A Clinical Study Investigating the Gingivitis Efficacy of a Stannous Fluoride Dentifrice in a Chinese Population.
Phase: NA
Conditions: Gingivitis
Sponsor: GlaxoSmithKline

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Clinical Protocol 
207014 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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 An unpublished work subject to trade secret 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. 

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CONFIDENTIAL 
 
SUMMARY INFORMATION 
 
 
 
Title: 
A Clinical Study Investigating the Gingivitis Efficacy 
of a Stannous Fluoride Dentifrice in a Chinese 
Population. 
Protocol Number: 
207014 
Sponsor: 
GlaxoSmithKline Consumer Healthcare (GSKCH; 
China) Co., Ltd 
23F, The Headquarters building, No. 168 Tibet Road 
(M), Shanghai, 200001 China 
Tel: 
Product Name: 
Dentifrice containing 0.454% w/w stannous fluoride 
and 0.0721% w/w sodium fluoride 
Development Phase: 
N/A 
PPD 
Expert Advice Outside of Normal 
Working Hours: 
PPD 
, DDS, PhD 
Tel: PPD 
Key Protocol Authors: 
PRIMARY CONTACT 
Clinical Study Manager: 
PPD 
, MSc 
PPD 
, BM, M.PHARM 
CH R&D China, GSK, 7th Floor, 168 
Mid. Xi Zang Road, Head quarter 
building, 200001 China 
Tel: PPD 
Clinical Research: 
PPD 
, PhD, BDS, MFDSRCS, 
MFGDP, FHEA 
GSKCH 
St. George’s Avenue, Weybridge, Surrey, 
KT13 0DE, United Kingdom (UK) 
Biostatistician: 
PPD 
, BSc, PhD 
GSKCH 
St. George’s Avenue, Weybridge, Surrey, 

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KT13 0DE, UK 
Clinical Supplies: 
PPD 
, BPharm, MSc 
GSKCH 
St. George’s Avenue, Weybridge, Surrey, 
KT13 0DE, UK 
 
 
 
Principal Investigator: 
Professor Feng Xiping, DDS, MSc 
Study Site Name & Address: 
Shanghai Ninth People’s Hospital, 
Shanghai Jiaotong University, School of 
Medicine, No. 639 Zhizaoju Road, 
Shanghai, 200011, China 
Study is conducted at: 
Room 105, 2nd Building, No. 427, Ju 
Men Road, Shanghai, 200023, China 
Study Site Telephone Number: 
86-21-23271699 
Study Examiner: 
Dr CR Goyal, BDS 
 
 
 
IND/ EUDRACT No: 
N/A 

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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: 
Professor Feng Xiping 
Investigator Qualifications: 
DDS, MSc 
Investigator Signature: 
PPD 
 
Date of Signature/ Agreement: 
PPD 
 
DD/MMM/YYYY 

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Table of Content 
SUMMARY INFORMATION ................................................. 2 
PRINCIPAL INVESTIGATOR PROTOCOL AGREEMENT 
PAGE ................................................................................. 4 
Table of Content ........................................................................ 5 
PROCESS FOR AMENDING THE PROTOCOL ................ 9 
PROTOCOL AMENDMENT PAGE ...................................... 10 
SCHEDULE OF EVENTS ....................................................... 12 
PROTOCOL SYNOPSIS FOR STUDY 207014 .................... 14 
1. INTRODUCTION ................................................................. 22 
2. OBJECTIVES AND ENDPOINTS ..................................... 24 
3. STUDY PLAN ........................................................................ 26 
3.1. Study Design ......................................................................... 26 
3.2. Subject Restrictions ............................................................. 29 
3.3. Type and Planned Number of Subjects ............................. 31 
3.4. Study Design and Dose Justification .................................. 31 
4. SELECTION OF STUDY POPULATION AND 
WITHDRAWAL CRITERIA ......................................... 34 
4.1. Inclusion Criteria ................................................................. 34 
4.2. Exclusion Criteria ................................................................ 36 
4.3. Screening/ Baseline Failures ............................................... 37 
4.4. Withdrawal/ Stopping Criteria .......................................... 38 
4.5. Subject Replacement ........................................................... 38 
4.6. Subject and Study Completion ........................................... 38 
5. PRODUCT INFORMATION .............................................. 39 

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5.1. Study Product ....................................................................... 39 
5.2. Dose Schedule ....................................................................... 40 
5.3. Dose Modification ................................................................ 40 
5.4. Product Compliance ............................................................ 40 
5.5. Precautions ........................................................................... 40 
5.6. Overdose ............................................................................... 41 
5.7. Rescue Therapy .................................................................... 41 
5.8. Product Assignment ............................................................. 41 
5.8.1 Randomization ..................................................................... 41 
5.8.2 Blinding ................................................................................ 42 
5.8.3 Code Breaks ......................................................................... 42 
5.9. Packaging and Labelling ..................................................... 42 
5.9.1. Accountability of Product .................................................. 43 
5.9.2. Storage of Product .............................................................. 43 
6. STUDY ASSESSMENTS AND PROCEDURES ............... 43 
6.1. Visit 1 - Screening Visit ....................................................... 43 
6.1.1 Telephone Screening ........................................................... 43 
6.1.2. Informed Consent ............................................................... 44 
6.1.3. Demographics ..................................................................... 44 
6.1.4. Medical History and Concomitant Medication ............... 44 
6.1.5. Urine Pregnancy Test ......................................................... 44 
6.1.6. Oral Soft & Hard Tissue Examination ............................. 45 
6.1.7. Gross Gingival Health Assessment ................................... 45 
6.2. Visits 2, 3 & 4........................................................................ 45 
6.2.1. Urine Pregnancy Test ......................................................... 45 
6.2.2. Oral Soft Tissue Examination (OST) ............................... 45 
6.2.3. Modified Gingival Index (MGI) Assessment (Lobene, 
1986) .................................................................................... 46 
6.2.4. Bleeding Index (BI) Assessment (Saxton, 1989) .............. 47 

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6.2.5. Plaque Index (PI) Assessment (Lobene, 1982) ................. 47 
6.2.6. Dental Prophylaxis ............................................................. 49 
6.2.7. Study Conclusion ................................................................ 49 
7. SAFETY ASSESSMENTS ................................................... 49 
7.1. Definitions of an Adverse Event and Serious Adverse 
Event ................................................................................... 49 
7.1.1. Adverse Events ................................................................... 50 
7.1.2. Serious Adverse Events ...................................................... 51 
7.2. Recording Adverse Events and Serious Adverse Events .52 
7.3. Evaluating Adverse Events and Serious Adverse Events 52 
7.4. Reporting Adverse Events and Serious Adverse Events..53 
7.5. Follow-up of Adverse Events and Serious Adverse Events 
..........................................................................................55 
7.6. Definition of and Procedure for Reporting Medical Device 
Incidents ............................................................................. 56 
7.6.1. Definition of an Incident .................................................... 56 
7.6.2. Reporting of Incidents and Malfunctions ........................ 56 
7.6.3. Follow-up of Incidents........................................................ 57 
7.7. Collection of Pregnancy Information ................................ 58 
7.7.1. Time Period for Collecting of Pregnancy Information ...58 
7.7.2. Action to be Taken if Pregnancy Occurs.......................... 58 
8. DATA MANAGEMENT ...................................................... 59 
8.1. Source Documents/ Data ..................................................... 59 
8.2. Electronic Case Report Form ............................................. 59 
8.3. Data Handling ...................................................................... 60 
8.3.1. Data Queries ....................................................................... 60 
8.4. Processing Patient Reported Outcomes ............................. 61 
9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES ....................................................................... 62 

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9.1 Sample Size Determination .................................................. 62 
9.2. General Considerations ....................................................... 62 
9.2.1. Definition of Analysis Populations .................................... 62 
9.2.2. Exclusion of Data from Analysis ....................................... 63 
9.2.3. Criteria for Evaluation ...................................................... 63 
9.2.4. Criteria for Assessing Efficacy .......................................... 63 
9.2.5. Criteria for Assessing Tolerability .................................... 63 
9.2.6. Handling of Dropouts and Missing Data .......................... 63 
9.3. Statistical Methods and Analytical Plan ............................ 63 
9.3.1. Demographic and Baseline Characteristics ..................... 63 
9.3.2. Primary Analysis ................................................................ 64 
9.3.3. Secondary Analyses ............................................................ 64 
9.3.4. Safety Analysis .................................................................... 65 
9.3.5. Repeatability Analysis ........................................................ 65 
10. STUDY GOVERNANCE CONSIDERATIONS.............. 65 
10.1. Posting of Information on Publicly Available Clinical 
Trials Registers .................................................................. 65 
10.2. Regulatory and Ethical Considerations, Including the 
Informed Consent.............................................................. 66 
10.3. Quality Control (Study Monitoring) ................................ 66 
10.4. Quality Assurance .............................................................. 67 
10.5. Conditions for Terminating the Study ............................ 67 
10.6. Records Retention .............................................................. 68 
10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials 
Registers and Publication ................................................. 69 
11. REFERENCES .................................................................... 70 
12. APPENDICES ..................................................................... 72 
12.1. Appendix 1 - Abbreviations and Trademarks ................ 72 

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PROCESS FOR AMENDING THE PROTOCOL 
Protocol modifications to ongoing studies which could potentially adversely affect the 
safety of subjects or which alter the scope of the investigation, the scientific quality of 
the study, the experimental design, dosages, duration of therapy, assessment 
variables, the number of subjects treated, or subject selection criteria are considered 
major/substantial amendments and must be made only after appropriate consultation 
between an appropriate representative of GSKCH and the investigator. 
 
Details of amendments to the protocols should be recorded on the following page. 
Protocol modifications must be prepared by a representative of GSKCH. All changes 
must be justified in the Reason for Amendment section of the following Protocol 
Amendment Page. Approval of amendments will be made by the original protocol 
signatories or their appropriate designees. 
 
All major/substantial protocol modifications must be reviewed and approved by the 
appropriate IRB/IEC in accordance with local requirements, before the revised 
edition can be implemented. 
 
All non-substantial/ minor/ administrative amendments should be submitted to the 
IRB/ 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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PROTOCOL AMENDMENT PAGE 
Details of all amendments should be recorded in the table below. Affected sections should be listed in the table; the actual 
amendment/ change should be made in the relevant section of the main protocol. 
To highlight the change, the following features will be used: 
To add text: Use of CAPITAL LETTERS, BOLD AND UNDERLINE 
To delete text: Use of Strikethrough e.g. strikethrough 
 
Amendment 
No. & New 
Protocol 
Version No. 
Type of Amendment 
Reason for Amendment 
Other 
Documents 
Requiring 
Amendment 
Section(s) Amended 
PI Amendment 
Agreement 
Signature & 
Date 
Amendment 
No.: 
1 
Non-Substantial/Minor 
This is Protocol amendment 
1 (Protocol version 5.0) as 
previous amendments (2.0, 
Informed 
Consent 
 Yes 
Safety 
Statement 
Yes 
 
CRF 
 Yes 
No 
No 
No 
Summary 
Information. 
Signature: 
PPD 
Protocol 
Version 
No.:
Substantial/ Major 
 
3.0 and 4.0) were made prior 
to Ethics submission. 
4.2 Exclusion 
Criteria 
Date: 
PPD 
5.0 
Ethics committee meeting
28Mar17 “approval after
modification” requesting
dental fluorosis addition and
clarification regarding
substance/ drug abuse within
the exclusion criteria. 
Change of Clinical Study
Manager details. 

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Amendment 
No.: 
Non-Substantial/Minor 
Informed 
Consent 
Yes 
No 
Safety 
Statement 
Yes 
No 
CRF 
Yes 
No 
Signature: 
PPD 
Protocol 
Version 
No.: 
Substantial/ Major 
Date: 
PPD 

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SCHEDULE OF EVENTS 
 
Procedure/Assessment 
Visit 1 
(Day -28 
to -1) 
1 – 28 days between Visit 1 and Visit 25 
Visit 2 
Week 0 
(Day 0)1 
Visit 3 
Week 6 
(Day 
42+/-3)1 
Visit 4 
Week 12 
(Day 
84+/-3)1 
Screening 
Baseline1 
Week 6 
Week 12 
Informed consent 
X 
Demographics 
X 
Medical History2 
X 
Current / Concomitant 
medication 
X 
X 
X 
X 
Urine pregnancy test6 
X 
X 
X 
X 
Oral soft and hard tissue 
(OST/OHT) examination3 
X 
Gross gingival assessment 
X 
Inclusion/ Exclusion Criteria 
X 
X 
Subject Eligibility/ Continuance 
X 
X 
X 
X 
Full OST examination 
X 
X 
X 
Modified Gingival Index (MGI), 
Bleeding Index (BI) & Plaque 
Index (PI; disclosing) 
X 
X 
X 
Stratification/ randomization 
X 
Sub- & supra-gingival 
prophylaxis and flossing (with 
second clinician check after 
disclosing & residual plaque 
removal, if applicable i.e. 
confirmed plaque score of zero) 
X 
Dispense study dentifrice, 
toothbrush, study instructions, 
diary & timer4 
X 
X 
Oral hygiene instruction review/ 
compliance checks including 
diary completion review 
X 
X 
X 
Supervised subject brushing at 
site 
X 
X 
Collect study dentifrice, 
toothbrush & diary 
X 
X 

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Compliance checks including 
diary review 
X 
X 
Optional dental prophylaxis 
X 
Adverse Events 
X 
X 
X 
Study Conclusion 
X 
 
1. Subjects will abstain from overnight toothbrushing for a minimum of 12hrs (+6hr, - 
2hr) immediately prior to the assessment visits (Visits 2, 3 & 4). 
2.  Including smoking status. 
3. In relation to the general dentition exclusion criteria. 
4. Timer only dispensed once, at visit 2 only. 
5. Subjects will be instructed to brush using their normal toothpaste and following 
their normal routine between screening and baseline visits. 
6. Female subjects of child bearing potential only. 

