Clinical trial NCT03238352
Conditions: Dentin Sensitivity
Sponsor: GlaxoSmithKline
Start date: 2017-08-07; Completion date: 2017-10-27
Enrollment: 89 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
To investigate the efficacy of an experimental oral rinse, containing 1.5% potassium oxalate (KOX) and 0 parts per million (ppm) fluoride in relieving dentine hypersensitivity (DH) after 8 weeks use compared with a placebo oral rinse and a commercialized fluoride oral rinse.

Detailed description:
This will be a single centre, eight week, randomized, examiner-blind, three treatment, parallel group, stratified study. It will be conducted in healthy participants, with at least two sensitive teeth that meet all of the study criteria at the Screening and Baseline visits. DH will be assessed at Baseline, and after 4 and 8 weeks twice daily treatment.

Arms: arm 1: Participants will rinse twice daily (morning and evening) with 10 milliliters (mL) of oral rinse for 60 timed seconds and expectorate. No further rinsing with water will be permitted after use of the oral rinse. arm 2: Participants will rinse twice daily (morning and evening) with 10 mL of oral rinse for 60 timed seconds and expectorate. No further rinsing with water will be permitted after use of the oral rinse. arm 3: Participants will rinse twice daily (morning and evening) with 10 mL of oral rinse for 60 timed seconds and expectorate. No further rinsing with water will be permitted after use of the oral rinse.
Interventions: intervention 1: Potassium oxalate intervention 2: Sodium fluoride intervention 3: Placebo
Intervention descriptions: intervention 1: Oral rinse containing 1.5 percent (%) KOX and 0 ppm fluoride intervention 2: Oral rinse containing 0.02% weight by weight (w/w) sodium fluoride (NaF) intervention 3: Oral rinse containing 0% KOX and 0 ppm fluoride

Protocol documents:
Prot_000.pdf: 
Copyright:  GlaxoSmithKline.  An unpublished work subject to trade secret 
protection.  This work contains confidential and proprietary information of 
GlaxoSmithKline and should not be copied, circulated, or distributed to persons not 
employed by GlaxoSmithKline unless specifically authorized.  Unauthorized 
disclosure of this work is expressly prohibited.
Clinical Protocol
207656
 
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CONFIDENTIAL
SUMMARY INFORMATION
Title:
A Method Development Clinical Study 
Investigating the Efficacy of an Experimental Oral 
Rinse in Providing Long Term Relief from Dentinal 
Hypersensitivity
Protocol Number:
207656
Sponsor:
GlaxoSmithKline Consumer Healthcare (GSKCH)
St Georges Avenue, Weybridge, Surrey, KT13 
0DE,
United Kingdom (UK)
Tel: 
Product Name:
1.5% w/w dipotassium oxalate monohydrate (KOX) 
and 0 ppm fluoride oral rinse
Development Phase:
N/A
Expert Advice Outside of Normal 
Working Hours:
Key Protocol Authors:
PRIMARY CONTACT
Clinical Study Manager:
184 Liberty Corner Rd.
Warren, NJ 07059 USA
Tel:
Biostatistician:
, PhD
Clinical Research:
, BSc
Clinical Supplies:
Principal Investigator:
Jeffrey Milleman, DDS, MPA
Study Site Name & Address:
Salus Research, Inc
1220 Medical Park Drive
Building No.4
Fort Wayne, IN 46825, USA
Study Site Telephone Number:
Study Examiner:
, RDH, BSEd, 
MS
 
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PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE
I confirm agreement to conduct the study in compliance with the protocol and 
any amendments and according to the current ICH GCP guidelines.
I acknowledge that I am responsible for overall study conduct. I agree to 
personally conduct or supervise the described study.
I agree to ensure that all associates, colleagues and employees assisting in the 
conduct of the study are informed about their obligations. Mechanisms are in 
place to ensure site staff receives all appropriate information throughout the 
study.
I agree to conduct this study in full conformance with the laws and regulations 
of the country in which the research is conducted and the Declaration of 
Helsinki.
Investigator Name:
Investigator Qualifications:
Investigator Signature:
Date of Signature/ Agreement:
DD/MMM/YYYY
 
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Table of Contents
SUMMARY INFORMATION...............................................2
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE..............................................................................3
PROCESS FOR AMENDING THE PROTOCOL...............9
Schedule of Events..................................................................10
PROTOCOL SYNOPSIS FOR STUDY 207656...................12
1. INTRODUCTION...............................................................23
2. OBJECTIVES AND ENDPOINTS....................................25
3. STUDY PLAN.....................................................................28
3.1. Study Design.......................................................................28
3.3. Type and Planned Number of Subjects............................33
3.4. Study Design and Dose Justification.................................33
4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA........................................35
4.1. Inclusion Criteria...............................................................35
4.2. Exclusion Criteria..............................................................37
4.3. Screening/ Baseline Failures..............................................39
4.4. Withdrawal/ Stopping Criteria.........................................40
4.5. Subject Replacement..........................................................41
4.6. Subject and Study Completion..........................................41
5. PRODUCT INFORMATION.............................................41
5.1. Study Product.....................................................................41
5.2. Dose Schedule.....................................................................42
5.3. Dose Modification..............................................................43
5.4. Product Compliance..........................................................43
 
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5.5. Precautions.........................................................................43
5.6. Overdose.............................................................................43
5.7. Rescue Therapy..................................................................44
5.8. Product Assignment...........................................................44
5.8.1 Randomisation....................................................................44
5.8.2. Blinding..............................................................................45
5.8.3. Code Breaks.......................................................................45
5.9. Packaging and Labelling...................................................45
5.9.1. Accountability of Product.................................................46
5.9.2. Storage of Product............................................................46
6. STUDY ASSESSMENTS AND PROCEDURES..............47
6.1. Visit 1 -Screening Visit......................................................47
6.1.1 Telephone Screening..........................................................47
6.1.2. Informed Consent.............................................................47
6.1.3. Demographics....................................................................47
6.1.4. Medical History and Concomitant Medication...............48
6.1.5. Oral Soft Tissue (OST) Examination...............................48
6.1.6.  Oral Hard Tissue (OHT) Visual Examination................48
6.1.7. Eligible Tooth Assessment................................................48
6.1.8. Acclimatisation Product Supervised Brushing................50
6.2. Visit 2 -Baseline Visit........................................................50
6.2.1. Oral Soft Tissue (OST) Examination...............................50
6.2.2. Tactile Assessment (Yeaple probe)...................................50
6.2.3.Evaporative Air Sensitivity Assessment...........................53
6.2.4. Selection of Two Test Teeth..............................................54
6.2.5. Supervised Product Use....................................................54
6.3. Visits 3, 4, 5, 7, 8 and 9.......................................................54
6.3.1. Supervised Product Use....................................................54
6.4. Visits 6 and 10....................................................................54
 
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6.4.1. OST Examination..............................................................54
6.4.2. Tactile Assessment (Yeaple Probe)..................................55
6.4.3. Evaporative Air Sensitivity Assessment...........................55
6.4.4. Supervised Product Use....................................................55
6.4.5. Study Conclusion...............................................................55
7. SAFETY ASSESSMENTS..................................................56
7.1. Definitions of an Adverse Event and Serious Adverse 
Event.................................................................................56
7.1.1. Adverse Events..................................................................56
7.1.2. Serious Adverse Events.....................................................57
7.2. Recording Adverse Events and Serious Adverse Events.58
7.3. Evaluating Adverse Events and Serious Adverse Events58
7.4. Reporting Adverse Events and Serious AdverseEvents..59
7.5. Follow-up of Adverse Events and Serious Adverse Events
..........................................................................................61
7.6. Definition of and Procedure for Reporting MedicalDevice 
Incidents...........................................................................62
7.6.1. Definition of an Incident...................................................62
7.6.2. Reporting of Incidents and Malfunctions........................62
7.6.3. Follow-up of Incidents......................................................63
7.7. Collection of Pregnancy Information................................64
7.7.1. Time Period for Collecting of Pregnancy Information...64
7.7.2. Action to be Taken if Pregnancy Occurs.........................64
8. DATA MANAGEMENT....................................................65
8.1. Source Documents/ Data....................................................65
8.2. Electronic Case Report Form............................................65
8.3. Data Handling....................................................................66
8.3.1. Data Queries......................................................................67
8.4. Processing Patient Reported Outcomes............................67
 
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9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES....................................................................67
9.1 Sample Size Determination.................................................67
9.2. General Considerations.....................................................68
9.2.1. Definition of Analysis Populations...................................68
9.2.2. Exclusion of Data from Analysis......................................68
9.2.3. Criteria for Evaluation.....................................................69
9.2.4. Criteria for Assessing Efficacy.........................................69
9.2.5. Criteria for Assessing Tolerability...................................69
9.2.6. Handling of Dropouts and Missing Data.........................69
9.3. Statistical Methods and Analytical Plan...........................69
9.3.1. Demographic and Baseline Characteristics.....................69
9.3.2. Primary Analysis...............................................................70
9.3.3. Secondary Analysis...........................................................70
9.3.4. Exploratory Analyses........................................................70
9.3.5. Safety Analyses..................................................................71
10. STUDY GOVERNANCE CONSIDERATIONS.............72
10.1. Posting of Information on Publicly Available Clinical 
Trials Registers................................................................72
10.2. Regulatory and Ethical Considerations, Including the 
Informed Consent............................................................72
10.3. Quality Control (Study Monitoring)...............................73
10.4. Quality Assurance............................................................74
10.5. Conditions for Terminating the Study............................74
10.6. Records Retention............................................................75
10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials 
Registers and Publication................................................76
11. REFERENCES..................................................................77
 
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12. APPENDICES...................................................................79
12.1. Appendix 1........................................................................79
 
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PROCESS FOR AMENDING THE PROTOCOL
Protocol modifications to ongoing studies which could potentially adversely affect the 
safety of subjects or which alter the scope of the investigation, the scientific quality of 
the study, the experimental design, dosages, duration of therapy, assessment 
variables, the number of subjects treated, or subject selection criteria are considered 
major/substantial amendments and must be made only after appropriate consultation 
between an appropriate representative of GSKCH and the investigator.
Details of amendments to the protocols should be recorded on the following page. 
Protocol modifications must be prepared by a representative of GSKCH.  All changes 
must be justified inthe Reason for Amendment section of the following Protocol 
Amendment Page. Approval of amendments will be made by the original protocol 
signatories or their appropriate designees.
All major/substantial protocol modifications must be reviewed and approvedby the 
appropriate IEC in accordance with local requirements, before the revised edition can 
be implemented. 
All non-substantial/ minor/ administrative amendments should be submitted to the 
IEC as per country specific requirements. In some countries pre-approval of a minor 
amendment is not required and will just be held on file by the sponsor and 
investigator.
 
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Schedule of Events
Procedure/Assessment
Screening
Visit1
Acclimatisation Period –2 to 3 weeks 
Baseline
Visit2 
(Day0)
Week 1 
Visit 3   
(Day 7±1)
Week 2    
Visit 4       
(Day 14±1)
Week 3    
Visit 5      
(Day 21±2)
Week 4 
Visit6
(Day28±2)
Week 5 
Visit7
(Day 35±2)
Week 6 
Visit8
(Day42±3)
Week 7 
Visit9
(Day49±3)
Week 8 
Visit10
(Day56 ±3)
Informed Consent
X
Demographics, Ethnicity, Medical 
History
X
Current/Concomitant Medications
X
X 
X
X
X
X
X
X
X
X
Inclusion/Exclusion
X
X
Subject Eligibility
X
X
Continued Eligibility
X 
X
X
X
X
X
X
X
X
Oral Soft Tissue (OST) Assessment
X
X
X
X
Eligible Teeth Assessments (Full Oral 
Hard Tissue (OHT), Dentition 
Exclusions, EAR, MGI, Tooth 
Mobility)
X
Qualifying Evaporative Air 
Sensitivity (Schiff Score 2/3)
X
Dispense Acclimatisation Kit
X
Supervised Acclimatisation Product 
Use
X
Subjects Return Acclimatisation Kit 
X
Tactile Assessment(Yeaple Probe)
1
X
Evaporative Air Assessment  (Schiff 
Sensitivity Score and VRS)2
X
Select two test teeth
X
Stratification / Randomisation
X
 
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Procedure/Assessment
Screening
Visit1
ation 
Period –2 
Baseline
Visit2 
(Day0)
Week 1 
Visit 3   
(Day 7±1)
Week 2    
Visit 4       
(Day 14±1)
Week 3    
Visit 5      
(Day 21±2)
Week 4 
Visit6
(Day28±2)
Week 5 
Visit7
(Day 35±2)
Week 6 
Visit8
(Day42±3)
Week 7 
Visit9
(Day49±3)
Week 8 
Visit10
(Day56 ±3)
Tactile Assessment (Yeaple Probe2–
test teeth only
X
X
Evaporative Air Assessment  (Schiff 
Sensitivity Score and VRS) –test 
teeth only
X
X
Dispense Study Kit / Redispense 
Oral Rinse and Assigned Dentifrice3
X
X
Supervised Brushing/Rinsing with 
Allocated Treatment4
X 
X
X
X
X
X
X
X
TreatmentCompliance5
X 
X
X
X
X
X
X
X
X
Adverse Events
X6
X 
X
X
X
X
X
X
X
X
Incidents
X6
X 
X
X
X
X
X
X
X
X
Subjects Return Study Kit
X
X
X
X
X
X
X
X
Site Reissue Study Kit to Subjects
X
X
X
X
X
X
X
Study Conclusion/ Medical Sign-off
X
1.  At Baseline, maximum force applied = 20g, at all subsequent visits maximum force = 80g.
2.  Evaporative air assessment to follow tactile assessment, minimum 5 mins between the two assessment types to allow for tooth recovery. 
3.  Subject Kit to includetimer, rinsing cup, diary, dentifrice, toothbrush, and assigned oral rinse. At Visit 6 the dentifrice and assigned oral rinsewill be 
re-dispensed. 
4.  Subject Kit to be returned to subject after supervised brushing/rinsing at all visits except for Visit10.
5.  Compliance with acclimatisation oral rinse at Visit 2 and with assigned treatment oral rinse at Visits 3, 4, 5, 6, 7, 8, 9 and 10 based on weight of oral 
rinse bottle and contents, and completed diaries. 
6.  After supervised use of acclimatisation products.
 
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PROTOCOL SYNOPSIS FOR STUDY 207656
Brief Summary
This single centre, randomised, examiner blind, three-treatment arm, parallel design 
method development study will be used to investigate the efficacy of an experimental 
oral rinse, containing 1.5% potassium oxalate (KOX) and 0 ppm fluoride in relieving 
dentine hypersensitivity (DH) after 8 weeks use compared with a placebo oral rinse 
and a commercialised fluoride oral rinse.
The study will be conducted in healthy subjects with pre-existing self-reported and 
clinically diagnosed tooth sensitivity at screening.
Objectivesand Endpoints
Objectives
Endpoints
Primary
To evaluate and compare the 
clinical efficacy of a 1.5% KOX 
containing oral rinse for the relief 
of DH, as elicited by an 
evaporative air stimulus (with 
Schiff Sensitivity Scale), against a 
negative control oral rinse, 
following use as an adjunct to 
twice daily brushing with a 
standard fluoride dentifrice, after 8 
weeks.
Change from baseline in Schiff 
sensitivity score at 8 weeks.
Secondary
To evaluate and compare the 
clinical efficacy of a 1.5% KOX 
containing oral rinse for the relief 
of DH, as elicited by a tactile 
stimulus (Yeaple probe), against a 
negative control oral rinse, 
following use as an adjunct to 
twice daily brushing with a 
standard fluoride dentifrice, after 8 
weeks.
Change from baseline in tactile 
threshold (Yeaple probe) at 8 
weeks.
 
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Exploratory
To evaluate and compare the 
clinical efficacy of a 1.5% KOX 
containing oral rinse for the relief 
of DH, as elicited by an 
evaporative air stimulus (with 
Schiff Sensitivity Scale), against a 
placebo oral rinse, following use 
as an adjunct to twice daily 
brushing with a standard fluoride 
dentifrice, after 8 weeks. 
Change from baseline in Schiff 
sensitivity score at 8 weeks.
To evaluate and compare the 
clinical efficacy of a 1.5% KOX 
containing oral rinse for the relief 
of DH, as elicited by a tactile 
stimulus (Yeaple probe), against a 
placebo oral rinse, following use 
as an adjunct to twice daily 
brushing with a standard fluoride 
dentifrice, after 8 weeks.
Change from baseline in tactile 
threshold (Yeaple probe) at 8 
weeks.
To evaluate and compare the 
clinical efficacy of a 1.5% KOX 
containing oral rinse for the relief 
of DH, as elicited by an 
evaporative air stimulus (with 
Schiff Sensitivity Scale), against a 
marketed negative control oral 
rinse and a placebo oral rinse, 
following use as an adjunct to 
twice daily brushing with a 
standard fluoride dentifrice, after 4 
weeks.
Change from baseline in Schiff 
sensitivity scoreat 4 weeks.
To evaluate and compare the 
clinical efficacy of a 1.5% KOX 
containing oral rinse for the relief 
of DH, as elicited by a tactile 
Change from baseline in tactile 
threshold (Yeaple probe) at 4 
weeks.
 
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stimulus (Yeaple probe), against a 
marketed negative control oral 
rinse and a placebo oral rinse, 
following use as an adjunct to 
twice daily brushing with a 
standard fluoride dentifrice, after 4 
weeks.
To evaluate and compare the 
clinical efficacy of a 1.5% KOX 
containing oral rinse for the relief 
of DH, as elicited an evaporative 
air stimulus (with VRS), against a 
marketed negative control oral 
rinse and a placebo oral rinse, 
following use as an adjunct to 
twice daily brushing with a 
standard fluoride dentifrice, after 4 
and 8 weeks.
Change from baseline in Visual 
Rating Score (VRS) at 4 and 8 
weeks.
To evaluate and compare the 
clinical efficacy of a 1.5% KOX 
containing oral rinse for the relief 
of DH, as elicited by an 
evaporative air stimulus (with
Schiff Sensitivity Scale), against 
the efficacy of the group obtained 
by combining themarketed 
negativecontrol and the placebo 
oral rinse, following use as an 
adjunct to twice daily brushing 
with a standard fluoride dentifrice, 
after 4 and 8 weeks.
Change from baseline in Schiff 
sensitivity score at 4 and 8 
weeks.
To evaluate and compare the 
clinical efficacy of a 1.5% KOX 
containing oral rinse for the relief 
of DH, as elicited by a tactile 
stimulus (Yeaple probe), against 
Change from baseline in tactile 
threshold (Yeaple probe) at 4 
and 8 weeks.
 
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theefficacy of the group obtained 
by combining themarketed 
negative control and the placebo 
oral rinse, following use as an 
adjunct to twice daily brushing 
with a standard fluoride dentifrice, 
after 4 and 8 weeks.
To evaluate and compare the 
clinical efficacy of a 1.5% KOX 
containing oral rinse for the relief 
of DH, as elicited an evaporative 
air stimulus (with VRS), against 
the efficacy of the group obtained 
by combining themarketed 
negative control and the placebo 
oral rinse, following use as an 
adjunct to twice daily brushing 
with a standard fluoride dentifrice, 
after 4 and 8 weeks.
Change from baseline in VRS at 
4 and 8 weeks.
Study Design
OverallDesign
This will be a single centre, eight week, randomised, examiner-blind, three treatment, 
parallel group design, stratified study in healthy subjects, with at least two sensitive 
teeth that meet all of the study criteria at the Screening and Baselinevisits. DH will 
be assessed at Baseline, and after 4 and 8 weeks twice daily treatment. 
At the Screening visit, subjects will give their written informed consent to participate 
in the study. Demography, medical history and concomitant medications will be 
recorded, followed by an oral examination. This will include an oral soft tissue (OST) 
examination, an oral hard tissue examination (OHT), dentition exclusions, assessment 
of erosion, abrasion, recession (EAR), gingival status, tooth mobility and subject
response to a qualifying air sensitivity assessment, subject response will be recorded 
as a numerical value (Schiff score 2/3). Eligible subjects will be supplied with a 
standard fluoride dentifrice and a fluoride oral rinse to use twice daily (morning and 
evening) during the acclimatisation period between the Screening and Baseline visits. 
 
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Each product use will be recorded in the diary provided. First use of the 
acclimatisation dentifrice and oral rinse will be carried out under supervision at the 
study site.
At the Baseline visit (2-3 weeks after Screening), eligibility to continue will be 
assessed. Subjects will undergo an OST examination, followed by tooth sensitivity 
assessments (a tactile stimulus [Yeaple probe, maximum 20g pressure], then an 
evaporative air stimulus [with Schiff Sensitivity Scale and VRS]), and a review of the 
inclusion/exclusion criteria. Two test teeth will then be identified and eligible subjects 
will be randomised to treatment (stratified by maximum baseline Schiff sensitivity 
score of the two selected test teeth). First use of allocated study product will be 
carried out under supervision at the study site, after the supervised brushing subjects 
will be requested to measure out the dose of the oral rinse using the dosing cup 
provided. Subjects will continue to use their assigned study treatment twice daily 
(morning and evening) for the next 8 weeks, recording each brushing and rinsing 
occasion in the diary provided.
Subjects will return to the study site each week (Visits 3, 4, 5,6, 7, 8, 9 and 10) over 
the eight week study period and asked to return their study kit so that the oral rinse 
bottle and its contents can be weighed to verify study compliance. Diaries will also be 
checked at each visit. A supervised brushing and rinse will also be conducted at each 
visit (except Visit 10). Following supervised product use all products will be returned 
to the subject. The dentifrice and oral rinse will be re-dispensed at Visit 6 (week 4).
Tooth sensitivity will be re-assessed after 4 and 8 weeks (Visits 6 and 10) of 
treatment, using first a tactile stimulus (Yeaple probe, maximum 80g pressure) and 
then anevaporative air stimulus (with Schiff Sensitivity Scale and VRS) on the two 
selected test teeth only. An OST examination will be completed at each of these 
visits, prior to the clinical assessments of sensitivity.
The study site will send twice daily (morning and evening) SMS reminders requesting 
that subjects remember to conduct their timed brush and rinse in the morning and 
evening.
Visit 1 -Screening Visit
The following assessments will be conducted:
Written informed consent.
Review inclusion/exclusion criteria.
Review of the oral care products the subject is currently using to confirm they 
do not contain any ingredients intended for treating sensitive teeth.
 
