and TPI and add the 
16.1.9 SAS outputs in the section 7.  Correct the 
presentation of Figure 14.2.2 based on raw means 
to be consistent with the Figure 14.2.4 template.   
 
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Addendum 1, 01FEB2018 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 3 of 10 
Table of contents 
Document History ............................................................................................................... 2 
Table of contents ................................................................................................................. 
3 
1 Introduction ......................................................................................................................... 
4 
5 Changes to the Statistical Analysis Plan ............................................................................. 
4 
7 Attachment 1: List of Data Displays 
................................
................................................... 
6 
8 Appendix 1: Template for Tables, Figures and Listings 
..................................................... 7 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Addendum 1, 01FEB2018 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 4 of 10 
1 
Introduction  
This RAP addendum describes the clarification  of the text related to figures and addition of 
figures to  the  planned  analysis  described  in  the  Statistical  Reporting  and Analysis Plan 
Amendment  1.These  changes were identified  during  draft  topline  TFLs  review stage,  and 
hence was after unblinding but prior to development of the non-topline TFLs. These changes 
will be reflected in the final CSR. 
The sections below provide the updated text that are required from the planned analysis, with 
section 5.0 providing further details on what was planned, the change and the reason for the 
change. A summary of the changes/clarifications are: 
• To add the figures based on the adjusted means change from baseline values for MLSI 
and TPI parameters.  
• To  add  a note  about the  presentation  of  Figure  14.2.2  based  on  raw  means  to  be 
consistent  with  the  Figure  14.2.4  template. To  add  the  16.1.9  SAS  outputs  in  the 
section “Attachment 1: List of displays”.  
5 
Changes to the Statistical Analysis Plan 
Any changes from the originally planned statistical analysis specified in the RAP amendment 
(dated 21-NOV-2017) are outlined in Table 1. 
 
Table 1 
Changes to SAP amendment Defined Analysis Plan 
SAP Analysis Plan 
Amendment 1 
Statistical Analysis 
Plan Addendum 
Rationale for Changes 
• Sect
ion 7.0 
Attachment 1: L
ist 
of d
isp
lays 
 
 
 
 
 
• Sect
ion 8.0 
Append
ix1: 
Temp
late for Tab
le, 
F
igure and L
ist
ings  
 
• Sect
ion 7.0 
Attachment 1: L
ist of 
d
isp
lays 
 
 
 
 
 
• Sect
ion 8.0  
Append
ix 1: Temp
late 
for Tab
le, F
igure and 
L
ist
ings 
 
 
• Wh
i
le de
l
iver
ing the non-top
l
ine TLFs, 
it was 
observed that the outputs re
lated to Sect
ion 
16.1.9 was deve
loped but was m
issed to 
number correct
ly 
in the RAP amendment. 
Therefore 
it 
is dec
ided to 
inc
lude the 
l
ist
ing 
numbers. 
 
 
• A
l
l f
igures were p
lanned based on the raw mean 
(+/-) SE and prov
ided as part of the top
l
ine and 
non-top
l
ine de
l
ivery. However the text 
in sect
ion 
of 4.4.1.2 of the RAP amendment was “Th
is w
i
l
l 
be ach
ieved v
ia the ad
justed means and 
conf
idence 
interva
ls (CIs) for the means a
long 
w
ith p
lots of MLSI over t
ime”. 
• It was rea
l
ized wh
i
le rev
iew
ing the draft top
l
ine 
TLFs that, the f
igures based on the ad
justed 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Addendum 1, 01FEB2018 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 5 of 10 
SAP Analysis Plan 
Amendment 1 
Statistical Analysis 
Plan Addendum 
Rationale for Changes 
means and CI w
i
l
l be more appropr
iate. Th
is 
ad
justed means w
i
l
l be used for rank
ing the 
study treatments for 
interpretat
ion. Therefore 
it 
was dec
ided to 
inc
lude the f
igures based on 
ad
justed means change from base
l
ine (+/- 95% 
CIs) 
in the RAP addendum. 
• Wh
i
le creat
ion of the F
igure 14.2.2 as part of 
non-top
l
ine de
l
ivery, 
it was observed that the 
presentat
ion of F
igure 14.2.2 
in RAP 
amendment temp
late was not appropr
iate. 
Therefore 
it was dec
ided to change the 
presentat
ion of F
igure 14.2.2 to be cons
istent 
w
ith F
igure 14.2.4.   
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Addendum 1, 01FEB2018 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 6 of 10 
7 
Attachment 1: List of Data Displays 
 
Study 208078_L
ist of 
Outputs.xlsx
 
 
 
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208078 
Final Statistical Reporting and Analysis plan Addendum 1, 01FEB2018 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 7 of 10 
8 
Appendix 1: Template for Tables, Figures and Listings 
 
Protocol 208078                  
  
  
  
  
  
  
  
 
   Program Run Date: DDMMYYYY 
Figure 14.2.3 
Change from Baseline in Overall MLSI (A×I) Score Adjusted Means (±95%CIs) Plot Over Time by Treatment 
Intent-to-Treat Population 
  Study Population: Intent-to-Treat Population (N=XX) 
 
Values are adjusted means +/- 95%CIs 
 
 
Test Product 1: 5% KNO3 / 0.2542% NaF dentifrice with 0.5% spherical silica (RDA~38) 
Test Product 2: 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% STP (RDA~58) 
Reference Product 1: Sensodyne Pronamel Daily Protection (RDA~36). 
 
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208078 
Final Statistical Reporting and Analysis plan Addendum 1, 01FEB2018 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 8 of 10 
Reference Product 2: Sensodyne Extra Whitening (RDA~166).  
 
 
Programming Note: 1) Adjusted Means and CIs plotted are from summary statistics 
. 
  
  
 2) Baseline should start from zero and CIs should not applicable.   
 
 
 
 
 
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Potassium Nitrate / Sodium Fluoride 
208078 
Final Statistical Reporting and Analysis plan Addendum 1, 01FEB2018 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 9 of 10 
Protocol 208078                  
  
  
  
  
  
  
  
 
   Program Run Date: DDMMYYYY 
Figure 14.2.4 
Change from Baseline (Pre-brushing) in Overall TPI Score Adjusted Means (±95%CI) Plot Over Time by Treatment 
Intent-to-Treat Population 
  Study Population: Intent-to-Treat Population (N=XX) 
 
Values are adjusted means +/- 95%CIs 
 
 
Test Product 1: 5% KNO3 / 0.2542% NaF dentifrice with 0.5% spherical silica (RDA~38) 
Test Product 2: 5% KNO3 / 0.2542% NaF dentifrice with 1% spherical silica and 5% STP (RDA~58) 
Reference Product 1: Sensodyne Pronamel Daily Protection (RDA~36). 
 
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208078 
Final Statistical Reporting and Analysis plan Addendum 1, 01FEB2018 
 
 
 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 10 of 10 
Reference Product 2: Sensodyne Extra Whitening (RDA~166).  
 
Programming Note: 1) Adjusted Means and CIs plotted are from summary statistics 
 
 2) Baseline should start from zero and CIs should not applicable.   
 
 
 
Note: Use the same template as Figure 14.2.4 for the figure 14.2.2.  
 
 
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