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PROTOCOL SYNOPSIS FOR STUDY 207014 
 
Brief Summary 
 
This will be a single-centre, examiner-blind, randomized, stratified, two-treatment, 
parallel group, clinical study in healthy adult volunteers with moderate gingivitis. 
Treatment effect will be determined by evaluating the efficacy, in a Chinese 
population, of a dentifrice containing 0.454% w/w stannous fluoride to control 
gingivitis and supra-gingival plaque following 6 and 12 weeks twice daily brushing, 
compared to a fluoride control dentifrice. During the 12 week treatment period, 
subjects will brush with their allocated study product twice daily. 
This clinical study will be conducted in China (Shanghai Ninth People’s Hospital 
Affiliated to Shanghai Jiaotong University School of Medicine) and will be funded by 
GlaxoSmithKline Consumer Healthcare (GSKCH). 
 
 
Objectives and Endpoints 
 
Objectives 
Endpoints 
Primary 
To compare gingivitis, as measured by BI, 
following twice daily use of an experimental 
0.454% w/w stannous fluoride dentifrice 
compared to a fluoride control dentifrice after 
12 weeks twice daily use. 
Mean BI at 12 weeks. 
Secondary 
To compare gingivitis, as measured by the 
number of bleeding sites using BI, following 
twice daily use of an experimental 0.454% 
w/w stannous fluoride dentifrice compared to 
a fluoride control dentifrice after 12 weeks 
twice daily use. 
Number of bleeding sites at 12 
weeks. 
To compare gingivitis, as measured by MGI, 
following twice daily use of an experimental 
0.454% w/w stannous fluoride dentifrice 
compared to a fluoride control dentifrice after 
12 weeks twice daily use. 
Mean MGI at 12 weeks. 
To compare dental plaque scores (PI; overall 
and interproximal) following twice daily use 
of an experimental 0.454% w/w stannous 
Mean PI (overall and interproximal) 
at 12 weeks. 

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fluoride dentifrice to a fluoride control 
dentifrice after 12 weeks twice daily use. 
Other 
To compare gingivitis, as measured by BI, 
following twice daily use of an experimental 
0.454% w/w stannous fluoride dentifrice 
compared to a fluoride control dentifrice after 
6 weeks twice daily use. 
Mean BI at 6 weeks. 
To compare gingivitis, as measured by the 
number of bleeding sites using BI, following 
twice daily use of an experimental 0.454% 
w/w stannous fluoride dentifrice compared to 
a fluoride control dentifrice after 6 weeks 
twice daily use. 
Number of bleeding sites at 6 weeks. 
To compare gingivitis, as measured by MGI, 
following twice daily use of an experimental 
0.454% w/w stannous fluoride dentifrice 
compared to a fluoride control dentifrice after 
6 weeks twice daily use. 
Mean MGI at 6 weeks. 
To compare dental plaque scores (PI; overall 
and interproximal) following twice daily use 
of an experimental 0.454% w/w stannous 
fluoride dentifrice to a fluoride control 
dentifrice after 6 weeks twice daily use. 
Mean PI (overall and interproximal) 
at 6 weeks. 
To evaluate and compare MGI and BI in low 
(<2.00) and high (>2.00) MGI subgroups 
following twice daily use of an experimental 
0.454% w/w stannous fluoride dentifrice after 
6 and 12 weeks twice daily use. 
Mean MGI & BI at 6 & 12 weeks (in 
subgroups). 
To evaluate examiner MGI & PI 
measurement reproducibility for a random 
subset of the study population. 
Kappa coefficient for MGI & PI 

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Study Design 
 
Overall Design 
This will be a single-centre, examiner-blind, randomized, stratified, two-treatment, 
parallel group, clinical study in healthy adult volunteers with moderate gingivitis. 
There will be four visits to the study site: Screening, Baseline, 6 Week and 12 Week. 
Gingivitis will be assessed using a Modified Gingival Index (MGI; Lobene, 1986) 
and a Bleeding Index (BI; Saxton, 1989). Plaque will be assessed by the Turesky 
modification of the Quigley & Hein Plaque Index (PI; Lobene, 1982). 
At the Screening visit (Visit 1), subjects will give their written informed consent to 
participate in the study. Demographics, medical history, current and concomitant 
medications will be recorded, followed by an oral examination and a gingival 
assessment. Pregnancy testing will be carried out on all female subjects of child 
bearing potential at each visit. This will include full oral soft tissue (OST) and oral 
hard tissue (OHT) examinations, including dentition exclusions and gingival status. 
Subjects will be instructed to brush using their normal toothpaste and following their 
normal routine between screening and baseline. 
Within 1-28 days of Screening (Visit 1), eligible subjects will return to the site for the 
Baseline visit (Visit 2) with overnight plaque (subjects will abstain from oral hygiene 
for 12hrs (+6hr, -2hr) i.e. overnight immediately before the visit). At the Baseline 
visit, subjects will undergo, in the following order, a full OST examination and 
assessments of gingival inflammation (MGI followed by BI), and supra-gingival 
plaque (PI). 
Subjects with a suitable number of gradable teeth, with a mean overall MGI score 
between 1.75-2.30 and mean overall PI score >1.5 will continue in the study. Subjects 
with a mean overall MGI or PI scores outside the study range will be discontinued 
from the study at this visit. To control inter-examiner variability, the same suitably 
qualified examiner will be used throughout the study for each of the measures. The 
same examiner can perform more than one assessment but the same examiner must 
perform each of these assessments for all subjects throughout the study. 
Subjects will be instructed to abstain from toothbrushing for a minimum of 12hrs 
(+6hr, -2hr) i.e. overnight immediately before each assessment visit. At the Baseline 
visit subjects will undergo a baseline oral soft tissue (OST) assessment, MGI 
followed by a BI followed by dental plaque (PI) assessment (assessments must occur 
in the order written) for all teeth meeting the inclusion criteria. Following the MGI & 
BI assessments, and after rinsing with 20ml of water, subjects will rinse their mouth 

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with disclosing solution before receiving a dental plaque assessment. 
Eligible subjects will be stratified based on gender (male/ female), smoking status 
(yes/ no) and baseline mean overall MGI score (low: <2.00; high >2.00) to ensure a 
balance in treatments across the strata, and then randomized into one of two treatment 
groups. Dental prophylaxis will be performed by a suitably qualified member of site 
staff for each subject using a standard dental prophylaxis paste followed by flossing 
by the examiner.  Subject’s teeth will be disclosed using a disclosing solution to 
check for residual plaque. A second clinician will check to ensure all plaque has been 
removed. Any residual plaque & calculus remaining will be removed by the second 
clinician by dental polishing with a standard dental prophylaxis paste, to bring the 
subject to a confirmed score of zero visible plaque (PI=0). 
Following dental prophylaxis, subjects will receive their assigned study dentifrice, a 
diary, a toothbrush, a timer and instructions on product usage and diary completion. 
Subjects will brush their teeth with their allocated dentifrice, in their usual manner for 
one timed minute, under supervision. Subjects will continue to brush twice daily 
(morning and evening) for one timed minute recording each brushing on their study 
diary. 
After using the study dentifrice twice daily for one timed minute at home for 6 and 12 
weeks, subjects will return to the study site (Visits 3 and 4, respectively) having 
abstained from oral hygiene for 12hrs (+6hr, -2hr) i.e. from overnight immediately 
before each assessment visit, if possible at approximately the same time of day as the 
baseline visit. The study dentifrice will be collected and the diary reviewed for 
treatment compliance. Pregnancy testing will be carried out on all female subjects of 
child bearing potential at each visit. Subjects will have a full OST examination and 
then undergo, in the following order, MGI, BI followed by PI assessments after 
disclosing. At Visit 3, subjects will receive another supply of assigned study 
toothpaste, a new toothbrush and diary. At Visit 4, subjects will return all study 
materials and have a dental prophylaxis if deemed appropriate by the investigator or 
examiner. 
At Visits 2, 3, 4, repeatability data will be generated for MGI & PI assessments from 
replicate examinations on the same subject. Depending on subject visit scheduling, 
every effort will be made to complete one repeatability examination for each clinical 
measure during each clinical session, that is, one in the morning and one in the 
afternoon on each assessment day. Repeatability examinations will be separated by a 
minimum of 10 minutes and, where possible, separated by another subject. Replicate 
BI examinations will not be performed. 

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Visit 1 - Screening Visit 
The following assessments will be conducted: 
• Informed consent 
• Demographics, medical history, current / concomitant medication, & smoking 
status. 
• Urine pregnancy testing will be carried out on all female subjects of child 
bearing potential. 
• Oral soft & hard tissue (OST/OHT) examination 
• Gross gingival assessment 
• Inclusion/exclusion criteria 
• Subject eligibility / continuance 
• Subjects will be instructed to brush using their normal toothpaste and 
following their normal routine between screening and baseline visits. 
Visit 2 - Baseline Visit; Day 0 
The following assessments will be conducted: 
• Review of current/concomitant medications, adverse events 
• Urine pregnancy testing will be carried out on all female subjects of child 
bearing potential. 
• Full OST examination 
• MGI 
• BI 
• PI (following plaque disclosure) 
• Inclusion/exclusion criteria 
• Subject eligibility / continuance 
• Stratification/randomization 
• Sub- & supra-gingival prophylaxis & flossing (with second clinician check 
after disclosing & residual plaque removal, if applicable) 
• Confirmed plaque score of 0 by second clinician following dental prophylaxis. 
• Dispense study dentifrice, toothbrush, study instructions, diary & timer 
• Oral hygiene instruction review / compliance checks including diary 
completion review with subject 
• Supervised subject brushing at site 
• Adverse events 
Visit 3 - Week 6; Day 42+/-3 
The following assessments will be conducted: 
• Review of current/concomitant medications, adverse events 
• Compliance checks including diary review 
• Urine pregnancy testing will be carried out on all female subjects of child 
bearing potential. 

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• Subject eligibility / continuance 
• Full OST examination 
• MGI 
• BI 
• PI (following plaque disclosure) 
• Collect study dentifrice, toothbrush & diary 
• Dispense study dentifrice, toothbrush, study product usage instructions, diary 
& timer 
• Oral hygiene instruction review / compliance checks including diary 
completion review with subject 
• Supervised subject brushing at site 
• Adverse events 
Visit 4 – Week 12; Day 84+/-3 
The following assessments will be conducted: 
• Review of current/concomitant medications, adverse events 
• Compliance checks including diary review 
• Urine pregnancy testing will be carried out on all female subjects of child 
bearing potential. 
• Subject eligibility / continuance 
• Full OST examination 
• MGI 
• BI 
• PI (following plaque disclosure) 
• Collect study dentifrice, toothbrush & diary 
• Oral hygiene instruction review / compliance checks including diary 
completion review with subject 
• Complete optional second dental prophylaxis (if deemed necessary by the 
examiner) 
• Adverse events 
• Study conclusion 
 
 
Type and Planned Number of Subjects 
 
A sufficient number of subjects will be screened to randomize at least 120 subjects to 
ensure approximately112 evaluable subjects complete the entire study (approximately 
56 per treatment group). 
With approximately 56 subjects per treatment group, the study has at least 80% power 
to detect a treatment difference of 0.08 in bleeding index over a period of 12 weeks 

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treatment. The standard deviation used in calculation is 0.14. The difference of 0.08 
represents more than 15% improvement in the test dentifrice compared to the fluoride 
control dentifrice reference product. CCI 
 
 
 
 
Diagnosis and Main Criteria for Inclusion 
 
Healthy adult subjects, aged 18 to 65 years, with moderate gingivitis at screening 
visit, with baseline overall mean MGI score between 1.75-2.30 and PI > 1.5 (for all 
eligible teeth in agreement with the inclusion/ exclusion criteria), minimum 20 
permanent natural teeth and with a minimum of 40 gradable surfaces free of 
irregularities and discoloration. 
 
Product Information 
 
Test Product 
Reference Product 
Product Name 
Experimental dentifrice 
containing 0.454% w/w 
stannous fluoride & 0.0721% 
w/w sodium fluoride (1450ppm 
fluoride in total) 
Regular fluoride dentifrice 
containing 0.14% w/w sodium 
monofluorophosphate – 
Colgate® Triple Protection 
Dentifrice (1400ppm fluoride as 
sodium monofluorophosphate; 
SMFP) 
Product 
Formulation 
Code (MFC) 
CCI 
Commercially available 
(Chinese marketplace) 
Dose 
Full ribbon of dentifrice to 
cover the head of the study 
toothbrush provided 
Full ribbon of dentifrice to cover 
the head of the study toothbrush 
provided 
Route of 
Administration 
Oral topical 
Oral topical 
Dosing 
Instructions 
Subjects will apply a full strip 
of dentifrice to cover the head 
of the toothbrush provided and 
brush their teeth with the 
assigned dentifrice twice daily 
(morning and evening) for one 
timed minute following their 
normal routine. 
Subjects will apply a full strip of 
dentifrice to cover the head of 
the toothbrush provided and 
brush their teeth with the 
assigned dentifrice twice daily 
(morning and evening) for one 
timed minute following their 
normal routine. 