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Demographics, current/concomitant medications and medical history.
Oral examinations including an oral soft tissue (OST) and oral hard tissue 
(OHT) examinations, and assessments to determine eligible teeth.
Qualifying evaporative air sensitivity assessment -record numerical value 
(Schiff score 2/3).
Confirmation of subject eligibility.
Dispensation of acclimatisation kit.
Supervised brushing and rinse with acclimatisation dentifrice and oral rinse, 
subjects will be requested to measure out the dose of the oral rinse using the 
dosing cup provided.
Adverse Events (AEs) and incidents will be documented from completion of 
the supervised use of the acclimatisation products.
Visit 2 -Baseline Visit
The following assessments will beconducted:
Review of current/concomitant medications, AEs and incidents.
Return of acclimatisation kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
Confirmation of subject eligibility and continuance.
OST examination.
Tactile sensitivity assessment of eligible teeth.
Evaporative air sensitivity assessment of eligible teeth (Schiff sensitivity score 
and VRS) 
Inclusion criteria 4d (please see inclusion criteria table below).
Selectionof two test teeth.
Stratification and Randomisation.
Dispensation of study kit.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided.
AEs and Incidents following supervised brushing and rinse.
Visit 3 -Week 1
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
 
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to measure out the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and Incidents following supervised brushing and rinse.
Confirmation of subject continuance.
Visit 4 -Week 2
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and Incidents following supervised brushing and rinse.
Confirmation of subject continuance.
Visit 5 -Week 3
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review ofcompleted diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and Incidents following supervised brushing and rinse.
Confirmation of subject continuance.
Visit 6 -Week 4
The following assessments will be conducted:
Review of current/concomitant medications, AEs.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
Confirmation of subject continuance.
OST examination.
Tactile sensitivity assessment of two eligible test teeth.
 
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Evaporative air sensitivity assessment of two eligible test teeth (Schiff 
sensitivity score and VRS).
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided. 
Study kit returnedto subject.
Re-dispensation of study dentifrice and oral rinse with usage instructions and 
diary.
AEs and Incidents following supervised brushing and rinse.
Visit 7 -Week 5
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measureout the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and Incidents following supervised brushing and rinse.
Confirmation of subject continuance.
Visit 8 -Week 6
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and Incidents following supervised brushing and rinse.
Confirmation of subject continuance.
Visit 9 -Week 7
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
 
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checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and incidents following supervised brushing and rinse.
Confirmation of subject continuance.
Visit 10 -Week 8/ LSLV
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
Confirmation of subject continuance.
OST examination.
Tactile sensitivity assessment of two eligible test teeth.
Evaporative air sensitivity assessment of two eligible test teeth (Schiff 
sensitivity score and VRS).
Subjects return all study products.
Completion of compliance check.
Type and Planned Number of Subjects
A sufficient number of healthy subjects will be screened to randomise at least 100 
subjects (approximately 50 to the experimental treatment, 25 to the negative control 
and 25 to placebo) to ensure 80 evaluable subjects complete the entire study. This 
will ensure approximately 40 evaluable subjects for the test treatment and 20 each for 
the negative control treatment and placebo.
With this 40/20/20 distribution of the subjects in the treatment arms, the study has 
less than 50% power to detect a mean treatment difference of 0.36 in the Schiff 
sensitivity score using a two-sided t-test of significance level 0.05 for the 
experimental product against the negative control. The standard deviation used in this 
calculation is 0.8; this estimate is obtained from the GSKCH study 204763. When the 
experimental treatment group is compared with the combined group comprising of 
the negative control group and the placebo group using the two-sided t-test with the 
same estimates of mean difference, significance level and standard deviation, the 
study will have 51.1% power.
 
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Diagnosis and Main Criteria for Inclusion
Subjects aged 18-65 years of age, with a minimum of 20 natural teeth and in good 
general health who suffer from tooth sensitivity. At Screening, subjects must have a 
minimum of two accessible non adjacent teeth (incisors, canines, or pre-molars) with 
signs of erosion or abrasion or facial/cervical gingival recession (EAR), with a 
modified gingival index (MGI) =0 adjacent to the test area and a clinical mobility of 
≤1, and with signs of sensitivity measured by qualifying evaporative air assessment. 
At Baseline subjects must have a minimum of two, non-adjacent accessible teeth 
(incisors, canines or pre-molars), with signs of sensitivity, measured by qualifying 
tactile stimulus (Yeaple ≤ 20g) and evaporative air assessment (Schiff Sensitivity 
Score ≥ 2).
Product Information
The following study products will be supplied by the Clinical Supplies Department, 
GSKCH:
Test Product
Negative Control 
Placebo Product
Product Name Experimental oral 
rinse containing 
1.5% KOX, 0ppm 
fluoride, pH 7
Oral rinse containing 
0.02% w/w NaF. 
Colgate Total Daily 
Repair(USA 
marketed product)
Oral rinse containing 
0% KOX and 0 ppm 
fluoride, pH 7
Product 
Formulation 
Code (MFC)
Commercially 
Available
Dose
10 ml
10 ml
10 ml
Route of 
Administration
Oral
Oral
Oral
Dosing 
Instructions
Rinse twice daily 
(morning and 
evening) with 10 ml 
of oral rinse for 60 
timed seconds and 
expectorate. No 
further rinsing with 
water will be 
permitted after use of 
the oral rinse. 
Rinse twice daily 
(morning and evening) 
with 10 ml of oral 
rinse for 60 timed 
seconds and 
expectorate. No further 
rinsing with water will 
be permitted after use 
of the oral rinse.
Rinse twice daily 
(morning and 
evening) with 10 ml 
of oral rinse for 60 
timed seconds and 
expectorate. No 
further rinsingwith 
waterwill be 
permitted after use of 
the oral rinse.
                                               
Colgateand Total Daily Repair areregistered trademarksof the Colgate-Palmolive group
 
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CCI
CCI


Statistical Methods
Changes from baseline to Week 4 and Week 8 in Schiff Sensitivity Score will be 
analysed using an analysis of covariance (ANCOVA) model. The model will include 
treatment as a factor and baseline Schiff Sensitivity Score as a covariate.
Changes from baseline in tactile score and VRS score will be analysed for weeks 4 
and 8 separately using ANCOVA analysis with treatment and baseline Schiff 
stratification as factors and the corresponding baseline scores as a covariate in the 
model.
The adjusted mean for each treatment, and the differences between each pair of 
treatments together with their corresponding 95% confidence intervals and the p-
values for treatment comparisons, will be provided.
Assumptions of normality and homogeneity of residuals will be evaluated and if 
serious departures are observed transformations will be investigated. If suitable 
transformations cannot be found, non-parametric tests such as Wilcoxon Rank Sum 
test or the van Elteren test will be used.
 
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1. INTRODUCTION
Dentine hypersensitivity (DH) has been defined as ‘pain derived from exposed 
dentine in response to chemical, thermal, tactile, or osmotic stimuli which can’t be 
explained as arising from any other dental defect or disease’ [Addy, 1985; Canadian 
Advisory Board on Dentin Hypersensitivity, 2003]. The primary aetiological factors 
associated with the onset of DH include gingival recession and/or enamel loss (e.g. 
through erosion or abrasion) that result in exposure of dentine with patent dentinal 
tubules [Orchardson, 1987]. The hydrodynamic theory
 of DH hypothesises that a 
stimulus external to the tooth (e.g. a temperature/osmotic differential) causes 
transport of the fluid resident within dentinal tubules [Brännström, 1962]. This fluid 
movement may stimulate nerve processes in the pulpal area of the dentine including 
irritation of odontoblasts, pulpal neurons,and even subodontonblastic blood vessels 
[Hall, 2000], resulting in the characteristic short, sharp pain of DH.
Currently there are two approaches to the management of DH using home use oral 
care products: either nerve depolarisation or dentinal tubule occlusion. Nerve 
depolarising agents, typically potassium salts, generally require a period of use (for 
example, 14 to 28 days) before their benefit is established. The delivery of potassium 
ions to the dentine-pulp junction (odontoblastic layer) viadentinal tubules is believed 
to result in depolarisation of the afferent nerve membrane thereby blocking the pain 
response. The second approach uses tubule occluding agents which physically block 
the exposed end of the dentinal tubules, thus reducing dentinal fluid movement and 
pulpal irritation. Tubule occluding agents such as strontium and stannous salts, 
bioglasses, silicas or oxalates serve to seal or block the dentine tubules and thereby 
reduce the effect of external stimuli. Such agents are believed to function by 
precipitating insoluble materials onto the dentine surface and/or within the dentinal 
tubules to reduce dentinal fluid transport. 
Tubule occluding agents have been formulated in a number of commercialised over-
the-counter (OTC) DH dentifrices, and more recently in DH oral rinses. A number of 
successful clinical studies have been conducted on oral rinses containing occluding 
agents 8% Arginine [Boneta, 2013; Hu, 2013; Markowitz, 2013], and 1.4% KOX 
[Sharma, 2013
a; Sharma, 2013
b], these products are marketed as Colgate
Sensitive 
Pro-relief
Mouthwash and Listerine** Advanced Defence Sensitive Mouthwash, 
respectively.
                                               
Colgate is a registered trademark of the Colgate-Palmolive group
Pro-relief is a registered trademark of the Colgate-Palmolive group
**Listerine is a registered trademark of Johnson & Johnson Limited
 
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GSKCH has evaluated the DH efficacy of two different technologies in rinse format, 
potassium nitrate (KNO
3) and KOX. 
Three studies of a similar design have been conducted to evaluate the DH efficacy of 
three different 1.5-2.0 % KOX containing oral rinses [GSKCH studies: 204762; 
204763; 204773]. When evaluated in randomised double-blind, placebo-controlled 
studies, similar statistically significant improvements were measuredfrom baseline in 
favour of all test oral rinses versus the placebo [GSKCH study 204763], but statistical 
differentiation versus placebo treatment was not reported for two of these studies 
[GSKCH studies: 204762 and 204773]. The reason for the lack of statistical 
differentiation in these studies is unclear as KOX has been shown to be effective in 
reducing DH in other published clinical studies [Sharma, 2013a; Sharma, 2013
b].
The mixed results that have been observed in GSKCH DH mouthrinse studies has 
prompted a piece of method development work to be completed. The aim of this 
method development study is to explore some of the areas of clinical design in an 8 
week DH clinical study that could be used for existing and future DH oral rinse 
technologies. 
 
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2. OBJECTIVES AND ENDPOINTS
Objectives
Endpoints
Primary
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by an evaporative air stimulus 
(with Schiff Sensitivity Scale), against 
a negative control oral rinse, 
following use as an adjunct to twice 
daily brushing with a standard 
fluoride dentifrice, after 8 weeks.
Change from baseline in Schiff 
sensitivity score at 8 weeks.
Secondary
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by a tactile stimulus (Yeaple 
probe), against a negative control oral 
rinse, following use as an adjunct to 
twice daily brushing with a standard 
fluoride dentifrice, after 8 weeks.
Change from baseline in tactile 
threshold (Yeaple probe) at 8 
weeks.
Exploratory
To evaluate and comparethe clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by an evaporative air 
stimulus (with Schiff Sensitivity 
Scale), against a placebo oral rinse, 
following use as an adjunct to twice 
daily brushing with a standard 
fluoride dentifrice, after 8 weeks.
Change from baseline in Schiff 
sensitivity score at 8 weeks.
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by a tactile stimulus (Yeaple 
probe), against a placebo oral rinse, 
Change from baseline in tactile 
threshold (Yeaple probe) at 8 
weeks.
 
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following use as an adjunct to twice 
daily brushing with a standard 
fluoride dentifrice, after 8 weeks.
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by an evaporative air 
stimulus (with Schiff Sensitivity 
Scale), against a marketed negative 
control oral rinse and a placebo oral 
rinse, following use as an adjunct to 
twice daily brushing with a standard 
fluoride dentifrice, after 4 weeks.
Change from baseline in Schiff 
sensitivity scoreat 4 weeks.
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by a tactile stimulus (Yeaple 
probe), against a marketed negative 
control oral rinse and a placebo oral 
rinse, following use as an adjunct to 
twice daily brushing with a standard 
fluoride dentifrice, after 4 weeks.
Change from baseline in tactile 
threshold (Yeaple probe) at 4 
weeks.
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited an evaporative air stimulus 
(with VRS), against a marketed 
negative control oral rinse and a 
placebo oral rinse, following use as an 
adjunct to twice daily brushing with a 
standard fluoride dentifrice, after 4 
and 8 weeks.
Change from baseline in Visual 
Rating Score (VRS) at 4 and 8 
weeks.
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by an evaporative air stimulus 
(withSchiff Sensitivity Scale), against 
Change from baseline in Schiff 
sensitivity score at 4 and 8 
weeks.
 
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the efficacy of the group obtained by 
combining themarketed negative 
control and the placebo oral rinse, 
following use as an adjunct to twice 
daily brushing with a standard 
fluoride dentifrice, after 4 and 8 
weeks.
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by a tactile stimulus (Yeaple 
probe), against theefficacy of the 
group obtained by combining the
marketed negative control and the 
placebo oral rinse, following use as 
an adjunct to twice daily brushing 
with a standard fluoride dentifrice, 
after 4 and 8 weeks.
Change from baseline in tactile 
threshold (Yeaple probe) at 4 
and 8 weeks.
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited an evaporative air stimulus 
(with VRS), against the efficacy of the 
group obtained by combining the
marketed negative control and the 
placebo oral rinse, following use as an 
adjunct to twice daily brushing with a 
standard fluoride dentifrice, after 4 
and 8 weeks.
Change from baseline in VRS at 
4 and 8 weeks.
 
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3. STUDY PLAN
3.1. Study Design

Overall Design
This will be a single centre, eight week, randomised, examiner-blind, three treatment, 
parallel group design, stratified study in healthy subjects, with at least two sensitive 
teeth that meet all of the study criteria at the Screening and Baseline visits. DH will 
be assessed at Baseline, and after 4 and 8 weeks twice daily treatment. 
At the Screening visit, subjects will give their written informed consent to participate 
in the study. Demography, medical history and concomitant medications will be 
recorded, followed by an oral examination. This will include an oral soft tissue (OST) 
examination, an oral hard tissue examination (OHT), dentition exclusions, assessment 
of erosion, abrasion, recession (EAR), gingival status, tooth mobility and subject 
response to a qualifying air sensitivity assessment, subject response will be recorded 
as a numerical value (Schiff score 2/3). Eligible subjects will be supplied with a 
standard fluoride dentifrice and a fluoride oral rinse to use twice daily (morning and 
evening) during the acclimatisation period between the Screening and Baseline visits. 
Each product use will be recorded in the diary provided. First use of the 
acclimatisation dentifrice and oral rinse will be carried out under supervision at the 
study site.
At the Baseline visit (2-3 weeks after Screening), eligibility to continue will be 
assessed. Subjects will undergo an OST examination, followed by tooth sensitivity 
assessments (a tactile stimulus [Yeapleprobe, maximum 20g pressure], then an 
evaporative air stimulus [with Schiff Sensitivity Scale and VRS]), and a review of the 
inclusion/exclusion criteria. Two test teeth will then be identified and eligible subjects 
will be randomised to treatment (stratified by maximum baseline Schiff sensitivity 
score of the two selected test teeth). First use of allocated study product will be 
carried out under supervision at the study site, after the supervised brushing subjects 
will be requested to measure out the dose of the oral rinse using the dosing cup 
provided. Subjects will continue to use their assigned study treatment twice daily 
(morning and evening) for the next 8 weeks, recording each brushing and rinsing 
occasion in the diary provided.
Subjects will return to the study site each week (Visits 3, 4, 5, 6, 7, 8, 9 and 10) over 
the eight week study period and asked to return their study kit so that the oral rinse 
bottle and its contents can be weighed to verify study compliance. Diaries will also be 
 
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checked ateach visit. A supervised brushing and rinse will also be conducted at each 
visit (except Visit 10). Following supervised product use all products will be returned 
to the subject. The dentifrice and oral rinse will be re-dispensed at Visit 6 (week 4).
Tooth sensitivity will be re-assessed after 4 and 8 weeks (Visits 6 and 10) of 
treatment, using first a tactile stimulus (Yeaple probe, maximum 80g pressure) and 
then anevaporative air stimulus (with Schiff Sensitivity Scale and VRS) on the two 
selected test teeth only. An OST examination will be completed at each of these 
visits, prior to the clinical assessments of sensitivity.
The study site will send twice daily(morning and evening)SMS reminders requesting 
that subjects remember to conduct their timed brush and rinse in the morning and 
evening.
Visit 1 -Screening Visit
The following assessments will be conducted:
Written informed consent.
Review inclusion/exclusion criteria.
Review of the oral care products the subject is currently using to confirm they 
do not contain any ingredients intended for treating sensitive teeth.
Demographics, current/concomitant medications and medical history.
Oral examinations including an oral soft tissue (OST) and full oral hard tissue 
(OHT) examinations, and assessmentsto determine eligible teeth.
Qualifying evaporative air sensitivity assessment -record numerical value 
(Schiff score 2/3).
Confirmation of subject eligibility.
Dispensation of acclimatisation kit.
Supervised brushing and rinse with acclimatisation dentifrice and oral rinse, 
subjects will be requested to measure out the dose of the oral rinse using the 
dosing cup provided.
Adverse Events (AEs) and incidents will be documented from completion of 
the supervised use of the acclimatisation products.
Visit 2 -Baseline Visit
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of acclimatisation kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
Confirmation of subject eligibility and continuance.
OST examination.
 
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Tactile sensitivity assessment of eligible teeth.
Evaporative air sensitivity assessment of eligible teeth (Schiff sensitivity score 
and VRS) 
Inclusion criteria 4d (please see inclusion criteria table below).
Selection of two test teeth.
Stratification and Randomisation.
Dispensation of study kit.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse usingthe dosing cup provided.
AEs and Incidents following supervised brushing and rinse.
Visit 3 -Week 1
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and Incidents following supervised brushing and rinse.
Confirmation of subject continuance.
Visit 4 -Week 2
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and Incidents following supervised brushing and rinse.
Confirmation of subject continuance.
Visit 5 -Week 3
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
 
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checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and Incidents following supervised brushing and rinse.
Confirmation of subject continuance.
Visit 6 -Week 4
The following assessments will be conducted:
Review of current/concomitant medications, AEs.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
Confirmation of subject continuance.
OST examination.
Tactile sensitivity assessment of two eligible test teeth.
Evaporative air sensitivity assessment of two eligible test teeth (Schiff 
sensitivity score and VRS).
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided. 
Study kit returned to subject.
Re-dispensation of study dentifrice and oral rinse with usage instructions and 
diary.
AEs and Incidents following supervised brushing and rinse.
Visit 7 -Week 5
The following assessments will beconducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and Incidents following supervised brushing and rinse.
Confirmation of subject continuance.
 
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Visit 8 -Week 6
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and Incidents following supervised brushing and rinse.
Confirmation of subject continuance.
Visit 9 -Week 7
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
A supervised brushing and rinse will be conducted, subjects will be requested 
to measure out the dose of the oral rinse using the dosing cup provided.
Study kit returned to subject.
AEs and incidents following supervised brushing and rinse.
Confirmation of subject continuance.
Visit 10 -Week 8/ LSLV
The following assessments will be conducted:
Review of current/concomitant medications, AEs and incidents.
Return of study kit.
Review of completed diary and weight of oral rinse bottle and contents will be 
checked to determine usage compliance.
Confirmation of subject continuance.
OST examination.
Tactile sensitivity assessment of two eligible test teeth.
Evaporative air sensitivity assessment of two eligible test teeth (Schiff 
sensitivity score and VRS).
Subjects return all study products.
Completion of compliance check.
 
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3.3. Type and Planned Number of Subjects
A sufficientnumber ofhealthy subjects will be screened to randomise at least 100 
subjects (approximately 50 to the experimental treatment, 25 to the negative control 
and 25 to placebo) to ensure 80 evaluable subjects complete the entire study. This 
will ensure approximately 40 evaluable subjects for the test treatment and 20 each for 
the negative control treatment and placebo.
With this 40/20/20 distribution of the subjects in the treatment arms, the study has 
less than 50% power to detect a mean treatment difference of 0.36 in the Schiff 
sensitivity score using a two-sided t-test of significance level 0.05 for the 
experimental product against the negative control. The standard deviation used in this 
calculation is 0.8; this estimate is obtained from the GSKCH study 204763. When the 
experimental treatment group is compared with the combined group comprising of 
the negative control group and the placebo group using the two-sided t-test with the 
same estimates of mean difference, significance level and standard deviation, the 
study will have 51.1% power.
3.4. Study Design and Dose Justification
This study will be a randomised, examiner blind, three treatment parallel group 
design. Subjectswill apply a full brush head of the standard fluoride dentifrice, brush 
for one timed minute (in their usual manner) and expectorate; rinse with 10ml of tap 
water for 5 seconds and expectorate; and then rinse with 10 ml of their randomly 
assigned oral rinse for 60 timed seconds and expectorate. No further rinsingwith 
waterwill be permitted after use of the oral rinse, and subjects will be asked to refrain 
from eating or drinking within 30 minutes of using the oral rinse. The dosage regimen 
of twice daily treatment (morning and evening) will be the same for all subjects, and 
has been selected based on widely recommended oral hygiene practice, and typical 
consumer habit. 
An experimental 1.5% w/w KOX rinse will be included in the study (1.5% w/w KOX 
/ 0 ppm fluoride, pH 7) as it has previously shown statistically significant DH 
efficacy compared to a placebo oral rinse [GSKCH study 204763]. KOX has also 
been selected as the DH active as it has been shown to be effective in reducing DH in 
other published studies [Sharma, 2013a; Sharma, 2013
b]. Efficacy will be compared 
to that of a placebo oral rinse and a US marketed rinse, with no known anti-sensitivity 
activity. 
 
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All subjects will receive the same regular fluoride dentifrice and a US marketed oral 
rinse during the acclimatisation period to familiarise themselves with the required 
brushing and rinsing regimen, and standardise oral hygiene practices. The sodium 
monofluorophosphate (SMFP) control paste and sodium fluoride (NaF) oral rinse 
have been selected for use in this study as they do not contain any knownanti-
sensitivity ingredients 
The control products will be a placebo oral rinse and a US marketed, twice daily use 
fluoride rinse. 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 the oral rinses evaluated in this study, 
the level of blindness for this study is described as ‘examiner blind’ only.
The study statistician and other employees of the Sponsor who may influence study 
outcomes are blinded to the product allocation of subjects. The examiner will be 
blinded to the treatment received. To ensure the examiner remains blinded throughout 
the study, the examiner is not permitted in the room whilst product is dispensed. All 
study products (including the acclimatisation products) will be overwrapped to 
conceal any labelling. In addition, subjects should be treated in a separate area. The 
dispensing staff will not be involved in any clinical assessments during the study. 
An acclimatisation period of 2 weeks is often utilised in DH oral rinse studies 
[Boneta, 2013; Hu, 2013; Markowitz, 2013; Sharma, 2013a, 2013b]. Therefore, an 
acclimatisation period of 2-3 weeks will be included in this study.
A weekly supervised rinsing at the study site and twice daily SMS reminders to 
subjects participating in the study will be conducted to aid compliance. During study
 
site visits subjects will be asked to measure out their own dose of oral rinse using the 
cups provided, so that dose amount compliance can be monitored by the study staff. 
Subjects will also be asked to return their assigned oral rinse at each visit, so that the 
bottle and its contents can be weighed and compliance assessments made. 
Furthermore, only regular (twice daily) oral rinse users will be recruited for this 
study.
Other causes of dental pain can present with the same symptoms as DH, for example 
cracked tooth syndrome, fractured restorations, chipped tooth, dental caries, post-
restorative sensitivity and teeth in acute hyperfunction [Dababneh, 1999]. While the 
 
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age range over which an individual can experience DH is wide (from early teens to 
70s) [Fischer, 1992], peak incidence is known to occur between the ages of 20-40 
years [Graf, 1977; Flynn, 1985]. The fall in prevalence observed in later decades 
reflects age related changes in the dentine and pulpof the tooth which act to reduce 
dentine permeability and the tooth’s response to the external triggers of DH [Seltzer, 
1975; Pashley, 2008]. Given that the dental pain experienced by older members of the 
population is less likely to be diagnosed as DH [Rees, 2000], the age range of 18-65 
selected for this study targets individuals suffering from tooth sensitivity whichis 
most likely due to DH. This will facilitate recruitment and minimise inconvenience to 
older participants who are more likely to be rejected at screening. 
4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA
Specific information regarding warnings,precautions, contraindications, adverse 
events, and other pertinent information on the GSK investigational product or other 
study treatment that may impact subject eligibility is provided in the Safety Statement 
and on the product label.
Deviations from inclusion and exclusion criteria are not allowed as they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability,or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is 
essential.
4.1. Inclusion Criteria
A subject will be eligible for inclusion in this study only if all of the following criteria 
apply:
1. CONSENT
Demonstrates understanding of the study procedures, restrictions and willingness to 
participate as evidenced by voluntary written informed consent and has received a 
signed and dated copy of the informed consent form. 
2. AGE
Aged between18-65 years.
 
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3. GENERAL HEALTH
Good general and mental health with, in the opinion of the investigator or medically 
qualified designee:
a) No clinically significant and relevant abnormalities in medical history or oral 
examination.
b) Absence of any condition that would impact on the subject’s safety or wellbeing or 
affect the individual’s ability to understand and follow study procedures and 
requirements.
4. DENTAL HEALTH
At Screening:
a) Self-reported history of DH lasting more than six months but not more than 10 
years.
b) Minimum of 20 natural teeth.
c) Minimum of 4 accessible non-adjacent teeth (incisors, canines, premolars), 
preferably in different quadrants, that meet all of the following criteria:
-Signs of facial/cervical gingival recession and/or signs of erosion or      
abrasion (EAR).
-Tooth with MGI score =0 adjacent to the test area (exposed dentine) only 
[Lobene, 1986] and a clinical mobility of ≤1.
-Tooth with signs of sensitivity measured by qualifying evaporative air 
assessment (Schiff sensitivity score ≥ 2).
At Baseline:
d) Minimum of two, non-adjacent accessible teeth (incisors, canines, premolars), that 
meet all of the following criteria:
-Tooth withsigns of sensitivity, measured by qualifying tactile stimulus (Yeaple ≤ 
20g) and evaporative air assessment (Schiff sensitivity score ≥ 2)
Note: Teeth which meet the EAR, MGI and mobility inclusion criteria and none of 
the dentition exclusion criteria atScreening should be assessed by tactile stimulus at 
Visit 2. Those teeth which meet the required tactile threshold (Yeaple ≤ 20g) should 
then be assessed by evaporative air stimulus. When two teeth that meet the study 
criteria are identified, no further testing is necessary. The examiner will selecttwo 
Test Teeth from those which meet both the tactile threshold and Schiff sensitivity 
score criteria. Test Teeth should not be adjacent to each other and preferably in 
different quadrants.
 
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5. CONTRACEPTION 
Females of childbearing potential who are, in the opinion of the investigator, 
practicing a reliable method of contraception. Adequate contraception is defined as 
abstinence, oral contraceptive, either combined or progestogen alone OR injectable 
progestogen OR implants of levonorgestrel OR estrogenic vaginal ring OR 
percutaneous contraceptive patches OR intrauterine device or intrauterine system OR 
double barrier method (condom or occlusive cap [diaphragm or cervical vault caps] 
plus spermicidal agent [foam, gel, film, cream, suppository]) OR male partner 
sterilisation prior to the female subject
's entry into the study, and this male is the sole 
partner for that subject.
6. COMPLIANCE 
Understands and is willing, able and likely to comply with all study procedures and 
restrictions.
7. ORAL RINSE USERS 
Subjects will be current and regular (twice daily), users of an OTC Monograph or 
cosmetic oral rinse.
8. CELL PHONE OWNERS
Subjects will be cell phone owners so that they can contactable by SMS.
4.2. Exclusion Criteria
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply:
1. PREGNANCY
A woman who is known to be pregnant or who is intending to become pregnant over 
the duration of the study. 
2. BREAST-FEEDING
A woman who is breast-feeding.
3. ALLERGY/ INTOLERANCE
Known or suspected intolerance or hypersensitivity to the study materials (or closely 
related compounds) or any of their stated ingredients.
 
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4. CLINICAL STUDY/ INVESTIGATIONAL PRODUCT
a) Participation in another clinical study (including cosmetic studies) or receipt of 
an investigational drug within 30 days of the screening visit.
b) Previous participation in this study.
5. SUBSTANCE ABUSE
Recent history (within the last year) of alcohol orother substance abuse.
6. PERSONNEL
An employee of the sponsor or the study site or members of their immediate family.
7. DISEASE
a) Presence of chronic debilitating disease which, in the opinion of the investigator, 
could affect study outcomes.
b) Any condition which, in the opinion of the investigator, causes xerostomia.
8. GENERAL DENTITION EXCLUSIONS
a) Dental prophylaxis within 4 weeks of Screening.
b) Tongue or lip piercing. 
c) Desensitising treatment within 8 weeks of Screening (professional sensitivity 
treatments and non-dentifrice sensitivity treatments).
d) Gross periodontal disease, treatment of periodontal disease (including surgery) 
within 12 months of Screening, scaling or root planning within 3 months of 
Screening.
e) Teeth bleachingand any teeth whitening procedureswithin 8 weeks of 
Screening.
9. SPECIFIC DENTITION EXCLUSIONS FOR TEST TEETH
a) Tooth with evidence of current or recent caries, or reported treatment of decay 
within 12 months of Screening.
b) Tooth with exposed dentine but with deep, defective or facial restorations, teeth 
used as abutments for fixed or removable partial dentures, dental implants, teeth 
with full crowns or veneers, orthodontic bands or cracked enamel.  Sensitive 
teeth with contributing aetiologies other than erosion, abrasion or recession of 
exposed dentine.
c) Sensitive tooth not expected to respond to treatment with an over-the-counter 
dentifrice in the opinion of the investigator.
 
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4.3. Screening/ Baseline Failures
Screen failures are defined as subjects who consent to participate in the study butare 
never subsequently randomised.The electronic case report form (eCRF)should be
used as the source documentation to the point of failure.In order to ensure transparent 
reporting of screen failure subjects, a minimal set of screen failure information is 
required:
Consent
Demography 
Study conclusion form (reason must include documentation of 
inclusion/exclusion criteria that was failed)
AE forms (Yes/No and specifics if Yes)
Re-screening of subjects will not be allowed in this study.
10. PRODUCT USE
Use of an oral care product indicated for the relief of dentine hypersensitivity within 8 
weeks of screening (subjects will be required to bring their current oral care products 
to the site in order to verify the absence of known anti-sensitivity ingredients).
11. CONCOMITANT MEDICATION/MEDICAL HISTORY
a) Daily doses of medication/treatments which, in the opinion of the investigator, 
could interfere with the perception of pain. Examples of such medications include 
analgesics, anticonvulsants, antihistamines that cause marked or moderate 
sedation, sedatives, tranquilisers, anti-depressants, mood-altering and anti-
inflammatory drugs.
b) Currently taking antibiotics or has taken antibiotics within two weeks of Baseline. 
c) Daily dose of a medication which, in the opinion of the investigator, is causing 
xerostomia.
d) Presence of kidney disease, hyperoxaluria, or any other condition that may be 
exacerbated by oxalic acid or oxalate salts.
e) Presence of chronic debilitating disease which, in the opinion of the investigator, 
could affect study outcomes.
12. OTHERCRITERIA
Any subject who, in the judgment of the investigator, should not participate in the 
study.
 
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4.4. Withdrawal/ Stopping Criteria
A subject may withdraw from the study at any time at his/her own request, or may be 
withdrawn at any time at the discretion of the investigator for safety, behavioural or 
administrative reasons. If the reason for removal of a subject from the study is an AE, 
the principal specific event or test will be recorded in the eCRF. If a subject is 
withdrawn from the study because of a product limiting AE, thorough efforts should 
be clearly made to document theoutcome. Any AEs ongoing at the final visit will be 
followed up until resolved, the condition stabilises, is otherwise explained, or the 
subject is lost to follow-up. Should a subject take an analgesic medication within 8 
hours of an assessment visit, or should any other factor, in the opinion of the 
investigator, be thought to affect study outcomes (e.g. analgesic or excessive alcohol 
consumption), every attempt will be made to reschedule the subject. If they cannot be 
reappointed they will be withdrawn from the study.
The following actions must be taken in relation to a subject who fails to attend the 
clinic for a required study visit:
The site must attempt to contact the subject and re-schedule the missed visit as 
soon as possible.
The site must counsel the subject on the importance of maintaining the 
assigned visit schedule and ascertain whether or not the subject wishes to 
and/or should continue in the study.
In cases where the subject is deemed ‘lost to follow up’, the investigator or 
designee must make every effort to regain contact with the subject (where 
possible, at least 2 telephone calls). The contact attempt should be 
documented in the subject’s record.
Should the subject continue to be unreachable, only then will he/she be 
considered to have withdrawn from the study with a primary reason of “Lost 
to Follow-up”.
Should a randomised subject take an analgesic medication within 8 hours of an 
assessment visit, or should any other factor, in the opinion of the investigator, be 
thought to affect study outcomes (e.g. excessive alcohol consumption), the following 
actions must be taken:
Baseline visit: every attempt will be made to reschedule the subject. If they 
cannot be reappointed they will be withdrawn from the study. No clinical 
efficacy measures willbe performed. The subject should not be replaced.
 
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Week 4 visit: every attempt will be made to reschedule the subject. If they 
cannot be reappointed they will continue in the study. No clinical efficacy 
measures will be performed at this visit.
Week 8 visit: every attempt will be made to reschedule the subject. If they 
cannot be reappointed they will be withdrawn from the study. No clinical 
efficacy measures will be performed. The subject should not be replaced.
4.5. Subject Replacement
Subjects who withdraw from the study post-randomisation will not be replaced.
4.6. Subject and Study Completion
A completed subject is one who has completed all phases of the study. The end of the 
study is defined as the date of the last subject’s last visit.
5. PRODUCT INFORMATION
5.1. Study Product
The following study products will be supplied by the Clinical Supplies Department, 
GSKCH:
Test Product
Negative Control 
Placebo Product
Product Name Experimental oral 
rinse containing 
1.5% KOX, 0ppm 
fluoride, pH 7
Oral rinse containing 
0.02% w/w NaF. 
Colgate Total Daily 
Repair(USA 
marketed product)
Oral rinse containing 
0% KOX and 0 ppm 
fluoride, pH 7
Product 
Formulation 
Code (MFC)
Commercially 
Available
Dose
10 ml
10 ml
10 ml
Route of 
Administration
Oral
Oral
Oral
Dosing 
Instructions
Rinse twice daily 
(morning and 
evening) with 10 ml 
of oral rinse for 60 
Rinse twice daily 
(morning and evening) 
with 10 ml of oral 
rinse for 60timed 
Rinse twice daily 
(morning and 
evening) with 10 ml 
of oral rinse for 60 
                                               
Colgateand Total Daily Repair areregistered trademarksof the Colgate-Palmolive group
 
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CCI
CCI


timed seconds and 
expectorate. No 
further rinsingwith 
waterwill be 
permitted after use of 
the oral rinse. 
seconds and 
expectorate. No further 
rinsingwith waterwill 
be permitted after use 
of the oral rinse.
timed seconds and 
expectorate. No 
further rinsingwith 
waterwill be 
permitted after use of 
the oral rinse.
Other items to be supplied by the Clinical Supplies Department, GSKCH:
Name of Item
Purpose
Dentifrice containing 0.76% w/w SMFP 
(1000ppm fluoride). ColgateCavity 
Protection (USA marketed product).
Acclimatisation and daily use dentifrice -
to standardise oral hygiene practice prior 
to treatment phase and use prior to 
rinsing with oral rinse during the 
treatment phase.
Oral rinse containing 0.02% w/w NaF. 
Crest Pro-Health Advanced with Extra 
Deep Clean mouthwash(USA marketed 
product).
Acclimatisation oral rinse -to standardise 
oral hygiene practice prior to treatment 
phase.
Oral-B Sensi Soft Manual Toothbrush
Dentifrice application by tooth brushing.
Countdown timers
To ensure accurate brushing.
Dosing cups
For accurately measuring out the oral 
rinse and rinsing with water after 
brushing.
The acclimatisation kit will include the following items: acclimatisation dentifrice, 
oral rinse, toothbrush, dosing cup, usage instructions, diary and timer.
The study kit will include the following items: study dentifrice, assigned oral rinse, 
toothbrush, dosing cup, usage instructions, timer and diary.
5.2. Dose Schedule
During the acclimatistion period, subjectswill apply a full brush head of the standard 
fluoride dentifrice,brush for one timed minute (in their usual manner) and 
expectorate; rinse with 10ml of tap water for 5 seconds and expectorate; and then 
rinse with 10 ml of the acclimatisation oral rinse for 60 timed seconds and 
expectorate. 
During the treatment period, subjectswill apply a full brush head of the standard 
fluoride dentifrice, brush for one timed minute (in their usual manner) and 
expectorate; rinse with 10 ml of tap water for 5 seconds and expectorate; and then 
 
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rinse with 10 ml of the allocated treatment oral rinse for 60 timed seconds and 
expectorate. 
No further rinsing with water will be permitted after use of theoral rinse during the 
acclimatisation phase or treatment period, and subjects will be asked to refrain from 
eating or drinking within 30 minutes of using the oral rinse.
The dosage regimen of twice daily treatment (morning and evening) will be applied 
during the acclimatisation and treatment period.
5.3. Dose Modification
No dose modification is permitted in this study.
5.4. Product Compliance
A weekly supervised rinsing at the study site and twice daily(morning and evening)
SMS reminders to subjects participating in the study will be conducted to aid 
compliance. During study site visits subjects will be asked to measure out their own 
dose of oral rinse using the cups provided, so that dose amount compliance can be 
monitored by the study staff. Subjects will also be asked to return their assigned oral 
rinse at each visit, so that the bottle and its contents can be weighed and compliance 
assessments made. Furthermore, only regular (twice daily) oral rinse users will be 
recruitedfor this study.
5.5. Precautions
No special precautions are necessary provided the study is carried out in accordance 
with this protocol.
5.6. Overdose
An overdose is a deliberate or inadvertent administration of a productat a dose higher 
than specified in the protocol.
Overdose is not likely to occur in this study. Limited quantities of the product will be 
supplied, and closely monitored by the site for each subject.
Overdose per se is not an AE. However, any clinical sequelae of an overdose should 
be reported as an AE (and serious adverseevent (SAE), if appropriate). For reporting, 
follow the AE and SAE reporting instructions.
 
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5.7. Rescue Therapy
No rescue therapy is required in this study.
5.8. Product Assignment
Subjects will be assigned to study productin accordance with the randomisation 
schedule generated byinVentiv Healthprior to the start of the study, using validated 
software.
prior to the start of the study, using validated software.
5.8.1 Randomisation
A unique screening number will identify each subject screened for study 
participation. Screening numbers will be assigned in ascending numerical order as 
each subject signs their consent form.Subjects who meet all inclusion and exclusion 
criteria will be randomised according to the randomisation schedule. Randomisation 
numbers will be assigned in ascending numerical order as each subject is determined 
to be fully eligible.
Subjects will be stratified according to their maximum baseline Schiff of the two 
selected teeth (2/3). Randomisation numbers within each stratum will be assigned in 
ascending numerical order according to appearance at the study site on the day 
subjects are randomised. The stratification factor will give rise to two strata.
Stratum 1:Subjects with maximum baseline Schiff sensitivity score of 2 for the 
two selected test teeth
Stratum 2:Subjects with the maximum baseline Schiff sensitivityscore of 3 for 
the two selected test teeth.
The randomisation list will be prepared using a randomisation block design with a 
2:1:1 ratio. The study site will receive two versions of the randomisation schedule, 
each in a sealed envelope and clearly markedas either “For Dispensing” or 
“Emergency Use Only”. 
The “For Dispensing” schedule will contain the list of randomisation numbers only 
and will not include any codeddescription, just a letter A,Bor C.
The ‘Emergency Use Only’ randomisation schedule will only be removed from the 
sealed envelope in an emergency situation (see Section 5.8.3). This schedule will 
 
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have a randomisation number followed by the letter A, Bor C. The schedule will be 
have a footnote with a key for A,Band Cidentifying the three treatments. However, 
to maintain the blinding of the study as far as possible, all treatment allocations for all 
randomisation numbers on this randomisation schedule will be masked with scratch-
off panels. Only the panels required for the unblinding the particular subject should 
be removed.
5.8.2.Blinding
The study statistician, other employees of the Sponsor, andvendors acting on behalf 
of the sponsor,who may influence study outcomes are blinded to the product 
allocation of subjects.The examiner will be blinded to the treatment received. To 
ensure the examiner remains blinded throughout the study, the examiner is not 
permitted in the room whilst product is dispensed, and subjects will be asked not to 
open their study kits outside of the dispensing room and until they are home.In 
addition, subjects should be treated in a separate area. The dispensing staff will not be 
involved in any efficacy assessments during thestudy.
5.8.3.Code Breaks
The blind must only be broken in an emergency where it is essential to know which 
product a subject received in order to givethe appropriate medical care. Wherever 
possible the Investigator (or designee) must contact the Sponsor prior to breaking the 
blind. The investigator must document the reason for breaking the code and sign and 
date the appropriate document.
The randomisation schedules must bereturned toGSKCH at the end of the study.
5.9. Packaging and Labelling
The acclimatisation products, the study dentifrice and negative control oral rinsewill 
be sourced from the US market.The test oral rinseand placebo oral rinsewill be
manufactured,filled and supplied by GSKCH. 
All products, including the acclimatisation products, will beoverwrapped in white 
vinyl to obscure any branding on the commercial packs. Each tubeand bottlewill 
have a study label affixed. Each subject will receive a sufficient number of tubes and 
bottles to cover usage during the treatment phase.
 
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The contents of the label will be in accordance with all applicable regulatory 
requirements and will be the responsibility of the Clinical Supplies Department, 
GSKCH.
All sundry items 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.
5.9.1. Accountability of Product
All products supplied are for use only in this clinical study and should notbe used for 
any other purpose.
Completion of diaries will be the responsibility of subjects, after they have been 
dispensed subjects will be asked to take them home and bring them back to the 
clinical site for each study visit.
The investigator or designee will maintain a full record of study product 
accountability. A Product Dispensing Log must be kept current and will contain the 
following information:
The identification of the subject to whom the study product was dispensed.
The datesand quantity of the study product dispensed to the subject.
The datesand quantity of the study product returned by the subject (if 
applicable).
The inventory must be available for inspection by the study monitor during the study. 
At the end of the study, study product supplies will be verified by the monitor. Study 
product supplies will then be either collected by the study monitor or returned by the 
investigator or designee to the GSKCH Clinical Supplies Department or designated 
vendor.
5.9.2. Storage of Product
Study product supplies must be stored in compliance with the label requirementsin a 
secure place with limited or controlled access.
 