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Statistical Methods 
 
BI score, MGI score and overall plaque score will be calculated as the average index 
values over all sites. Interproximal plaque score will be calculated as the average 
index values over all interproximal sites. Number of bleeding sites will be calculated 
as the number of sites with BI 1 or 2. 
 
BI score, number of bleeding sites, overall plaque score and interproximal plaque 
score will be analysed using ANCOVA with treatment, gender, smoking status and 
baseline MGI stratification as factors and baseline score as covariate. Adjusted means 
of two treatments and treatment difference will be provided together with 95%CI and 
P-values. 
 
MGI score will be analysed using ANCOVA with treatment, gender and smoking 
status as factors and baseline score as covariate. Baseline MGI stratification will not 
be included in the model since baseline MGI score is already included as covariate. 
Adjusted means of two treatments and treatment difference with be provided together 
with 95%CI and P-values. 
 
Assumptions in ANCOVA analyses will be checked. If violated, data transformations 
or nonparametric methods will be used. 

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1. INTRODUCTION 
Gingivitis is a reversible inflammation of the periodontal tissues surrounding the  
tooth in response to the presence of dental plaque (Kinane et al. 2001). Gingivitis is 
reported to have a high prevalence worldwide as recognized by large population 
surveys (Albandar et al. 2002) and the World Health Organisation (Petersen  & 
Ogawa 2012). 
 
Plaque-induced gingivitis is a reversible condition that can be managed or prevented 
with regular effective oral hygiene (Brook et al. 2003; Ower et al. 2003) which is 
important not only in maintaining health and managing the signs and symptoms of 
gingivitis, but also to prevent the development of periodontitis (Kinane & Attstr1m 
2005). Approaches to the prevention and treatment of gingivitis are essentially two- 
fold including mechanical cleaning along with the use of an antibacterial mouthrinse 
(Chapple et al. 2015). 
 
The addition of antimicrobial ingredients to a dentifrice will further complement the 
mechanical removal by helping to inhibit the growth of bacterial plaque from sites in 
the mouth that are less accessible to mechanical removal and/or prevent subsequent 
re-colonisation of dental plaque bacteria. Antimicrobial agents have  been 
incorporated into dentifrices for many years with a view to delivering plaque control 
and periodontal benefits (Cummins et al. 1992). The stannous ion is a well known 
chemotherapeutic agent that has been used in dentifrices as stannous fluoride since  
the 1940’s (van Loveren et al. 1990, 2001; Miller et al. 1994; Makin 2013). Stannous 
fluoride is a broad-spectrum antimicrobial agent that has been shown to inhibit and 
reduce bacterial biomass, virulence and metabolism (Tinanoff et al. 1990). 
 
Clinically, the effects of stannous fluoride containing dentifrices (at a concentration  
of between 0.4-0.454% w/w) on gingivitis have been described in numerous clinical 
studies demonstrating that using a low water content, stabilized 0.454% w/w stannous 
fluoride dentifrice twice daily for 24 weeks resulted in 20.5% less gingivitis (P<0.05) 
and 33.4% less bleeding (P<0.05) when compared with a negative control (Perlich et 
al. 1995; Paraskevas et al. 2006). An additional study reported that subject’s who  
used a low water content, stabilized stannous fluoride dentifrice twice daily for 24 
weeks showed a statistically significant reduction in plaque when compared with a 
negative control dentifrice (Williams et al. 1997). In three other 24 week 
plaque/gingivitis clinical studies a 0.454% w/w low water content, stabilized stannous 
fluoride dentifrice exhibited statistically significant >20% plaque reduction compared 
with a negative control (Mankodi et al. 1997, 2005; Mallatt et al. 2007). 
 
The literature reports that the largest reductions in gingivitis are observed following 
the use of “stabilized” stannous fluoride dentifrice formulations (Tinanoff et  al. 
1990).  The  stannous  fluoride  formulation  to  be  evaluated  in  this  study  has been 

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stabilized   by   employing   non-aqueous  excipients. CCI 
 
 
 
 
 
 
 
 
Furthermore an additional study was currently 
reported (GSKCH 205045) investigating the efficacy of a 0.454% w/w stannous 
fluoride dentifrice to control gingivitis in subjects who demonstrate blood in 
toothpaste expectorate, showing significant improvements in measures of gingivitis 
(number of bleeding sites, BI and MGI) following 4 and 12 weeks of twice daily use 
compared to a reference control dentifrice. Whilst there is a well proven data  
package, GSK are investigating the effect of stannous fluoride in the wider worldwide 
population. 
 
The aim of this clinical study is to evaluate the efficacy of a 0.454% w/w stannous 
fluoride dentifrice compared to a reference control to control gingivitis (gingival 
bleeding and visual signs of gingival inflammation) in dentally and periodontally 
healthy adult volunteers over 12 weeks’ use in a Chinese population. 

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2. OBJECTIVES AND ENDPOINTS 
 
Objectives 
Endpoints 
Primary 
To compare gingivitis, as measured by BI, 
following twice daily use of an experimental 
0.454% w/w stannous fluoride dentifrice 
compared to a fluoride control dentifrice after 
12 weeks twice daily use. 
Mean BI at 12 weeks. 
Secondary 
To compare gingivitis, as measured by the 
number of bleeding sites using BI, following 
twice daily use of an experimental 0.454% 
w/w stannous fluoride dentifrice compared to 
a fluoride control dentifrice after 12 weeks 
twice daily use. 
Number of bleeding sites at 12 
weeks. 
To compare gingivitis, as measured by MGI, 
following twice daily use of an experimental 
0.454% w/w stannous fluoride dentifrice 
compared to a fluoride control dentifrice after 
12 weeks twice daily use. 
Mean MGI at 12 weeks. 
To compare dental plaque scores (PI; overall 
and interproximal) following twice daily use 
of an experimental 0.454% w/w stannous 
fluoride dentifrice to a fluoride control 
dentifrice after 12 weeks twice daily use. 
Mean PI (overall and interproximal) 
at 12 weeks. 
Other 
To compare gingivitis, as measured by BI, 
following twice daily use of an experimental 
0.454% w/w stannous fluoride dentifrice 
compared to a fluoride control dentifrice after 
6 weeks twice daily use. 
Mean BI at 6 weeks. 
To compare gingivitis, as measured by the 
number of bleeding sites using BI, following 
twice daily use of an experimental 0.454% 
w/w stannous fluoride dentifrice compared to 
a fluoride control dentifrice after 6 weeks 
twice daily use. 
Number of bleeding sites at 6 weeks. 
To compare gingivitis, as measured by MGI, 
following twice daily use of an experimental 
0.454% w/w stannous fluoride dentifrice 
compared to a fluoride control dentifrice after 
Mean MGI at 6 weeks. 

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6 weeks twice daily use. 
To compare dental plaque scores (PI; overall 
and interproximal) following twice daily use 
of an experimental 0.454% w/w stannous 
fluoride dentifrice to a fluoride control 
dentifrice after 6 weeks twice daily use. 
Mean PI (overall and interproximal) 
at 6 weeks. 
To evaluate and compare MGI and BI in low 
(<2.00) and high (>2.00) MGI subgroups 
following twice daily use of an experimental 
0.454% w/w stannous fluoride dentifrice after 
6 and 12 weeks twice daily use. 
Mean MGI & BI at 6 & 12 weeks (in 
subgroups). 
To evaluate examiner MGI & PI 
measurement reproducibility for a random 
subset of the study population. 
Kappa coefficient for MGI & PI 

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3. STUDY PLAN 
3.1. Study Design 
 
Overall Design 
This will be a single-centre, examiner-blind, randomized, stratified, two-treatment, 
parallel group, clinical study in healthy adult volunteers with moderate gingivitis. 
There will be four visits to the study site: Screening, Baseline, 6 Week and 12 Week. 
Gingivitis will be assessed using a Modified Gingival Index (MGI; Lobene, 1986) 
and a Bleeding Index (BI; Saxton, 1989). Plaque will be assessed by the Turesky 
modification of the Quigley & Hein Plaque Index (PI; Lobene, 1982). 
At the Screening visit (Visit 1), subjects will give their written informed consent to 
participate in the study. Demographics, medical history, current and concomitant 
medications will be recorded, followed by an oral examination and a gingival 
assessment. Pregnancy testing will be carried out on all female subjects of child 
bearing potential at each visit. This will include full oral soft tissue (OST) and oral 
hard tissue (OHT) examinations, including dentition exclusions and gingival status. 
Subjects will be instructed to brush using their normal toothpaste and following their 
normal routine between screening and baseline. 
Within 1-28 days of Screening (Visit 1), eligible subjects will return to the site for the 
Baseline visit (Visit 2) with overnight plaque (subjects will abstain from oral hygiene 
for 12hrs (+6hr, -2hr) i.e. overnight immediately before the visit). At the Baseline 
visit, subjects will undergo, in the following order, a full OST examination and 
assessments of gingival inflammation (MGI followed by BI), and supra-gingival 
plaque (PI). 
Subjects with a suitable number of gradable teeth, with a mean overall MGI score 
between 1.75-2.30 and mean overall PI score >1.5 will continue in the study. Subjects 
with a mean overall MGI or PI scores outside the study range will be discontinued 
from the study at this visit. To control inter-examiner variability, the same suitably 
qualified examiner will be used throughout the study for each of the measures. The 
same examiner can perform more than one assessment but the same examiner must 
perform each of these assessments for all subjects throughout the study. 
Subjects will be instructed to abstain from toothbrushing for a minimum of 12hrs 
(+6hr, -2hr) i.e. overnight immediately before each assessment visit. At the Baseline 
visit subjects will undergo a baseline oral soft tissue (OST) assessment, MGI 

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followed by a BI followed by dental plaque (PI) assessment (assessments must occur 
in the order written) for all teeth meeting the inclusion criteria. Following the MGI & 
BI assessments, and after rinsing with 20ml of water, subjects will rinse their mouth 
with disclosing solution before receiving a dental plaque assessment. 
Eligible subjects will be stratified based on gender (male/ female), smoking status 
(yes/ no) and baseline mean overall MGI score (low: <2.00; high >2.00) to ensure a 
balance in treatments across the strata, and then randomized into one of two treatment 
groups. Dental prophylaxis will be performed by a suitably qualified member of site 
staff for each subject using a standard dental prophylaxis paste followed by flossing 
by the examiner.  Subject’s teeth will be disclosed using a disclosing solution to 
check for residual plaque. A second clinician will check to ensure all plaque has been 
removed. Any residual plaque & calculus remaining will be removed by the second 
clinician by dental polishing with a standard dental prophylaxis paste, to bring the 
subject to a confirmed score of zero visible plaque (PI=0). 
Following dental prophylaxis, subjects will receive their assigned study dentifrice, a 
diary, a toothbrush, a timer and instructions on product usage and diary completion. 
Subjects will brush their teeth with their allocated dentifrice, in their usual manner for 
one timed minute, under supervision. Subjects will continue to brush twice daily 
(morning and evening) for one timed minute recording each brushing on their study 
diary. 
After using the study dentifrice twice daily for one timed minute at home for 6 and 12 
weeks, subjects will return to the study site (Visits 3 and 4, respectively) having 
abstained from oral hygiene for 12hrs (+6hr, -2hr) i.e. from overnight immediately 
before each assessment visit, if possible at approximately the same time of day as the 
baseline visit. The study dentifrice will be collected and the diary reviewed for 
treatment compliance. Pregnancy testing will be carried out on all female subjects of 
child bearing potential at each visit. Subjects will have a full OST examination and 
then undergo, in the following order, MGI, BI followed by PI assessments after 
disclosing. At Visit 3, subjects will receive another supply of assigned study 
toothpaste, a new toothbrush and diary. At Visit 4, subjects will return all study 
materials and have a dental prophylaxis if deemed appropriate by the investigator or 
examiner. 
At Visits 2, 3, 4, repeatability data will be generated for MGI & PI assessments from 
replicate examinations on the same subject. Depending on subject visit scheduling, 
every effort will be made to complete one repeatability examination for each clinical 
measure during each clinical session, that is, one in the morning and one in the 