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6. STUDY ASSESSMENTS AND PROCEDURES
This section lists the procedures and parameters of each planned study assessment.  
The exact timing of each assessment is listed in the Schedule of Events section.
Adherence to the study design requirements, including all assessments and 
procedures are essential and required for study conduct.
6.1. Visit 1 -Screening Visit
6.1.1 Telephone Screening
Prior to the screening visit, telephone screening of interested subjects will be 
conducted using a telephone script. This will be conducted by the site recruitment 
staff or designee.  
6.1.2. Informed Consent
The investigator, or designee, must obtain written (signed and dated by the subject) 
informed consent from each subject participating in this study after adequate 
explanation of the aims, methods, objectives, and potential hazards of the study.
The investigator, or designee, must also explain to the subjects that they are 
completely free to refuse to enter the study or to withdraw from it at any time.  
Appropriate forms for documenting a written consent will be provided by the 
investigator or by GSKCH.The investigator, or designee, should sign and date the 
consent form to confirm that the consent process was completed correctly. The 
subjectwill be provided with a copy of their signed and dated consent form and any 
other written information which they should be instructed to retain.
If, during a subject’s participation in the study, any new information becomes 
available that may affect the subject’s willingness to participate in the study, each 
ongoing subject should receive a copy of this new information and be re-consented 
into the study. Subjectsshould be provided with a copy of the signed and dated 
amended consent form. The date of consent will be recorded on the eCRF.
6.1.3. Demographics
The following demographic detail will be captured by the Investigator or designee 
and recorded on the eCRF: year of birth, gender,raceand ethnicity.
 
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6.1.4. Medical History and Concomitant Medication
Medical history will be assessed as related to the inclusion/exclusion criteria by the 
Investigator or medically qualified designee.Details of any relevant dental, medical 
or surgical history (within the last year), including allergies or drug sensitivity, will 
be recorded on the eCRF. Any concomitant therapy taken in the 30 days prior to the 
Screening Visit and throughout the study will also be recorded.
6.1.5. Oral Soft Tissue (OST) Examination
Where possible, this procedure should be conducted by a single trained dental 
examiner. The examination will be accomplished by direct observation and palpation 
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 eCRF 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 the 
administration of the acclimatisation or treatment toothpastes will be recorded as an 
AE. 
An OST examination will be conducted at every study visit prior to any clinical 
assessments. While it is preferable to use the same OST examiner throughout the 
study, to facilitate subject flow, OST examinations may be carried out by different 
examiners.
6.1.6.  Oral Hard Tissue (OHT) Visual Examination
A suitable qualified individual will perform an examination of the oral hard tissue to 
confirm that the subject has a minimum of 20 natural teeth and to evaluate dentition 
exclusions. The examination will be performed by direct observation.
6.1.7. Eligible Tooth Assessment
Eligible tooth assessment will include an oral hard tissue examination (visual 
assessment only to evaluate dentition exclusions -see Exclusion Criteria 8 and 9); 
erosion, abrasion and/or gingival recession; gingival index; tooth mobility and 
qualifying evaporative air assessment. Assessments will be carried out by the 
 
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Investigator or medically qualified designee against the inclusion/exclusion criteria 
and recorded in the eCRF.
6.1.7.1.  Erosion, Abrasion and Recession (EAR) assessment
The presence of cervical erosion, abrasion and/or gingival recession [Addy, 2000]
will be determined on the facial surfaces of individual teeth. Teeth exhibiting EAR 
will be assessed to ensure they do not meet any of the general dentition exclusion 
criteria and the specific dentition exclusion criteria for test teeth (see Exclusion 
Criteria 8 and 9).
6.1.7.2. Modified Gingival Index (MGI)Assessment
The MGI is a non-invasive visual evaluation of gingival health [Lobene, 1986]scored 
on a scale of 0-4. MGI will be assessed for the facial gingiva adjacent to the test area 
(exposed dentine) only of teeth exhibiting facial cervical erosion, abrasion and/or 
recession at the Screening visit. MGI = 0 is required for eligible teeth.
Score
Description
0
Absence of inflammation
1
Mild inflammation; slight change in colour, little change in colour; little 
change in texture of any portion of the marginal or papillary gingival unit.
2
Mild inflammation; criteria as above but involving the entire marginal or 
papillar gingival unit.
3
Moderate inflammation; glazing, redness, edema, and/or hypertrophy of 
the marginal or papillary gingival unit.
4
Severe inflammation; marked redness, edema and/or hypertrophy of the 
marginal or papillary gingival unit, spontaneous bleeding, congestion, or 
ulceration.
6.1.7.3. Tooth Mobility Assessment
The clinical mobility assessment will only be performed on teeth exhibiting facial 
cervical erosion, abrasion and/or recession and that have a MGI = 0. Clinical mobility 
will be classified in the following way (based on a modification to the Miller Index) 
[Laster, 1975]and the degree of mobility will be recorded. A clinical mobility of ≤1 
is required for eligible teeth.
 
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Degree 0
No movementor mobility of the crown of the tooth < 0.2mm in a 
horizontal direction.
Degree 1
Mobility of the crown of the tooth 0.2 –1mm in a horizontal direction
Degree 2
Mobility of the crown of the tooth exceeding 1mm in a horizontal 
direction
Degree 3
Mobility of the crown of the tooth in a vertical direction as well.
6.1.7.4. Qualifying Evaporative air Sensitivity
The screening dentist will assess sensitivity by a simple air blast on the facial surface 
of all teeth that meet the EAR, MGI and mobility criteria. This assessment is made by 
directing a one second application of air from a standard dental syringe perpendicular 
to the tooth surface approximately 1-2 mm coronal to the free gingival margin and 
from a distance of approximately 1cm. Following the air blast, the dentist will ask the 
subject if they experienced sensitivity. In order to qualify, the subject should confirm 
they experienced sensitivity and a qualifying score of ≥2 will be recorded.
6.1.8. Acclimatisation Product Supervised Brushing
Subjectswill apply a full brush head of the standard fluoride dentifrice, brush for one 
timed minute (in their usual manner) and expectorate; rinse with 10 ml of tap water 
for 5 seconds and expectorate; and then rinse with 10 ml of the acclimatisation oral 
rinse for 60 timed seconds and expectorate. 
6.2. Visit 2 -Baseline Visit
6.2.1. Oral Soft Tissue (OST) Examination
Complete as described in Section 6.1.5.
6.2.2. Tactile Assessment (Yeaple probe)
Tactile assessments will be performed by a single trained examiner.
Testing shall begin at 10 g and increase by 10 g with each successive challenge until a 
"yes" response is recorded. The force setting which elicited the “yes” response will be 
repeated.If a second "yes" is not obtained, the force setting will be increased by 10 g 
 
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and continue until a force is found which elicits two consecutive "yes" responses.If 
no sensitivity is found below the session maximum, the tooth is disqualified from 
further testing. The gram setting, which elicits the two consecutive “yes” responses, 
will be recorded as the threshold.
At this visit (pre-treatment) the upper test limit is 20g.  If no pain response is found, 
the threshold will be recorded as >20 g and the tooth will be disqualified from further 
tactile testing.Examiners discretion may be used to discontinue further tactile testing 
once they have determined the qualifying teeth.
The recording/calibration assistant or examiner will make adjustments and record the 
micro-amperage force setting and subject
's responses onto the source document.The 
assistant will not give verbal cues to the examiner (the individual applying the probe 
tip to the tooth) other than when it is okay to proceed as this may bias the subject
's 
response. For example, if the assistant feels that the subject did not give a true 
response, they may then elect to repeat the same force setting without telling the 
examiner.In this respect the examiner is also blinded, to avoid investigator bias.  
Since this places more responsibility on the assistant, it is imperative that the assistant 
be well trained in this procedure.It is also possible that the investigator may be 
unsure of the reliability of the subject
's response.In thiscase, the investigator may 
then opt to re-probe at the same force setting. This can be indicated to the assistant by 
a non-verbal signal (i.e. a hand gesture).
The evaporative air stimulus (with Schiff Sensitivity Score) should follow the tactile 
assessment, with a minimum of five minutes in between each assessment type to 
allow recovery time.
6.2.2.1.Subject Response
The probe tip should be placed perpendicular to the buccal surface and moved in a 
slow motion while drawn across the tooth surface in orderto ensure application of the 
stimulus across the sensitive area of the exposed dentine. After each challenge, 
subjects will be asked to indicate whether the sensation caused pain or discomfort.  
Only "yes" and "no" are acceptable answers. The examiner will tell the subject that 
they should indicate "yes" only if they feel PAIN or DISCOMFORT each time the 
probe is applied to their tooth. The subject may respond "yes" if they feel pressure, so 
it is important to remind them, as much as necessary, that they will feel pressure but 
to only respond "yes" if they feel pain or discomfort.If the subject fails to give a 
definite answer, the examiner should re-prompt them to provide a “yes” or “no” 
response.If they continue to be reluctant, their uncertainty should be indicated on the 
 
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score sheet and the next stimulus should be at the nextstep in the upward direction. 
The gram setting, which elicits the two consecutive “yes” responses, will be recorded 
as the threshold.
The evaporative air stimulus should follow thetactile assessment, with a minimum of 
five minutes in between each assessment type to allow recovery time.
6.2.2.2.Calibration of the Yeaple Probe
A digital video disc (DVD) demonstration of this procedure will be providedby 
GSKCH. Either of the two procedures described below are preferred; however other 
comparable procedures may be acceptable. 
The microamp settings will vary from day to day (partly due to battery power 
consumption), but the difference should not be significant. Thus, previous probe 
settings will serve as a guide. Calibration should start at the lowest microamp setting 
and then increase.
1. The yeaple probe is fixed to a clamp attached to a ring stand so that the probe tip is 
vertical. A small paper cup attached with cotton thread is balanced over the end of 
the yeaple probe, without the probe tripping. The probe dial is set to the microamp 
setting and water is fed into the paper cup using a dropper until the probe trips. 
The gram setting is recorded and the yeaple probe reset to the nextmicroamp 
value. The procedure is repeated until data has been collected to more than 80 
grams.
2. The yeaple probe is fixed to a clamp attached to a ring stand so that the top is 
perpendicular to the pan of an ohaus dial-o-gram® balance or equivalent. The
probe tip is positioned to just touch the pan when the balance is set at zero grams. 
The probe dial is set to the microamp setting and the gram setting is increased on 
the balance until the probe trips. The gram setting is recorded and the yeaple probe 
reset to the next microamp value. 
The data are plotted and the points connected with line segments in order to 
interpolate the micro-amp values equivalent to 10, 20, 30, 40, 50, 60, 70, and 80 
grams. This calibration should be repeated three times, and the average of the three 
used for the day’s settings.
The settings will be recorded on the yeaple probe calibration record. This form must 
also be dated and initialed by whoever performs the calibration. For convenience a 
separate form should be used for each probe (record the unit’s serial number on the 
 
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form). This record will serve as the guide for the force setting for that day’s 
examinations.
6.2.3. Evaporative Air Sensitivity Assessment 
This assessment will be conducted by a single examiner for all subjects at each visit 
by directing a maximum one second application of air from a dental air syringe to the 
exposed dentine surface from a distance of approximately 1 cm. The examiner should 
take appropriate measures to isolate the test tooth surface in order to prevent stimulus 
exposure to adjacent tooth or surrounding soft tissue. Response to this stimulus will 
be evaluated using the Schiff Sensitivity Scale.
The examiner will assess the evaporative air sensitivity of all clinically eligible teeth 
identified at Screening (teeth that qualified on EAR, MGI and tooth mobility criteria, 
and had none of the dentition exclusions), that qualified for the tactile assessment 
usingthe Schiff Sensitivity Scale. Two test teeth will be selected according to specific 
eligibility criteria in an individual subject. 
6.2.3.1. Schiff Sensitivity Scale
This is an examiner based index [Schiff, 1994], scored immediately following 
administration of the evaporative airstimulus. This scale focuses on a combination of 
specific, observable, physical, behavioural and verbal responses from the subject as a 
result of the stimulation of exposed dentine, rather than solely an oral request from 
the subject to discontinue stimulation and may facilitate discrimination.  
Those teeth which meet the tactile threshold inclusion criterion (tactile threshold ≤ 
20g) will be assessed.The examiner will indicate the subject’s response to the 
evaporative air stimulus, after the stimulation of each individual tooth, using the 
Schiff Sensitivity Scale as follows.  
0
Subject does not respond to air stimulation
1
Subject responds to air stimulus but does not request 
discontinuation of stimulus
2
Subject responds to air stimulus and requests discontinuation or 
moves from stimulus
3
Subject responds to stimulus, considers stimulus to be painful, 
and requests discontinuation of the stimulus
 
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Those teeth which meet the required tactile threshold (Yeaple ≤20g) should then be 
assessed by evaporative air stimulus. When two teeth that meet the study criteria are 
identified, no further testing is necessary.
6.2.3.2. Visual Rating Scale (VRS)
Subjects will rate the intensity of their response to the stimulus using a VRS scale as 
shown below of 1 (“No Pain”) to 10 (“Intense Pain”). A member of study staff will 
record this value in the eCRF. 
6.2.4. Selection of Two Test Teeth 
Two test teeth will be selected by the examiner that meet the inclusion criteria.
6.2.5.Supervised Product Use
After stratification and randomisation subjects will perform a supervised brushing and 
rinsing. See Section 5.1 for dosing and instructions, subjectswill be asked to measure 
out their own dose of oral rinse using the cups provided.
6.3. Visits3, 4, 5, 7, 8 and 9
6.3.1. Supervised Product Use
See Section 5.1 for dosing and instructions, subjectswill be asked to measure out 
their own dose of oral rinse using the cups provided.
6.4. Visits 6 and 10
6.4.1. OSTExamination
Complete as described in section 6.1.5.
 
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6.4.2. Tactile Assessment (Yeaple Probe)
Tactile assessment will be conducted as described in section 6.2.2,of thetwo selected 
test teeth only. The upper force setting will be 80g, ifno sensitivity is found, the 
threshold will be recorded as >80g.
6.4.3. Evaporative Air Sensitivity Assessment
The evaporative air assessment should follow the tactile assessment with a minimum 
of 5 minutes between the last tactile assessment and the first evaporative air 
assessment to allow the teeth recovery time.
6.4.3.1. Schiff Sensitivity Scale
The examiner will record the subjects’ response to each of the two selected test teeth 
immediately following administration of the evaporative air stimulus as described in 
section 6.2.3. 
6.4.3.2. VRS
Subjects will rate the intensity of their response to the stimulus using a VRS scale as 
described in Section 6.2.3.2. A member of study staff will record this value in the 
eCRF. 
6.4.4. Supervised Product Use
See Section5.1 for dosing and instructions, subjectswill be asked to measure out 
their own dose of oral rinse using the cups provided.
6.4.5. Study Conclusion
At Visit 10, subjects will be evaluated to determine if they completed all study 
procedures or if they were discontinued from the study early. If the subject 
discontinued at any point during the study, the primary reason for withdrawal should 
be recorded on the Study Conclusion page of the eCRF by selecting one of the 
options below.
1.
Subject did not meet study criteria
2.
Adverse Event
3.
Lost to Follow Up
4.
Protocol Violation
5.
Withdrawal of Consent
 
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6.
Other
7. SAFETY ASSESSMENTS
7.1. Definitions of an Adverse Event and Serious Adverse Event 
7.1.1. Adverse Events
The investigator or site staff will be responsible for detecting, documenting and 
reporting events that meet the definition of an AE or SAE.
Adverse Event Definition:
An AE is any untoward medical occurrence in a patient or clinical 
investigation subject, temporally associated with the use of an investigational 
or washout product, whether or not considered related to the investigational or 
washout product.
NOTE: An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom, or disease (new or 
exacerbated) temporally associated with the use of an investigational or 
washout product.
Events meeting AE definition include:
Any abnormal laboratory test results (if applicable) or other safety 
assessments, including those that worsen from baseline, and felt to be 
clinically significant in the medical and scientific judgment of the 
investigator.
Exacerbation of a chronic or intermittent pre-existing condition including 
either an increase in frequency and/or intensity of the condition.
New condition(s) detected or diagnosed after study product administration 
even though it may have been present prior to the start of the study.
Signs, symptoms, or the clinical sequelae of a suspected interaction.
Signs, symptoms, or the clinical sequelae of a suspected overdose of either 
study product or a concomitant medication (overdose per se will not be 
reported as an AE/SAE).
Events NOT meeting definition of an AE include:
Any clinically significant abnormal laboratory findings (if applicable) or other 
abnormal safety assessments which are associated with the underlying disease, 
unless judged by the investigator to be more severe than expected for the 
subject’s condition. 
The disease/disorder/ condition being studied or expected progression, signs, 
or symptoms of the disease/disorder being studied, unless more severe than 
expected for the subject’s condition.. 
 
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Medical or surgical procedure (e.g., endoscopy, appendectomy): the condition 
that leads to the procedure is an AE.
Situations where an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital).
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) 
present or detected at the start of the study that do not worsen.
7.1.2. Serious Adverse Events
Serious Adverse Event is defined as any untoward medical occurrence that, at 
any dose:
Results in death
Is life-threatening
NOTE: The term 
'life-threatening
' in the definition of 
'serious
' refers to an 
event in which the subject was at risk of death at the time of the event.It does 
not refer to an event, which hypothetically might have caused death, if it were 
more severe.
Requires hospitalisation or prolongation of existing hospitalisation
NOTE: In general, hospitalisation signifies that the subject has been detained 
(usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatmentthat would not have been appropriate in 
the physician’s office or out-patient setting. Complications that occur during 
hospitalisation are AEs. If a complication prolongs hospitalisation or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether 
“hospitalisation” occurred or was necessary, the AE should be considered 
serious.
Hospitalisation for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE.
Results in disability/incapacity
NOTE: The term disability means a substantial disruption of a person’s ability 
to conduct normal life functions.
This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere or prevent everyday life functions but do not constitute a substantial 
disruption.
Is a congenital anomaly/birth defect
Other Situations
Medical or scientific judgment should be exercised in deciding whether 
reporting is appropriate in other situations, such as important medical events 
that may not be immediately life-threatening or result in death or 
 
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hospitalisation but may jeopardise the subject or may require medical or 
surgical intervention to prevent one of the other outcomes listed in the above 
definition. These should also be considered serious.
Examples of such events are invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalisation or development 
of drug dependency or drug abuse or reports of spontaneous abortion.
7.2. Recording Adverse Events and Serious Adverse Events
Recording of adverse events and serious adverse events:
The investigator or site staff will be responsible for detecting, documenting 
and reporting events that meet the definition of an AE or SAE. 
Theinvestigator or site staff will then record all relevant information 
regarding an AE/SAE in the eCRF.
There may be instances when copies of medical records for certain cases are 
requested by GSK. In this instance, all subject identifiers, with the exception 
of the subject number, will be blinded on the copies of the medicalrecords 
prior to submission to GSK.
The investigator will attempt to establish a diagnosis of the event based on 
signs, symptoms, and/or other clinical information. In such cases, the 
diagnosis will be documented as the AE/SAE and not the individual 
signs/symptoms. Clinical AEs will be described by diagnosis and not by 
symptoms when possible (e.g., upper respiratory tract infection, seasonal 
allergy, etc. instead of runny nose).
AEs willbe collected from the start of the acclimatisation periodand until 5 
days following last administration of the study product.
SAEs will be collected over the same time period as stated above for AEs.  
However, any SAEs assessed as relatedto study participation (e.g., 
investigational product, protocol mandated procedures, invasive tests, or 
change in existing therapy) or related to a GSK concomitant medication will 
be recorded from the time a subject consents to participate in the study up to 
and including any follow-up contact.  
Medical conditions reported prior to the time period for reporting AEs/SAEs 
should be recorded as part of the subject’s medical history.
7.3. Evaluating Adverse Events and Serious Adverse Events
Assessment of Intensity:
The investigator or designee will make an assessment of intensity for each AE and 
SAE reported during the study and will assign it to one of the following categories:
Mild: An event that is easily tolerated by the subject, causing minimal 
discomfort and not interfering with everyday activities.
 
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Moderate: An event that is sufficiently discomforting to interfere with normal 
everyday activities
Severe: An event that prevents normal everyday activities-an AE that is 
assessed as severe will not be confused with an SAE. Severity is a category 
utilised for rating the intensity of an event; and both AEs and SAEs can be 
assessed as severe.
Note: An event is defined as ‘serious’ when it meets at least one of the pre-defined 
outcomes as described in the definition of an SAE.
Assessment of Causality:
The investigator is obligated to assess the relationship between study product 
and the occurrence of each AE/SAE.
A "reasonable possibility" is meant to convey that there are facts/evidence or 
arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out.
The investigator will use clinical judgment to determine the relationship.
Alternative causes, such as natural history of the underlying diseases, 
concomitant therapy, other risk factors, and the temporal relationship of the 
event to the study product will be considered and investigated.
The investigator will also consult the Safety Assessment or Product 
Information, for marketed products, in the determination of his/her 
assessment.
For each AE/SAE the investigator must document in the medical notes 
(source document) or eCRF that he/she has reviewed the AE/SAE and has 
provided an assessment of causality.
There may be situations when an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK.However, it is 
very important that the investigator always make an assessment of 
causality for every event prior to the initial transmission of the SAE data 
to GSK.
The investigator may changehis/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly.
The causality assessment is one of the criteria used when determining 
regulatory reporting requirements.
7.4. Reporting Adverse Events andSerious Adverse Events
AE Reporting to GSKCH:
AEs will be recorded in the AE section of the eCRF. 
Medical conditions recorded by the subject on a diary
 card or similar 
document that meet the definition of an AE must also be recorded in the AE 
section of the eCRF, if not previously well-characterised by the investigator in 
the subject’s medical history. 
 