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afternoon on each assessment day. Repeatability examinations will be separated by a 
minimum of 10 minutes and, where possible, separated by another subject. Replicate 
BI examinations will not be performed. 
Visit 1 - Screening Visit 
The following assessments will be conducted: 
• Informed consent 
• Demographics, medical history, current / concomitant medication, & smoking 
status. 
• Urine pregnancy testing will be carried out on all female subjects of child 
bearing potential. 
• Oral soft & hard tissue (OST/OHT) examination 
• Gross gingival assessment 
• Inclusion/exclusion criteria 
• Subject eligibility / continuance 
• Subjects will be instructed to brush using their normal toothpaste and 
following their normal routine between screening and baseline visits. 
Visit 2 - Baseline Visit; Day 0 
The following assessments will be conducted: 
• Review of current/concomitant medications, adverse events 
• Urine pregnancy testing will be carried out on all female subjects of child 
bearing potential. 
• Full OST examination 
• MGI 
• BI 
• PI (following plaque disclosure) 
• Inclusion/exclusion criteria 
• Subject eligibility / continuance 
• Stratification/randomization 
• Sub- & supra-gingival prophylaxis & flossing (with second clinician check 
after disclosing & residual plaque removal, if applicable) 
• Confirmed plaque score of 0 following dental prophylaxis. 
• Dispense study dentifrice, toothbrush, study instructions, diary & timer 
• Oral hygiene instruction review / compliance checks including diary 
completion review with subject 
• Supervised subject brushing at site 
• Adverse events 
Visit 3 - Week 6; Day 42+/-3 
The following assessments will be conducted: 

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• Review of current/concomitant medications, adverse events 
• Compliance checks including diary review 
• Urine pregnancy testing will be carried out on all female subjects of child 
bearing potential. 
• Subject eligibility / continuance 
• Full OST examination 
• MGI 
• BI 
• PI (following plaque disclosure) 
• Collect study dentifrice, toothbrush & diary 
• Dispense study dentifrice, toothbrush, study instructions, diary & timer 
• Oral hygiene instruction review / compliance checks including diary 
completion review with subject 
• Supervised subject brushing at site 
• Adverse events 
Visit 4 - Week 12; Day 84+/-3 
The following assessments will be conducted: 
• Review of current/concomitant medications, adverse events 
• Compliance checks including diary review 
• Urine pregnancy testing will be carried out on all female subjects of child 
bearing potential. 
• Subject eligibility / continuance 
• Full OST examination 
• MGI 
• BI 
• PI (following plaque disclosure) 
• Collect study dentifrice, toothbrush & diary 
• Oral hygiene instruction review / compliance checks including diary 
completion review with subject 
• Complete optional second dental prophylaxis (as/ if deemed necessary by 
examiner) 
• Adverse events 
• Study conclusion 
 
3.2. Subject Restrictions 
 
Lifestyle/ Dietary 
The following lifestyle restrictions apply for the duration of the study: 

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Screening to study completion: 
• Subjects should abstain from chewing gum and consuming confectionery 
containing xylitol (e.g. mints). 
• Subjects should abstain from interproximal cleaning (use of dental floss, 
waterpick and toothpicks). Use of toothpicks is permitted to remove impacted 
food only. 
Baseline/Randomization, 6 and 12 week visits: 
• Subjects should only use the dentifrice and toothbrushes provided and must 
abstain from use of all other oral hygiene products including mouthwash from 
the baseline visit. 
• Subjects must abstain from using oral hygiene products for 12hrs (+6hr, -2hr) 
i.e. overnight immediately before an assessment visit and until the visit is 
complete. 
• Subjects must abstain from eating (and smoking where necessary) for at least 
4 hours, and from drinking for at least 1 hour prior to all clinical assessments 
and until all assessments are complete. 
Medications and Treatments 
The following lifestyle restrictions apply for the duration of the study: 
• If current/concomitant medications and/or treatments are used during the 
study, their identity, as well as their dosage and frequency, start and stop dates 
must be reported to the Investigator and recorded in the CRF. Should a 
randomized subject embark on a course of treatment during the study which 
includes a prohibited medication, the identity of that medication/treatment, 
dosage and frequency and start date will be recorded. The subject will not be 
withdrawn. 
• Subjects may not take any of the medications prohibited in the exclusion 
criteria (as directed in the section). In addition, the subjects are to refrain from 
the use of any over-the-counter anti-inflammatory products or traditional 
Chinese medicines (TCM) which are not permitted within 2 weeks prior to 
any gingival examination and throughout the study following the baseline 
examination. 
• Subjects will be requested to not have any elective dental procedures other 
than those performed within the study (excluding emergency dental 
treatment). 
• Subjects will not be able to receive a dental prophylaxis (except that 
administered by the site), or use any professional or over-the-counter 
whiteners or antimicrobial mouthrinses during the course of the study. 

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3.3. Type and Planned Number of Subjects 
 
A sufficient number of subjects will be screened to randomize at least 120 subjects to 
ensure approximately112 evaluable subjects complete the entire study (approximately 
56 per treatment group). 
 
3.4. Study Design and Dose Justification 
 
This will be a single-center, examiner-blind, randomized, stratified (by gender, 
smoking status, baseline mean overall MGI value), two-treatment, parallel group, 
clinical study in healthy adult volunteers with moderate gingivitis. There will be four 
visits to the study site: Screening, Baseline, 6 Week, and 12 Week. Gingivitis will be 
assessed using a MGI (Lobene, 1986) and a BI (Saxton, 1989). Plaque will be 
assessed by the Turesky modification of the Quigley Hein PI (Lobene, 1982). All 
evaluable teeth (in relation to the inclusion/ exclusion general dentition criteria) will 
be assessed. 
 
This clinical study design has been chosen as this is recommended by the dental 
research communities and is consistent with the “Efficacy evaluation of toothpaste 
guidelines” of Health Industrial Standard of the People’s Republic of China 
guidelines for such studies. The study will be blinded with respect to the dental 
examiner. 
 
A parallel group design has been selected as more appropriate for this investigation. 
The dosage regimen of twice daily use (morning and evening) will be the same for 
each treatment and is based on consumer habit and common practice within oral care 
clinical trials. 
 
According to the International Conference on Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for Human Use (ICH) guidelines, 
for a study to be classified 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 as to the treatment the subject receives, but 
the products under test must be identical in every way (color, flavor, appearance, 
packaging). Given it is almost impossible to ensure identical appearance, taste and 
packaging for the dentifrices evaluated in oral care studies, the level of blindness for 
this study is described as ‘examiner blind’ only.  The same examiner will be used 

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throughout the study for each clinical index to eliminate the possibility of inter- 
examiner variability. 
 
At the Screening visit (Visit 1), subjects will give their written informed consent to 
participate in the study. Demographics, medical history, current and concomitant 
medications will be recorded, followed by an oral examination and a gingival 
assessment. This will include an OST and OHT examination, dentition exclusions and 
gingival status. 
 
Within 1 to 28 days of Screening (Visit 1), eligible subjects will return to the site for 
the Baseline visit (Visit 2) with overnight plaque (subjects will abstain from oral 
hygiene for 12hrs (+6hr, -2hr) i.e. overnight immediately before the visit). At the 
Baseline visit, subjects will undergo, in the following order, a full OST examination 
and assessments of gingival inflammation (MGI), gingival bleeding (BI) and supra- 
gingival plaque (PI).  Subjects with a mean whole mouth MGI score between 1.75 – 
2.30 and mean whole mouth PI score ≥1.5 will continue in the study. Subjects with 
mean MGI or PI scores outside the study range will be discontinued from the study at 
this visit. To control inter-examiner variability, the same examiner will be used 
throughout the study. 
 
Eligible subjects will be stratified based on gender, smoking status and baseline mean 
whole mouth MGI score (Low: ≤2.00/High >2.00), to ensure a balance of treatments 
within the strata, and then randomized into one of two treatment groups. Healthy 
subjects with moderate gingivitis will be stratified according to their gender, smoking 
status and baseline mean overall MGI to ensure a balance in gender, smoking status 
and gingival health across both treatment groups. Gender & smoking are known 
modifiers of the initiation and outcome of conditions related to gingival health (Alam, 
2012).  Stratifying by MGI will also facilitate evaluation of gingivitis (BI and MGI) 
in low and high MGI subgroups. 
 
Dental prophylaxis will be performed for each subject using a conventional non- 
fluoride dental prophylaxis paste followed by flossing. Subject’s teeth will be 
disclosed using a disclosing solution to check for residual plaque. A second clinician 
will check to ensure all plaque has been removed.  Any residual plaque remaining 
will be removed by the second clinician by dental polishing with a standard polishing 
dental compound, to bring the subject to a confirmed zero plaque score PI=0). 
 
Following dental prophylaxis, subjects will receive their assigned study dentifrice, a 
diary, a toothbrush, a timer and instructions on product usage and diary completion. 
Subjects will brush their teeth with their allocated dentifrice, in their usual manner for 

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one timed minute, under supervision. Subjects will continue to brush twice daily 
(morning and evening) for one timed minute and record on their study diary 
completed brushings. 
 
After using the study dentifrice for 6 and 12 weeks, subjects will return to the study 
site (Visits 3 and 4, respectively) with overnight plaque (subjects will abstain from 
overnight toothbrushing for 12hrs (+6hr, -2hr) immediately before each assessment 
visit), if possible at approximately the same time of day as the baseline visit.  The 
study dentifrice will be collected and the diary reviewed for treatment compliance. 
Subjects will have a full OST examination and then undergo, in the following order, 
MGI, BI and PI assessments. At Visit 3, subjects will receive another supply of 
assigned study toothpaste, a new toothbrush and diary. At Visit 4, subjects will return 
all study materials and have a dental prophylaxis if deemed appropriate by the 
investigator or examiner. 
 
At Visits 2, 3, 4, repeatability data will be generated for MGI and PI assessments 
from replicate examinations on the same subject. Depending on subject visit 
scheduling, every effort will be made to complete one repeatability examination for 
each clinical measure during each clinical session, that is, one in the morning and one 
in the afternoon on each assessment day.  Repeatability examinations will be 
separated by a minimum of 10 minutes and, where possible, separated by another 
subject.  Replicate BI examinations will not be carried out. 
 
The dosing regimen of twice daily brushing with a brush length of toothpaste will be 
the same for each treatment and is based on consumer habit and common practice 
within oral care clinical trials. Subjects will apply a full ribbon of dentifrice to the 
study toothbrush and brush their teeth in their usual manner for one timed minute 
twice daily (morning and evening). Subjects will brush their teeth for one timed 
minute twice daily for 12 weeks, once in the morning and once in the evening. No 
dose modification is permitted in this study. Any variation from the brushing 
instructions should be communicated to study site personnel and recorded as a 
deviation on the CRF. 

Page 34 of 73 
 
 
Document Name 
207014 protocol 
Type 
Version 
Document Identifier 
Effective Date 
eldo_clinical_doc 
5.0; Most-Recent; Effective; CURRENT 
090032d580d1fee8 
05-Apr-2017 13:38:03 
Reason For Issue 
Auto Issue 
 
 
 
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. 
 
Deviations from inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability or 
subject safety. Therefore, adherence to the criteria as specified in the protocol is 
essential. 
4.1. Inclusion Criteria 
A subject will be eligible for inclusion in this study only if all of the following criteria 
apply: 
 
1. CONSENT 
Demonstrates understanding of the study procedures, restrictions and willingness to 
participate as evidenced by voluntary written informed consent and has received a 
signed and dated copy of the informed consent form. 
 
 
2. AGE 
Aged 18 to 65 years. 
 
 
3. COMPLIANCE 
Understands and is willing, able and likely to comply with all study procedures and 
restrictions. 
 
 
4. GENERAL HEALTH 
Good general and mental health with, in the opinion of the investigator or medically 
qualified designee: 
a. No clinically significant and relevant abnormalities in medical history or upon 
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. 

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5.0; Most-Recent; Effective; CURRENT 
090032d580d1fee8 
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Reason For Issue 
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5. DENTAL HEALTH 
a. A minimum of 20 natural teeth (all teeth; incisors, canines, pre-molars & 
molars), and a minimum of 40 gradable surfaces for MGI, BI and PI. A 
scorable surface is defined as a surface that has 50% of the surface gradable 
for each clinical index. Third molars, orthodontically banded/bonded, fully 
crowned or extensively restored or grossly carious teeth are not included in 
the tooth count. 
b. Moderate gingivitis present at the screening visit (in the opinion of the clinical 
examiner from a gross visual examination). 
c. Mean whole mouth MGI between 1.75 and 2.30 and a mean overall PI score 
>1.5 at Baseline visit. 

Page 36 of 73 
 
 
Document Name 
207014 protocol 
Type 
Version 
Document Identifier 
Effective Date 
eldo_clinical_doc 
5.0; Most-Recent; Effective; CURRENT 
090032d580d1fee8 
05-Apr-2017 13:38:03 
Reason For Issue 
Auto Issue 
 
 
 
4.2. Exclusion Criteria 
 
A subject will not be eligible for inclusion in this study if any of the following criteria 
apply: 
 
1. PREGNANCY 
Women who are known to be pregnant or who are intending to become pregnant over 
the duration of the study (including women who have a positive urine pregnancy test; 
pregnancy testing will be carried out for all female subjects who are of child bearing 
potential). 
 
 
2. BREAST-FEEDING 
Women who are 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. 
 
 
4. CONCURRENT MEDICATION 
Screening: 
a. Currently taking antibiotics or requiring antibiotic use prior to dental 
prophylaxis or other dental procedures. 
b. Currently taking an anti-inflammatory medication or traditional Chinese 
medicines (TCM) which, in the opinion of the Investigator, could affect 
gingival condition. 
c. Currently taking a systemic medication which, in the opinion of the 
Investigator, could affect gingival condition (e.g. calcium channel blockers, or 
aspirin therapy). 
Baseline (Visit 2): 
d. Has taken, or currently taking, antibiotics in the previous 14 days. 
e. Has taken, or currently taking, an anti-inflammatory medication which, in the 
opinion of the Investigator, could affect gingival condition in the previous 14 
days. 
f. Has taken, or currently taking, a systemic medication which, in the opinion of 
the Investigator, could affect gingival condition in the previous 14 days (e.g. 
calcium channel blockers, or aspirin therapy). 