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AEs elicited by the investigator in a standard manner at the study visits should 
also be recorded in the AE section of the eCRF. The investigator or designee 
must ask the subject the following question during each visit including any 
follow-up visits:  “Have you felt unwell, experienced any symptoms or taken 
any medication (since your last visit) (today) (since your last dose) (since the 
last session)?”
The medically qualified investigator should review adverse events in a timely 
manner; this review should be documented in writing in the source document 
or in the eCRF. 
After the study is completed at a given site, and the site has received their 
study data on Compact Discs (CDs), the electronic data collection tool will be 
removed from the internet to prevent the entry of new data or changes to 
existing data.
SAE Reporting to GSKCH:
A paper copy of the SAE form provided in the investigator study master file should 
be completed as fully as possible. 
It is essential to enter the following information: 
Protocol and subject identifiers
Subject’s demography
Description of events, with diagnosis if available
Investigator opinion of relationship to study product (see section 8.3)
Criterion for seriousness.
The following are desirable and are of particular relevance for investigator and 
GSKCH assessment of the SAE report:
Date of onset of AE 
Date AE stopped, if relevant
Study product start date
Study product end date if relevant
Action taken on study product
Outcome if known
The SAE form, completed as fully as possible, and SAE fax cover sheet must be 
faxed or e-mailed to the appropriate GSKCH Study Manager as soon as possible, but 
not later than 24 hoursafter study site personnel learn of the event.The GSKCH 
Study Manager should be notified of the situation by telephone or email.
Fax Serious Adverse Events to:
US: 
Email Serious Adverse Events to:
 
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The GSKCH Study Managerwill be responsible for forwarding the SAE form to the 
Case Management Group, Global Clinical Safety and Phamacovigilance, the Medical 
Director responsible for the study and other GSKCH personnel as appropriate via 
email.
The initial report will be followed up with more information as relevant, or as 
requested by the GSKCH study manager.
7.5. Follow-up of Adverse Events and Serious Adverse Events
Follow-up of AEs and SAEs:
After the initial report, the investigator is requiredto proactively follow up 
with each subject and provide further information on the subject’s condition.
All AEs/SAEs will be followed until resolution, until the condition stabilises, 
until the event is otherwise explained, or until the subject is lost to follow-up.  
The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations as may be indicated or as 
requested by GSK to elucidate as fully as possible the nature and/or causality 
of the AE or SAE.
Investigators are not obliged to actively seek AEs or SAEs in former subjects.  
However, if the investigator learns of any SAE, including the death, at any 
time after a subject has been discharged from the study, and considers the 
event reasonably related to the investigational product or study participation, 
the investigator will promptly notify GSKCH.
The investigator will submit any updated SAE data to GSK within the 
designated reporting time frames.
Regulatory and ethics reporting requirements for SAEs:
The investigator will promptly report all SAEs to GSKCH within the 
designated reporting timeframes (within 24 hours of learning of the event).  
GSKCH has a legal responsibility to notify, as appropriate, the local 
regulatory authority and other regulatory authorities about the safety of a 
product under clinical investigation.Prompt notification of SAEs by the 
investigator to GSKCH is essential so that legal obligations and ethical 
responsibilities towards the safety of subjects are met.
GSKCH will comply with country specific regulatory requirements relating to 
safety reporting to the regulatory authority, IEC and investigators.
Investigator safety reports are prepared according to GSKCH policy and are 
forwarded to investigators as necessary. An investigator safety report is 
prepared for a SAE(s) that is both attributable to investigational product and 
unexpected.  The purpose of the report is to fulfill specific regulatory and 
GCP requirements, regarding the product under investigation.
 
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An investigator who receives an investigator safety report describing a SAE(s) 
or other specific safety information (e.g., summary of listing of SAEs) from 
GSKCH will file it with the safety statementand will notify the IEC, if 
appropriate according to local requirements.
7.6. Definition of and Procedure for Reporting Medical Device 
Incidents
Medical devices are being provided by GSKCH for use in this study; the medical 
device in this study is the toothbrush. GSKCH medical device incidents, including 
those resulting from malfunctions of thedevice, must be detected, documented, and 
reported by the investigator on the eCRF throughout the study.
7.6.1. Definition of an Incident
Definition of an Incident:
Any malfunction or deterioration in the characteristics and/or performance of 
a device, as wellas any inadequacy in the labelling or the instructions for use 
which, directly or indirectly,might lead to or might have ledto the death of a 
patient or user or of other persons or to a serious deterioration in their state of 
health.
7.6.2. Reporting of Incidents and Malfunctions
Incident Reporting to GSKCH:
All incidents must bereported to GSKCH, within 24 hours (or sooner if 
possible) of the investigator or designee becoming aware of the situation.
Any medical device incident occurring during the study will be documented in 
the subject
's medical records, in accordance with the investigator
's normal 
clinical practice, and on the appropriate Incident Report Form. In addition, for 
incidents fulfilling the definition of an AE or an SAE, the appropriate AE 
eCRF page or SAE form will be completed and reported as per the AE and 
SAE reporting sections.
The Incident Report Form will be completed as thoroughly as possible and 
signed by the investigator before transmittal to GSKCH. It is very important 
that the investigator describes any corrective or remedial actions taken to 
prevent recurrence of the incident.
The completed Incident Report Form should be faxed or emailed to the 
appropriate GSKCH Study Manager as soon as possible, but not later than 
24 hoursafter study site personnel learn of the event. If there is an SAE, the 
completed SAE pages should be sent together with this report form. However, 
if a copy of the SAE report is sent with this form, this does not replace the 
procedure to report an SAE. The original Incident Report Form will remain 
 
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with the subject’s records.
The GSKCH Study Manager should be notified of the situation by telephone 
or email.
Fax the Incident Report Forms to:
US: 
The GSKCH Study Manager will be responsible for forwarding the Incident 
Report Form to the Case Management Group, Global Clinical Safety and 
Pharmacovigilance, the Medical Director responsible for the study and other 
GSKCH personnel as appropriate.
The initial report will be followed up with more information as relevant, or as 
requested by the GSKCH study manager.
Reporting of Malfunctions to GSKCH:
The investigator will follow the following directions regarding device failure 
(malfunction):
Notify GSKCH immediately.
Schedule the subject to return to the site promptly to return the failed device.
Record any incidents on the eCRF and Incident Report Form following 
instructions given in the section above.
Return the failed device to the sponsor as soon as possible, including 
documentation of the details of the failure.
7.6.3. Follow-up of Incidents
Follow-up of Incidents:
During the study:
All incidents will be followed until resolution of the event, until the condition 
stabilises, until the condition is otherwise explained, or until the subject is lost 
to follow-up. This applies to all subjects, including those withdrawn 
prematurely. The investigator is responsible for ensuring that follow-up 
includes any supplemental investigations as may be indicated to elucidate as 
completely as practical the nature of the incident.
New or updated information will be recorded on the originally completed 
form with all changes signed and dated by
 the investigator.
After the study:
Investigators are not obligated to actively seek reports of incidents in former 
subjects. However, if the investigator learns of any incident at any time after a 
subject has been discharged from the study, and such incident is reasonably 
related to a GSKCH medical device provided for the study, the investigator 
will promptly notify GSKCH.
 
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Regulatory and Ethics Reporting Requirements for Incidents:
The investigator will promptly report all incidents occurring with any GSKCH 
medical device provided for use in the study within 24 hours. GSKCH has a 
legal responsibility to notify appropriate regulatory bodies and other entities 
about certain safety information relating to medical devices being used in 
clinical studies. Prompt notification of incidents by the investigator to 
GSKCH is essential in order to meet legal obligations and ethical 
responsibility towards the safety of subjects.
The investigator, or responsible person according to local requirements, will 
comply with the applicable local regulatory requirements relating to the 
reporting of incidents to the IEC.
7.7. Collection of Pregnancy Information
7.7.1. Time Period for Collecting of Pregnancy Information
Collection of Pregnancy Information:
Pregnancy information will be collected on all pregnancies reported following 
administration of any investigational product (or washout product). 
Information on pregnancy identified during the screening phase and prior to 
investigational product (or washout product) administration does not need to 
be collected.
7.7.2. Action to be Taken if Pregnancy Occurs
Action to be Taken:
The investigator will collect pregnancy information on any subject who 
becomes pregnant while participating in the study after administration of the 
investigational product (or washout product). The investigator will record 
pregnancy information on the appropriate form and submit it to the following 
GSKCH mailbox:
Pregnancy information must be submitted within 2 weeks of learning of the 
subject becoming pregnant. 
The subject will be followed to determine the outcome of the pregnancy. 
Information on the status of the mother and infant / neonate (including 
concomitant medications taken by the mother during the pregnancy) will be 
forwarded to GSKCH.Generally, follow-up will be no longer than 6 to 8 
weeks following the estimated delivery date. Any termination of the 
pregnancy will be reported.
While pregnancy itself is not considered to be an AE, any pregnancy 
complication or elective termination for medical reasons will be recorded as 
an AE or SAE.
 
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A spontaneous abortion is always considered to be an SAE and will be 
reported as such. An SAE occurring in association with a pregnancy, brought 
to the investigator’s attention after the subject completed the study and 
considered by the investigator as possibly related to the investigational 
product, must be promptly forwarded to GSK.
While the investigator is not obliged to actively seek this information in 
former study participants, he or she may learn of an SAE through spontaneous 
reporting.
If the subject becomes pregnant during the study they should be withdrawn 
from the study and this should be recorded in the appropriate section of the 
eCRF.
8. DATA MANAGEMENT
For this study subject data will be entered into an electroniccase report form, using 
an inVentiv Health or GSKCH validated data system.
8.1. Source Documents/ Data
The source documents (e.g. hospital records, clinical and office charts, memoranda, 
subjects’ diaries or evaluation checklists, pharmacy dispensing records, recorded data 
from automated instruments, microfiches, photographicnegatives, microfilm or 
magnetic media, x-rays, subject files and records kept at the pharmacy, at the 
laboratory and at the medico-technical departments involved in the clinical study) 
which contain the source of data recorded in the eCRF should be specified in the 
Source Document Designation Form.In some cases the eCRF can be used as a source 
document.
Each subject will be assigned and identified by a unique Screening Number. Any 
reference made to an individual subject within the study must be done using the 
unique Screening Number.
8.2. Electronic Case Report Form
ACRF is a printed, optical, or electronic document designed to record all of the 
protocol required information to be reported to the sponsor on each trial subject.
For each subject who has given informed consent/assent and has been screened, 
eCRF must be completed and signed by the Principal Investigator (or authorised 
designee) to certify that the data are complete and correct.  
 
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Management of clinical data will be performed in accordance with applicable 
GSKCH standards and data cleaning procedures to ensure the integrity of the data e.g. 
removing errors and inconsistencies in the data. 
In order to protect the privacy of subjects, no Personally Identifiable Information 
(PII) (including the subject
's name or initials or birth date) is to be recorded in the 
eCRF or as part of the query text.
Adverse events and concomitant medications terms (if applicable) will be coded 
using MedDRA (Medical Dictionary for Regulatory Activities) and an internal
validated medication dictionary, GSKDrug.  
Subject data will be entered into GSKCH defined eCRFs and transmitted 
electronically to GSKCH in a validated (21 CFR Part 11 compliant) web-based 
electronic data capture system.
All eCRF pages should be completed during a subject assessment when the eCRF has 
been designated as the source. Data that is sourced elsewhere should be entered into 
the eCRF in an agreed upon timeframe between the Investigator and Sponsor.  
At the conclusion of the study, the occurrenceof any protocol deviations will be 
determined. After these actions have been completed and the database has been 
declared to be complete and accurate, it will be locked and made available for data 
analysis. Any changes to the database after that time can only be made by joint 
written agreement between the GSKCH Principal Clinical Research Scientist, the 
Project Statistician and the Project Data Manager with the authorization from Head of 
Clinical Research.
Throughout the duration of the study, eCRFs (including queries, query responses and 
audit trails) will be retained by inVentiv Health. Following decommissioning of the 
study site data archived compact discs (CD(s)) prepared by inVentiv Health will be 
sent to the investigator and GSKCH
8.3. Data Handling
Documentationof 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 forchanges. The EDC system has an audit trail, which 
will provide a complete record of the changes and corrections endorsed by the 
Investigator.
 
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8.3.1. Data Queries
Programmed edit checks will be generated automatically, as the data is being entered 
into the system. Data Management will also run reports and listings on the eCRF data, 
in addition to the queries already programmed and generated by the system, to raise 
manual queries as needed for site clarification or correction. The Clinical Dictionary 
Development and Management Group will raise queries as needed on safety data to 
code the terms (Adverse Events and Drugs) are reported appropriately. 
The study monitor at the study site will review the eCRFs in accordance with the 
monitoring plan, and any queries will be generated in the EDC System to the 
Investigator or designee, enabling the errors to be addressed in parallel with Data 
Management review. Monitor can also run reports and listings on the eCRFs, to raise 
manual queries as needed for site clarification or correction
8.4. Processing Patient Reported Outcomes
Patient reported outcome (PRO) data are collected directly from the subject PRO 
measures e.g. diary cards, questionnaires etc, and entered into the sponsor’s clinical 
data management system (DMS) by the study site representative. PRO’s that are 
source will be retained by the investigator and certified copies will be sent to the third 
party CRO. 
In order to protect the privacy of subjects, no Personally Identifiable Information 
(PII) (including the subject
's name or initials or birth date) is to be recorded on all 
PRO’s that will be forwarded to GSKCH, or the third party CRO.
9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES
All statistical activities will be conducted by inVentiv Health under the guidance of 
GSKCH.
9.1 Sample Size Determination
A sufficient number of healthy subjects will be screened to randomise at least 100 
subjects (approximately 50 to the experimental treatment, 25 to the negative control 
and 25 to placebo) to ensure 80 evaluable subjects complete the entire study. This 
will ensure approximately 40 evaluable subjects for the test treatment and 20 each for 
the negative control treatment and placebo.
 
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With this 40/20/20 distribution of the subjects in the treatment arms, the study has 
less than 50% power to detect a mean treatment difference of 0.36 in the Schiff 
sensitivity score using a two-sided t-test of significance level 0.05 for the 
experimental product against the negative control. The standard deviation used in this 
calculation is 0.8; this estimate is obtained from the GSKCH study 204763. When the 
experimental treatment group is compared with the combined group comprising of 
the negative control group and the placebo group using the two-sided t-test with the 
same estimates of mean difference, significance level and standard deviation, the 
study will have 51.1% power.
9.2. General Considerations
9.2.1. Definition of Analysis Populations
The Safety population will include all subjects who are randomised and receive at 
least one dose of investigational product and will be reported by treatment received.
The Intent-To-Treat (ITT) population will include all subjects who are randomised, 
receive at least one dose of investigational product and have at least one post-baseline 
efficacy evaluation and will be reported by randomised treatment.
The Per Protocol (PP) population will include all subjects in the ITT population for 
whom all efficacy assessments are not deemed to be affected by protocol violations.
Protocol violations deemedto affect efficacywill be identified betweenthe 
Biostatistician and Clinical ResearchDirector or designee, ahead of breaking the 
study blind.
The primary population for assessment of efficacy will be the ITT population. A PP 
analysis will be performed on the primary variable only if more than 10% of the 
subjects in the ITT population have protocol deviationsdeemed to affect efficacy.
The Safety population will be used for all safety and tolerability reporting.
9.2.2. Exclusion of Data from Analysis
The following will be considered as major protocol deviations leading to the 
exclusion of subjects / data for PP analysis:
Deviation from the inclusion/exclusion criteria likely to affect efficacy.
 
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The use of prohibited medication likely to affect efficacy.
Other deviations likely to result in exclusion from the PP population will be detailed 
in the statistical analysis plan (SAP).
9.2.3. Criteria for Evaluation
DH measures captured in the study will be used for efficacy evaluations of the study 
treatments. OST abnormalities, incidents and AEs reported in the studywill be used 
for safety evaluations of the study treatments.
9.2.4. Criteria for Assessing Efficacy
The primary treatment comparison is between the experimental mouthwash and the 
negative control marketed mouthwash for the change from baseline in the Schiff 
Sensitivity score at 8 weeks. However a statistically significant difference is not 
expected as the study is not powered. The magnitude of the treatment difference is 
more important and is expected to be in favour of the experimental mouthwash.
9.2.5. Criteria for Assessing Tolerability
The safety profile of the study treatments will be assessed with respect to adverse 
events (AEs) and oral soft tissue (OST) abnormalities.
9.2.6. Handling of Dropouts and Missing Data
Dropouts and missing data are expected to be low (only 2.3% subjects were 
discontinued orhad missing data after randomisation in the 8 week GSKCH study 
204763). A robustness analysis based on worst case imputation might be elaborated 
in the SAP.
9.3. Statistical Methods and Analytical Plan
Additional details of the proposed statistical analysis will be documented in the 
statistical analysis plan (SAP), which will be written following finalisation of the 
protocol and prior to study unblinding.
9.3.1. Demographic and Baseline Characteristics
Descriptive statistics (number of subjects, mean, standard deviation, median, 
minimum and maximum for continuous variables, and frequency
 and percentage for 
categorical variables) will be provided for demographic and baseline data.
 
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9.3.2. Primary Analysis
The change from baseline to week 8 in the Schiff Sensitivity Score is the primary 
efficacy variable. This will be analysed using an analysis of covariance (ANCOVA) 
model. The model will include treatment as a factor and baseline Schiff Sensitivity 
Score as a covariate.
The primary treatment comparison is between the experimentaloral rinse and the 
marketed oral rinsefor the primary efficacy variable. The adjusted mean for each 
treatment, and the difference between thepair of treatments together with their 
corresponding 95% confidence intervals and the p-value for treatment comparison, 
will be provided.
Assumptions of normality and homogeneity of residuals will be evaluated and if 
serious departures are observed, data transformations will be investigated. If suitable 
transformations cannot be found, non-parametric tests such as Wilcoxon Rank Sum 
test or the van Elteren test will be used.
9.3.3. Secondary Analysis
The change from baseline to week 8 in tactile threshold is the secondary efficacy 
variable. This will be analysed using an ANCOVA with treatment and baseline Schiff 
stratification as factors and baseline tactile threshold as a covariate.
The secondary treatment comparison is between the experimental oral rinse and the 
marketed oral rinse for this variable. The adjusted mean for each treatment, and the 
difference between the pair of treatments together with their corresponding 95% 
confidence intervals and the p-value for treatment comparison, will be provided.
Assumptions of normality and homogeneity of residuals will be evaluated and if 
serious departures are observed, datatransformations will be investigated. If suitable 
transformations cannot be found, non-parametric tests such as Wilcoxon Rank Sum 
test or the van Elteren test will be used.
9.3.4. Exploratory Analyses
Treatment comparisons other than the primaryand secondarytreatment comparisons
mentioned above for the primary efficacy variable are exploratory. These will be 
performed in the similarway as the primary treatment comparison.
 
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The changefrom baseline to week 4 in the Schiff Sensitivity Score will be analysed 
using the same ANCOVA modelas mentioned for the change from baseline to week 
8 for this measure.
The change from baseline to week 4 in the tactile threshold will be analysed using the 
same ANCOVA modelas mentioned for the change from baseline to week 8 for this 
measure.
Changes from baseline to weeks 4 and 8 in VRS will be analysed separately using the 
similar ANCOVA model as mentioned for thechanges from baseline intactile 
threshold.
Changes from baseline to weeks 4 and 8 in Schiff Sensitivity Score will furtherbe 
analysed separately using the same ANCOVA model as mentioned above for this 
measure but by combining the marketed oral rinse group and the placebo group as 
one treatment group.
Similar analyses for the combined control group will also be done for the changes 
from baseline to weeks 4 and 8 for the tactile threshold and VRS using the same 
ANCOVA model mentioned above for the analysis of the secondary variable.
The adjustedmean for each treatment, and the difference between the pairsof 
treatments together with their corresponding 95% confidence intervals and the p-
valuesfor treatment comparisons, will be provided.
Assumptions of normality and homogeneity of residuals willbe evaluated and if 
serious departures are observed, data transformations will be investigated. If suitable 
transformations cannot be found, non-parametric tests such as Wilcoxon Rank Sum 
test or the van Elteren test will be used.
9.3.5. Safety Analyses
For the assessment of safety and tolerability, treatment emergent AEs will be 
summarised by treatment group. AEs andincidents will be listed. No inferential 
analyses will be performed to compare treatments with respect to safety data.
The safety profile ofthe study treatments will be assessed with respect to AEs. OST 
abnormalities are included as AEs if they appear or worsen after the initial 
assessment.
 
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All safety data will be reported for the Safety population as per actual treatment 
received. All subjects screened will be included in the list of AEs.
All AEs will be reviewed by the Clinical Research Director or Designee prior to 
database freeze and will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA). During this review stage, AEs will be further categorised as 
oral or non-oral.
AEs will be regarded as treatment emergentif they occur on or after the start date and 
time of the first treatment usage (as determined by start date and time from the 
EXPOSURE/dispensing panel; if this date is missing a suitable alternative will be 
used eg date and time of randomisation). All other AEs prior to this will be 
considered non-treatment emergent.
The following summary tables and listings will be presented by treatment group.
Table of treatmentemergent AEs by Oral/Non-Oral  and Preferred Term
Table of  treatment emergent AEs by SOC and Preferred Term
Table of Treatment emergent treatment related AEs by Oral/Non-Oral and 
Preferred Term
Table of  treatment emergent treatment related AEs by SOC and Preferred Term
Listing of all AEs (including Non-treatment emergent from All Subjects)
Listing of serious AEs
Listing of incidents (if there are none a null listing will be produced) 
No inferential analyses will be performed to compare treatments with respect to 
safety.
10. STUDY GOVERNANCE CONSIDERATIONS
10.1. Posting of Information on Publicly Available Clinical Trials 
Registers
Study information from this protocol will be posted on publicly available clinical trial 
registers before enrollment of subjects begins.
10.2. Regulatory and Ethical Considerations, Including the Informed 
Consent
The study will be conducted in accordance with all applicable regulatory 
requirements, and with GSK policy.
 
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The study will also be conducted in accordance with ICH Good Clinical Practice 
(GCP), all applicable subject privacy requirements, and the guiding principles of the 
current version of the Declaration of Helsinki. This includes, but isnot limited to, the 
following:
Before initiating a trial, the investigatorshould have written and dated 
approval/favourable opinion from the IEC for the trial protocol (including 
amendments), written informed consent form, consent form updates, subject 
recruitment procedures (e.g., advertisements), safety statement (including any 
updates) and any other written information to be provided to subjects. A letter 
or certificate of approval will be sent by the investigator to the sponsor prior 
to initiation of the study, and also when subsequentamendments to the 
protocol are made.
Signed informed consent  to be obtained for each subject before participation 
in the study (and for amendments as applicable)
Investigator reporting requirements (e.g. reporting of AEs/SAEs/protocol 
deviations to IEC)
GSK will provide full details of the above procedures, either verbally, in 
writing, or both.
10.3. Quality Control (Study Monitoring)
In accordance with applicable regulations including GCP, and GSK procedures, the 
study monitor will contact the site prior to the start of the study to review with the site 
staff the protocol, study requirements, and their responsibilities to satisfy regulatory, 
ethical, and GSK requirements.
When reviewing data collection procedures, the discussion will include identification, 
agreement and documentation of data items for which the eCRF will serve as the 
source document.
The study monitor will monitor the study and 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 the third party CRO.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.
 
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10.4. Quality Assurance
To ensure compliance with GCP and all applicable regulatory requirements, GSK 
may conduct a quality assurance assessment and/or audit of the site records, and the 
regulatory agencies may conduct a regulatory inspection at any time during or after 
completion of the study. 
In the event of an assessment, audit or inspection, the investigator (and institution) 
must agree to grant the advisor(s), auditor(s) and inspector(s) direct access to all 
relevant documents and to allocate their time and the time of their staff to discuss the 
conduct of the study, any findings/relevant issues and to implement any corrective 
and/or preventative actions to address any findings/issues identified.
The sponsor will be available to help investigators prepare for an inspection.
10.5. Conditions for Terminating the Study
Upon completion or premature discontinuation of the study, the study monitor will 
conduct site closure activities with the investigator or site staff, as appropriate, in 
accordance with applicable regulations including GCP, GSKCH Standard Operating 
Procedures(SOPs), and the third party CRO SOPs.
Both GSKCHand the Investigator reserve the right to temporarily suspend or 
prematurely discontinue this study at any time for reasons including, but not limited 
to, safety or ethical issues or severe non-compliance. 
If the trial is prematurely terminated or suspended for any reason, the investigator site 
should promptly inform the trial subjects and should assure appropriate therapy/ 
follow-up for the subjects. 
In addition: 
If the investigator terminates orsuspends a trial without prior agreement of 
GSKCH, the investigator site should promptly inform the sponsor and the 
IEC, and should provide the sponsor and the IEC a detailed written 
explanation of the termination or suspension.
If the GSKCH terminates orsuspends a trial, the investigator should promptly 
inform the IEC and provide the IEC a detailed written explanation of the 
termination or suspension. 
If the IEC terminates or suspends its approval/favourable opinion of a trial, 
the investigator should promptly notify the GSKCH and provide GSKCH with 
a detailed written explanation of the termination or suspension.
 
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10.6. Records Retention
Following closure of the study, the investigator must maintain all site study records 
(except for those required by local regulations to be maintained elsewhere), in a safe 
and secure location.  
The records (study/ site master file) must be maintained to allow easy and timely 
retrieval, when needed (e.g., for a GSK audit or regulatory inspection) and must be 
available for reviewin conjunction with assessment of the facility, supporting 
systems, and relevant site staff.
Where permitted by local laws/regulations or institutional policy, some or all of these 
records can be maintained in a format other than hard copy (e.g., microfiche, scanned, 
electronic); however, caution needs to be exercised before such action is taken. 
The investigator must ensure that all reproductions are legible and are a true and 
accurate copy of the original and meet accessibility and retrieval standards, including 
re-generating a hard copy, if required. Furthermore, the investigator must ensure there 
is an acceptable back-up of these reproductions and that an acceptable quality control 
process exists for making these reproductions.
The investigator must assure that the subject’s anonymity will be maintained on 
eCRFs or other documents submitted to inVentiv Health,GSKCH, or any other 
GSKCH approved vendors. Subjects should not be identified by their names or 
initials, but by an identification code. The investigator should keep a separate log of 
subjects’ codes, names and addresses. Documents not for submission to inVentiv 
Health,GSKCH, or any other GSKCH approved vendors, e.g. subjects’ written 
consent forms, should be maintained by the investigator in strict confidence.
GSKCH will inform the investigator of the time period for retaining these records to 
comply with all applicable regulatory requirements (GSKCH recommends that 
documents be kept for 10 years). The investigator is also required to keep subject
identification codes on file for at least 15 years after completion or discontinuation of 
the study. The minimum retention time will meet the strictest standard applicable to 
that site for the study, as dictated by any institutional requirements or local laws or 
regulations, GSKCH standards/procedures, and/or institutional requirements.  
No study document should be destroy
ed without a prior written agreement between 
GSKCH and the investigator. The investigator must notify GSKCHof any changes in 
the archival arrangements, including, but not limited to, archival at an off-site facility 
 
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or transfer of ownership of the records in the event the investigator is no longer 
associated with the site.
10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials Registers 
and Publication
Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approvalof the clinical study report. The investigator will be 
provided reasonable access to statistical tables, figures, and relevant reports and will 
have the opportunity to review the complete study results at a GSK site or other 
mutually-agreeable location.
GSKCHwill also provide the investigator with the fullsummary of the study results. 
The investigator is encouraged to share the summary results with the study subjects, 
as appropriate.
The procedures and timing for public disclosureof the results summary and for 
development of a manuscript for publication will bein accordance with GSK Policy.
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge.
 
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11. REFERENCES
Addy M., Mostafa P., Absi E., Adams D., Cervical dentin hypersensitivity. Etiology and 
management with particular reference to dentifrice. In Proceedings of Symposium on 
Hypersensitive Dentin. Origin and Management; Rowe, N., Ed.; University of 
Michigan, Ann Arbor, MI, 1985; pp 147–167.
Addy M., Absi E. G., Adams D., Dentine hypersensitivity. The effects in vitro of acids 
and dietary substances on root-planed and burred dentine. J. Clin. Periodontol.1987, 14, 
274–279.
AddyM., Dentine Hypersensitivity: definition, prevalence, distribution and aetiology. In 
Tooth Wear and Sensitivity; 2000; pp 239–248.
Boneta A., Ramirez K., Naboa J., Mateo L., Stewart B., Panagokos F., De Vizio W., 
Efficacy in reducing dentine hypersensitivity of a regimen using a toothpaste containing 
8% arginine and calcium carbonate, a mouthwash containing 0.8% arginine, 
pyrophosphate and PVM/MA copolymer and a toothbrushcompared to potassium and 
negative control regimens: An eight-week randomized clinical trial. Journal of 
Dentistry. 2013, 41S; 42-49.
Brännström M., A hydrodynamic mechanism in the transmission of pain producing 
stimuli through dentin. In Sensory Mechanisms in Dentin; Anderson, D., Ed.; Oxford: 
Pergamon Press, 1962; pp 73–79.
Canadian Advisory Board on Dentin Hypersensitivity, Consensus-based 
recommendations for the diagnosis and management of dentin hypersensitivity. J. Can. 
Dent. Assoc.2003, 69, 221–226.
Dababneh R. H., Khouri a T., Addy M., Dentine hypersensitivity -an enigma? A review 
of terminology, mechanisms, aetiology and management. Br. Dent. J.1999, 187, 606–
611; discussion 603.
Fischer C., Fischer R. G., Wennberg A., Prevalence and distribution of cervical dentine 
hypersensitivity in a population in Rio de Janeiro, Brazil. J. Dent.1992, 20, 272–276.
Flynn J., Galloway R., Orchardson R., The incidence of “hypersensitive” teeth in the 
West of Scotland. J. Dent.1985, 13, 230–236.
Graf H., Galasse R., Morbidity, prevalence and intraoral distribution of hypersensitive 
teeth. J. Dent. Res.1977, 56, A162.
GSKCH Study 204762. A Clinical Study Investigating the Efficacy of 2 Experimental 
Oral Rinses in Providing Long Term Relief From Dentinal Hypersensitivity, 2016.
GSKCH Study 204763. A Clinical Study Investigating the Efficacy of2 Experimental 
Oral Rinses in Providing Long Term Relief From Dentinal Hypersensitivity, 2016.
GSKCH Study 204773. A Clinical Study Investigating the Efficacy ofTwo 
Experimental Oral Rinses in Providing Long Term Relief From Dentinal 
 
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Hypersensitivity, 2016.
Hall R., Embery G., Shellis R., Biological and structural features of enamel and dentin: 
current concepts relevant to erosion and dentin hypersensitivity. In Tooth Wear and 
Sensitivity; Addy, M., Embery, G., Edgar, W., Orchardson, R., Eds.; Martin Dunitz Ltd, 
London, 2000; pp 3–19.
Hu D., Stewart B., Mello S., Arvanitidou L., Panagakos F., De Vizio W., Zhang Y., 
Mateo L., Yin W., Efficacy of a mouthwash containing 0.8% arginine, PVM/MA 
copolymer, pyrophosphates, and 0.05% sodium fluoride comparedto a negative control 
mouthwash on dentin hypersensitivity reduction. A randomized clinical trial.Journal of 
Dentistry. 2013, 41S; 26-33.
Holland G. R., Narhi M. N., Addy M., Gangarosa L., Orchardson R., Guidelines for the 
design and conduct of clinicaltrials on dentine hypersensitivity. J. Clin. Periodontol.
1997, 24, 808–813.
ICH Topic 6 Guideline for Good Clinical Practice CPMP/ICH/135/95 17th July 1996.
Laster L., Laudenbach K. W., Stoller N. H., An evaluation of clinical tooth mobility 
measurements. J. Periodontol.1975, 46, 603—607.
Lobene R. R., Weatherford T., Ross N. M., Lamm R. A., Menaker L., A modified 
gingival index for use in clinical trials. Clin. Prev. Dent.1986, 8, 3–6.
Markowitz R., A new treatment alternative for sensitive teeth:A desensitizing oral rinse. 
Journal of Dentistry. 2013, 41S; 1-11.
Orchardson R., Collins W., Clinical features of hypersensitive teeth. Br. Dent. J.1987, 
162, 253–256.
Pashley D., Tay F., Haywood V., Collins M., Drisko C., Consensus-based 
recommendations for the diagnosis and management of dentin hypersensitivity. 
Compend Cont Edu Dent2008, 29, 1–35.
Rees J. S., The prevalence of dentine hypersensitivity in general dental practice in the 
UK. J. Clin. Periodontol.2000, 27, 860–865.
Seltzer S., Bender I., The Dental Pulp: Biologic Considerations in Dental Procedures; 
JP Lippincott, 1975.
Sharma D., McGuire J. A., Gallob J. T., Amini P., Randomised clinical efficacy trial of 
potassium oxalate mouthrinse in relieving dentinal sensitivity. J. Dent.2013a, 41 Suppl 
4, S40–S48.
Sharma D., McGuire J. A., Amini P., Randomized trial of the clinical efficacy of a 
potassium oxalate-containing mouthrinse in rapid relief of dentin sensitivity. J. Clin. 
Dent.2013b, 24, 62–67.
 
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12. APPENDICES
12.1. Appendix 1 
Abbreviations
AE 
Adverse Event
CD
Compact Disc
CRO
Contract Research Organisation
CRF
Case Report Form
EDC
Electronic Data Capture
GCP
Good Clinical Practice
GSKCH
GlaxoSmithKline Consumer Healthcare
ICH
International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
IRB
Institutional Review Board
ITT
Intention to Treat
KOX
Potassium Oxalate
NaF
Sodium Fluoride
PII
Personally Identifiable Information
PP
Per Protocol
SAE
Serious Adverse Event
SMFP
Sodium Monofluorophosphate
SOP
Standard Operating Procedure
PRO
Patient Reported Outcome
 
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SIGNATURE PAGE 
 
  
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
 
Date 
Signed By
 
 
Justification 
 
 
24-May-2017 03:05:29
 
Biostatistics Approval
25-May-2017 00:11:35
Approved
23-May-2017 10:13:18
Approved
Clinical Operations Approval
207656 Clinical Protocol
23-May-2017 09:12:08
 
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PPD
PPD
PPD
PPD

SAP_001.pdf: 
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207656 
Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
 
 
 
 
 
 
STATISTICAL REPORTING AND ANALYSIS PLAN 
 
 
 
 
A METHOD DEVELOPMENT CLINICAL STUDY 
INVESTIGATING THE EFFICACY OF AN EXPERIMENTAL ORAL 
RINSE IN PROVIDING LONG TERM RELIEF FROM DENTINAL 
HYPERSENSITIVITY 
 
 
 
 
 
 
Protocol Number: 207656 
Phase: 
N/A 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 47 


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Document History 
 
 
Document 
Version Date 
Summary of Changes (New analysis or Change 
in planned analysis) 
Final Analysis Plan 
5-Oct-2017 
Not applicable (N/A) 


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Table of contents 
Document History ............................................................................................................... 2 
Table of contents ................................................................................................................. 3 
Abbreviation ........................................................................................................................ 5 
1 
Summary of Key Protocol Information ............................................................................... 6 
1.1 
Study Design ............................................................................................................ 6 
1.2 
Study Objectives ...................................................................................................... 7 
1.3 
Treatment ............................................................................................................... 10 
1.4 
Sample Size Calculation ........................................................................................ 11 
2 
Planned Analyses ............................................................................................................... 11 
2.1 
Interim Analysis ..................................................................................................... 11 
2.2 
Final Analyses ....................................................................................................... 11 
3 
Considerations for Data Analyses and Data Handling Conventions ................................. 11 
3.1 
Baseline Definition ................................................................................................ 11 
3.2 
Subgroups/Stratifications ....................................................................................... 12 
3.3 
Centers Pools ......................................................................................................... 12 
3.4 
Timepoints and Visit Windows ............................................................................. 12 
4 
Data Analysis ..................................................................................................................... 12 
4.1 
Populations for Analysis ........................................................................................ 12 
4.1.1 
Subject Disposition ............................................................................... 12 
4.1.2 
Protocol Deviations ............................................................................... 13 
4.1.3 
Analysis Populations ............................................................................. 13 
4.2 
Subject Demographics and Other Baseline Characteristics ................................... 14 
4.2.1 
Demographic Characteristics ................................................................ 14 
4.2.2 
General Medical History ....................................................................... 15 
4.3 
Study Product Compliance and Use of Other Therapy .......................................... 15 
4.3.1 
Study Product Compliance and Exposure ............................................. 15 
4.3.2 
Prior and Concomitant Medication ....................................................... 15 
4.3.3 
Other Therapy/Rescue Medication ....................................................... 15 
4.4 
Analysis of Efficacy .............................................................................................. 15 
4.4.1 
Primary Efficacy Endpoint .................................................................... 15 
The change from baseline in Schiff sensitivity score at Week 8 is the primary 
efficacy endpoint.................................................................................................... 15 
4.4.2 
Secondary Efficacy Variables ............................................................... 17 
4.4.3 
Handling of Missing Values/Censoring/Discontinuations .................... 17 


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4.5 
Analysis of Secondary Objectives ......................................................................... 17 
4.5.1 
Efficacy (Secondary) ............................................................................. 17 
The change from baseline in tactile threshold at Week 8 .................................................. 17 
4.5.2 
Pharmacokinetic (Secondary) ............................................................... 18 
4.6 
Analysis of Exploratory Objective ........................................................................ 18 
4.7 
Analysis of Safety .................................................................................................. 19 
4.7.1 
Adverse Events and Serious Adverse Events ........................................ 19 
4.7.2 
Other Safety Variables .......................................................................... 20 
4.8 
Analysis of Other Variables ................................................................................... 20 
5 
Changes to the Protocol Defined Statistical Analysis Plan ............................................... 20 
6 
Top-line Summary ............................................................................................................. 21 
Attachment 1: List of Data Displays ........................................................................................ 22 
Appendix 1: Templates for Tables, Figures & Listings .................................................... 23 


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Abbreviation 
 
 
AE 
Adverse Event 
ANCOVA 
Analysis Of Covariance 
BDRM 
Blinded Data Review Meeting 
CI 
Confidence Interval 
DH 
Dentinal Hypersensitivity 
EAR 
Erosion, Abrasion, Recession 
eCRF 
Electronic Case Report Form 
GSK CH 
Glaxosmithkline Consumer Healthcare 
ITT 
Intent-To-Treat 
MedDRA 
Medical Dictionary For Regulatory 
N 
Number Of Subjects 
OHT 
Oral Hard Tissue 
OST 
Oral Soft Tissue 
PP 
Per Protocol 
ppm 
Parts Per Million 
RAP 
Reporting And Analysis Plan 
RLR 
Review Listing Requirement 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard Deviation 
SEs 
Standard Error 
SMS 
Short Service Message 
SOC 
System Organ Class 
VRS 
Visual Rating Scale 
w/w 
Weight/Weight 


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The purpose of this Statistical Reporting and Analysis Plan is to describe the planned analyses 
and outputs to be included in the Clinical Study Report for Protocol 207656. 
 
1 
Summary of Key Protocol Information 
The purpose of this trial is to demonstrate the efficacy and safety of a 1.5% dipotassium 
oxalate monohydrate (KOX) containing oral rinse to treat the symptoms of Dentinal 
Hypersensitivity (DH). Efficacy will be demonstrated as a treatment difference in favour of 
the 1.5% KOX containing oral rinse vs. the negative control oral rinse for the primary efficacy 
outcome, Schiff sensitivity score at Week 8. Safety will be demonstrated through assessment 
of adverse events (AEs). 
 
1.1 
Study Design 
 
 
Overall Design 
This will be a single centre, eight week, randomized, examiner-blind, three treatment, 
parallel group design, stratified study in healthy subjects, with at least two sensitive teeth 
that meet all of the study criteria at the Screening and Baseline visits. DH will be assessed 
at Baseline, and after 4 and 8 weeks of twice daily treatment. 
At the Screening visit, subjects will give their written informed consent to participate in the 
study. Demography, medical history and concomitant medications will be recorded, 
followed by an oral examination. This will include an oral soft tissue (OST) examination, 
an oral hard tissue examination (OHT), dentition exclusions, assessment of erosion, 
abrasion, recession (EAR), gingival status, tooth mobility and subject response to a 
qualifying air sensitivity assessment, subject response will be recorded as a numerical value 
(Schiff score 2/3). Eligible subjects will be supplied with a standard fluoride dentifrice and 
a fluoride oral rinse to use twice daily (morning and evening) during the acclimatization 
period between the Screening and Baseline visits. Each product use will be recorded in the 
diary provided. First use of the acclimatization dentifrice and oral rinse will be carried out 
under supervision at the study site. 
At the Baseline visit (2-3 weeks after Screening), eligibility to continue will be assessed. 
Subjects will undergo an OST examination, followed by tooth sensitivity assessments (a 
tactile stimulus [Yeaple probe, maximum 20g pressure], then an evaporative air stimulus 
[with Schiff Sensitivity Scale and Visual Rating Score VRS]), and a review of the 
inclusion/exclusion criteria. Two test teeth will then be identified and eligible subjects will 
be randomized to treatment (stratified by maximum baseline Schiff sensitivity score of the 
two selected test teeth). First use of allocated study product will be carried out under 
supervision at the study site, after the supervised brushing subjects will be requested to 
measure out the dose of the oral rinse using the dosing cup provided. Subjects will continue 
to use their assigned study treatment twice daily (morning and evening) for the next 8 
weeks, recording each brushing and rinsing occasion in the diary provided. 


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1.2 
Study Objectives 
 
 
Objectives 
Endpoints 
Primary Objective 
Primary Endpoint 
• To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by an evaporative air stimulus 
(with Schiff Sensitivity Scale), 
against a negative control oral rinse, 
following use as an adjunct to twice 
daily brushing with a standard 
fluoride dentifrice, after 8 weeks. 
• 
Change from baseline in Schiff 
sensitivity score at 8 weeks. 
Secondary Objectives 
Secondary Endpoints 
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by a tactile stimulus (Yeaple 
probe), against a negative control oral 
rinse, following use as an adjunct to 
twice daily brushing with a standard 
fluoride dentifrice, after 8 weeks. 
• Change from baseline in tactile 
threshold (Yeaple probe) at 8 
weeks. 
Exploratory Objectives 
Exploratory Endpoints 
Subjects will return to the study site each week (Visits 3, 4, 5, 6, 7, 8, 9 and 10) over the 
eight week study period and asked to return their study kit so that the oral rinse bottle and 
its contents can be weighed to verify study compliance. Diaries will also be checked at each 
visit. A supervised brushing and rinse will also be conducted at each visit (except Visit 10). 
Following supervised product use all products will be returned to the subject. The dentifrice 
and oral rinse will be re-dispensed at Visit 6 (Week 4).Tooth sensitivity will be re-assessed 
after 4 and 8 weeks (Visits 6 and 10) of treatment, using first a tactile stimulus (Yeaple 
probe, maximum 80g pressure) and then an evaporative air stimulus (with Schiff  
Sensitivity Scale and VRS) on the two selected test teeth only. An OST examination will be 
completed at each of these visits, prior to the clinical assessments of sensitivity. 
The study site will send twice daily (morning and evening) short message service (SMS) 
reminders requesting that subjects remember to conduct their timed brush and rinse in the 
morning and evening. 
For further details please refer to Section 3.1 of the protocol. 