Page 37 of 73 
 
 
Document Name 
207014 protocol 
Type 
Version 
Document Identifier 
Effective Date 
eldo_clinical_doc 
5.0; Most-Recent; Effective; CURRENT 
090032d580d1fee8 
05-Apr-2017 13:38:03 
Reason For Issue 
Auto Issue 
 
 
5. GENERAL DENTITION EXCLUSIONS 
a. Have current active caries or periodontitis that may, in the opinion of the 
investigator, compromise the study or the oral health of the subjects if they 
participate in the study. 
b. Restorations in a poor state of repair. 
c. Partial dentures or orthodontic appliances. 
d. Teeth bleaching within 12 weeks of screening. 
e. Use of an antibacterial mouthwash (e.g. chlorhexidine) currently, or within 14 
days of baseline. 
f. EVIDENCE OF DENTAL FLUOROSIS, AS DETERMINED BY THE 
INVESTIGATOR. 
 
 
6. CLINICAL STUDY/  EXPERIMENTAL PRODUCT 
a. Participation in another clinical study or receipt of an investigational drug or 
investigational oral care product within 30 days of Baseline (Visit 2). 
b. Previous participation in this study. 
 
 
7. SUBSTANCE/ DRUG ABUSE 
Recent history (within the last year) of alcohol or other substance (E.G. ILLICIT 
DRUG) abuse. 
 
 
8. PERSONNEL 
a. An employee of the sponsor or the study site or members of their immediate 
family. 
b. Employed by any dentifrice manufacturer or their immediate family. 
 
 
4.3. Screening/ Baseline Failures 
 
Screen failures are defined as subjects who consent to participate in the study but are 
never subsequently randomized. In order to ensure transparent reporting of screen 
failure subjects, a minimal set of screen failure information is required including 
Demography, Screen Failure details, Eligibility Criteria, and any Serious Adverse 
Events. Re-screening of subjects will not be allowed in this study. 

Page 38 of 73 
 
 
Document Name 
207014 protocol 
Type 
Version 
Document Identifier 
Effective Date 
eldo_clinical_doc 
5.0; Most-Recent; Effective; CURRENT 
090032d580d1fee8 
05-Apr-2017 13:38:03 
Reason For Issue 
Auto Issue 
 
 
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 or an abnormal 
laboratory test result, the principal specific event or test will be recorded on the 
electronic case report form (CRF). If a subject is withdrawn from the study because 
of a product limiting AE, thorough efforts should be clearly made to document the 
outcome. Any AEs ongoing at the final visit will be followed up until resolved, the 
condition stabilizes, is otherwise explained, or the subject is lost to follow-up. 
 
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”. 
 
4.5. Subject Replacement 
 
Subjects who withdraw from the study post-randomization will not be replaced. 
 
4.6. Subject and Study Completion 
 
A completed subject is one who has completed all phases of the study including the 
follow-up visit. 
 
The end of the study is defined as the date of the last subject’s last visit. 

Page 39 of 73 
 
 
Document Name 
207014 protocol 
Type 
Version 
Document Identifier 
Effective Date 
eldo_clinical_doc 
5.0; Most-Recent; Effective; CURRENT 
090032d580d1fee8 
05-Apr-2017 13:38:03 
Reason For Issue 
Auto Issue 
 
 
 
5. PRODUCT INFORMATION 
5.1. Study Product 
The following study products will be supplied by the Clinical Supplies Department, 
GSKCH: 
 
Test Product 
Reference Product 
Product Name 
Experimental dentifrice 
containing 0.454% w/w 
stannous fluoride & 0.0721% 
w/w sodium fluoride (1450ppm 
fluoride in total) 
Regular fluoride dentifrice 
containing 0.14% w/w sodium 
monofluorophosphate – 
Colgate® Triple Protection 
Dentifrice (1400ppm fluoride as 
sodium monofluorophosphate; 
SMFP) 
Product 
Formulation 
Code (MFC) 
CCI 
Commercially available 
(Chinese marketplace) 
Dose 
Full ribbon of dentifrice to 
cover the head of the study 
toothbrush provided 
Full ribbon of dentifrice to cover 
the head of the study toothbrush 
provided 
Route of 
Administration 
Oral topical 
Oral topical 
Dosing 
Instructions 
Subjects will apply a full strip 
of dentifrice to cover the head 
of the toothbrush provided and 
brush their teeth with the 
assigned dentifrice twice daily 
(morning and evening) for one 
timed minute following their 
normal routine. 
Subjects will apply a full strip of 
dentifrice to cover the head of 
the toothbrush provided and 
brush their teeth with the 
assigned dentifrice twice daily 
(morning and evening) for one 
timed minute following their 
normal routine. 
 
Other items to be supplied by the Clinical Supplies Department, GSKCH: 
 
Name of Item 
Purpose 
Aquafresh®  Clean Control (Everyday 
Clean) toothbrushes (UK market place) 
To apply dentifrice to the teeth and 
facilitate toothbrushing 
Countdown Timers 
To accurately measure toothbrushing for 
one timed minute and assist subject 
compliance for brushing time. 
Plaque disclosing solution CCI 
To disclose the presence of dental plaque 

Page 40 of 73 
 
 
Document Name 
207014 protocol 
Type 
Version 
Document Identifier 
Effective Date 
eldo_clinical_doc 
5.0; Most-Recent; Effective; CURRENT 
090032d580d1fee8 
05-Apr-2017 13:38:03 
Reason For Issue 
Auto Issue 
 
 
CCI 
Opaque Bags 
To carry study supplies 
 
Subject diaries (including product usage instructions) will be supplied by GSKCH, 
China. 
 
Urine pregnancy test kits (to test for pregnancy on female subjects of child bearing 
potential) will be provided by the site. 
 
5.2. Dose Schedule 
Subjects will brush their teeth for one timed minute twice daily for 12 weeks, once in 
the morning and once in the evening. 
 
 
5.3. Dose Modification 
No dose modification is permitted in this study. Any variation from brushing 
instructions should be communicated to study site personnel and recorded as a 
deviation on the CRF. 
 
 
5.4. Product Compliance 
A record of the administration of the study treatments will be kept using the 
dispensing log and the CRF. 
 
At Visits 2 and 3, site staff will review the study instructions with the subjects to 
ensure subjects understand how to use the study products, complete the diary and 
operate the timer.  Subjects will complete their first brushing at the study site under 
the supervision of trained study personnel who will assess the subject’s understanding 
of study procedures and stress the importance of completing the study diary each time 
they brush their teeth. The diary will have a place to note when daily the brushings 
were completed and the date/time of the first and last brushings which will be 
recorded on the CRF. 
 
5.5. Precautions 
No special precautions are necessary provided the study is carried out in accordance 
with this protocol. Study products will be labelled “For Clinical Trial Use Only”. 

Page 41 of 73 
 
 
Document Name 
207014 protocol 
Type 
Version 
Document Identifier 
Effective Date 
eldo_clinical_doc 
5.0; Most-Recent; Effective; CURRENT 
090032d580d1fee8 
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Reason For Issue 
Auto Issue 
 
 
5.6. Overdose 
An overdose is a deliberate or inadvertent administration of a product at a dose higher 
than specified in the protocol. 
 
Overdose is not likely to occur in this study. Limited quantities of the product will be 
supplied, and closely monitored by the site for each subject. 
 
Overdose per se is not an AE. However, any clinical sequelae of an overdose should 
be reported as an AE (and serious adverse event (SAE), if appropriate). For 
reporting, follow the AE and SAE reporting instructions. 
 
5.7. Rescue Therapy 
No rescue therapy is required in this study. 
 
5.8. Product Assignment 
Subjects will be assigned to study product in accordance with the randomization 
schedule generated by the Biostatistics Department, GSKCH, prior to the start of the 
study, using validated internal software. 
 
5.8.1 Randomization 
A unique screening number will identify each subject screened for study 
participation. Screening numbers will be assigned in ascending numerical order as 
each subject signs their consent form. Subjects who meet all inclusion and exclusion 
criteria will be randomized according to the randomization schedule. 
 
There will be eight strata according to gender, smoking status and baseline mean 
whole mouth MGI score (Low≤2.0/High>2.0): 
 
• Stratum 1: Male, Smoker, Baseline MGI <=2.00 
• Stratum 2: Male, Smoker, Baseline MGI >2.00 
• Stratum 3: Male, Non-smoker, Baseline MGI <=2.00 
• Stratum 4: Male, Non-smoker, Baseline MGI >2.00 
• Stratum 5: Female, Smoker, Baseline MGI <=2.00 
• Stratum 6: Female, Smoker, Baseline MGI >2.00 
• Stratum 7: Female, Non-smoker, Baseline MGI <=2.00 
• Stratum 8: Female, Non-smoker, Baseline MGI >2.00 
 
Subjects will be allocated to one of the eight strata and within each stratum, 
randomization numbers will be assigned in ascending numerical order as each subject 
is determined to be fully eligible. 

Page 42 of 73 
 
 
Document Name 
207014 protocol 
Type 
Version 
Document Identifier 
Effective Date 
eldo_clinical_doc 
5.0; Most-Recent; Effective; CURRENT 
090032d580d1fee8 
05-Apr-2017 13:38:03 
Reason For Issue 
Auto Issue 
 
 
 
5.8.2 Blinding 
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 will not be permitted in the room 
where the test products are stored or dispensed. The product dispensing area will be 
separate from the subjects’ examination area. The dispensing staff will not be 
involved in any study efficacy assessments. 
 
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 give the appropriate medical care. Wherever 
possible the Investigator (or designee) must contact the Sponsor prior to breaking the 
blind. The investigator must document the reason for breaking the code and sign and 
date the appropriate document. 
 
The study blind must be returned to GSKCH at the end of the study. 
 
5.9. Packaging and Labelling 
The study dentifrice tubes [Experimental dentifrice containing 0.454%w/w stannous 
fluoride and 0.0721% w/w sodium fluoride CCI 
and Colgate Triple 
Protection fluoride dentifrice (China market place product)] will be overwrapped in 
opaque white vinyl to obscure any branding on the commercial tube pack. Each tube 
will have a study label affixed. Each subject will receive a sufficient number of tubes 
to cover usage during the treatment phase. 
 
Each study label will contain, but not be limited to, protocol number, product code 
letter, directions for storage, emergency contact telephone number and “For Clinical 
Trial Use Only”. 
 
Care should be taken with the supplied study 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. 
 
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. 

Page 43 of 73 
 
 
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Type 
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Document Identifier 
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5.0; Most-Recent; Effective; CURRENT 
090032d580d1fee8 
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Reason For Issue 
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All sundry items will be supplied in commercial packaging to be distributed by site 
staff as required throughout the study duration. 
 
 
5.9.1. Accountability of Product 
All products supplied are for use only in this clinical study and should not be used for 
any other purpose. 
 
The investigator or designee will maintain a full record of study product 
accountability. A Product Dispensing Log must be kept current and will contain the 
following information: 
 
• The identification of the subject to whom the study product was dispensed. 
• The date(s) and quantity of the study product dispensed to the subject. 
• The date(s) and quantity of the study product returned by the subject (if 
applicable). 
 
The inventory must be available for inspection by the study monitor during the study. 
At the end of the study, study product supplies will be verified by the monitor. Study 
product supplies will then be either collected by the study monitor or returned by the 
investigator or designee to the GSKCH Clinical Supplies Department or designated 
vendor. 
 
5.9.2. Storage of Product 
Study product supplies must be stored in compliance with the label requirements in a 
secure place with limited or controlled access. 
 
 
6. STUDY ASSESSMENTS AND PROCEDURES 
This section lists the procedures and parameters of each planned study assessment. 
The exact timing of each assessment is listed in the Schedule of Events section. 
 
Adherence to the study design requirements, including all assessments and 
procedures are essential and required for study conduct. 
 
6.1. Visit 1 - Screening Visit 
6.1.1 Telephone Screening 
Prior to the screening visit, telephone screening of interested subjects may be 
conducted using a telephone script. This will be conducted by the site recruitment 
staff or designee. 

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5.0; Most-Recent; Effective; CURRENT 
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6.1.2. Informed Consent 
The investigator, or designee, must obtain written (signed and dated by the subject) 
informed consent from each subject before starting any study specific procedures 
after adequate explanation of the aims, methods, objectives, and potential hazards of 
the study. 
 
The investigator, or designee, must also explain to the subjects that they are 
completely free to refuse to enter the study or to withdraw from it at any time. 
Appropriate forms for documenting a written consent will be provided by the 
investigator or by GSKCH. The investigator, or designee, should sign and date the 
consent form to confirm that the consent process was completed correctly. The 
subject will be provided with a copy of their signed and dated consent form and any 
other written information which they should be instructed to retain. 
 
If, during a subject’s participation in the study, any new information becomes 
available that may affect the subject’s willingness to participate in the study, each 
ongoing subject should receive a copy of this new information and be re-consented 
into the study. Subjects or should be provided with a copy of the signed and dated 
amended consent form. The date of consent will be recorded on the CRF. 
 
6.1.3. Demographics 
The following demographic parameters will be captured by the Investigator or 
designee and recorded on the CRF: year of birth, gender and race. 
 
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. Smoking status will also be detailed. 
Details of any relevant medical or surgical history, including allergies or drug 
sensitivity, will be recorded on the CRF. Any concomitant therapy taken in the 30 
days prior to the Screening Visit and throughout the study will also be recorded. 
 
6.1.5. Urine Pregnancy Test 
Urine pregnancy testing will be performed on females of child bearing potential at 
every visit according to the test kit manufacturer’s instructions. Urine collected for 
urine pregnancy testing will be disposed of as appropriate immediately following the 
test result. 
 
Female subjects of non-childbearing potential must meet at least one of the following 
criteria: 

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a. Achieved postmenopausal status, defined as follows: cessation of 
regular menses for at least 12 consecutive months with no alternative 
pathological or physiological cause; 
 
b. Have undergone a documented hysterectomy and/or bilateral 
oophorectomy; 
 
c. Have medically confirmed ovarian failure. 
 
All other female subjects (including females with tubal ligations) will be considered 
to be of childbearing potential. 
 
6.1.6. Oral Soft & Hard Tissue Examination 
The screening clinician will perform an initial oral soft tissue examination in order to 
capture any abnormalities, in agreement with section 6.2.1. 
 
The screening dentist will also perform a visual examination of the oral hard tissues 
to confirm that the subject has a minimum of 20 natural teeth and to evaluate the 
dentition for exclusions. 
 
The examinations will be performed by direct observation. 
 
6.1.7. Gross Gingival Health Assessment 
The screening dentist will determine gingival health by visual examination of the 
subject’s oral soft tissue. Subjects considered to have generalized moderate gingivitis 
will continue in the study. 
 
6.2. Visits 2, 3 & 4 
6.2.1. Urine Pregnancy Test 
Complete as described in Section 6.1.5. 
 
 
6.2.2. Oral Soft Tissue Examination (OST) 
Where possible, this procedure should be conducted by a single dental examiner or 
clinically qualified designee. The examination will be accomplished throughout the 
study by direct observation and palpation with retraction aids as appropriate. The 
examiner will include examination of the labial mucosa (including lips), buccal 
mucosa, mucogingival folds, gingival mucosa, hard palate, soft palate, tonsilar area, 
pharyngeal area, tongue, sublingual area, submandibular area and salivary glands. 

Page 46 of 73 
 
 
Document Name 
207014 protocol 
Type 
Version 
Document Identifier 
Effective Date 
eldo_clinical_doc 
5.0; Most-Recent; Effective; CURRENT 
090032d580d1fee8 
05-Apr-2017 13:38:03 
Reason For Issue 
Auto Issue 
 
 
The results of the examination will be recorded in the CRF as either normal or 
abnormal, with details of any abnormalities. Any post-treatment soft tissue 
abnormality, or worsening of a pre-existing condition, observed by the examiner or 
reported by the subject will be recorded on the CRF. Any abnormalities, or 
worsening of pre-existing conditions, that occur from Visit 2 onwards will be 
recorded as AEs. 
 
 
6.2.3. Modified Gingival Index (MGI) Assessment (Lobene, 1986) 
The MGI assessment is a non-invasive evaluation which focuses on the visual 
symptoms of gingivitis (for example, redness, texture, edema). The MGI will be 
assessed on the facial and lingual surfaces of each scorable tooth (7-7 in each arch). 
Two scores will be recorded bucally/labially (papilla and margin) and two scores 
lingually/palatally (papilla and margin). The scoring of the MGI will be performed 
under dental office conditions using a standard dental light for illuminating the oral 
cavity. 
 
The MGI scoring system will be as follows: 
0 = absence of inflammation 
1 = mild inflammation; slight change in color, little change in color; 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. 
The MGI will be assessed by the same examiner on all evaluable teeth at 
Baseline/Visit 2, Visit 3 and Visit 4. 
 
 
Repeatability Exercise 
 
Data for MGI assessments will be taken from replicate examinations performed by 
the Examiner during the study.  Depending on subject visit scheduling, every effort 

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will be made to do repeatability examinations during each session, that is, one in the 
morning and one in afternoon every day examinations are carried out. 
 
Repeatability examinations will have a minimum of 10 minutes between and, where 
possible, will be separated by another subject. 
 
6.2.4. Bleeding Index (BI) Assessment (Saxton, 1989) 
The BI assesses the number of bleeding points elicited on probing as a measure of 
gingival condition. The gingivae will be air dried and then the examiner will use an 
Oulix color coded periodontal PCPII 5B Hufreidy or blunt-ended CPI probe to assess 
bleeding. The probe will be gently inserted into the gingival crevice to a depth of 
approximately 1 millimeter (mm) and then run around the tooth (at angle of ~ 60º to 
the long axis of the tooth), gently stretching the epithelium while sweeping from 
interproximal to interproximal along the sulcular epithelium. Minimum force should 
be used to avoid damage to the gingival tissue. The BI will be assessed on the facial 
and lingual gingival surfaces of each scorable tooth (7-7 in each arch). Three scores 
(according to the scale below) should be recorded bucally/labially (distal, body, 
mesial sites) and three scores lingually/palatally. All scorable teeth in one quadrant 
should be probed first (approximately 30 seconds) before recording the number of 
gingival units which bleed. 
 
The BI scoring system will be as follows: 
0 = no bleeding after 30 seconds 
1 = bleeding upon probing after 30 seconds 
2 = immediate bleeding observed 
The BI will be assessed by the same examiner on all evaluable teeth at 
Baseline/Visit 2, Visit 3 and Visit 4. 
 
Repeatability exercise will not be performed for BI. Due to the invasive nature of 
the BI assessment it is not feasible to conduct a repeatability exercise. 
 
6.2.5. Plaque Index (PI) Assessment (Lobene, 1982) 
The Turesky Modification of the Quigley Hein Plaque Index (Lobene, 1982) will be 
used to assess plaque on all gradable teeth meeting the inclusion/ exclusion criteria. 

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Document Name 
207014 protocol 
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5.0; Most-Recent; Effective; CURRENT 
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Only natural teeth can be assessed. This means no crowns, bridges, and teeth with 
fillings (surface that has 50% of the surface gradable or no more than 50% of the 
surface filled) which, in the examiner’s judgment, would prevent an accurate grading 
should be assessed.  Third molars should not to be assessed. 
 
The plaque will first be disclosed using a dye solution (Plaque disclosing solution 
(CCI 
 
, in agreement with the manufacturer’s instructions. The PI will be 
assessed on the facial and lingual surfaces of each scorable tooth. (7-7 in each arch). 
Three scores should be recorded bucally/ labially (distal, body, mesial sites) and three 
scores lingually/ palatally (distal, body, mesial sites). 
 
Disclosed plaque will be scored as follows: 
0 = No plaque 
1 = Slight flecks of plaque at the cervical margin of the tooth 
 
2 = A thin continuous band of plaque (1mm or smaller) at the cervical margin of the 
tooth 
 
3 = A band of plaque wider than 1mm but covering less than 1/3 of the area 
4 = Plaque covering at least 1/3 but less than 2/3 of the area 
5 = Plaque covering 2/3 or more of the crown of the tooth 
 
The PI will be assessed by the same examiner on all evaluable teeth at 
Baseline/Visit 2, Visit 3 and Visit 4. 
 
Repeatability Exercise 
 
Data for plaque assessments will be taken from replicate examinations performed by 
the examiner during the study. Depending on subject visit scheduling, every effort 
will be made to do repeatability examinations during each session, that is, one in the 
morning and one in afternoon every day examinations are carried out. 
 
Repeatability examinations will have a minimum of 10 minutes between (where 
possible separated by another subject). 

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6.2.6. Dental Prophylaxis 
A suitable qualified member of clinical staff will provide professional dental 
prophylaxis for each subject using a standard prophylaxis polishing paste followed by 
flossing to ensure teeth are free of all supra and gingival calculus and plaque, both 
visually and by tactile assessment using a dental explorer.  A second suitable 
qualified examiner will then visually check that all plaque has been removed 
following plaque disclosure.  Subjects will have their plaque disclosed and any 
residual plaque remaining will be removed by the second clinician by dental polishing 
with a standard prophylaxis polishing paste to bring the subject to zero plaque. 
 
In addition, at the final study visit, subjects will be offered a dental prophylaxis if 
determined appropriate in the opinion of the investigator or suitably clinically 
qualified designee. 
 
6.2.7. Study Conclusion 
Subjects will be evaluated to determine if they completed all study procedures or if 
they were discontinued from the study early. If the subject discontinued at any point 
during the study, the primary reason for withdrawal should be recorded on the Study 
Conclusion page of the CRF by selecting one of the options below. 
 
1. 
Subject did not meet study criteria 
 
2. 
Adverse Event 
 
3. 
Lost to Follow Up 
 
4. 
Protocol Violation 
 
5. 
Withdrawal of Consent 
 
6. 
Other 
 
 
7. SAFETY ASSESSMENTS 
 
7.1. Definitions of an Adverse Event and Serious Adverse Event 

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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.. 
• 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. 

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7.1.2. Serious Adverse Events 
 
Serious Adverse Event is defined as any untoward medical occurrence that, at 
any dose: 
A.  Results in death 
B.  Is life-threatening 
NOTE: The term 'life-threatening' in the definition of 'serious' refers to an 
event in which the subject was at risk of death at the time of the event. It does 
not refer to an event, which hypothetically might have caused death, if it were 
more severe. 
C.  Requires hospitalization or prolongation of existing hospitalization 
NOTE: In general, hospitalization signifies that the subject has been detained 
(usually involving at least an overnight stay) at the hospital or emergency 
ward for observation and/or treatment that would not have been appropriate in 
the physician’s office or out-patient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills 
any other serious criteria, the event is serious. When in doubt as to whether 
“hospitalization” occurred or was necessary, the AE should be considered 
serious. 
Hospitalization for elective treatment of a pre-existing condition that did not 
worsen from baseline is not considered an AE. 
D.  Results in disability/incapacity 
NOTE: The term disability means a substantial disruption of a person’s ability 
to conduct normal life functions. 
This definition is not intended to include experiences of relatively minor 
medical significance such as uncomplicated headache, nausea, vomiting, 
diarrhea, influenza, and accidental trauma (e.g. sprained ankle) which may 
interfere or prevent everyday life functions but do not constitute a substantial 
disruption. 
E.  Is a congenital anomaly/birth defect 
F. Other Situations 
• Medical or scientific judgment should be exercised in deciding 
whether reporting is appropriate in other situations, such as important 
medical events that may not be immediately life-threatening or result 
in death or hospitalization but may jeopardize the subject or may 
require medical or surgical intervention to prevent one of the other 
outcomes listed in the above definition. These should also be 
considered serious. 
• Examples of such events are invasive or malignant cancers, intensive 
treatment in an emergency room or at home for allergic bronchospasm, 
blood dyscrasias or convulsions that do not result in hospitalization or 

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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. 
• The investigator or site staff will then record all relevant information 
regarding an AE/SAE in the CRF. 
• There may be instances when copies of medical records for certain cases are 
requested by GSK. In this instance, all subject identifiers, with the exception 
of the subject number, will be blinded on the copies of the medical records 
prior to submission of to GSK. 
• The investigator will attempt to establish a diagnosis of the event based on 
signs, symptoms, and/or other clinical information. In such cases, the 
diagnosis will be documented as the AE/SAE and not the individual 
signs/symptoms. Clinical AEs will be described by diagnosis and not by 
symptoms when possible (e.g., upper respiratory tract infection, seasonal 
allergy, etc. instead of runny nose). 
• AEs will be collected from the start of the assigned treatment product and 
until 5 days following last administration of the study product. 
• SAEs will be collected over the same time period as stated above for AEs. 
However, any SAEs assessed as related to 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. 
• Moderate: An event that is sufficiently discomforting to interfere with normal 
everyday activities 
• Severe: An event that prevents normal everyday activities. - an AE that is 
assessed as severe will not be confused with an SAE. Severity is a category 
utilized for rating the intensity of an event; and both AEs and SAEs can be 

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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 Investigator Brochure (IB) and/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 CRF that he/she has reviewed the AE/SAE and has 
provided an assessment of causality. 
• There may be situations when an SAE has occurred and the investigator has 
minimal information to include in the initial report to GSK. However, it is 
very important that the investigator always make an assessment of 
causality for every event prior to the initial transmission of the SAE data 
to GSK. 
• The investigator may change his/her opinion of causality in light of follow-up 
information, amending the SAE data collection tool accordingly. 
• The causality assessment is one of the criteria used when determining 
regulatory reporting requirements. 
 