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Objectives 
Endpoints 
• To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by an evaporative air stimulus 
(with Schiff Sensitivity Scale), 
against a placebo oral rinse, following 
use as an adjunct to twice daily 
brushing with a standard fluoride 
dentifrice, after 8 weeks. 
• Change from baseline in Schiff 
sensitivity score at 8 weeks. 
• 
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by a tactile stimulus (Yeaple 
probe), against a placebo oral rinse, 
following use as an adjunct to twice 
daily brushing with a standard 
fluoride dentifrice, after 8 weeks. 
• 
Change from baseline in tactile threshold 
(Yeaple probe) at 8 weeks. 
• 
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by an evaporative air stimulus 
(with Schiff Sensitivity Scale), 
against a marketed negative control 
oral rinse and a placebo oral rinse, 
following use as an adjunct to twice 
daily brushing with a standard 
fluoride dentifrice, after 4 weeks. 
• 
Change from baseline in Schiff 
sensitivity score at 4 weeks. 
• 
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by a tactile stimulus (Yeaple 
probe), against a marketed negative 
control oral rinse and a placebo oral 
rinse, following use as an adjunct to 
twice daily brushing with a standard 
fluoride dentifrice, after 4 weeks. 
• 
Change from baseline in tactile threshold 
(Yeaple probe) at 4 weeks. 
• 
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited an evaporative air stimulus 
(with VRS), against a marketed 
negative control oral rinse and a 
• 
Change from baseline in Visual Rating 
Score (VRS) at 4 and 8 weeks. 


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Objectives 
Endpoints 
placebo oral rinse, following use as 
an adjunct to twice daily brushing 
with a standard fluoride dentifrice, 
after 4 and 8 weeks. 
• 
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by an evaporative air stimulus 
(with Schiff Sensitivity Scale), 
against the efficacy of the group 
obtained by combining the marketed 
negative control and the placebo oral 
rinse,following use as an adjunct to 
twice daily brushing with a standard 
fluoride dentifrice, after 4 and 8 
weeks. 
• 
Change from baseline in Schiff 
sensitivity score at 4 and 8 weeks. 
• 
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited by a tactile stimulus (Yeaple 
probe), against the efficacy of the 
group obtained by combining the 
marketed negative control and the 
placebo oral rinse, following use as 
an adjunct to twice daily brushing 
with a standard fluoride dentifrice, 
after 4 and 8 weeks. 
• 
Change from baseline in tactile threshold 
(Yeaple probe) at 4 and 8 weeks. 
• 
To evaluate and compare the clinical 
efficacy of a 1.5% KOX containing 
oral rinse for the relief of DH, as 
elicited an evaporative air stimulus 
(with VRS), against the efficacy of 
the group obtained by combining the 
marketed negative control and the 
placebo oral rinse, following use as 
an adjunct to twice daily brushing 
with a standard fluoride dentifrice, 
after 4 and 8 weeks. 
• 
Change from baseline in VRS at 4 and 8 
weeks. 


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1.3 
Treatment 
 
 
Test Product 
Negative control 
Placebo Product 
Product Name 
Experimental 
oralrinse containing 
1.5% KOX, 0ppm 
fluoride, pH 7 
Oral rinse containing 
0.02% w/w NaF. Colgate 
Total Daily 
Repair® (USA marketed 
product) 
Oral rinse containing 
0% KOX and 0 
ppmfluoride, pH 
Product 
Formulation 
Code (MFC) 
CCI 
 
Commercially Available 
CCI 
 
Route of 
Administration 
Oral 
Oral 
Oral 
Dosing 
Instructions 
Rinse twice daily 
(morning and 
evening) with 10 ml 
of oral rinse for 60 
timed seconds and 
expectorate. No 
further rinsing with 
water will be 
permitted after use of 
the oral rinse. 
Rinse twice daily 
(morning andevening) 
with 10 mlof oral rinse 
for 60 timed seconds 
andexpectorate. 
Nofurther rinsing 
withwater will 
bepermitted after use 
ofthe oral rinse. 
Rinse twice daily 
(morning andevening) 
with 10 mlof oral rinse 
for 60 timed seconds 
andexpectorate. 
Nofurther rinsing 
withwater will 
bepermitted after use 
ofthe oral rinse. 
All subjects will receive the same regular fluoride dentifrice and a US marketed oral rinse 
during the acclimatization period to familiarise themselves with the required brushing and 
rinsing regimen, and standardise oral hygiene practices. 
Subjects will apply a full brush head of the standard fluoride dentifrice, brush for one timed 
minute (in their usual manner) and expectorate; rinse with 10 ml of tap water for 5 seconds 
and expectorate; and then rinse with 10 ml of their randomly assigned oral rinse for 60 timed 
seconds and expectorate. No further rinsing with water will be permitted after use of the oral 
rinse, and subjects will be asked to refrain from eating or drinking within 30 minutes of using 
the oral rinse. The dosage regimen of twice daily treatment (morning and evening) will be the 
same for all subjects. 


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1.4 
Sample Size Calculation 
A sufficient number of healthy subjects will be screened to randomise at least 100 subjects 
(approximately 50 to the experimental treatment, 25 to the negative control and 25 to placebo) 
to ensure 80 evaluable subjects complete the entire study. This will ensure approximately 40 
evaluable subjects for the test treatment and 20 each for the negative control treatment and 
placebo. 
With this 2:1:1 distribution of the subjects in the treatment arms, the study has less than 50% 
power to detect a mean treatment difference of 0.36 in the Schiff sensitivity score using a two- 
sided t-test of significance level 0.05 for the experimental product against the  negative 
control. The standard deviation used in this calculation is 0.8; this estimate is obtained from 
the GSKCH study 204763. When the experimental treatment group is compared with the 
combined group comprising of the negative control group and the placebo group using the 
two-sided t-test with the same estimates of mean difference, significance level and standard 
deviation, the study will have 51.1% power. 
The magnitude of the treatment difference is more important and is expected to be in favour of 
the experimental mouthwash. 
 
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 Day-0 pre-dose assessment with a non- 
missing value. 
Unless otherwise stated, if baseline data is missing no derivation will be performed and will  
be set to missing. 


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3.2 
Subgroups/Stratifications 
Eligible subjects will be stratified according to their maximum baseline Schiff sensitivity 
score of the two selected teeth. The stratification factor will give rise to two strata. 
Stratum 1: Subjects with maximum baseline Schiff sensitivity score of 2 for the two selected 
test teeth. 
Stratum 2: Subjects with the maximum baseline Schiff sensitivity score of 3 for the two 
selected test teeth. 
Efficacy variables will be analyzed accounting for strata. 
Subgroups are not defined for this trial. 
3.3 
Centers Pools 
This is a single centre study, therefore pooling of centers is not required. 
 
3.4 
Timepoints and Visit Windows 
The study schedule should be followed as per protocol. Deviations from the study schedule 
with respect to visit timings will be reviewed on a case-by-case basis to determine whether the 
data should be excluded from the Per-Protocol (PP) analysis (Section 4.1.2). 
 
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 Blinded Data Review Meeting (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 
4.1.1 Subject Disposition 
Screen failures will be defined as subjects who do not satisfy all of the inclusion/exclusion 
criteria. A summary will be provided of the number of subjects screened and the number of 
screen failures with reasons why subjects were not randomized (Table 14.1.1). Percentages 
will be based on the total number of subjects randomized. 
Subject disposition will also be summarized as the number and percentage of subjects who 
complete the study, with the number who discontinue broken down by reason for 
discontinuation (Table 14.1.1). The percentages are based on the total number of subjects 
randomized. The table will also summarise the number and percent of subjects assigned to 
each analysis population (defined in Section 4.1.3). The summary will be presented by 
treatment and overall. 


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Subject disposition including the subject status (completer, Yes/No), critical demographic  
data (age, sex, race and ethnicity), the duration of treatment before discontinuation and the 
specific reason for discontinuation, will be listed by treatment group for randomized subjects 
(Listing 16.2.1.1) and non-randomized subjects (Listing 16.2.1.2) separately. 
 
4.1.2 Protocol Deviations 
Important major protocol deviations (including deviations related to study inclusion/exclusion 
criteria, conduct of the trial, patient management or patient assessment) will be summarized 
and listed. 
Protocol deviations will be tracked by the study team throughout the conduct of the study. 
Data will be reviewed prior to unblinding and closure of the database to ensure all important 
deviations are captured and categorized. 
Major deviations of the protocol procedures identified as liable to influence the efficacy 
outcome may include, but will not be necessarily limited to, the following: 
• Violations of inclusion or exclusion criteria 
 
• Prior / concomitant medications 
 
• Ineligible teeth 
 
• Treatment non-compliance 
 
• Not receiving randomized treatment 
 
• Visit outside the planned schedule 
Further deviations liable to influence the efficacy outcome will be given in the Review Listing 
Requirement (RLR) document where major deviations will be identified at the blinded data 
review meeting. The number and percentage of subjects with any major protocol deviations 
and with each type of major protocol deviations will be presented by treatment (Table 14.1.2) 
and listed in Listing 16.2.2.1. Any minor protocol deviations will be listed similarly (Listing 
16.2.2.2). 
 
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 


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Population 
Definition / Criteria 
Analyses Evaluated 
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 randomized subjects who 
receive at least one dose of study 
treatment. 
• This population will be based on the 
treatment the subject actually received. 
• Safety 
Intent-To-Treat 
• Comprise of all randomized subjects who 
receive at least one dose of study 
treatment and have at least one post- 
baseline efficacy evaluation. 
• This population will be based on the 
treatment to which the subject was 
randomized. 
• Efficacy 
Per-Protocol 
• The ‘Per-Protocol’ (PP) population will 
include all subjects in the ITT population 
who have no protocol deviations deemed 
to affect efficacy. 
• Efficacy 
 
The primary population for assessment of efficacy will be the ITT population. A PP analysis 
will be performed on the primary and secondary efficacy variable if more than 10% of the 
subjects in the ITT population are excluded from the PP population. 
The numbers of subjects included in each of the populations, and the number excluded from 
each population broken down by the reason for exclusion will be presented (Table 14.1.2). 
Subjects excluded from any of the analysis populations will be listed (Listing 16.2.3.1). 
 
4.2 
Subject Demographics and Other Baseline Characteristics 
4.2.1 Demographic Characteristics 
Descriptive statistics (number of subjects, mean, standard deviation, median, minimum and 
maximum for continuous variables, and frequency and percentage for categorical variables) 
will be presented for demographic data by treatment group and overall. These data include 
age, gender, race, ethnicity and Schiff stratification categories and will be presented for the 
Safety (Table 14.1.4.1), ITT (Table 14.1.4.2) and if required the PP populations (Table 
14.1.4.3). 
Demographic information will be listed (Listing 16.2.4.1) for all randomized subjects. 


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4.2.2 General Medical History 
Medical history data will be listed (Listing 16.2.4.2) with start date and end date or ongoing at 
the start of study drug. A data listing will also be produced for evaluation of protocol 
violations at the blinded data review stage. 
 
4.3 
Study Product Compliance and Use of Other Therapy 
Supervised brushing/rinsing non complince (subject number, date of visit and time of the 
supervised procedure and reason why the supervised brushing was not performed according to 
the protocol) will be listed for the blinded data review and specified in the RLR document. 
 
4.3.1 Study Product Compliance and Exposure 
Brushing/rinsing compliance (using study product twice daily) will be listed for the blinded 
data review and specified in the RLR document. 
 
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 16.2.5.1). Prior medications are defined as those stopped 
before the first administration of the study products.Concomitant medications will be listed 
similarly (Listing 16.2.5.2). Concomitant medications are defined as those ongoing or started 
on or after the first administration of the study products. 
 
4.3.3 
Other Therapy/Rescue Medication 
Not Applicable. 
 
4.4 
Analysis of Efficacy 
4.4.1 Primary Efficacy Endpoint 
 
4.4.1.1 
Primary Efficacy Endpoint Definition 
 
The change from baseline in Schiff sensitivity score at Week 8 is the primary efficacy 
endpoint. 
The subjects Schiff sensitivity score will be derived as the mean of the two test teeth at each 
visit assessed and the change from baseline will be derived from this mean Schiff score. For 
for post-baseline observations, the average will be calculated only across teeth that have both 
a valid baseline and a valid postbaseline assessment. 
Summary statistics of the observed mean Schiff sensitivity scores and changes from basline 
will be presented by treatment at Baseline, Week 4 and Week 8 (Table 14.2.1.1.1). 
To visually inspect the treatment effect on Schiff sensitivity scores, a plot across time, with  
the raw means together with standard error (SEs) bars will be produced. The plot will display 
a different symbol line for each treatment group (Figure 14.2.1). 


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4.4.1.2 
Statistical Hypothesis, Model, and Method of Analysis 
The primary analysis is a comparison of the mean change from baseline Schiff sensitivity 
score between Test Product and Negative Control at Week 8. 
The null hypothesis for the primary endpoint is that the mean change from baseline in Schiff 
sensitivity score is equal between the two products. 
H0: µ1 = µ2 
The alternative hypothesis is that the mean change from baseline in Schiff sensitivity score is 
not equal between the two products. 
H1: µ1 ≠ µ2 
The change from baseline in Schiff sensitivity score at Week 8 will be analyzed using 
ANCOVA with treatment as factor and mean baseline Schiff sensitivity score as covariate. 
Note that since the baseline Schiff sensitivity score will be included as a covariate,  the 
baseline Schiff stratification value will not be included in the model. Adjusted means of all 
treatments and their SEs, P-value and 95% confidence interval (CIs) will be presented on the 
ITT population (Table 14.2.1.1.2). Treatment differences of the treatment comparisons will 
also be provided together with P-values and 95% CIs. 
The assumption of normality and homogeneity of variance in the ANCOVA model will be 
investigated and if violated, data transformations will be investigated. If suitable 
transformations cannot be found, non-parametric Van Elteren tests will be performed 
adjusting for the maximum baseline Schiff sensitivity scores and results will be compared  
with the ANCOVA results. If the inferences from the two analyses are similar then both sets  
of results will be reported and emphasis will be made on the ANCOVA results. In case of 
discrepancies between p-values of ANCOVA and Van Elteren analysis, inferences will be 
drawn on the non-parametric analysis. 
To visually inspect the treatment effect on Schiff sensitivity scores, a plot across time 
(Baseline, Week 4 and Week 8) will be displayed with raw means and SE bars. The plot will 
display a different symbol line for each treatment group (Figure 14.2.1). 
 
4.4.1.3 
Supportive Analyses 
The change from baseline in Schiff sensitivity score to post-treatment (Week 4 and 8) will be 
summarized and analyzed as detailed for the primary endpoint. Analysis assumptions will be 
investigated as detailed for the primary efficacy analysis. 
The analysis will be conducted for: 
 
• Test Product versus Placebo Product at Week 4 and 8 
• Test Product versus Negative Control at Week 4 
 
Similar analyses for a Combined Control group (Negative Control and Placebo) will also be 
performed for the changes from baseline in Schiff sensitivity score to Weeks 4 and 8 using the 
same ANCOVA model mentioned above for the analysis of the primary efficacy variable. 


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The adjusted mean for each treatment, and the difference between the pairs of treatments 
together with their corresponding 95% CIs and the P-values for treatment comparisons, will  
be provided (Table 14.2.1.1.2). 
Test Product versus Combined Control group will be obtained by using contrast at Week 4 
and 8. Below comparison will be tested: 
• Test product versus Combined Control group  at Week 4 and 8 
4.4.2 Secondary Efficacy Variables 
Secondary efficacy variables are defined in section 4.5 
 
4.4.3 
Handling of Missing Values/Censoring/Discontinuations 
Missing data will not be replaced or imputed. Subjects who withdraw from the study 
prematurely will be included in the statistical analyses up to the point of discontinuation. 
 
4.5 
Analysis of Secondary Objectives 
4.5.1 
Efficacy (Secondary) 
 
The change from baseline in tactile threshold at Week 8 
The change from baseline in tactile threshold at Week 8 is the secondary efficacy endpoint. 
The null hypothesis for the secondary endpoint is that the mean change from baseline in  
tactile threshold is equal between the two products. 
H0: µ1 = µ2 
The alternative hypothesis is that the mean change from baseline in tactile threshold score is 
not equal between the two products. 
H1: µ1 ≠ µ2 
The primary treatment comparison of this secondary efficacy variable is: 
Test Product versus Negative Product at Week 8. 
All other treatment comparisons based on secondary efficacy variable are part of the 
exploratory objectives. 
The subjects tactile threshold will be derived as the mean of the two test teeth at each visit 
assessed and the change from baseline will be derived from this mean tactile threshold. If 
tactile threshold for test teeth reported greater than 80g for post baseline assessment then in 
that case it will be consider as 90g. 
Summary statistics of the observed mean tactile threshold scores and changes from baseline 
will be presented by treatment at Baseline, Week 4 and Week 8  (Table 14.2.2.1). 
The change from baseline in tactile threshold at Week 8 will be calculated as the subject level 
mean change from baseline (on the two test teeth) and analyzed at Week 8 using ANCOVA 
with treatment and baseline Schiff stratification value as factors and baseline tactile threshold 
included as a covariate. Adjusted means of all treatments and their SEs, P-value and 95%  CIs 


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will be presented . Treatment differences of all pairs of treatments will be provided together 
with P-values and 95% CIs (Table 14.2.2.2). 
To visually inspect the treatment effect on tactile threshold scores, a plot across time, with the 
raw means together with SE bars will be produced. The plot will display a different symbol 
line for each treatment group (Figure 14.2.2). 
The assumption of normality and homogeneity of variance in the ANCOVA model will be 
investigated and if violated, data transformations will be investigated. If suitable 
transformations cannot be found, non-parametric Van Elteren tests will be performed 
adjusting for the maximum baseline Schiff sensitivity scores and results will be compared  
with the ANCOVA results. If the inferences from the two analyses are similar then both sets  
of results will be reported and emphasis will be made on the ANCOVA results. In case of 
discrepancies between p-values of ANCOVA and van Elteren analysis, inferences will be 
drawn on the non-parametric analysis. 
 
4.5.1.1 
Exploratory Analysis of Secondary Efficacy Variable 
The change from baseline in tactile threshold score to post-treatment (Week 4 and 8) will be 
summarized and analyzed as detailed for the secondary endpoint. Analysis assumptions will 
be investigated as detailed for the secondary efficacy analysis (Section 4.5.1). 
The analysis will be conducted for: 
• Test Product versus Placebo at Week 4 and 8 
• Test Product versus Negative Control at Week 4 
Analyses for the Combined Control group (Placebo and Negative Control) will also be done 
for the changes from baseline in tactile threshold score to Weeks 4 and 8 using the same 
ANCOVA model mentioned above for the analysis of the secondary efficacy variable. 
The adjusted mean for each treatment, and the difference between the pairs of treatments 
together with their corresponding 95% CIs and the P-values for treatment comparisons, will  
be provided (Table 14.2.2.2). 
Test Product versus Combined Control group will be obtained by using contrast at Week 4 
and 8. 
 
4.5.2 
Pharmacokinetic (Secondary) 
Not Applicable 
 
4.6 
Analysis of Exploratory Objective 
Exploratory analysis based on the primary and secondary efficacy variable (change from 
baseline in Schiff sensitivity score and change from baseline in tactile threshold) are discussed 
in the section above. 
Raw values of the visual rating score (VRS) (averaged over the two test teeth) at Week 4 and 
Week 8 together with changes from baseline will be summarized by treatment at each study 
time  point  (Table  14.2.3.1).  To  visually inspect  the  treatment  effect  on  Schiff sensitivity 


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scores, a plot across time, with the raw means together with SEs bars will be produced. The 
plot will display a different symbol line for each treatment group (Figure 14.2.3). 
The change from baseline in VRS will be calculated as the subject level mean change from 
baseline (on the two test teeth) and analyzed separately at Week 4 and 8 using ANCOVA with 
treatment and baseline Schiff stratification value as factors and baseline VRS score included  
as a covariate. Adjusted means of all treatments and their SE, P-value and 95% CIs will be 
presented. Treatment differences of all pairs of treatments will be provided together with P- 
values and 95% CIs  (Table 14.2.3.2). 
The assumption of normality and homogeneity of variance in the ANCOVA model will be 
investigated and if violated, data transformations will be investigated. If suitable 
transformations cannot be found, non-parametric Van Elteren tests will be performed 
adjusting for the maximum baseline Schiff sensitivity scores and results will be compared  
with the ANCOVA results. If the inferences from the two analyses are similar then both sets  
of results will be reported and emphasis will be made on the ANCOVA results. In case of 
discrepancies between p-values of ANCOVA and van Elteren analysis, inferences will be 
drawn on the non-parametric analysis. 
Analyses for the Combined Control group will also be performed on the change from baseline 
in VRS to Weeks 4 and 8 using the same ANCOVA model mentioned above . 
The adjusted mean for each treatment, and the difference between the pairs of treatments 
together with their corresponding 95% CIs and the p-values for treatment comparisons, will  
be provided (Table 14.2.3.2). 
Test Product versus Combined Control group will be obtained by using contrast at Week 4 
and 8. 
All data for each efficacy measure will be presented for each subject at Baseline, Week 4 and 
Week 8 (Listing 16.2.6.1, Listing 16.2.6.2 and  Listing 16.2.6.3 ). 
 
4.7 
Analysis of Safety 
4.7.1 
Adverse Events and Serious Adverse Events 
All safety data will be reported for the Safety population as per actual treatment received. The 
safety profile of the study treatments will be assessed with respect to AEs. OST abnormalities 
are included as AEs if they appear or worsen after the initial assessment. 
All AEs will be reviewed by the Clinical Research Director or Designee prior to database 
freeze and will be coded using the Medical Dictionary for Regulatory Activities (MedDRA). 
During this review stage, AEs will be further categorized as oral or non-oral. 
AEs will be regarded as treatment-emergent if they occur on or after the start date and time of 
the 
first 
treatment 
usage 
(as determined by start date and time 
from the 
EXPOSURE/dispensing panel; if this date is missing a suitable alternative will be used eg  
date of randomization). All other AEs prior to this will be considered non-treatment emergent. 
The following summary tables and listings will be presented by treatment group. 