7.4. Reporting Adverse Events and Serious Adverse Events 
 
AE Reporting to GSKCH: 
• AEs will be recorded in the AE section of the CRF. 
• Medical conditions recorded by the subject on a diary card or similar 
document that meet the definition of an AE must also be recorded in the AE 
section of the CRF, if not previously well-characterized by the investigator in 
the subject’s medical history. 
• AEs elicited by the investigator in a standard manner at the study visits should 
also be recorded in the AE section of the CRF. The investigator or designee 
must ask the subject the following question during each visit including any 
follow-up visits: “Have you felt unwell, experienced any symptoms or taken 
any medication (since your last visit) (today) (since your last dose) (since the 

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last session)?” 
• The medically qualified investigator should review adverse events in a timely 
manner; this review should be documented in writing in the source document 
or in the CRF. 
• After the study is completed at a given site, and the site has received their 
study data on Compact Discs (CDs), the electronic data collection tool will be 
removed from the 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 hours after 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: 
China: PPD 
 
The GSKCH Study Manager will be responsible for forwarding the SAE form to the 
Case Management Group, Global Clinical Safety and Phamacovigilance, the Medical 
Director responsible for the study and other GSKCH personnel as appropriate via 
email. 
The initial report will be followed up with more information as relevant, or as 
requested by the GSKCH study manager. 

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7.5. Follow-up of Adverse Events and Serious Adverse Events 
 
Follow-up of AEs and SAEs: 
• After the initial report, the investigator is required to proactively follow up 
with each subject and provide further information on the subject’s condition. 
• All AEs/SAEs will be followed until resolution, until the condition stabilizes, 
until the event is otherwise explained, or until the subject is lost to follow-up. 
• The investigator is obligated to perform or arrange for the conduct of 
supplemental measurements and/or evaluations as may be indicated or as 
requested by GSK to elucidate as fully as possible the nature and/or causality 
of the AE or SAE. 
• Investigators are not obliged to actively seek AEs or SAEs in former subjects. 
However, if the investigator learns of any SAE, including the death, at any 
time after a subject has been discharged from the study, and considers the 
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, IRB/IEC and investigators. 
• Investigator safety reports are prepared according to GSKCH policy and are 
forwarded to investigators as necessary. An investigator safety report is 
prepared for a SAE(s) that is both attributable to investigational product and 
unexpected. The purpose of the report is to fulfill specific regulatory and 
GCP requirements, regarding the product under investigation. 
• An investigator who receives an investigator safety report describing a SAE(s) 
or other specific safety information (e.g., summary of listing of SAEs) from 
GSKCH will file it with the Investigator Brochure (or safety statement) and 
will notify the IRB or IEC, if appropriate according to local requirements. 

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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 plaque disclosing solution. GSKCH medical device 
incidents, including those resulting from malfunctions of the device, must be 
detected, documented, and reported by the investigator on the CRF throughout the 
study. 
 
7.6.1. Definition of an Incident 
 
Definition of an Incident: 
• Any malfunction or deterioration in the characteristics and/or performance of 
a device, as well as any inadequacy in the labelling or the instructions for use 
which, directly or indirectly, might lead to or might have led to 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 be reported to GSKCH within 24 hours (or sooner if 
possible) of the investigator or designee becoming aware of the situation. 
• Any medical device incident occurring during the study will be documented in 
the subject's medical records, in accordance with the investigator's normal 
clinical practice, and on the appropriate Incident Report Form.  In addition, 
for incidents fulfilling the definition of an AE or an SAE, the appropriate AE 
CRF page or SAE form will be completed and reported as per the AE and 
SAE reporting sections. 
• The Incident Report Form will be completed as thoroughly as possible and 
signed by the investigator before transmittal to GSKCH. It is very important 
that the investigator describes any corrective or remedial actions taken to 
prevent recurrence of the incident. 
• The completed Incident Report Form should be faxed or emailed to the 
appropriate GSKCH Study Manager as soon as possible, but not later than 
24 hours after study site personnel learn of the event. If there is an SAE, the 
completed SAE pages should be sent together with this report form. 
However, if a copy of the SAE report is sent with this form, this does not 
replace the procedure to report an SAE. The original Incident Report Form 
will remain with the subject’s records. 
• The GSKCH Study Manager should be notified of the situation by telephone 
or email. 
Fax the Incident Report Forms to: 
China: PPD 

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• The GSKCH Study Manager will be responsible for forwarding the Incident 
Report Form to the Case Management Group, Global Clinical Safety and 
Pharmacovigilance, the Medical Director responsible for the study and other 
GSKCH personnel as appropriate. 
• The initial report will be followed up with more information as relevant, or as 
requested by the GSKCH study manager. 
 
Reporting of Malfunctions to GSKCH: 
The investigator will follow the following directions regarding device failure 
(malfunction): 
• Notify GSKCH immediately. 
• Schedule the subject to return to the site promptly to return the failed device. 
• Record any incidents on the CRF and Incident Report Form following 
instructions given in the section above. 
• Return the failed device to the sponsor as soon as possible, including 
documentation of the details of the failure. 
 
7.6.3. Follow-up of Incidents 
 
Follow-up of Incidents: 
During the study: 
• All incidents will be followed until resolution of the event, until the condition 
stabilizes, until the condition is otherwise explained, or until the subject is lost 
to follow-up. This applies to all subjects, including those withdrawn 
prematurely. The investigator is responsible for ensuring that follow-up 
includes any supplemental investigations as may be indicated to elucidate as 
completely as practical the nature of the incident. 
• New or updated information will be recorded on the originally completed 
form with all changes signed and dated by the investigator. 
After the study: 
• Investigators are not obligated to actively seek reports of incidents in former 
subjects.  However, if the investigator learns of any incident at any time after 
a subject has been discharged from the study, and such incident is reasonably 
related to a GSKCH medical device provided for the study, the investigator 
will promptly notify GSKCH. 
 
Regulatory and Ethics Reporting Requirements for Incidents: 
• The investigator will promptly report all incidents occurring with any GSKCH 
medical device provided for use in the study within 24 hours. GSKCH has a 
legal responsibility to notify appropriate regulatory bodies and other entities 
about certain safety information relating to medical devices being used in 

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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 IRB. 
 
 
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 or washout product. Information on 
pregnancy identified during the screening phase and prior to investigational 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 
washout product. The investigator will record pregnancy information on the 
appropriate form and submit it to GSKCH within 2 weeks of learning of the 
subject becoming pregnant. The subject will be followed to determine the 
outcome of the pregnancy. Information on the status of the mother and infant / 
neonate (including concomitant medications taken by the mother during the 
pregnancy) will be forwarded to GSKCH. Generally, follow-up will be no 
longer than 6 to 8 weeks following the estimated delivery date. Any 
termination of the pregnancy will be reported. 
• While pregnancy itself is not considered to be an AE, any pregnancy 
complication or elective termination for medical reasons will be recorded as 
an AE or SAE. 
• A spontaneous abortion is always considered to be an SAE and will be 
reported as such. An SAE occurring in association with a pregnancy, brought 
to the investigator’s attention after the subject completed the study and 
considered by the investigator as possibly related to the investigational 
product, must 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 

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CRF. 
 
 
 
8. DATA MANAGEMENT 
For this study subject data will be entered into an electronic case report form, using a 
GSKCH validated data system. 
 
8.1. Source Documents/ Data 
The source documents (e.g. hospital records, memoranda, subjects’ diaries, subject 
files and records kept at the laboratory and at the medico-technical departments 
involved in the clinical study) which contain the source of data recorded in the CRF 
should be specified in the Source Document Designation Form. In some cases the 
CRF can be used as a source document. 
 
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. 
 
All PRO source data should be reviewed by the Study Staff/ Study Monitor (as 
appropriate) in order to ensure that any potential AEs reported on these documents 
are represented in the DMS, as detailed in section 8.4. 
 
 
8.2. Electronic Case Report Form 
A CRF is a printed, optical, or electronic document designed to record all of the 
protocol required information to be reported to the sponsor on each trial subject. 
 
For each subject who has given informed consent/assent and has been screened, CRF 
must be completed and signed by the Principal Investigator (or authorized designee) 
to certify that the data are complete and correct. 
 
Management of clinical data will be performed in accordance with applicable 
GSKCH standards and data cleaning procedures to ensure the integrity of the data e.g. 
removing errors and inconsistencies in the data. 
 
In order to protect the privacy of subjects, no Personally Identifiable Information 
(PII) (including the subject's name or initials or birth date) is to be recorded in the 
CRF or as part of the query text. 

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Adverse events and concomitant medications terms (if applicable) will be coded 
using MedDRA (Medical Dictionary for Regulatory Activities) and an internal 
validated medication dictionary, GSKDrug. 
 
Subject data will be entered into GSKCH defined CRFs and transmitted electronically 
to GSKCH in a validated (21 CFR Part 11 compliant) web-based electronic data 
capture system (InFormTM). 
 
All CRF pages should be completed during a subject assessment when the CRF has 
been designated as the source. Data that is sourced elsewhere should be entered into 
the CRF in an agreed upon timeframe between the Investigator and Sponsor. 
 
The CRFs (including queries, query responses and audit trails) will be retained by 
GSKCH. Site data archived compact discs (CD(s)) prepared by a third party will be 
sent to the investigator to maintain as the investigator copy following the 
decommissioning of the study. 
 
8.3. Data Handling 
Documentation of all data management activities should allow step-by-step 
retrospective assessment of data quality and study performance. Any changes or 
corrections to data will be performed in the Electronic Data Capture (EDC) System, 
and it will include rationale for changes. The EDC system has an audit trail, which 
will provide a complete record of the changes and corrections endorsed by the 
Investigator. 
 
8.3.1. Data Queries 
Programmed edit checks will be generated automatically, as the data is being entered 
into the system. Data Management will also run reports and listings on the CRF data, 
in addition to the queries already programmed and generated by the system, to raise 
manual queries as needed for site clarification or correction. The Clinical Dictionary 
Development and Management Group will raise queries as needed on safety data to 
code the terms (Adverse Events and Drugs) are reported appropriately. 
 
The study monitor at the study site will review the CRFs in accordance with the 
monitoring plan, and any queries will be generated in the EDC System to the 
Investigator or designee, enabling the errors to be addressed in parallel with Data 
Management review. Monitor can also run reports and listings on the CRFs, to raise 
manual queries as needed for site clarification or correction 

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8.4. Processing Patient Reported Outcomes 
Patient reported outcome (PRO) data are collected directly from the subject PRO 
measures e.g. diary cards, questionnaires etc, and entered into the sponsor’s clinical 
data management system (DMS) by the study site representative. In instances where 
the PRO data is entered into the DMS by GSKCH, the PROs will be anonymised, and 
forwarded to GSKCH for entry, as agreed and documented ahead of the study 
starting. PROs that are source will be retained by the investigator and certified copies 
will be sent to GSKCH. 
 
In order to protect the privacy of subjects, no Personally Identifiable Information 
(PII) (including the subject's name or initials or birth date) is to be recorded on all 
PRO’s that will be forwarded to GSKCH. 
 
All PRO source data should be reviewed by the Study Staff/ Study Monitor (as 
appropriate) in order to ensure that any potential AEs reported on these documents 
are represented in the DMS. 

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9. STATISTICAL CONSIDERATIONS AND DATA 
ANALYSES 
9.1 Sample Size Determination 
 
A sufficient number of subjects will be screened to randomize at least 120 subjects to 
ensure approximately112 evaluable subjects complete the entire study (approximately 
56 per treatment group). 
 
With 56 subjects per treatment group, the study has at least 80% power to detect a 
treatment difference of 0.08 in bleeding index over a period of 12 weeks treatment. 
The standard deviation used in calculation is 0.14. The difference of 0.08 represents 
more than 15% improvement in the test dentifrice compared to the fluoride control 
dentifrice reference product. CCI 
 
. 
 
9.2. General Considerations 
9.2.1. Definition of Analysis Populations 
The intent to treat (ITT) population is defined as those subjects who are randomized, 
receive at least one dose of study product and have at least one post-baseline efficacy 
measurement. 
 
The Per Protocol (PP) population will be a subset of the ITT population. Subjects 
with a protocol violation that is deemed to affect efficacy for all efficacy assessments 
will be excluded from the PP population. Subjects with a protocol violation that is 
deemed to affect efficacy for only some (but not all) of the efficacy assessments will 
be part of the PP population, but their data will be excluded from the assessment at 
which the protocol violation occurred. Efficacy analysis will be based on ITT 
population. A PP analysis will be performed only if 10% or more ITT subjects are 
excluded from PP population 
 
Safety population is defined as all subjects who are randomized and have received at 
least one dose of study products. 
 
The repeatability population is defined as all subjects who have a repeat clinical 
assessment (MGI or PI) at any visit. 

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9.2.2. Exclusion of Data from Analysis 
Data listings of protocol violations, including but not necessarily limited to those 
listed below will be reviewed. Those protocol violations considered to have had 
affected efficacy will lead to exclusion of either subject or data from PP analyses. 
 
1. 
Major violation of inclusion or exclusion criteria. 
2. 
Significant non-compliance with assigned product regimen (e.g., under- or 
over- use) 
3. 
Significant non-compliance with the visit schedule 
4. 
Use of prohibited treatment or medication before or during the study. 
All protocol violations reported and their impact on efficacy analyses will be 
determined between the Biostatistician and Medical Director or designee, ahead of 
database lock and unblinding. 
 
9.2.3. Criteria for Evaluation 
Efficacy will be evaluated by ITT or PP population. Safety will be assessed by safety 
population. 
 
9.2.4. Criteria for Assessing Efficacy 
The success criterion of the study is to observe a statistically significant reduction in 
Bleeding Index in the test dentifrice group compared to the reference dentifrice group 
after 12 weeks of study treatments. 
 
9.2.5. Criteria for Assessing Tolerability 
No specific safety criteria are planned for this study. Adverse Events and OST 
abnormalities will be assessed in each treatment group. 
 
9.2.6. Handling of Dropouts and Missing Data 
Subjects who withdraw from the study early will be included in the statistical analysis 
up to the point of when they withdraw. Missing data will not be imputed. 
 
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 finalization 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 
Primary efficacy endpoint will be the Bleeding Index (BI) score after 12 weeks of 
study treatments. BI score will be calculated as the average index over all tooth sites. 
ANCOVA model will be applied for primary analysis with treatment, gender, 
smoking status and baseline MGI stratification as factors and baseline score as 
covariate. Adjusted means of two treatments and treatment difference will be 
provided together with 95%CI and P-values. 
 
The assumption of residual normality and variance homogeneity in ANCOVA 
analysis will be investigated. If violated, data transformation or a non-parametric 
method will be used. 
 
9.3.3. Secondary Analyses 
BI score at Week 6 
BI score at Week 6 will be analysed using the same ANCOVA model as used for 
primary analysis. 
 
Number of bleeding sites at Week 6 and Week 12 
Number of bleeding sites will be calculated as the number of sites with a BI score of 
1 or 2. At each post-baseline visit, number of bleeding sites will be analysed using 
ANCOVA model with treatment, gender, smoking status and baseline MGI 
stratification as factors and baseline score as covariate. Adjusted means of two 
treatments and treatment difference will be provided together with 95%CI and P- 
values. 
 
MGI score at Week 6 and Week 12 
MGI score will be calculated as the average index over all tooth sites. At each post- 
baseline visit, MGI score will be analysed using ANCOVA model with treatment, 
gender, smoking status as factors and baseline score as covariate. As baseline MGI is 
included as covariate, baseline MGI stratification will not be included again. Adjusted 
means of two treatments and treatment difference will be provided together with 
95%CI and P-values 
 
Overall plaque score at Week 6 and Week 12 
Overall plaque score will be calculated as the average index over all tooth sites. At 
each post-baseline visit, overall plaque score will be analysed using ANCOVA model 
with treatment, gender, smoking status and baseline MGI stratification as factors and 
baseline score as covariate. Adjusted means of two treatments and treatment 
difference will be provided together with 95%CI and P-values. 
 
Interproximal plaque score at Week 6 and Week 12 

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Interproximal plaque score will be calculated as the average index over interproximal 
sites. Interproximal plaque score will be analysed similarly as overall plaque score. 
 
For all of the above secondary analyses, Normality assumptions in ANCOVA models 
will be checked and accounted for in the same way as for the primary variable. 
 
9.3.4. Safety Analysis 
All AEs will be coded using MedDRA. AEs will be categorized as oral and non-oral 
by the Medical Director or designee prior to database lock. AEs and oral soft tissue 
abnormalities will be listed by treatment and reviewed. Only treatment emergent AEs 
(i.e. those occurring after first use of either of the study treatments) will be tabulated. 
AEs occurring prior to randomisation will be included in the AE listing. 
 
9.3.5. Repeatability Analysis 
A number of subjects will have repeat gingivitis (MGI and TPI) assessments 
conducted by the examiner. The repeat assessments will be compared to the original 
assessments. The repeat assessments will not be used in any efficacy analysis. The 
purpose of repeated assessments is to check the consistency of the examiner. As each 
subject will provide around 100 records for repeatability judgement, one subject on 
the morning and one subject in the afternoon in each visit day over the course of the 
study is sufficient for repeatability assessment. The first and second assessments on 
each tooth at a given visit will be cross-tabulated and a weighted Kappa coefficient 
(κ) will be calculated, along with the 95% confidence interval, to assess the intra- 
examiner repeatability.  Repeatability will be deemed [Fleiss]: 
• Excellent, 
if κ > 0.75 
• Fair to good, if 0.4 ≤  κ   ≥ 0.75 
• Poor 
if κ  < 0.4 
All subjects who have repeatability data will be included in this analysis. 
 
 
10. 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. 

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

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

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• If the GSKCH terminates or suspends a trial, the investigator should promptly 
inform the IRB/IEC and provide the IRB/IEC a detailed written explanation of 
the termination or suspension. 
• If the IRB/IEC terminates or suspends its approval/favorable opinion of a trial, 
the investigator should promptly notify the GSKCH and provide GSKCH with 
a detailed written explanation of the termination or suspension. 
 
10.6. Records Retention 
Following closure of the study, the investigator must maintain all site study records 
(except for those required by local regulations to be maintained elsewhere), in a safe 
and secure location. 
 
The records (study/ site master file) must be maintained to allow easy and timely 
retrieval, when needed (e.g., for a GSK audit or regulatory inspection) and must be 
available for review in conjunction with assessment of the facility, supporting 
systems, and relevant site staff. 
 
Where permitted by local laws/regulations or institutional policy, some or all of these 
records can be maintained in a format other than hard copy (e.g., microfiche, scanned, 
electronic); however, caution needs to be exercised before such action is taken. 
 
The investigator must ensure that all reproductions are legible and are a true and 
accurate copy of the original and meet accessibility and retrieval standards, including 
re-generating a hard copy, if required. Furthermore, the investigator must ensure 
there is an acceptable back-up of these reproductions and that an acceptable quality 
control process exists for making these reproductions. 
 
The investigator must assure that the subject’s anonymity will be maintained. On 
CRFs or other documents submitted to GSKCH, subjects should not be identified by 
their names or initials, but by an identification code. The investigator should keep a 
separate log of subjects’ codes, names and addresses. Documents not for submission 
to GSKCH, e.g. subjects’ written consent forms, should be maintained by the 
investigator in strict confidence. 
 
GSK will inform the investigator of the time period for retaining these records to 
comply with all applicable regulatory requirements (GSKCH recommends that 
documents be kept for 10 years). The investigator is also required to keep subject 
identification codes on file for at least 15 years after completion or discontinuation of 
the study. The minimum retention time will meet the strictest standard applicable to 
that site for the study, as dictated by any institutional requirements or local laws or 
regulations, GSK standards/procedures, and/or institutional requirements. 

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No study document should be destroyed without a prior written agreement between 
GSKCH and the investigator. The investigator must notify GSK of any changes in the 
archival arrangements, including, but not limited to, archival at an off-site facility or 
transfer of ownership of the records in the event the investigator is no longer 
associated with the site. 
 
10.7. Provision of Study Results to Investigators, posting of 
Information on Publicly Available Clinical Trials Registers 
and Publication 
Where required by applicable regulatory requirements, an investigator signatory will 
be identified for the approval of the clinical study report. The investigator will be 
provided reasonable access to statistical tables, figures, and relevant reports and will 
have the opportunity to review the complete study results at a GSK site or other 
mutually-agreeable location. 
 
GSK will also provide the investigator with the full summary of the study results. 
The investigator is encouraged to share the summary results with the study subjects, 
as appropriate. 
 
The procedures and timing for public disclosure of the results summary and for 
development of a manuscript for publication will be in accordance with GSK Policy. 
 
A manuscript will be progressed for publication in the scientific literature if the 
results provide important scientific or medical knowledge. 

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11. REFERENCES 
 
Albandar JM. Periodontal diseases in North America. Periodontology 2000. 2002; 29: 
31-69 
Brook I. Microbiology and management of periodontal infections. General Dentistry 
2003; 51: 242-428 
Chapple IL. Primary prevention of periodontitis: managing gingivitis. J Clin 
Periodontol. 2015; 42 (Suppl. 16); S71 
Cummins D, Creeth JE. Delivery of antiplaque agents from dentifrices, gels and 
mouthwashes. J Dent Res. 1992;71; 1439-1449 
CCI 
CCI 
CCI 
GSKCH Clinical Study 205045 – A Clinical Study Investigating the Gingivitis 
Efficacy of a Stannous Fluoride Dentifrice 
ICH Topic 6 Guideline for Good Clinical Practice CPMP/ICH/135/95 17th July 1996 
Kinane DF, Hodge PJ. Periodontal disease in children and adolescents: introduction 
and classification. Periodontology 2000, 2001; 26; 7-15 
Kinane DF, Attstr1m R. Advances in the pathogenesis of periodontitis. Group B 
consensus report of the fifth European Workshop in Periodontology. J Clin 
Periodontol, 2005; 32 (Suppl. 6): 130-131 
Lobene R R. A Modified Gingival Index for Use in Clinical Trials. Clinical 
Preventative Dentistry. 1986; 8(1): 3 
Makin SA. Stannous fluoride dentifrices. Am J Dent, 2013; 26 (Spec No. A); 3A-9A 
Mallatt M, Mankodi S, Bauroth K, Bsoul SA, Bartizek RD, He T. A controlled 6- 
month clinical trial to study the effects of a stannous fluoride dentifrice on gingivitis. 
J Clin Periodontol, 2007; 34: 762-767 
Mankodi S, Petrone DM, Battista G, Petrone ME, Chaknis P, DeVizio W, Volpe AR, 
Proskin HM. Clinical efficacy of an optimized stannous fluoride dentifrice, Part 2: a 
6-month plaque/gingivitis clinical study, northeast USA. Compendium of Continuing 
Education in Dentistry, 1997: 18 (Spec No.); 10-15 
Mankodi S, Bartizek RD, Winston JL, Biebrock AR, McClanahan SF, He T. Anti- 
gingivitis efficacy of a stabilized 0.454% stannous fluoride/sodium 
hexametaphosphate dentifrice. J Clin Periodontol, 2005; 32; 75-80 
Miller S, Truong T, Heu R, Stranick M, Bouchard D, Gaffar A. Recent advances in 
stannous fluoride technology: antibacterial efficacy and mechanism of action towards 
hypersensitivity. Int Dent J, 1994; 44 (Suppl. 1); 83-98 

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Ower P. The role of self-administered plaque control in the management of 
periodontal disease: I. A review of the evidence. Dental Update, 2003; 30: 60-68 
Paraskevas S, van der Weijden GA. A review of the effects of stannous fluoride on 
gingivitis. J Clin Periodontol, 2006; 33: 1-13 
Perlich MA, Bacca LA, Bollmer BW, Lanzalaco AC, McClanahan SF, Sewak LK, 
Beiswanger BB, Eichold WA, Hull JR, Jackson RD, Mau MS. The clinical effect of a 
stabilized stannous fluoride dentifrice on plaque formation, gingivitis and gingival 
bleeding: a six-month study. Journal of Clinical Dentistry 1995: 6 (Spec No.); 54-58 
Petersen PE, Ogawa H. The global burden of periodontal disease: towards integration 
with chronic disease prevention and control. Periodontology 2000, 2012; 60; 15 
Saxton C, Van der Ouderra F G J. The Effect of a Dentifrice Containing Zinc 
Citrate & Triclosan on Developing Gingivitis. Journal of Periodontal 
Research.1989; 24: 75 
Tinanoff N. Review of the antimicrobial action of stannous fluoride. Journal of 
Clinical Dentistry, 1990; 2: 22-27 
van Loveren C. The antimicrobial action of fluoride and its role in caries inhibition. J 
Dent Res, 1990; 9 ((Spec No.): 676-683 
van Loveren C. Antimicrobial activity of fluoride and its in vivo importance: 
identification of research questions. Caries Res, 2001; 35 (Suppl. 1); 65-70 
Williams C, McBride S, Bolden TE, Mostler K, Petrone DM, Petrone ME, Chaknis P, 
DeVizio W, Volpe AR, Proskin HM, Paraskevas HM, van der Weijden. Clinical 
efficacy of an optimized stannous fluoride dentifrice, Part 3: a 6-month 
plaque/gingivitis clinical study, southeast USA. Compendium of Continuing 
Education in Dentistry, 1997: 18 (Spec No.); 16-20 
World Medical Association Declaration of Helsinki, 59th General Assembly, Seoul 
2008 

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12. APPENDICES 
12.1. Appendix 1 - Abbreviations and Trademarks 
Abbreviations 
 
AE 
Adverse Event 
CD 
Compact Disc 
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 
PII 
Personally Identifiable Information 
PP 
Per Protocol 
SAE 
Serious Adverse Event 
PRO 
Patient Reported Outcome 
 
Trademark Information 
 
Trademarks of the GlaxoSmithKline group of companies: 
Aquafresh 
Sensodyne 
 
Trademarks not owned by the GlaxoSmithKline group of companies: 
Colgate 

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SIGNATURE PAGE 
 
207014 protocol 
 
 
 
 
 
Date 
Signed By 
04-Apr-2017 05:36:49 
PPD 
Justification 
Biostatistics Approval 
 
 
Date 
Signed By 
04-Apr-2017 07:06:33 
PPD 
Justification 
Approved 
 
 
Date 
Signed By 
04-Apr-2017 07:15:52 
PPD 
Justification 
Approved 
 
 
Date 
Signed By 
05-Apr-2017 13:37:52 
PPD 
Justification 
Approved 
 
 
Date 
Signed By 
Justification 
 
 
Date 
Signed By 
Justification