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• Table of treatment emergent AEs by system organ class (SOC) and Preferred Term 
(Table 14.3.1.1) 
• Table of treatment emergent AEs by Oral/Non-Oral and Preferred Term (Table 
14.3.1.2) 
• Table of treatment emergent treatment related AEs by SOC and Preferred Term (Table 
14.3.1.3  ) 
• Table of Treatment emergent treatment related AEs by Oral/Non-Oral and Preferred 
Term (Table 14.3.1.4) 
• Listing of all AEs (Listing 16.2.7.1 for all randomized subjects; Listing 16.2.7.2 for 
non-randomized subjects) 
• Listing of deaths (Listing 14.3.2.1) 
• Listing of non-fatal SAEs (Listing 14.3.2.2) 
• Listing of treatment emergent AEs leading to study or drug 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 (refer to section 7.6 of the protocol for further details on incidents) captured in 
the study will be listed in Listing 16.2.7.3. In the event that there is nothing to report, a null 
listing will be produced. 
 
4.8 
Analysis of Other Variables 
Not applicable. 
 
5 
Changes to the Protocol Defined Statistical Analysis Plan 
Changes from the originally planned statistical analysis specified in the protocol are outlined 
in below table: 


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Protocol 
Reporting & Analysis Plan 
Statistical Analysis section 
Statistical Analysis Plan 
Rationale for Changes 
9.2.1. Definition of Analysis 
Populations 
A Per protocol (PP) analysis 
will be performed on the 
primary variable only if more 
than 10% of the subjects in the 
ITT population have protocol 
deviations deemed to affect 
efficacy 
• 
A PP analysis will be 
performed on the 
primary and 
secondary efficacy 
variable if more than 
10% of the subjects in 
the ITT population 
are excluded from the 
PP population 
• 
Endpoints based on 
the secondary 
efficacy variable 
(tactile threshold) 
are important in 
this trial. 
 
6 
Top-line Summary 
The outputs required for the topline is summary is documented in the attached worksheet 
excel file. 


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Attachment 1: List of Data Displays 
Study 207656_List of 
Outputs_01Oct2017. 


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Appendix 1: Templates for Tables, Figures & 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. 
Note to programmer: 
1) The treatment labels for the column heading will be as follow: 
• Test Product 
• Negative Control 
• Placebo 
 
2) Use following footnotes in all the TLFs: 
Test Product: Oral Rinse  (1.5%  KOX, 0ppm F, pH 7) - MFC04905 
Negative Control: Oral Rinse 2 (0.02% w/w NaF) Colgate Total Daily Repair 
Placebo: Oral Rinse (0%  KOX, 0ppm F, pH 7) – MFC04939 
 
3) Check actual races captured in eCRF to adjust the race name and abbreviations. 


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Page 24  of 47 
 
 
 
 
Protocol 207656 
Program Run Date:xxxx 
Table 14.1.1 
Subject Disposition 
All Subjects 
Study Population: All Screened Subjects (N=xxx) 
 
 
Test Product 
N (%) 
Negative Control 
N (%) 
Placebo 
N (%) 
Overall 
N (%) 
TOTAL SUBJECTS SCREENED 
xxx 
SUBJECTS NOT RANDOMIZED 
xxx 
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 
COMPLETED STUDY 
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) 
DID NOT MEET STUDY 
CRITERIA 
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) 
LOST TO FOLLOW-UP 
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) 
WITHDRAWAL OF CONSENT 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 


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GlaxoSmithKline Consumer Healthcare Confidential 
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Test Product 
N (%) 
Negative Control 
N (%) 
Placebo 
N (%) 
Overall 
N (%) 
OTHER 
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) 
ITT POPULATION 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
PP POPULATION 
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 
 
PPD 
 
Page x of y 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 26  of 47 
 
 
 
 
Protocol 207656 
Program Run Date:xxxx 
Table 14.1.2 
Analysis Populations 
Randomized Population 
 
 
Study Population: Randomized (N=xxx) 
 
Test Product 
N (%) 
Negative Control 
N (%) 
Placebo 
N (%) 
Overall 
N (%) 
SUBJECTS EXCLUDED FROM SAFETY 
POPULATION 
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) 
REASON 2 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
... 
SUBJECTS EXCLUDED FROM ITT 
POPULATION 
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) 
REASON 2 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
... 
SUBJECTS WITH AT LEAST ONE 
DATA POINT EXCLUDED FROM PP 
ANALYSIS 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
SUBJECTS COMPLETELY EXCLUDED 
FROM PP POPULATION 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
PROTOCOL DEVIATIONS LEADING TO 
EXCLUSION FROM PP 
All VISITS 
DEVIATION 1 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
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Test Product 
N (%) 
Negative Control 
N (%) 
Placebo 
N (%) 
Overall 
N (%) 
DEVIATION 2 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
... 
WEEK4 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
DEVIATION 3 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
DEVIATION 4 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
... 
WEEK8 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
DEVIATION 5 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
DEVIATION 6 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
xxx (xx.x) 
... 
 
 
 
 
PPD 
 
Page x of y 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 28  of 47 
 
 
 
Protocol 207656 
Program Run Date:xxxx 
Table 14.1.2.1 
Subject Demographics and Baseline Characteristics 
Safety Population 
 Study Population: Safety Population (N=XX) 
 
Test Product 
(N=XX) 
Negative Control 
(N=XX) 
Placebo 
(N=XX) 
Overall 
(N=XX) 
SEX n (%) 
xx (xx.x) 
xx (xx.x) 
... 
xx (xx.x) 
MALE 
xx (xx.x) 
xx (xx.x) 
... 
xx (xx.x) 
FEMALE 
RACE n (%) 
xx (xx.x) 
xx (xx.x) 
... 
xx (xx.x) 
ASIAN 
xx (xx.x) 
xx (xx.x) 
... 
xx (xx.x) 
BLACK or AFRICAN 
xx (xx.x) 
xx (xx.x) 
... 
xx (xx.x) 
AMERICAN INDIAN OR ALASKA 
NATIVE 
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 
xx (xx.x) 
xx (xx.x) 
... 
xx (xx.x) 
MULTIPLE 
ETHNICITY N (%) 
xx (xx.x) 
xx (xx.x) 
... 
xx (xx.x) 
HISPANIC OR LATINO 
xx (xx.x) 
xx (xx.x) 
... 
xx (xx.x) 
NOT HISPANIC OR LATINO 
AGE (YEARS) 
XX 
XX 
... 
XX 
 n 


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GlaxoSmithKline Consumer Healthcare Confidential 
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Test Product 
(N=XX) 
Negative Control 
(N=XX) 
Placebo 
(N=XX) 
Overall 
(N=XX) 
XX.X 
XX.X 
... 
XX.X 
MEAN 
XX.XX 
XX.XX 
... 
XX.XX 
SD 
XX.X 
XX.X 
... 
XX.X 
MEDIAN 
XX 
XX 
... 
XX 
MINIMUM 
XX 
XX 
... 
XX 
MAXIMUM 
STRATIFICATION 
MAXIMUM BASELINE SCHIFF SCORE 2 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
MAXIMUM BASELINE SCHIFF SCORE 3 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
xx (xx.x) 
 
 
 
PPD 
 
 
Page x of y 
 
 


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GlaxoSmithKline Consumer Healthcare Confidential 
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Protocol 207656 
Program Run Date:xxxx 
Table 14.2.1.1 
Summary Statistics of Evaporative (Air) Schiff Sensitivity Score 
Intent-to-Treat Population 
Study Population: Intent to Treat (N=XXX) 
 
 
Test Product 
  
(N=XX) 
 
Negative Control 
  
(N=XX) 
 
Placebo 
  
(N=XX) 
 
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 4 
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 8 
SAME 
AS 
ABOVE 
 
 
PPD 
 
Page x of y 
 
 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
GlaxoSmithKline Consumer Healthcare Confidential 
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Protocol 207656 
Program Run Date:xxxx 
 
Table 14.2.1.2 
Statistical Analysis of Change from Baseline in Evaporative (Air) Schiff Sensitivity Score 
Intent-to-Treat Population 
Study Population: Intent to Treat (N=XXX) 
 
Test Product 
(N=XX) 
Negative Control 
(N=XX) 
Placebo 
(N=XX) 
WEEK 4 
ADJUSTED MEAN [1] 
XX.XX 
XX.XX 
XX.XX 
SE [1] 
XX.XXX 
XX.XXX 
XX.XXX 
95% CI [1] 
(XX.XXX, XX,XXX) 
(XX.XXX, XX.XXX) 
(XX.XXX, XX.XXX) 
P-VALUE [1] 
0.XXXX 
0.XXXX 
0.XXXX 
 
COMPARISONS BETWEEN TREATMENTS 
DIFFERENCE (SE) [1] 
95% CI [1] 
P-VALUE [1] 
 
TEST PRODUCT VERSUS NEGATIVE CONTROL [1] * 
XX.XX (XX.XXX) 
(XX.XXX, XX.XXX) 
0.XXX 
TEST PRODUCT VERSUS PLACEBO [1] 
XX.XX (XX.XXX) 
(XX.XXX, XX.XXX) 
0.XXX 
TEST PRODUCT VERSUS COMBINED CONTROL [1,2] 
XX.XX (XX.XXX) 
(XX.XXX, XX.XXX) 
0.XXX 
WEEK 8 (AS ABOVE FOR WEEK 4) 
... 
 
* Test Product versus Negative Control at Week 8 is a primary endpoint comparision. 
[1] From ANCOVA model with treatment as factor and baseline Schiff score as covariate. Difference is first named treatment minus second named treatment 
such that a negative difference favors the first named treatment. 
[2] Test Product versus Combined Control (Placebo and Negative Control) group is obtained by using contrast. 
 
 
PPD 
 
Page x of y 
Program: 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 32  of 47 
 
 
 
 
Programming Note: For Table 14.2.2.2 and 14.2.2.4: please update footnote [1] as 
[1] From ANCOVA model with treatment and baseline Schiff stratification as factors and baseline tactile threshold as a covariate. Difference is the first named treatment minus 
second named treatment such that a positive difference favors the first named treatment. 
 
For table Table 14.2.3.2 please update footnote [1] as 
[1] From ANCOVA model with treatment and baseline Schiff stratification as factors and baseline VRS as a covariate. Difference is the first named treatment minus second named 
treatment such that a negative difference favors the first named treatment. 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 33  of 47 
 
 
 
Protocol 207656 
Program Run Date:xxxx 
 
Table 14.3.1.1 
Treatment Emergent Adverse Event by SOC and Preferred Term 
Safety Population 
 Study Population: Safety Population (N=xx) 
 
SOC 
Preferred Term 
Test Product 
(N=XX) 
Negative Control 
(N=XX) 
Placebo 
(N=XX) 
Overall 
(N=XX) 
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 
NUMBER OF SUBJECTS WITH NO 
AE 
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 
ERYTHEMA 
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 
GASTROINTESTINAL SYSTEM 
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 
DRY MOUTH 
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 
n (%) = Number (percent) of subjects nAE = Number of adverse events. 
 
 
PPD 
 
 
Page x of y 
 
 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
GlaxoSmithKline Consumer Healthcare Confidential 
Page 34  of 47 
 
 
PPD 
 
 
 
Protocol 207656 
Program Run Date:xxxx 
 
 
 
 
Study Population: Randomized (N=xx) 
Listing 16.1.7 
Randomization Information 
Randomized Population 
 Stratum 1: Maximum Schiff score =2 
 
Subject 
Number 
Age/Sex/ 
Race/Ethinicity[1] 
Randomization Number 
Planned Randomized 
Treatment 
Actual Treatment Received 
Date of Randomization 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A = Asian, B = Black or African American, I = American Indian or Alaska Native, H = Native Hawaiian or 
Other Pacific Islander, W = White, M = Multiple; Ethinicity: H = Hispanic or Latino, NH = Not Hispanic or Latino 
 
 
 
PPD 
 
 
Page x of y 
 
 


GlaxoSmithKline Consumer Healthcare Confidential 
Page 35  of 47 
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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
Protocol 207656 
Program Run Date:xxxx 
 
 
 
Listing 16.2.1.1 
Subject Disposition 
Randomized Population 
 
Study Population: Randomized (N=xx) 
Treatment Group: Test Product 
 
Subject 
Age/Sex/Race/ 
Ethinicity [1] 
Screen 
ing 
Date 
Treatment 
Start 
Date 
and Time [2] 
Completion/ 
Withdrawal Date 
Duration of 
Treatment 
(Days) 
Completed? 
Primary Reason for 
Withdrawal 
Further Details [3] 
PPD 
[1] Age in years; Sex: F = Female, M = Male; Race: A = Asian, B = Black or African American, I = American Indian or Alaska Native, H = 
Native Hawaiian or Other Pacific Islander, W = White, M = Multiple; Ethinicity: H = Hispanic or Latino, NH = Not Hispanic or Latino. 
[2] Date and time of the brushing/rinsing with allocated treatment date at baseline visit. 
[3] Further details of reasons for withdrawal. 
 
 
 
PPD 
 
Page x of y 
 
 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
 
 
PPD 
 
Protocol 207656 
Program Run Date:xxxx 
 
 
 
 
Study Population: Non-Randomized (N=xx) 
Listing 16.2.1.2 
Subject Disposition 
Non-Randomized Subjects 
 
Subject 
Number 
Age/Sex/Race/ 
Ethinicity [1] 
Screening Date 
Reason for Screen Failure 
Further Details [2] 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A = Asian, B = Black or African American, I = American Indian or Alaska Native, H = 
Native Hawaiian or Other Pacific Islander, W = White, M = Multiple; Ethinicity: H = Hispanic or Latino, NH = Not Hispanic or Latino. 
[2] Further details of reasons for screen failure. 
 
 
PPD 
 
Page x of y 
 
 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
 
 
 
 
Protocol 207656 
Program Run Date:xxxx 
 
Listing 16.2.2.1 
Major Protocol Deviations 
Randomized Population 
 
Study Population: Randomized (N=xx) 
 Treatment Group: XXXXXX 
 
 
 
Subject 
Sex/Age/Race/ 
Ethinicity [1] 
Week(s)Excluded 
from PP Population 
Deviation Reason 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A = Asian, B = Black or African American, I = American Indian or Alaska Native, H = 
Native Hawaiian or Other Pacific Islander, W = White, M = Multiple; Ethinicity: H = Hispanic or Latino, NH = Not Hispanic or Latino. 
 
PPD 
 
PPD 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
 
 
PPD 
 
 
Protocol 207656 
Program Run Date:xxxx 
Listing 16.2.2.2 
Minor Protocol Deviations 
Randomized Population 
 
Study Population: Randomized (N=xx) 
Treatment Group: Test Product 
 
Subject 
Number 
Age/Sex/Race/ 
Ethinicity [1] 
Visit 
Deviation Sequence 
Protocol Deviation 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A = Asian, B = Black or African American, I = American Indian or Alaska Native, H = 
Native Hawaiian or Other Pacific Islander, W = White, M = Multiple; Ethinicity: H = Hispanic or Latino, NH = Not Hispanic or Latino. 
 
 
PPD 
 
Page x of y 
 
Programming Note for Listing 16.2.2.2: Listing 16.2.2.2 lists only those identified in population definition document. 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
Protocol 207656 
Program Run Date:xxxx 
 
 
PPD 
 
 
 
 
Study Population: Randomized (N=xx) 
Listing 16.2.3.1 
Exclusion from Analysis Population 
Randomized Population 
 
Subject 
Number 
Age/Sex/Race/ 
Ethinicity [1] 
Treatment Start Date 
and Time 
Safety Population 
ITT Population 
PP population 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A = Asian, B = Black or African American, I = American Indian or Alaska Native, H = 
Native Hawaiian or Other Pacific Islander, W = White, M = Multiple; Ethinicity: H = Hispanic or Latino, NH = Not Hispanic or Latino. 
 
 
PPD 
 
Page x of y 
 
 
 
Programming Note for Listing 16.2.3: This listing is based on population definition document. 


GlaxoSmithKline Consumer Healthcare Confidential 
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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
Protocol 207656 
Program Run Date:xxxx 
Listing 16.2.4.1 
 
 
Demographic Characteristics 
Randomized Popualtion 
 
Study Population: Randomized (N=xx) 
Treatment Group: Test Product 
 
Subject 
Number 
Age (years) 
Sex 
Race 
Ethnicity 
Stratum 
 
 
 
 
 
 
 
 
 
 
PPD 
 
Page x of y 
PPD 


GlaxoSmithKline Consumer Healthcare Confidential 
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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
Protocol 207656 
Program Run Date:xxxx 
Listing 16.2.4.2 
 
 
PPD 
Medical History and Current Medical Conditions 
Randomized Population 
 
Study Population: Randomized (N=xx) 
 Treatment Group: Test Product 
 
 
Subject 
Age/Sex/Race/ 
Ethinicity [1] 
Any Medical History? 
Medical Condition 
Start Date 
Ongoing? 
End Date 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A = Asian, B = Black or African American, I = American Indian or Alaska Native, H = 
Native Hawaiian or Other Pacific Islander, W = White, M = Multiple; Ethinicity: H = Hispanic or Latino, NH = Not Hispanic or Latino. 
 
 
PPD 
 
Page x of y 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
Protocol 207656 
Program Run Date:xxxx 
Listing 16.2.5.1 
 
 
PPD 
Concomitant Medications and Significant Non-drug Therapies Prior to Treatment 
Randomized Population 
 
Study Population: Randomized (N=xx) 
Treatment Group: Test Product 
 
Subject 
Number 
Age/Sex/Race/ 
Ethinicity [1] 
Treatment 
GSK Drug 
Synonym 
Reason for 
Medication 
Frequency 
Start Date (Study 
Day [2]) 
End Date/Ongoing 
 
 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A = Asian, B = Black or African American, I = American Indian or Alaska Native, H = 
Native Hawaiian or Other Pacific Islander, W = White, M = Multiple; Ethinicity: H = Hispanic or Latino, NH = Not Hispanic or Latino. 
[2] Study day relative to the date of Randomization. 
Page x of y 
PPD 
 
Programming note: sort the listing by subject number, treatment start date. 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
 
 
PPD 
 
 
Protocol 207656 
Program Run Date:xxxx 
 
 
 
 
Study Population: Randomized (N=xx) 
Treatment Group: Test Product 1 
Listing 16.2.6.1 
Individual Efficacy Data for Schiff Sensitivity Score for Two Test Teeth 
Randomized Population 
 
Subject 
Number 
Age/Sex/Race/ 
Ethinicity [1] 
Tooth Number 
(Universal/FDI) 
Timepoint 
Score 
Subject level 
Average 
Change from 
Baseline 
 
 
 
 
 
 
 
 
 
 
 
[1] Age in years; Sex: F = Female, M = Male; Race: A = Asian, B = Black or African American, I = American Indian or Alaska Native, H = 
Native Hawaiian or Other Pacific Islander, W = White, M = Multiple; Ethinicity: H = Hispanic or Latino, NH = Not Hispanic or Latino. 
 
 
Page x of y 
PPD 
 
Programming Note : 1) Subject level average is based raw values for selected 2 test teeth. 
2) Please create a similar listsing for tactile and VRS score 


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Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
 
 
 
 
Protocol 207656 
Program Run Date:xxxx 
 
 
 
 
Study Population: Randomized (N=xx) 
Treatment Group: Test Product 1 
Listing 16.2.7.1 
All Adverse Events 
Randomized Population 
 
Subject 
Number 
 
Age/Sex/ 
Race/ 
Ethinici 
ty [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: A = Asian, B = Black or African American, I = American Indian or Alaska Native, H = Native Hawaiian or 
Other Pacific Islander, W = White, M = Multiple; Ethinicity: H = Hispanic or Latino, NH = Not Hispanic or Latino. 
[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 
PPD 
 
Programming Note for Listing 16.2.7.2: 
• 
Repeat the same layout for listing 16.2.7.2 
• 
Population should be used ‘Non randomized Subjects’ 
• 
The fourth column should be only ‘Start Date’ 
PPD 
HEADACHE 
(NERVOUS SYSTEM 
DISORDER) 
[Non-Oral] 
PPD 
20:30 
MILD 
No 
NOT 
APPLICAB 
LE 
RECOVERE 
D/RESOLV 
ED 
NO 
NO 


GlaxoSmithKline Consumer Healthcare Confidential 
Page 45  of 47 
1.5% w/w dipotassium oxalate monohydrate (KOX) and 0 ppm fluoride oral rinse 
207656 
Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
 
 
 
 
• 
Add footnote ‘Only SAEs are collected for non randomized subjects’ 
• 
Delete the footnote related to study day and adjust the numbers accordingly. 


GlaxoSmithKline Consumer Healthcare Confidential 
Page 46  of 47 
1.5% w/w dipotassium oxalate monohydrate (KOX) and 0 ppm fluoride oral rinse 
207656 
Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
 
 
 
 
 
Protocol 207656 
Program Run Date:xxxx 
Figure 14.2.1 
Evaporative (Air) Sensitivity Schiff Sensitivity Score by Time and Treatment 
Intent to Treat Population 
Study Population: Intent-to-Treat (N=XX) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
*Mean and SE plotted are from summary statistics in T 14.2.1.1.1 
Note to programmer: (1) Add ‘Baseline’, ‘Week 4’ and ‘Week 8’ to X-axis (2) Use different symbols and line-styles for three treatments 
(3) For Figures 14.2.4 & 14.2.5 use ‘Per Protocol Population’ in header.4. Please make sure that Y-axis scale should be 0-3 for Schiff 
score 5) 1) Please make sure that Y-axis scale should be 0-80 g for tactile 
Schiff Sensitivity Score 
3 
2.5 
2 
1.5 
1 
TEST Product 
Negative Control 
Placebo Product 
0.5 
0 
0 
2 
4 
-0.5 
Timepoint 


GlaxoSmithKline Consumer Healthcare Confidential 
Page 47  of 47 
1.5% w/w dipotassium oxalate monohydrate (KOX) and 0 ppm fluoride oral rinse 
207656 
Final Statistical Reporting and Analysis plan V1.0 5 Oct 2017 
 
 
 
 
 
PPD 
 
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